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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 -
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 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 -
The World Allergy Organization Journal Sep 2023Beta-lactams (BLs) are the most prescribed antibiotics, being the most frequent cause of drug allergy. However, the association between BL allergy and genetic variations...
IMPORTANCE
Beta-lactams (BLs) are the most prescribed antibiotics, being the most frequent cause of drug allergy. However, the association between BL allergy and genetic variations is still unclear.
OBJECTIVE
This systematic review and meta-analysis aimed to summarize the genetic effects of BL-induced hypersensitivity using existing evidence.
METHODS
We searched PubMed, Medline, Scopus, EMBASE, CINAHL, and Cochrane Library from inception to September 15, 2022 with no language restriction. Genetic association studies investigating genetic variant/polymorphism and risk of drug-induced hypersensitivity reactions among individuals receiving BL-antibiotics were included. We excluded studies of acute interstitial nephritis, drug-induced liver injury, serum sickness, and isolated drug fever. Data were comprehensively synthesized and quality of study were assessed using STrengthening the Reporting of Genetic Association Studies (STREGA). The record screening, extraction and quality assessment were performed by two reviewers and discussions were made to resolve discrepancies. The effects of each variant were pooled and evaluated by modified Venice criteria.
RESULTS
A total of 9276 records were identified, and 31 studies were eligible for inclusion. Twenty-seven were candidate-gene association studies (5416 cases and 5939 controls), while the others were next-generation sequencing (NGS) or genome-wide association studies (GWASs) (119 838 cases and 1 487 111 controls). Forty-nine polymorphisms were identified and most of them located in allergic reaction pathways. Meta-analyses of 15 candidate variants in a mixture of both immediate and non-immediate reactions revealed weak genetic effects of rs1801275 (8 studies; n = 1,560; odd ratio 0.73; 95%CI: 0.57-0.93) and rs20541 (4 studies; n = 1,482; odd ratio 1.34; 95%CI: 1.07-1.68) in and , respectively. Results from GWASs and NGS identified, and confirmed associations in HLA regions including and .
CONCLUSION
Our study summarized genetic evidence influencing BL-induced hypersensitivity and estimated effects of potential variants. We postulated that the genomic studies provide better insights to the mechanism of reactions and suggest potential effects of HLA Class II variants. However, results were inconsistent and unable to generalize in different settings. Further high-throughput studies with a well-defined function, epigenetic interaction, incorporated with clinical factors, would be beneficial for risk identification in BL-induced hypersensitivity.
PubMed: 37780578
DOI: 10.1016/j.waojou.2023.100816 -
BMC Pulmonary Medicine Jul 2023Asthma exacerbations reduce the patient's quality of life and are also responsible for significant disease burdens and economic costs. Machine learning (ML)-based... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asthma exacerbations reduce the patient's quality of life and are also responsible for significant disease burdens and economic costs. Machine learning (ML)-based prediction models have been increasingly developed to predict asthma exacerbations in recent years. This systematic review and meta-analysis aimed to identify the prediction performance of ML-based prediction models for asthma exacerbations and address the uncertainty of whether modern ML methods could become an alternative option to predict asthma exacerbations.
METHODS
PubMed, Cochrane Library, EMBASE, and Web of Science were searched for studies published up to December 15, 2022. Studies that applied ML methods to develop prediction models for asthma exacerbations among asthmatic patients older than five years and were published in English were eligible. The prediction model risk of bias assessment tool (PROBAST) was utilized to estimate the risk of bias and the applicability of included studies. Stata software (version 15.0) was used for the random effects meta-analysis of performance measures. Subgroup analyses stratified by ML methods, sample size, age groups, and outcome definitions were conducted.
RESULTS
Eleven studies, including 23 prediction models, were identified. Most of the studies were published in recent three years. Logistic regression, boosting, and random forest were the most used ML methods. The most common important predictors were systemic steroid use, short-acting beta2-agonists, emergency department visit, age, and exacerbation history. The overall pooled area under the curve of the receiver operating characteristics (AUROC) of 11 studies (23 prediction models) was 0.80 (95% CI 0.77-0.83). Subgroup analysis based on different ML models showed that boosting method achieved the best performance, with an overall pooled AUROC of 0.84 (95% CI 0.81-0.87).
CONCLUSION
This study identified that ML was the potential tool to achieve great performance in predicting asthma exacerbations. However, the methodology within these models was heterogeneous. Future studies should focus on improving the generalization ability and practicability, thus driving the application of these models in clinical practice.
Topics: Humans; Quality of Life; Asthma; Steroids; Machine Learning; Cost of Illness
PubMed: 37507662
DOI: 10.1186/s12890-023-02570-w -
Archives of Dermatological Research Jun 2024Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), grouped together under the terminology of epidermal necrolysis (EN), are a spectrum of... (Review)
Review
Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), grouped together under the terminology of epidermal necrolysis (EN), are a spectrum of life-threatening dermatologic conditions. A lack of standardization and validation for existing endpoints has been identified as a key barrier to the comparison of these therapies and development of evidenced-based treatment. Following PRISMA guidelines, we conducted a systematic review of prospective studies involving systemic or topical treatments for EN, including dressing and ocular treatments. Outcomes were separated into mortality assessment, cutaneous outcomes, non-cutaneous clinical outcomes, and mucosal outcomes. The COSMIN Risk of Bias tool was used to assess the quality of studies on reliability and measurement error of outcome measurement instruments. Outcomes across studies assessing treatment in the acute phase of EN were varied. Most data came from prospective case reports and cohort studies representing the lack of available randomized clinical trial data available in EN. Our search did not reveal any EN-specific validated measures or scoring tools used to assess disease progression and outcomes. Less than half of included studies were considered "adequate" for COSMIN risk of bias in reliability and measurement error of outcome measurement instruments. With little consensus about management and treatment of EN, consistency and validation of measured outcomes is of the upmost importance for future studies to compare outcomes across treatments and identify the most effective means of combating the disease with the highest mortality managed by dermatologists.
Topics: Humans; Stevens-Johnson Syndrome; Reproducibility of Results; Outcome Assessment, Health Care; Treatment Outcome; Bandages
PubMed: 38878166
DOI: 10.1007/s00403-024-03062-5 -
Frontiers in Medicine 2023Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug,...
BACKGROUND
Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug, oxcarbazepine, may cause Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). However, the clinical features of oxcarbazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) remain ambiguous. This article aims to explore the clinical features of SJS/TEN.
METHODS
Systematic searches of several Chinese and English databases were conducted for case reports published on PubMed, EMBASE, Web of Science, MEDLINE, CNKI from January 1, 2007 to March 1, 2023.
RESULTS
A total of seventeen patients (10 males and 7 females) were included in this study, including nine adult patients and eight pediatric patients. The results showed that males seem to have a higher prevalence of SJS/TEN than females, and SJS/TEN usually occurs within 2 weeks after administration of oxcarbazepine (OXC). The main clinical manifestations among the included patients were rashes or maculopapules (17 cases, 100%), fever (11 cases, 64.7%), mucosal lesions (15 cases, 88.2%), conjunctivitis with/without ocular discharge (12 cases, 70.6%), and blisters (12 cases, 70.6%). After stopping OXC or switching to other drugs that treat primary disease as well as treatment with IVIG, glucocorticoid, anti-allergy, and fluid replacement, eight of the included patients recovered completely, and another eight of the included patients reported symptomatic improvement, while the prognosis of one of the included patients was not reported.
CONCLUSION
Diverse clinical signs and symptoms of SJS/TEN might result in misinterpretation and delayed diagnosis. It should be identified and treated immediately to avoid significant consequences and potentially jeopardize patients' lives.
PubMed: 37881633
DOI: 10.3389/fmed.2023.1232969