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The Lancet. Global Health Feb 2023Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key... (Review)
Review
Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials-mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.
Topics: Humans; Consensus; Outcome Assessment, Health Care; Snake Bites; Surveys and Questionnaires; Treatment Outcome; Clinical Trials as Topic; Global Health
PubMed: 36669810
DOI: 10.1016/S2214-109X(22)00479-X -
Critical Reviews in Oncology/hematology May 2024Cancer cachexia is a clinical condition characterized by recognizable "sickness behaviors" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition... (Review)
Review
INTRODUCTION
Cancer cachexia is a clinical condition characterized by recognizable "sickness behaviors" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed.
METHODS
A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS).
RESULTS
A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2165) on LDH and weight loss, 17 studies (n=7540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n=32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 - 2.07; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.00, 1.70 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29-2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64-1.90; p<0.00001) as elevated NLR (HR 1.61, 1.48 - 1.77; p<0.00001) or CRP (HR 1.55, 1.43 - 1.69; p<0.00001).
CONCLUSION
Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.
PubMed: 38754770
DOI: 10.1016/j.critrevonc.2024.104378 -
European Review For Medical and... Oct 2012Hemophagocytic lymphohistiocytosis (HLH), is a potentially fatal hyperinflammatory syndrome characterized fever, hepatosplenomegaly, and cytopenias. HLH can be either... (Review)
Review
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH), is a potentially fatal hyperinflammatory syndrome characterized fever, hepatosplenomegaly, and cytopenias. HLH can be either primary, with a genetic aetiology, or secondary, associated with malignancies, autoimmune diseases, or infections. Among rheumatic disorders, HLH occurs most frequently in systemic juvenile idiopathic arthritis.
AIM
To draw attention on this severe syndrome that may often go undiagnosed in patient with rheumatic diseases.
MATERIALS AND METHODS
PubMed search was performed by combining the terms (haemophagocytic, haemophagocytosis, hemophagocytosis, hemophagocytic, erythrophagocytosis, macrophage activation syndrome) and (rheumatic, rheumatologic, arthritis, lupus, Sjögren's syndrome, scleroderma, polymyositis, dermatomyositis, polymyalgia rheumatic, mixed connective tissue disease, polychondritis, sarcoidosis, polyarteritis nodosa, Henoch-Schönlein, serum sickness, wegener's granulomatosis, giant cell arteritis, temporal arteritis, Takayasu's arteritis, Behçet's syndrome, Kawasaki, Buerger's).
RESULTS
117 papers describing 421 patients were considered. HLH was described in systemic lupus erythematosus in 94 patients, in Still's disease in 37 patients, in rheumatoid arthritis in 13 patients, in systemic juvenile arthritis in 219 patients, in dermatomyositis in 7 patients, in Kawasaki disease in 25 patients, in systemic sclerosis in 5 patients, in Behcet disease in one patient, in polyarteritis nodosa in 6 patients, in ankylosing spondylitis in 2 patients, in mixed connective tissue disease in one patient, in sarcoidosis in 5 patients, in Sjögren's syndrome in 3 patients, in Wegener's granulomatosis in one patient, and in unclassifiable disorders in two patients.
CONCLUSIONS
HLH occurring in the course of rheumatic diseases is an important and often underdiagnosed clinical entity, which can affect prognosis.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Prognosis; Rheumatic Diseases
PubMed: 23104659
DOI: No ID Found -
Academic Emergency Medicine : Official... Feb 2012Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation.
METHODS
The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration.
RESULTS
The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta-analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21).
CONCLUSIONS
In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline envenomations appear to be lower than previously reported, at 0.08 and 0.13, respectively.
Topics: Animals; Antivenins; Humans; Hypersensitivity, Immediate; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Incidence; Serum Sickness; Snake Bites; United States
PubMed: 22320362
DOI: 10.1111/j.1553-2712.2011.01276.x -
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 -
Toxins Dec 2021Botulism is a rare, sometimes fatal paralytic illness caused by botulinum neurotoxins. BAT (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) is an...
Botulism is a rare, sometimes fatal paralytic illness caused by botulinum neurotoxins. BAT (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) is an equine-derived heptavalent botulinum antitoxin indicated for the treatment of symptomatic botulism in adult and pediatric patients. This review assesses the cumulative safety profile for BAT product from 2006 to 2020, using data received from clinical studies, an expanded-access program, a post-licensure registry, spontaneous and literature reports. The adverse event (AE) incidence rate for BAT product was calculated conservatively using only BAT product exposures for individuals with a record (512) and was alternatively estimated using all BAT product exposure data, including post-licensure deployment information (1128). The most frequently reported BAT product-related AEs occurring in greater than 1% of the 512-1128 BAT product-exposed individuals were hypersensitivity, pyrexia, tachycardia, bradycardia, anaphylaxis, and blood pressure increase reported in 2.3-5.1%, 1.8-3.9%, 1.0-2.2%, 0.89-2.0%, 0.62-1.4%, and 0.62-1.4%, respectively. For patients properly managed in an intensive care setting, the advantages of BAT product appear to outweigh potential risks in patients due to morbidity and mortality of botulism. AEs of special interest, including bradycardia, hemodynamic instability, hypersensitivity, serum sickness, and febrile reactions in the registry, were specifically solicited.
Topics: Botulinum Antitoxin; Botulism; Humans
PubMed: 35050996
DOI: 10.3390/toxins14010019