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Transplantation and Cellular Therapy Jan 2024Chimeric antigen receptor T cell (CAR-T) therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), are innovative treatments for patients... (Meta-Analysis)
Meta-Analysis
Chimeric antigen receptor T cell (CAR-T) therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), are innovative treatments for patients with relapsed or refractory (r/r) large B cell lymphoma (LBCL). Following initial regulatory approvals, real-world evidence (RWE) of clinical outcomes with these therapies has been accumulating rapidly. Notably, several large registry studies have been published recently. Here we comprehensively describe clinical outcomes with approved CAR-T therapies in patients with r/r LBCL using available RWE. We systematically searched Embase, MEDLINE, and 15 conference proceedings to identify studies published between 2017 and July 2022 that included ≥10 patients with r/r LBCL treated with commercially available CAR-T therapies. Eligible study designs were retrospective or prospective observational studies. Key outcomes of interest were objective response rate (ORR), complete response (CR) rate, overall survival (OS), progression-free survival (PFS), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Random-effects meta-analyses were used to compare real-world outcomes with those of pivotal clinical trials and to compare clinical outcomes associated with axi-cel and tisa-cel. Study cohort mapping was conducted to avoid including patients more than once. Of 76 cohorts we identified, 46 reported patients treated specifically with either axi-cel or tisa-cel, with 39 cohorts (n = 2754 patients) including axi-cel and 20 (n = 1649) including tisa-cel. No studies of liso-cel that met the inclusion criteria were identified during the search period. One-half of the tisa-cel cohorts were European, compared with 33% of the axi-cel cohorts. Among studies with available data, axi-cel had a significantly shorter median time from apheresis to CAR-T infusion than tisa-cel. Despite including broader patient populations, real-world effectiveness and safety of both axi-cel and tisa-cel were consistent with data from the pivotal clinical trials. Comparative meta-analysis of axi-cel versus tisa-cel demonstrated adjusted hazard ratios for OS and PFS of .60 (95% confidence interval [CI], .47 to .77) and .67 (95% CI, .57 to .78), respectively, both in favor of axi-cel. Odds ratios (ORs) for ORR and CR rate, both favoring axi-cel over tisa-cel, were 2.05 (95% CI, 1.76 to 2.40) and 1.70 (95% CI, 1.46 to 1.96), respectively. The probability of grade ≥3 CRS was comparable with axi-cel and tisa-cel, whereas axi-cel was associated with a higher incidence of grade ≥3 ICANS (OR, 3.95; 95% CI, 3.05 to 5.11). Our meta-analysis indicates that CAR-T therapies have manageable safety profiles and are effective in a wide range of patients with r/r LBCL, and that axi-cel is associated with improved OS and PFS and increased risk of grade ≥3 ICANS compared with tisa-cel. Limitations of this study include nonrandomized treatments, potential unknown prognostic factors, and the lack of available real-world data for liso-cel.
Topics: Humans; Cytokine Release Syndrome; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Neurotoxicity Syndromes; Observational Studies as Topic; Pathologic Complete Response; Receptors, Chimeric Antigen; Retrospective Studies; T-Lymphocytes
PubMed: 37890589
DOI: 10.1016/j.jtct.2023.10.017 -
Basic & Clinical Pharmacology &... Jul 2016Antibacterials are frequently associated with idiosyncratic drug-induced liver injury (DILI). The objective of this study was to estimate the risk of macrolides and... (Meta-Analysis)
Meta-Analysis Review
Antibacterials are frequently associated with idiosyncratic drug-induced liver injury (DILI). The objective of this study was to estimate the risk of macrolides and amoxicillin/clavulanate (AMC) on DILI. We conducted a systematic review (SR) and meta-analysis (MA) with studies retrieved from PubMed, Cochrane Library Plus, Web of Knowledge, clinicaltrials.gov, Livertox and Toxline (1980-2014). We searched for macrolides, AMC and MeSH and synonym terms for DILI. We included all study designs except case reports/series, all population ages and studies with a placebo/non-user comparator. We summarized the evidence with a random-effects MA. Quality of the studies was appraised with a checklist developed for SR of adverse effects. Heterogeneity and publication bias were assessed with different exploratory tools. We finally included 10 (two randomized clinical trials, six case-control, one cohort and one case-population studies) and 9 (case-population excluded) articles in the SR and MA, respectively. The overall summary relative risk of DILI for macrolides was 2.85 [95% confidence interval (CI) 1.81-4.47], p < 0.0001, I(2) = 57%. Three studies were perceived to be missing in the area of low statistical significance. Year of study and selected exposure window partly explained the variability between studies. For AMC, the risk of DILI was 9.38 (95% CI 0.65-135.41) p = 0.3, I2 = 95%. In conclusion, although spontaneous reports and case series have long established an association between macrolides and AMC with acute liver injury, these SR and MA have assessed the magnitude of this association. The low incidence of DILI and the therapeutic place of these antibiotics might tilt the balance in favour of their benefits.
Topics: Amoxicillin; Chemical and Drug Induced Liver Injury; Clavulanic Acid; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Macrolides; Randomized Controlled Trials as Topic
PubMed: 26707367
DOI: 10.1111/bcpt.12550 -
International Journal of Molecular... Mar 2023According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones... (Review)
Review
According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances' cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome.
Topics: Mice; Rats; Humans; Animals; Synthetic Cathinone; Zebrafish; Central Nervous System Stimulants; Fever; Amphetamine; Neurotoxicity Syndromes; Psychotropic Drugs
PubMed: 37047201
DOI: 10.3390/ijms24076230 -
Injury Prevention : Journal of the... Jun 2022The prevention of dog bites is an increasingly important public health topic, as the incidence of serious injury continues to rise. (Review)
Review
BACKGROUND
The prevention of dog bites is an increasingly important public health topic, as the incidence of serious injury continues to rise.
OBJECTIVES
To evaluate the effectiveness of interventions to prevent dog bites and aggression.
METHODS
Online databases were searched (PubMed, Cochrane Library, Embase and Google Scholar), using the search terms: , for studies between 1960 and 2021. All study designs were considered. Outcomes of interest were the incidence of dog bites or dog aggression. Non-English studies, and those without full-text access were excluded.
RESULTS
Forty-three studies met the review criteria, including 15 observational and 27 interventional studies. Fifteen studies investigating dog-control legislation, including leash laws, stray dog control and infringements indicated this can reduce dog bite rates. Breed-specific legislation had less of an effect. Six studies investigating sterilisation, showed while this may reduce dog bites through a reduction in the dog population, the effect on dog aggression was unclear. An alcohol reduction programme showed a significant reduction in dog bite rates in one study. Seven studies assessing educational approaches found that intensive adult-directed education may be effective, with one study showing child-directed education was not effective. Eight studies on dog training (two police-dog related), and six evaluating dog medication or diet were generally low quality and inconclusive.
CONCLUSIONS
Multiple strategies including effective engagement with indigenous communities and organisations will be required to reduce dog-bites and other incidents involving dog aggression. This review provides some evidence that legislated dog control strategies reduce dog bite rates. Available evidence suggests greater restrictions should be made for all dogs, rather than based on breed alone. Due to a burden of child injury, protection of children should be a focus of legislation and further investigations. Prevention strategies in children require redirection away from a focus on child-directed education and future research should investigate the effectiveness of engineering barriers and reporting strategies.
Topics: Accidents; Aggression; Animals; Bites and Stings; Breeding; Dogs; Humans; Incidence
PubMed: 35393286
DOI: 10.1136/injuryprev-2021-044477 -
Archives of Public Health = Archives... 2018Acute poisoning is a common reason for emergency department visit and hospitalization worldwide with major morbidity and mortality. The burden of poisoning exposures in... (Review)
Review
BACKGROUND
Acute poisoning is a common reason for emergency department visit and hospitalization worldwide with major morbidity and mortality. The burden of poisoning exposures in Africa is a significant public health concern, but only 10 of 58 countries have poisons information centers (PICs).
OBJECTIVE
The primary intention of our current review is to explore and summarize the published evidence on the patterns and epidemiology of poisoning in Ethiopia.
METHOD
PubMed and Scopus were searched for primary, case series and human studies for publications from inception to July 2017. A manual search for additional relevant studies using references from retrieved articles was also performed. Only studies that reported acute poisoning in both pediatric and adult patients were included. From the screened articles, data were extracted for baseline characteristics and relevant end points such as case fatality rate, time for health institution presentation and length of hospital stay.
RESULT
Initial entry and search resulted in the retrieval of 332 articles. Finally, 9 studies comprised of 4763 participants were included in this current review. In 78% of the studies included in this review, acute poisoning is reported to be more prevalent in females. Acute poisoning was revealed to be prevalent in less than 30 years old. Organophosphates and household cleaning agents were the predominant agents of acute poisoning. Intentional poisoning was identified responsible for the majority of acute poisoning cases and factors such as psychiatric problems, and quarrel were identified as the underlying reasons for poisoning. Time of presentation to health institution after poisoning, length of hospital stay and case fatality rate were reported and lies in the ranges between 0.2 h-24 h, 0.5 days-17.7 days and 0-14.8%, respectively.
CONCLUSION
The occurrence of acute poisoning was higher in females and common in less than 30 years of age, making this a real public health burden in Ethiopia. Psychiatric problems, quarrel and substance abuse were identified as the most common reasons for acute poisoning. Awareness creation how to handle chemicals and prescribed drugs and psychiatric consultations should be in place for the community.
PubMed: 29988616
DOI: 10.1186/s13690-018-0275-3 -
Clinical Toxicology (Philadelphia, Pa.) Aug 2021Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is...
CONTEXT
Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is available for purchase online. Thus, accidental exposure to azide or use as a homicidal or suicidal agent could be on the rise, and secondary exposure to medical personnel can occur. No antidote exists for azide poisoning. We conducted a systematic review of azide poisoning to assess recent poisoning reports, exposure scenarios, clinical presentations, and treatment strategies.
METHODS
We searched both medical and newspaper databases to review the literature between 01/01/2000 and 12/31/2020, pairing the controlled vocabulary and keyword terms "sodium azide" or "hydrazoic acid" with terms relating to exposures and outcomes, such as "ingestion," "inhalation," "exposure," "poisoning," and "death." We included all peer-reviewed papers and news articles describing human azide poisoning cases from English and non-English publications that could be identified using English keywords. Data abstracted included the number, age, and gender of cases, mode of exposure, exposure setting, azide dose and route of exposure, symptoms, outcome, and treatment modalities.
RESULTS
We identified 663 peer-reviewed papers and 303 newspaper articles. After removing duplicated and non-qualifying sources, 54 publications were reviewed describing 156 cases, yielding an average of 7.8 reported azide poisoning cases per year. This rate is three times higher than in a previous review covering the period of 1927 to 1999. Poisoning occurred most commonly in laboratory workers, during secondary exposure of medical personnel, or from a ripped airbag. Hypotension occurred commonly, in some cases requiring vasopressors and one patient received an intra-aortic ballon pump. Gastric lavage and/or activated charcoal were used for oral azide ingestion, and sodium nitrite, sodium thiosulfate, and/or hydroxocobalamin were used in severely poisoned patients.
CONCLUSIONS
Recent increases in azide poisoning reports may stem from greater commercial use and availability. Treatment of systemic poisoning may require aggressive hemodynamic support due to profound hypotension. Based on mechanistic considerations, hydroxocobalamin is a rational choice for treating azide poisoning.
Topics: Adult; Aged; Antidotes; Female; Humans; Hypotension; Male; Middle Aged; Occupational Exposure; Poisoning; Sodium Azide; Sodium Nitrite; Suicide, Attempted; Thiosulfates
PubMed: 34128439
DOI: 10.1080/15563650.2021.1906888 -
Addiction (Abingdon, England) Dec 2023Many countries have recently legalized medicinal and recreational cannabis. With increasing use and access come the potential for harms. We aimed to examine the effect... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Many countries have recently legalized medicinal and recreational cannabis. With increasing use and access come the potential for harms. We aimed to examine the effect of cannabis legalization/decriminalization on acute poisoning.
METHODS
A systematic review and meta-analysis registered with PROSPERO (CRD42022323437). We searched Embase, Medline, Scopus and Cochrane Central Register of Controlled Trials from inception to March 2022. No restrictions on language, age or geography were applied. Abstracts from three main clinical toxicology conferences were hand-searched. Included studies had to report on poisonings before and after changes in cannabis legislation, including legalization and decriminalization of medicinal and recreational cannabis. Where possible, relative risk (RR) of poisoning after legalization (versus before) was calculated and pooled. Risk of bias was assessed with ROBINS-I.
RESULTS
Of the 1065 articles retrieved, 30 met inclusion criteria (including 10 conference abstracts). Studies used data from the United States, Canada and Thailand. Studies examined legalization of medicinal cannabis (n = 14) and decriminalization or legalization of recreational cannabis (n = 21). Common data sources included poisons centre records (n = 18) and hospital presentations/admissions (n = 15, individual studies could report multiple intervention types and multiple data sources). Most studies (n = 19) investigated paediatric poisoning. Most (n = 24) reported an increase in poisonings; however, the magnitude varied greatly. Twenty studies were included in quantitative analysis, with RRs ranging from 0.81 to 29.00. Our pooled estimate indicated an increase in poisoning after legalization [RR = 3.56, 95% confidence interval (CI) = 2.43-5.20], which was greater in studies that focused on paediatric patients (RR = 4.31, 95% CI = 2.30-8.07).
CONCLUSIONS
Most studies on the effect of medicinal or recreational cannabis legalization/decriminalization on acute poisoning reported a rise in cannabis poisoning after legalization/decriminalization. Most evidence is from US legalization, despite legalization and decriminalization in many countries.
Topics: Humans; United States; Child; Cannabis; Medical Marijuana; Legislation, Drug; Hallucinogens; Canada
PubMed: 37496145
DOI: 10.1111/add.16280 -
Systematic Reviews Oct 2023Food-borne diseases are a global public health issue with 1 in 10 people falling ill after eating contaminated food every year. In response, the food industry has... (Meta-Analysis)
Meta-Analysis Review
Food-borne diseases are a global public health issue with 1 in 10 people falling ill after eating contaminated food every year. In response, the food industry has implemented several new pathogen control strategies, such as biotechnological tools using the direct application of bacteriophages for biological control. We have undertaken a systematic review and meta-analysis that evaluated the efficiency of patented phages as a biological control for food-borne pathogens and determined the physical-chemical characteristics of the antimicrobial effect. Included and excluded criteria was developed. Included criteria: Phage patent files with an application in biological control on food and scientific articles and book chapters that used phages patented for food biological control. Excluded criteria: Patent documents, scientific articles, and book chapters that included phage therapy in humans, animals, and biological control on plants but did not have an application on food were not considered in our study. The systematic analysis identified 77 documents, 46 scientific articles, and 31 documents of patents and 23 articles was included in the meta-analysis. Listeria monocytogenes and Salmonella sp. comprised most of the targets identified in the screening, so that we focused on these strains to do the meta-analysis. There are a total of 383 and 192 experiments for Listeria and Salmonella phages for quantitative data analysis.Indexing databases for the bibliographic search (Scopus, Web of Science (WoS) and PubMed (Medline) were addressed by an automated script written in Python 3 Python Core Team (2015) and deposited on GitHub ( https://github.com/glenjasper ).A random-effects meta-analysis revealed (i) significant antimicrobial effect of Listeria phages in apple, apple juice, pear, and pear juice, (ii) significant antimicrobial effect of Salmonella phages in eggs, apple, and ready-to-eat chicken, (iii) no heterogeneity was identified in either meta-analysis, (iv) publication bias was detected for Listeria phages but not for Salmonella phages. (v) ListShield and Felix01 phages showed the best result for Listeria and Salmonella biological control, respectively, (vi) concentration of phage and bacteria, time and food had significant effect in the biological control of Listeria, (vii) temperature and time had a significant effect on the antimicrobial activity of Salmonella phages. The systematic review and meta-analyses to determine the efficiency of bacteriophages previously patented against pathogenic bacteria on dairy products, meat, fruits and vegetables. Besides, the discovering of key factors for efficacy, so that future applications of phage biotechnology in foods can be optimally deployed.
Topics: Anti-Infective Agents; Bacteriophages; Foodborne Diseases; Listeria monocytogenes; Meat
PubMed: 37898821
DOI: 10.1186/s13643-023-02352-9 -
The Indian Journal of Medical Research Sep 2016Amitraz is a member of formamidine family of pesticides. Poisoning from amitraz is underrecognized even in areas where it is widely available. It is frequently... (Review)
Review
BACKGROUND & OBJECTIVES
Amitraz is a member of formamidine family of pesticides. Poisoning from amitraz is underrecognized even in areas where it is widely available. It is frequently misdiagnosed as organophosphate poisoning. This systematic review provides information on the epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, diagnosis and management of amitraz poisoning.
METHODS
Medline and Embase databases were searched systematically (since inception to January 2014) for case reports, case series and original articles using the following search terms: 'amitraz', 'poisoning', 'toxicity', 'intoxication' and 'overdose'. Articles published in a language other than English, abstracts and those not providing sufficient clinical information were excluded.
RESULTS
The original search yielded 239 articles, of which 52 articles described human cases. After following the inclusion and exclusion criteria, 32 studies describing 310 cases (151 females, 175 children) of human poisoning with amitraz were included in this systematic review. The most commonly reported clinical features of amitraz poisoning were altered sensorium, miosis, hyperglycaemia, bradycardia, vomiting, respiratory failure, hypotension and hypothermia. Amitraz poisoning carried a good prognosis with only six reported deaths (case fatality rate, 1.9%). Nearly 20 and 11.9 per cent of the patients required mechanical ventilation and inotropic support, respectively. The role of decontamination methods, namely, gastric lavage and activated charcoal was unclear.
INTERPRETATION & CONCLUSIONS
Our review shows that amitraz is an important agent for accidental or suicidal poisoning in both adults and children. It has a good prognosis with supportive management.
Topics: Adult; Child; Child, Preschool; Female; Humans; Male; Pesticides; Poisoning; Prognosis; Toluidines
PubMed: 28139533
DOI: 10.4103/0971-5916.198723 -
Bulletin of the World Health... Mar 2017To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses),... (Review)
Review
OBJECTIVE
To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost-effectiveness and recommendations for use, particularly in high-risk settings.
METHODS
We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines.
FINDINGS
Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability.
CONCLUSION
Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.
Topics: Age Factors; Animals; Bites and Stings; Chiroptera; Cost-Benefit Analysis; Developing Countries; Dogs; Health Services; Humans; Immunization Programs; Immunization Schedule; Models, Econometric; Peru; Philippines; Rabies Vaccines; Risk Factors; Time Factors
PubMed: 28250534
DOI: 10.2471/BLT.16.173039