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Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review.International Journal of Toxicology 2024The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main... (Review)
Review
The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.
Topics: Banisteriopsis; Humans; N,N-Dimethyltryptamine; Animals; Plant Extracts; Harmine; Harmaline
PubMed: 38363085
DOI: 10.1177/10915818241230916 -
Expert Review of Clinical Pharmacology Nov 2022Interstitial lung disease (ILD) events associated with anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) have aroused wide attention. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Interstitial lung disease (ILD) events associated with anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) have aroused wide attention.
RESEARCH DESIGN AND METHODS
In meta-analysis, we systematically reviewed literatures, and the outcomes were the proportion and risk of ILD related to anti-HER2 ADCs. A disproportionality analysis based on data from VigiBase was conducted to characterize the main features of anti-HER2 ADC-related ILD/pneumonitis.
RESULTS
Two hundred and forty-five all-grade and 47 grade ≥ 3 ILD events with the proportion of 4.4% (95% confidence interval (CI) [2.0%, 6.8%]) and 0.5% (95% CI [0.3%, 0.8%]) were observed for anti-HER2 ADCs, respectively. Trastuzumab emtansine, trastuzumab deruxtecan and trastuzumab duocarmazine significantly increased the risk of all-grade and grade ≥ 3 ILD events with Peto odd ratios of 2.62 (95% CI [1.71, 4.04], P < 0.0001) and 2.82 (95% CI [1.07, 7.42], P = 0.04), respectively. In VigiBase, 271 cases of ILD/pneumonitis related to trastuzumab emtansine and trastuzumab deruxtecan were extracted. The median time to the onset of event was 86 days and 54.95% of events occurred within 3 months.
CONCLUSIONS
Trastuzumab emtansine, trastuzumab deruxtecan and trastuzumab duocarmazine increased the risk of ILD, which can lead to serious outcomes and tends to occur early.
Topics: Humans; Female; Ado-Trastuzumab Emtansine; Pharmacovigilance; Trastuzumab; Receptor, ErbB-2; Immunoconjugates; Antineoplastic Agents; Lung Diseases, Interstitial; World Health Organization; Breast Neoplasms
PubMed: 36111954
DOI: 10.1080/17512433.2022.2121705 -
Vaccine Mar 2017Kawasaki disease is a complex and potentially serious condition. It has been observed in temporal relation to immunisation. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kawasaki disease is a complex and potentially serious condition. It has been observed in temporal relation to immunisation.
METHODS
We conducted a systematic literature review using various reference sources to review the available evidence published in the literature.
RESULTS
We identified twenty seven publications reporting a temporal association between immunisation and Kawasaki disease. We present a systematic review of data drawn from randomised controlled trials, observational studies, case series and reports, and reviews. Overall there was a lack of standardised case definitions, making data interpretation and comparability challenging.
CONCLUSIONS
Although a temporal relationship between immunisation and Kawasaki disease is suggested, evidence for an increased risk or a causal association is lacking. Implementation of a standardised Kawasaki disease case definition would increase confidence in the findings and add value to future studies of pre- or post-licensure vaccine safety studies.
Topics: Humans; Immunization; Mucocutaneous Lymph Node Syndrome; Risk; Vaccination; Vaccines
PubMed: 28259442
DOI: 10.1016/j.vaccine.2016.09.033 -
Pharmacoepidemiology and Drug Safety Jun 2021Andrographis paniculata is one of the commonly used herbal medicines worldwide. Nevertheless, evidences on adverse events (AEs) associated with Andrographis paniculata... (Meta-Analysis)
Meta-Analysis
PURPOSE
Andrographis paniculata is one of the commonly used herbal medicines worldwide. Nevertheless, evidences on adverse events (AEs) associated with Andrographis paniculata are very limited. This systematic review and meta-analysis was conducted to estimate and to compare the AE incidence of oral monotherapy Andrographis paniculata with others among patients with upper respiratory tract infection, noninfective diarrhea, and autoimmune disease.
METHODS
Systematic search was performed through six databases from inception until August 2018. Randomized controlled trial (RCT), cohort, or intensive monitoring of AEs was eligible for review if AE incidence was examined. The incidence of AEs was, then, pooled across studies using meta-analysis.
RESULTS
Ten RCTs and 3 intensive monitoring studies were included. Incidence of serious AEs was very rare with the pooled incidence (95% CI) from RCTs of 0.02 per 1000 patients (0.0-0.5). However, the incidence of nonserious AEs was considered very common with the pooled incidence (95% CI) from RCTs of 102.6 per 1000 patients (10.7-256.1), and the pooled incidence (95% CI) from intensive monitoring of 34.2 per 1000 patients (0.0-229.6). The most common nonserious AEs were related to gastrointestinal disorder, and skin and subcutaneous disorder system.
CONCLUSIONS
Like other medicine, Andrographis paniculata can cause some AEs. However, it may be generally safe. Nevertheless, prospective patients who plan to use Andrographis paniculata should be thoroughly advised and closely monitored for common AEs. Due to the increasing use of Andrographis paniculata worldwide, larger studies with adequate methodological quality are warranted to monitor the safety of such product.
Topics: Andrographis; Cohort Studies; Humans
PubMed: 33372366
DOI: 10.1002/pds.5190 -
Drug Safety Dec 2020Checkpoint inhibitor drugs including ipilimumab have been reported to induce intestinal injury. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Checkpoint inhibitor drugs including ipilimumab have been reported to induce intestinal injury.
OBJECTIVE
We aimed to evaluate the risk of chronic (> 6 weeks) enterocolitis following ipilimumab administration, and the likelihood that an enteritis vs colitis or enterocolitis is seen.
PATIENTS AND METHODS
We searched MEDLINE, EMBASE, CENTRAL, the World Health Organization International Clinical Trials Registry, and conference proceedings. We included: (1) randomized controlled trials comparing ipilimumab administration with placebo/standard care/other active chemotherapy regimens and (2) prospective observational studies. Separate meta-analyses were performed for randomized controlled trials and observational studies.
RESULTS
Of 4760 records, we included ten unique randomized controlled trials (n = 5814 subjects) and 34 unique prospective observational studies (n = 3699 subjects). In randomized controlled trials, the pooled relative risk of ≥ grade 3 enterocolitis or ≥ grade 3 diarrhea associated with ipilimumab was 13.31 (95% confidence interval 6.01-29.48, I = 0%, ten trials) and 6.72 (95% confidence interval 3.30-13.65, I = 63%, ten trials), respectively. In observational studies, the 3-monthly risk of developing grade 3 or higher enteritis, colitis, or enterocolitis was 4% (95% confidence interval 3-7, I = 77.40%, 25 studies). Randomized controlled trials and observational studies did not distinguish between acute and chronic enterocolitis. Of the included observational studies, the pooled risk of incurring small bowel involvement associated with ipilimumab was 1% (95% CI 0-4, I = 0%, four studies) per every 3-month time period.
CONCLUSIONS
Insufficient data exist to quantify or distinguish the risk of acute vs chronic enterocolitis following ipilmumab use. Because of the serious impact of chronic enterocolitis on quality of life and further cancer treatment, future trials evaluating the safety of immunotherapy should report gastrointestinal events in greater detail.
Topics: Enterocolitis; Humans; Immune Checkpoint Inhibitors; Ipilimumab; Pharmacovigilance; Randomized Controlled Trials as Topic
PubMed: 32749630
DOI: 10.1007/s40264-020-00979-4 -
Expert Opinion on Drug Safety Nov 2018Social media mining could be a possible strategy to retrieve drug safety information. The mining of social media is a complex process under progressive evolution,... (Review)
Review
Social media mining could be a possible strategy to retrieve drug safety information. The mining of social media is a complex process under progressive evolution, falling into three broad categories: listening (safety data reporting), engaging (follow-up), and broadcasting (risk communication). This systematic review is aimed at evaluating the usefulness and quality of proto-signals by social media listening. Areas covered: In this systematic search, performed according to MOOSE and PRISMA statements, we selected studies, published in MEDLINE, EMBASE, and Google Scholar until 31 December 2017, that listened at least one social media to identify proto-adverse drug events and proto-signals. Expert opinion: The selected 38 studies identified serious and unexpected proto-adverse drug events characterized by poorer information quality as compared with spontaneous reporting databases. This feature allows rarely the evaluation of causal relationships. Proto-signals identified by social media listening had the potential of anticipating pre-specified known signals in only six studies. Moreover, the personal perception of patients reported in social media could be used to implement effective risk communication strategies. However, signal detection in social media cannot be currently recommended for routine pharmacovigilance, due to logistic and technical issues.
Topics: Adverse Drug Reaction Reporting Systems; Data Mining; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacovigilance; Social Media
PubMed: 30285501
DOI: 10.1080/14740338.2018.1531847 -
Human Reproduction Update Nov 2020Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated...
BACKGROUND
Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment.
OBJECTIVE AND RATIONALE
The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes.
SEARCH METHODS
A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data.
OUTCOMES
A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-α inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressive drug exposure was reported.
WIDER IMPLICATIONS
Evidence regarding the safety of immunosuppressive drugs in men with a wish to become a father is inconclusive. The lack of standardisation on how to evaluate and report male sexual function, fertility and reproduction as study outcomes in men exposed to immunosuppressive drugs is an important contributor to this result. Future research on this topic is needed and should be preferably done using standardised methods.
Topics: Adult; Female; Fertility; Gonadal Hormones; Humans; Immunosuppressive Agents; Infant, Newborn; Infertility, Male; Male; Paternal Exposure; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Risk Factors; Sexual Behavior; Sexual Dysfunction, Physiological; Young Adult
PubMed: 32743663
DOI: 10.1093/humupd/dmaa022 -
Journal of Virus Eradication Apr 2018The integrase strand transfer inhibitor dolutegravir (DTG) is being introduced into low- and middle-income countries (LMICs) as an alternative to first-line treatment...
BACKGROUND
The integrase strand transfer inhibitor dolutegravir (DTG) is being introduced into low- and middle-income countries (LMICs) as an alternative to first-line treatment with non-nucleoside reverse transcriptase inhibitors. However, DTG is not yet widely recommended for use in pregnant women. The aim of this systematic review was to analyse all available data on birth outcomes and congenital anomalies in the infants of pregnant women treated with DTG.
METHODS
A PubMed and Embase search was conducted using the terms "dolutegravir" or "DTG" and "pregnancy" or "pregnant" from the earliest available date on the database to 26 July 2017. Any reports involving women who were pregnant, HIV positive and taking DTG were included. The percentage of pregnant women with adverse birth outcomes or congenital anomalies in their infants after taking dolutegravir was compared with five historical control databases.
RESULTS
There were six databases included in the main analysis of birth outcomes and congenital anomalies, with a total of 1200 pregnant women. The percentage of pregnant women taking DTG with adverse birth outcomes and congenital abnormalities was similar to results from historical control studies of HIV-positive women. However, there was significant heterogeneity among the six databases - the percentage of infants with congenital anomalies ranged from 0.0% in Botswana (0/116 infants) to 13.3% in IMPAACT P1026S (2/15 infants).
CONCLUSIONS
Up to 15 million people could be on treatment with DTG in LMICs within the next 5 years, of whom a substantial percentage is likely to be women of child-bearing potential. In many countries with large HIV epidemics, unplanned pregnancies are common and access to antenatal clinic facilities may be limited. Continued pharmacovigilance is essential, but it is reassuring that no clear safety signals have been detected, to date, for pregnant women treated with DTG in terms of birth outcomes or congenital anomalies.
PubMed: 29682297
DOI: No ID Found -
The European Respiratory Journal Mar 2022Obstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH exposure. To clarify this major issue, we conducted a systematic review and meta-analysis to quantify the impact of IH on systemic artery structure and function depending on the different IH exposure designs.
METHODS
We searched PubMed, Embase and Web of Science, and included 125 articles in a meta-analysis, among them 112 using wild-type rodents and 13 using apolipoprotein E knockout (ApoE) mice. We used the standardised mean difference (SMD) to compare results between studies.
RESULTS
IH significantly increased mean arterial pressure (+13.90 (95% CI 11.88-15.92) mmHg), and systolic and diastolic blood pressure. Meta-regressions showed that mean arterial pressure change was associated with strain and year of publication. IH altered vasodilation in males but not in females and increased endothelin-1-induced but not phenylephrine-induced vasoconstriction. Intima-media thickness significantly increased upon IH exposure (SMD 1.10 (95% CI 0.58-1.62); absolute values +5.23 (2.81-7.84) µm). This increase was observed in mice but not in rats and was negatively associated with age. Finally, IH increased atherosclerotic plaque size in ApoE mice (SMD 1.08 (95% CI 0.80-1.37)).
CONCLUSIONS
Our meta-analysis established that IH, independently of other confounders, has a strong effect on vascular structure and physiology. Our findings support the interest of identifying and treating sleep apnoea in routine cardiology practice.
Topics: Animals; Blood Pressure; Carotid Intima-Media Thickness; Disease Models, Animal; Female; Humans; Hypoxia; Male; Mice; Rats; Rodentia
PubMed: 34413154
DOI: 10.1183/13993003.00866-2021 -
Kidney360 Jan 2024There is dramatic global variability in the prevalence of ESKD. Higher health care spending in each country is associated with increased delivery of care for ESKD.
KEY POINTS
There is dramatic global variability in the prevalence of ESKD. Higher health care spending in each country is associated with increased delivery of care for ESKD.
BACKGROUND
Approaches to treating ESKD may vary internationally on the basis of the availability of care and other factors. We performed a systematic review to understand the international variability in ESKD epidemiology, management, and outcomes.
METHODS
We systematically searched PubMed for population-based studies of CKD and ESKD epidemiology and management. Population-level data from 23 predesignated nations were eligible for inclusion if they pertained to people receiving dialysis or kidney transplant for ESKD. When available, government websites were used to identify and extract data from relevant kidney registries. Measures gathered included those related to the prevalence and mortality of ESKD; the availability of nephrologists; health care expenditures; and use of erythropoietin-stimulating agents.
RESULTS
We obtained data from the United States; seven nations in Eastern Europe; four each in Western Europe, Latin America, and Africa; and three in Asia. The documented prevalence of ESKD per million population varied from a high of 3600 (Malaysia) to a low of 67 (Senegal). The annual mortality associated with ESKD varied from 31% (Ethiopia and Senegal) to 10% (the United Kingdom). Nephrologist availability per million population varied from 40 (Japan) to <1 (South Africa) and was associated with health care expenditures.
CONCLUSIONS
The delivery of kidney care related to ESKD varies widely among countries. Higher health care spending is associated with increased delivery of kidney care. However, in part because documentation of kidney disease varies widely, it is difficult to determine how outcomes related to ESKD may vary across nations.
Topics: Humans; Kidney Failure, Chronic; Disease Progression
PubMed: 38055708
DOI: 10.34067/KID.0000000000000335