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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 -
Frontiers in Pediatrics 2023Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin... (Review)
Review
BACKGROUND
Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin receptor agonist, provides a hematologic improvement in adults with severe aplastic anemia (SAA) refractory to immunosuppressive therapy (IST). The association of ELT and IST was approved by the US Food and Drug Administration (FDA) for adults and children ≥2 years of age as a first-line treatment for SAA. However, the effects of ELT on pediatric patients with SAA remain controversial and limited.
METHODS AND FINDINGS
We conducted a systematic review of the most recent literature from Pubmed, Web of Science, and Embase, published up to 20th December 2022, in order to evaluate the available evidence on the efficacy and safety of ELT added to IST for the treatment of SAA in the pediatric population.
CONCLUSION
Eltrombopag added to the IST has shown a good safety profile, without manifestations of excessive toxic effects, although not all the results obtained from our studies support the addition of ELT to the IST in the first-line treatment of children with SAA.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42022325859.
PubMed: 37168802
DOI: 10.3389/fped.2023.1149718 -
International Journal of Environmental... Dec 2022Immune checkpoint inhibitors (ICIs) are recommended for various types of cancer. On the other hand, these ICIs may cause immune-related adverse events (irAEs). Lichen... (Review)
Review
INTRODUCTION
Immune checkpoint inhibitors (ICIs) are recommended for various types of cancer. On the other hand, these ICIs may cause immune-related adverse events (irAEs). Lichen sclerosus (LS) and lichen planus (LP) are two distinct phenotypes of irAEs that occur in a subset of patients treated with ICIs. These adverse effects have a detrimental effect on the patient's quality of life and treatment phases; however, the clinical evaluation and assessment of LS and LP remain uncertain. This study aims to assess and evaluate the risk of LS and LP associated with the use of ICIs via a systematic review of the literature and the USA FDA Adverse Events FAERS database.
METHOD
The study searched electronic databases such as PubMed, Medline, Cochrane, and Google Scholar for case reports on immune-checkpoint-inhibitor-associated lichen sclerosus and lichen planus published in English between inception and 31 December 2021. The FDA's adverse event reporting system (FAERS) database was also analyzed.
RESULTS
Thirty-eight case reports and two retrospective studies with a total of 101 patients, in addition to the FAERS data, were evaluated. More cases involved lichen planus (78.9%) than lichen sclerosis (21%). Nivolumab and pembrolizumab were most frequently reported with LS and LP, among other ICIs. Thirty-six out of thirty-eight patients with LS or LP experienced complete remission, while two patients experienced partial remission. Most of the cases had an excellent response to corticosteroids (92.1%), while the remainder had moderate (5.2%) and poor (2.6%) responses. Additionally, the reporting odds ratio (ROR) of the FAERS database indicated a favorable association for ICIs, the risk of LP, and LS. A stronger association was uniquely found between nivolumab and pembrolizumab.
CONCLUSION
There have been published case reports for these adverse events. Healthcare providers should be aware of the possibility of lichen sclerosis and lichen planus developing in patients receiving ICIs which could necessitate hospitalization or discontinuation. Regulatory agencies are advised to monitor the risks as a potential safety signal.
Topics: Humans; Immune Checkpoint Inhibitors; Lichen Planus; Lichen Sclerosus et Atrophicus; Nivolumab; Quality of Life; Retrospective Studies
PubMed: 36612904
DOI: 10.3390/ijerph20010580 -
Health Technology Assessment... May 2016Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.
OBJECTIVES
To (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu(®), Roche) treatment on mortality in patients with 2009A/H1N1 influenza.
METHODS
We searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators' comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies.
RESULTS
Effect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%). Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65).
CONCLUSIONS
Oseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002245.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Antiviral Agents; Asthma; Child; Dose-Response Relationship, Drug; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Neuraminidase; Oseltamivir; Randomized Controlled Trials as Topic; Zanamivir
PubMed: 27246259
DOI: 10.3310/hta20420 -
A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among older adults.Vaccine Jul 2018New adjuvants have been developed to improve the efficacy of vaccines and for dose-sparing capacity and may overcome immuno senescence in the elderly. We reviewed the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
New adjuvants have been developed to improve the efficacy of vaccines and for dose-sparing capacity and may overcome immuno senescence in the elderly. We reviewed the safety of newly-adjuvanted vaccines in older adults.
METHODS
We searched Medline for clinical trials (CTs) including new adjuvant systems (AS01, AS02, AS03, or MF59), used in older adults, published between 01/1995 and 09/2017. Safety outcomes were: serious adverse events (SAEs); solicited local and general AEs (reactogenicity); unsolicited AEs; and potentially immune-mediated diseases (pIMDs). Standard random effects meta-analyses were conducted by type of safety event and adjuvant type, reporting Relative Risks (RR) with 95% confidence intervals (95% CI).
RESULTS
We identified 1040 publications, from which we selected 7, 7, and 12 CTs on AS01/AS02, AS03 and MF59, respectively. 47,602 study participants received newly-adjuvanted vaccine and 44,521 control vaccine, or placebo. Rates of SAEs (RR = 0.99, 95% CI = 0.96-1.02), deaths (RR = 0.99, 95% CI = 0.92-1.06) and pIMDs (RR = 0.94, 95% CI = 0.79-1.1) were comparable in newly-adjuvanted and control groups. Vaccine-related SAEs occurred in <1% of the subjects in both groups. The reactogenicity of AS01/AS02 and AS03 adjuvanted vaccines was higher compared to control vaccines, whereas MF59-adjuvanted vaccines resulted only in more pain. Grade 3 reactogenicity was reported infrequently, with fatigue (RR = 2.48, 95% CI = 1.69-3.64), headache (RR = 2.94, 95% CI = 1.24-6.95), and myalgia (RR = 2.68, 95% CI = 1.86-3.80) occurring more frequently in newly-adjuvanted groups. Unsolicited AEs occurred slightly more frequently in newly-adjuvanted groups (RR = 1.04, 95% CI = 1.00-1.08).
CONCLUSIONS
Our review suggests that, within the clinical trial setting, the use of new adjuvants in older adults has not led to any safety concerns, with no increase in SAEs or fatalities. Higher rates for solicited AEs were observed, especially for AS01/AS02 and AS03 adjuvanted vaccines, but AEs were mostly mild and transient. Further evidence will need to come from the use of new adjuvants in the real-world setting, where larger numbers can be studied to potentially detect rare reactions.
Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Middle Aged; Vaccines
PubMed: 29885773
DOI: 10.1016/j.vaccine.2018.06.004 -
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 -
International Immunopharmacology Dec 2022Acute kidney injury (AKI) is a rare but severe adverse event of immune checkpoint inhibitors (ICIs). With the increasing reports of ICIs, it's necessary to put new... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute kidney injury (AKI) is a rare but severe adverse event of immune checkpoint inhibitors (ICIs). With the increasing reports of ICIs, it's necessary to put new insights into ICIs-related AKI. We conducted a systematic review of randomized controlled trials(RCTs) and a real-world study by extracting data from the US FDA Adverse Event Reporting System (FAERS) database.
METHODS
We explored ICIs-related AKI events in RCTs available in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to August 2021. Meta-analysis was performed by using risk ratios (RRs) with 95 %CIs. In a separate retrospective pharmacovigilance study of FAERs, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC).
RESULTS
A total of 79 RCTs (500,09 patients) were included, and ICIs were associated with increased risk of all-grade (RR = 1.37, 95 %CI:1.14-1.65) and high-grade AKI (RR = 1.60, 95 %CI:1.16-2.20). Results of subgroup analysis indicated that RR of ICI-related AKI did not vary significantly by cancer type, treatment regimen (monotherapy or combination of ICIs), study design (double-blind or open-label), individual ICIs and publication status (published or unpublished). FAERS pharmacovigilance data identified 1918 cases of AKI related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of AKI (ROR = 2.38, 95 %CI:2.27-2.49; IC = 1.22, 95 %CI:1.16-1.27). The median onset time of AKI was 48 days, 77.5 % of patients discontinued the use of ICIs, and 15.9 % of patients resulted in death.
CONCLUSIONS
These data suggest that ICIs were significantly associated with increased risk of AKI in both trial settings and clinical practice.
Topics: Humans; Pharmacovigilance; Immune Checkpoint Inhibitors; Retrospective Studies; Drug-Related Side Effects and Adverse Reactions; Acute Kidney Injury; Randomized Controlled Trials as Topic
PubMed: 36272360
DOI: 10.1016/j.intimp.2022.109350 -
Drug Safety Mar 2022In addition to the growing interest of different cannabinoids for therapeutic purposes, the safety profile of these substances has changed, with the recent... (Review)
Review
INTRODUCTION
In addition to the growing interest of different cannabinoids for therapeutic purposes, the safety profile of these substances has changed, with the recent identification of new events such as acute pancreatitis.
OBJECTIVE
The aim of this study was to characterize cannabinoid-related acute pancreatitis, based on the recent literature and the analysis of pharmacovigilance data available worldwide.
METHODS
Nine national and international pharmacovigilance databases were requested for individual case safety reports of acute pancreatitis related to cannabinoid exposure. A systematic review was performed searching in PubMed, Web of Science, and Google Scholar for any publication dealing with acute pancreatitis and cannabinoid exposure (cannabis, cannabinoid, cannabidiol, tetrahydrocannabinol, nabilone, dronabinol), to identify case reports, observational studies, clinical trials, or reviews. All queries were updated on 1 January, 2021.
RESULTS
Twenty-two individual case safety reports were identified in the pharmacovigilance databases and 51 in the literature, corresponding to a predominantly young male population (74% of men, median age 28 interquartile range [21-39]) using recreational Cannabis sativa with high intensity. A therapeutic purpose was identified in 13 cases (including tetrahydrocannabinol, cannabidiol, and dronabinol). The outcome was often favorable after dechallenge (except three deaths), and frequent recurrences were observed in the case of rechallenge or sustained consumption. Eleven cross-sectional studies and one ecological study showed an increasing trend of cannabis use in in-patients with acute pancreatitis, with a significantly lower in-hospital mortality.
CONCLUSIONS
This review underlines that acute pancreatitis is a potential adverse effect of cannabinoid use. It remains often unrecognized and can occur during recreational or therapeutic use. The development of the therapeutic use of cannabinoids in frail patients deserves a better investigation of the benefit-risk ratio of these different products.
Topics: Acute Disease; Adult; Cannabidiol; Cannabinoids; Cannabis; Cross-Sectional Studies; Dronabinol; Humans; Male; Pancreatitis
PubMed: 35179705
DOI: 10.1007/s40264-022-01146-7 -
Daru : Journal of Faculty of Pharmacy,... Jun 2024Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the... (Meta-Analysis)
Meta-Analysis Review
Educational interventions in pharmacovigilance to improve the knowledge, attitude and the report of adverse drug reactions in healthcare professionals: Systematic Review and Meta-analysis.
OBJECTIVES
Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance.
EVIDENCE ACQUISITION
A systematic literature review was carried out to identify randomized clinical trials evaluating the efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward pharmacovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition, the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry CRD42021254270.
RESULTS
Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46 to 9.12], I = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I = 57%, 3 studies) increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I = 29%, 2 studies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I = 93%, 3 studies). No difference was observed in pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge (SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and showed a positive effect after the intervention.
CONCLUSION
EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to increase ADR reporting.
Topics: Pharmacovigilance; Humans; Health Knowledge, Attitudes, Practice; Health Personnel; Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions
PubMed: 38427161
DOI: 10.1007/s40199-024-00508-z -
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