1,720,996 research outputs found
Dipeptidyl peptidase-4 inhibitors and heart failure: Analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System
No full textBackground and aims: We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). Methods: FAERS data reporting HF and DPP-4-Is use in the period from the fourth quarter of 2006 through 2013 were extracted, using the Standardized MedDRA Query "Cardiac failure". Disproportionality (case/non-case method) was implemented by calculating Reporting Odds Ratios (RORs) with 95% Confidence Interval (CI): (1) exploratory analysis on the entire FAERS (using rosiglitazone as positive control); (2) consolidated analyses by therapeutic area (within antidiabetics), correcting for event- and drug-related competition bias and adjusting for co-reported drugs as confounders. Results: HF during DPP4-I use was recorded in 390 reports (4.4% of total reports). In exploratory analysis, statistically significant ROR emerged for DPP-4-I as a class (ROR = 1.17; 95% CI = 1.05-1.29), saxagliptin (1.68; 1.29-2.17), vildagliptin (2.39; 1.38-4.14), and rosiglitazone (13.98; 13.30-14.70). In consolidated analyses, the ROR for saxagliptin (2.60; 1.92-3.50) and vildagliptin (4.07; 2.28-7.27) increased, and became also significant for sitagliptin (1.61; 1.40-1.86). Concomitant drugs were reported in more than 50% of cases; the adjusted RORs of saxagliptin (2.30; 1.70-3.10), vildagliptin (3.15; 1.76-5.63), and sitagliptin (1.48; 1.28-1.71) were nonetheless significant. Conclusion: FAERS data are consistent with clinical studies on a possible association between saxagliptin and HF. The disproportionate reporting of HF with sitagliptin, conflicting with a recent phase IV trial, suggests that cardiovascular safety requires close post-marketing vigilance by clinicians of individual DPP-4-I in the community until the issue of class effect is solved
Assessing intravitreal anti-VEGF drug safety using real-world data: methodological challenges in observational research
No full textIt is generally acknowledged that the ocular safety profile of intravitreal anti-VEGF drugs is acceptable, while the burden of systemic safety of these intravitreal agents is still being debated. The evaluation of the systemic safety of these drugs using real-world data (RWD), such as spontaneous reporting systems (SRS), electronic medical records (EMRs) and claims databases has several advantages, including the capture of outcomes among real-world populations over long observational periods. Nevertheless, there is a relatively small body of research exploring the post-marketing safety of these drugs
Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System
No full textImmune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death 1 or its ligand (PD1/PDL1), elicit different immune-related adverse events (irAEs), but their global safety is incompletely characterized
SARS-CoV-2 pandemic waves and Mental Health management: an Interrupted Time Series analysis in Northern Italy.
No full textBackground and aim: The coronavirus disease (COVID-19) outbreak, caused by the SARS-CoV-2, represents one of the most important public health threat in the last few decades. The rapid spread of the virus and the increasing number of COVID-19 cases worldwide imposed measures such lockdowns to reduce its transmission. The characteristics of this catastrophic event, together with the lockdown measures and societal changes, have had impacted on the population’s mental health. For this reason, this study aimed at assessing the impact of COVID-19 pandemic waves on mental health services utilization in one of the most heavily affected Italian regions, the province of Bergamo. Specifically, the study aimed at assessing the impact of the first and second lockdowns on emergency department access and hospitalization due to psychiatric diseases, the new use of psychiatric therapies, and access to mental health services in the general population.
Methods: A population-based study using the healthcare administrative database of the Health Protection Agency (HPA) of Bergamo was conducted. Weekly time series data on emergency department access/Hospitalization due to psychiatric diseases, along with the new use of antidepressants/antipsychotics, and outpatient mental health service utilization from January 1, 2017 to December 31, 2022 were collected. The study period was segmented as follows: pre-first lockdown period (January 1, 2017 - March 7, 2020), first lockdown (March 8, 2020 - June 1, 2020), post-first lockdown (June 2, 2020 - November 5, 2020), second lockdown (November 6, 2020 - June 27, 2021), and post-second lockdown (June 28, 2021-o December 31, 2022). Frequency measures across these periods were compared using nonparametric tests and relative changes in mean values. Then, an interrupted time series (ITS) analysis with Poisson generalized additive model was used to assess significant changes (p-value ≤0.05) in either the level (meaning an abrupt change) or the slope (meaning a gradual change) of the time series for study events. Results were reported as point estimates with corresponding 95% Confidence Intervals (95%CI). The impact of lockdowns was estimated across different age groups (adult and young) and sex (female and male).
Results: The first lockdown was associated with a significant reduction in the incidence of the study events across the different study subgroup populations. The post-first lockdown was associated with an increase of the study event. The second lockdown was associated with a new reduction of the study events followed by an increase in occurrence during the post-second lockdown. A distinct pattern was observed for the use psychiatric drugs use among younger individuals, which showed an increasing trend following the first lockdown. Analyses stratified by sex among adults showed similar pattern for both males and females.
Conclusion: The findings reveal the impact of the COVID-19 pandemic on the mental health of the general population, indicating a deterioration in well-being during each lockdown, followed by a rebound effect in the post-lockdown periods. Given the differential impact of pandemic on adult and young individuals, there is a need for targeted public health interventions to address the mental health needs of these distinct groups. Future studies should explore the long-term effects of the pandemic on additional subpopulations to identify potential areas of need for mental health support
Occurrence of Multiple Sclerosis After Drug Exposure: Insights From Evidence Mapping
No full textIntroduction: The role of drugs in the occurrence of multiple sclerosis (MS) is perceived to be insufficiently investigated. Objective: The aim of this study was to map and assess the evidence on MS occurrence after drug exposure, in order to identify possible signals of causal association. Methods: A search strategy was performed in MEDLINE and Embase as of July 2016; references consistent with the aim of the study were analysed to extract relevant measures of causal association between drugs and MS. The Newcastle-Ottawa Scale and appropriate guidelines from the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) were used to assess the quality of included studies. Results: After screening 832 articles, 58 were selected (of which 14 were found by checking the reference lists of reviews): 30 case reports and case series, 24 longitudinal studies and four randomized controlled trials. Seven longitudinal studies had good (at least 7 out of 9) quality scores, whereas case reports/case series presented several limitations. Half of included articles focused on immunomodulatory drugs (etanercept, infliximab and adalimumab), especially in case reports/series, suggesting an association with MS occurrence. Contraceptives and antibacterials were investigated in some population-based studies, without definite results. Conclusion: A heterogeneous pharmacological profile of identified classes emerged. Low strength of evidence and conflicting results highlighted the difficulties in addressing the possible contribution of drugs in MS occurrence. Methodological advances are needed, especially to control the confounding role of underlying disease for specific drug classes
Pharmacovigilance and Multiple Sclerosis (MS): drugs as risk factors for MS, and safety profile of drugs used in MS treatment
Full text linkSeveral risk factors have been associated with Multiple Sclerosis onset (MSo). However, the role of previous drug exposure in MSo is far to be completely elucidated. In this intricate scenario, another important issue is represented by the safety profile of MS therapies. This thesis aimed to explore the role of drugs as possible risk factor in MSo by performing an evidence mapping of literature and a disproportionality analysis by using the FDA-Adverse Event Reporting System (FAERS) database. In the last part of the thesis, signal of Drug Induced Liver Injury (DILI) events during MS therapies was assessed by using in the same database.
The analysis of the literature showed that drugs acting on immune system, hormone balance and infections were suspected as possible cause of MSo in case reports and case series, whereas contrasting results emerged from the few longitudinal studies. These data were in part in line with FAERS analysis, which resulted in disproportionality for drugs acting on immune system, insulin, bisphosphonates and contraceptives.
Analysis of DILI events in MS treated patients suggests that a careful clinical monitoring should be applied to these patients. In addition, longitudinal studies should be planned in order to evaluate safety profile of MS drugs in monotherapy as well as in combination with other drugs.
In conclusion, the submission of exhaustive reports of adverse drug reactions would permit stratified analyses and a better characterization of rare and unpredictable adverse events. Moreover, case-control studies performed on electronic medical records could confirm or refuse safety signals emerged from this thesis
Assessment of adverse reactions to α-lipoic acid containing dietary supplements through spontaneous reporting systems
No full textAlpha-lipoic acid (ALA)-containing dietary supplements are widely used in clinical practice, although their safety assessment is under-investigated. We characterize the safety profile of ALA-containing products by analysing spontaneous reports of suspected adverse reactions (ARs)
Reply-Letter to the editor - The valuable support of spontaneous reporting systems in exploring safety profile of dietary supplements
No full textLetter to the editor; repl
Multiple sclerosis as an adverse drug reaction: clues from the FDA Adverse Event Reporting System
No full textBackground: Possible relationship between drug exposure and multiple sclerosis (MS) development is insufficiently investigated, and further challenged by the incomplete understanding of MS etiopathogenesis. The study aims to investigate whether drug exposure could contribute to MS, by analyzing worldwide spontaneous reporting archives of adverse drug reaction (ADRs). Research design and methods: We retrieved information from the US Food and Drug Administration Adverse Event Reporting System (FAERS) over a 13-year period. Reporting odds ratio (ROR) for MS was calculated for each single substance. Disproportionality signals were considered when at least 10 cases were retrieved with a lower limit of the 95% confidence interval (CI) >1. Results: After a customized data-mining process, 3,226 reports of MS were retrieved. ‘Antineoplastic and immunomodulating drugs’ (33% of total reports) were the most frequently reported, with 10 disproportionality signals, including etanercept (445 cases; ROR: 2.48; 95% Cl: 2.24–2.74), adalimumab (329; 2.05; 1.83–2.30), and infliximab (119; 2.25; 1.87–2.70). We also observed signals for drugs acting on hormone balance, bone density, and central nervous system. Conclusion: Our findings suggest that immunomodulatory drugs increase the risk of MS and point out that some other drug classes should be further investigated for this risk.</p
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