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Children (Basel, Switzerland) Nov 2022QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However,... (Review)
Review
QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, the interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neonates. Further research in this age category is needed to improve primary screening practices and QTcthresholds, earlier detection of risk factors and precision pharmacovigilance.
PubMed: 36421220
DOI: 10.3390/children9111771 -
Vaccine Sep 2017While vaccination injection site adverse reactions are usually mild and transient in nature, several cases of bursitis and other shoulder injuries have been reported in... (Review)
Review
While vaccination injection site adverse reactions are usually mild and transient in nature, several cases of bursitis and other shoulder injuries have been reported in the medical literature. However, these lesions are not included in vaccine label inserts. To identify the characteristics of post-vaccination shoulder injuries and those of patients and involved vaccines, as well as their potential causes, a systematic review of the cases of vaccination-related bursitis and other shoulder injuries reported in the literature and notified to the Spanish Pharmacovigilance System database (FEDRA) have been conducted. We found 45 cases of bursitis and other shoulder injuries that appeared following the vaccine intramuscular injection given into the deltoid muscle (37 from the systematic review of the literature, and 8 from the scrutiny in the Spanish Pharmacovigilance System database, FEDRA). All the patients were adult, 71.1% females, with a mean and median age of 53.6years (range: 22-89). The most frequently involved vaccines were influenza and pneumococcal vaccines, respectively; followed by diphtheria-tetanus-pertussis, diphtheria-tetanus toxoid, human papillomavirus, and hepatitis A vaccines. The most frequent shoulder lesion was bursitis. Most of patients required medical care due to severe local pain and arm mobility restriction. In a majority of cases, symptoms started 48h post vaccination. Subdeltoid or subacromial bursitis and other shoulder lesions may be more common than suspected. Such lesions predominantly affect women. The cause may be related to antigens or adjuvants contained in the vaccines that would trigger an immune or inflammatory response. However, they are more likely to be the consequence of a poor injection technique (site, angle, needle size, and failure to take into account patient's characteristics, i. e., sex, body weight, and physical constitution). Therefore, vaccination-related shoulder injuries would be amenable to prevention.
Topics: Bursitis; Humans; Injections, Intramuscular; Joint Diseases; Shoulder Injuries; Vaccination; Vaccines
PubMed: 28774564
DOI: 10.1016/j.vaccine.2017.07.055 -
European Journal of Clinical... Oct 2022Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring... (Review)
Review
PURPOSE
Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring emergency department visits. In addition to conventional strategies for SAEs (inhaled β-agonists, anticholinergics, and systemic corticosteroids), another pharmacological option is represented by ketamine. We performed a systematic review to explore the role of ketamine in refractory SAEs.
METHODS
We performed a systematic search on PubMed and EMBASE up to August 12th, 2021. We selected prospective studies only, and outcomes of interest were oxygenation/respiratory parameters, clinical status, need for invasive ventilation and effects on weaning.
RESULTS
We included a total of seven studies, five being randomized controlled trials (RCTs, population range 44-92 patients). The two small prospective studies (n = 10 and n = 11) did not have a control group. Four studies focused on adults, and three enrolled a pediatric population. We found a large heterogeneity regarding sample size, age and gender distribution, inclusion criteria (different severity scores, if any) and ketamine dosing (bolus and/or continuous infusion). Of the five RCTs, three compared ketamine to placebo, while one used fentanyl and the other aminophylline. The outcomes evaluated by the included studies were highly variable. Despite paucity of data and large heterogeneity, an overview of the included studies suggests absence of clear benefit produced by ketamine in patients with refractory SAE, and some signals towards side effects.
CONCLUSION
Our systematic review does not support the use of ketamine in refractory SAE. A limited number of prospective studies with large heterogeneity was found. Well-designed multicenter RCTs are desirable.
Topics: Adrenal Cortex Hormones; Adult; Aminophylline; Anti-Asthmatic Agents; Asthma; Child; Cholinergic Antagonists; Fentanyl; Humans; Ketamine; Multicenter Studies as Topic; Prospective Studies
PubMed: 36008492
DOI: 10.1007/s00228-022-03374-3 -
Endocrine Mar 2015Concerns raised by several animal studies, case reports, and pharmacovigilance warnings over incretin-based therapy potentially exposing type two diabetes patients to an... (Meta-Analysis)
Meta-Analysis Review
Concerns raised by several animal studies, case reports, and pharmacovigilance warnings over incretin-based therapy potentially exposing type two diabetes patients to an elevated risk of pancreatitis have cast a shadow on the overall safety of this class of drugs. This systematic review evaluates the data from observational studies that compared treatment with or without incretins and the risk of pancreatitis. We searched PubMed for publications with the key terms incretins or GLP-1 receptor agonists or DPP-4 inhibitors or sitagliptin or vildagliptin or saxagliptin or linagliptin or alogliptin or exenatide or liraglutide AND pancreatitis in the title or abstract. Studies were evaluated against the following criteria: design (either cohort or case-control); outcome definition (incidence of pancreatitis); exposure definition (new or current or past incretins users); and comparison between patients receiving incretins or not for type 2 diabetes. Two authors independently selected the studies and extracted the data. Six studies meeting the inclusion criteria were reviewed. No difference was found in the overall risk of pancreatitis between incretin users and non-users (odds ratio 1.08; 95 % CI [0.84-1.40]). A risk increase lower than 35 % cannot be excluded according to the power calculation. This systematic review and meta-analysis suggests that type 2 diabetes patients receiving incretin-based therapy are not exposed to an elevated risk of pancreatitis. Limitations of this analysis are the low prevalence of incretin users and the lack of a clear distinction by the studies between therapy with DPP-4 inhibitors or with GLP-1 receptor agonists.
Topics: Diabetes Mellitus, Type 2; Humans; Incretins; Observational Studies as Topic; Pancreatitis
PubMed: 25146552
DOI: 10.1007/s12020-014-0386-8 -
Microorganisms Jul 2023Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review... (Review)
Review
Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine.
Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.
PubMed: 37512988
DOI: 10.3390/microorganisms11071816 -
Paediatric Drugs May 2024In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.
INTRODUCTION
In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.
OBJECTIVE
We aimed to review information on compassionate use, clinical pharmacology, efficacy, and safety of dapagliflozin and empagliflozin in children.
METHODS
We conducted a systematic review of published clinical trials, case reports, and observational studies in Medline, Excerpta Medica, and Web of Science databases from inception to September 2023. For the two randomised controlled trials on type 2 diabetes mellitus (T2DM), we implemented a meta-analysis on the primary outcome (mean difference in glycosylated haemoglobin [HbA1c] between intervention and placebo groups). Review Manager (RevMan), version 5.4.1, was used for this purpose.
RESULTS
Thirty-five articles (nine case reports, ten case series, one prospective non-controlled trial, four controlled randomised trials, two surveys, six pharmacokinetic studies, and three pharmacovigilance studies) were selected, in which 415 children were exposed to either dapagliflozin or empagliflozin: 189 diabetic patients (mean age 14.7 ± 2.9 years), 32 children with glycogen storage disease type Ib (GSD Ib), glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, or severe congenital neutropenia type 4 (8.5 ± 5.1 years), 47 children with kidney disease or heart failure (11.2 ± 6.1 years), 84 patients in pharmacokinetic studies (15.1 ± 2.3 years), and 63 patients in toxicological series. The effect of dapagliflozin and empagliflozin in T2DM was demonstrated by HbA1c reduction in two randomised trials among a total of 177 adolescents, with a mean HbA1c difference of -0.82% (95% confidence interval -1.34 to -0.29) as compared to placebo (no heterogeneity, I = 0%). Dosage ranged between 5 and 20 mg (mean 11.4 ± 3.7) once daily for dapagliflozin and between 5 and 25 mg (mean 15.4 ± 7.4) once daily for empagliflozin. Among the paediatric cases of GSD Ib, empagliflozin 0.1-1.3 mg/kg/day improved neutropenia, infections, and gastrointestinal health. Dapagliflozin (mean dosage 6.9 ± 5.2 mg once daily) was well-tolerated in children with chronic kidney disease and heart failure. Side effects were generally mild, the most frequent being hypoglycaemia in children with GSD Ib (33% of patients) or T2DM (14% of patients) on concomitant hypoglycaemic drugs. Diabetic ketoacidosis is rare in children.
CONCLUSION
Early evidence suggests that dapagliflozin and empagliflozin are well tolerated in children. A clinical pharmacology rationale currently exists only for adolescents with diabetes mellitus.
PROSPERO REGISTRATION NUMBER
CRD42023438162.
Topics: Benzhydryl Compounds; Humans; Glucosides; Child; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Adolescent
PubMed: 38635113
DOI: 10.1007/s40272-024-00623-z -
Acta Ophthalmologica Aug 2016Several pharmacoepidemiologic studies have been carried out evaluating the risk of retinal detachment associated with systemic fluoroquinolones. This meta-analysis aims... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Several pharmacoepidemiologic studies have been carried out evaluating the risk of retinal detachment associated with systemic fluoroquinolones. This meta-analysis aims to investigate such association, in the light of the best scientific evidence available.
METHODS
A literature search was conducted to identify relevant studies evaluating the risk for retinal detachment associated with systemic fluoroquinolones. A meta-analysis was performed to pool rate ratios (RRs). Meta-regressions were conducted aiming to evaluate the influence of time interval between fluoroquinolones use and retinal detachment diagnosis or treatment risk estimates.
RESULTS
Ten observational studies from seven publications were included. Overall, fluoroquinolones were not associated with an increased risk for retinal detachment [RR 1.47 (95% CI 0.95-2.27): p = 0.09; I(2) = 92.8%]. When the analysis was stratified according to different study designs, the result was statistically significant for retrospective cohort studies [RR 1.87 (95% CI 1.36-2.58); p < 0.001; I(2) = 0.0%] and for past users of fluoroquinolones, based on data from case-control studies [RR 1.07 (95% CI 1.01-1.12); p = 0.01; I(2) = 0.0%]. According to meta-regressions, the risk for retinal detachment did not vary due to different time intervals between fluoroquinolones prescription and retinal detachment occurrence. No statistically significant results were identified among studies evaluating only rhegmatogenous retinal detachments, as well as among studies that evaluated patients not requiring a prior ophthalmologist visit to be included.
CONCLUSIONS
In light of the current available evidence, systemic fluoroquinolones do not seem to be associated with retinal detachment.
Topics: Anti-Bacterial Agents; Databases, Factual; Fluoroquinolones; Humans; Retinal Detachment; Risk Factors
PubMed: 26846201
DOI: 10.1111/aos.12931 -
Frontiers in Pharmacology 2021Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile,... (Review)
Review
Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population. In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form. Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6-68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%. ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=96513, identifier CRD42018096513.
PubMed: 35185536
DOI: 10.3389/fphar.2021.777498 -
British Journal of Clinical Pharmacology Dec 2023Studies assessing the impact of pharmacovigilance regulatory interventions often focus on the expected (or intended) outcomes, while any possible unintended impact may... (Review)
Review
AIMS
Studies assessing the impact of pharmacovigilance regulatory interventions often focus on the expected (or intended) outcomes, while any possible unintended impact may be overlooked. The update of the Good Pharmacovigilance Practice guideline in 2017 elaborated on impact assessment, emphasizing the need also to assess possible unintended impact. This systematic literature review investigated how often the unintended impact of regulatory interventions was considered in publications of studies investigating pharmacovigilance regulatory interventions in Europe.
METHODS
We conducted a systematic review of the literature on MEDLINE and EMBASE from 1 January 2012 to 28 February 2022 to identify publications that investigated the impact of regulatory interventions in Europe. The primary outcome of the study was the number of publications reporting assessments of unintended impact. In addition, we studied the characteristics of these publications, including the type of outcomes assessed, the analytical methods applied and the type of data used.
RESULTS
In total, 96 publications were included in the analysis. The unintended impact of pharmacovigilance regulatory interventions was investigated in 23 of 96 publications (24%). The drug classes most frequently studied in the publications assessing unintended impact of regulatory interventions were oral glucose-lowering drugs (n = 6, 26%), opioids (n = 4, 17%), antidepressants (n = 4, 17%) and antipsychotics (n = 3, 13%). The reported methods to assess the unintended impact were interrupted time series (n = 10, 43%) and descriptive statistics with or without significance testing (n = 2 [9%] and n = 9 [39%], respectively). The outcomes selected for unintended impact assessments included the use of other drugs (n = 16, 70%), health outcomes (n = 8, 35%) and behavioural changes (n = 4, 17%). Most of the publications reported on the use of electronic health record databases (n = 13, 57%) or claims databases (n = 13, 57%), while registries were used in 4 publications (17%).
CONCLUSION
The unintended impact of pharmacovigilance regulatory interventions was reported in only a quarter of identified publications. There was no apparent increase in attention to unintended impact assessments after the update of the Good Pharmacovigilance Practice guidelines.
Topics: Humans; Pharmacovigilance; Europe; Interrupted Time Series Analysis
PubMed: 37553757
DOI: 10.1111/bcp.15874 -
Neurology Apr 2016We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS).
OBJECTIVE
We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS).
METHODS
We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS.
RESULTS
We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies.
CONCLUSION
Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to "real world" settings where the MS population commonly has comorbid conditions.
Topics: Clinical Trials as Topic; Comorbidity; Humans; Multiple Sclerosis
PubMed: 26888986
DOI: 10.1212/WNL.0000000000002471