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JAMA Pediatrics Aug 2022Neonatal early-onset sepsis (EOS) is a severe disease, particularly in preterm infants. Timely diagnosis can be challenging owing to unspecific presentation and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Neonatal early-onset sepsis (EOS) is a severe disease, particularly in preterm infants. Timely diagnosis can be challenging owing to unspecific presentation and questionable performance of the common markers of infection. Presepsin was recently proven to be a promising biomarker for the diagnosis of EOS.
OBJECTIVE
To assess presepsin accuracy for the diagnosis of EOS.
DATA SOURCES
PubMed Medline, EMBASE, Web of Science, and Google Scholar. No publication date restrictions were applied. The literature search was limited to the English language. Articles were checked for duplication.
STUDY SELECTION
Inclusion criteria were studies that (1) included term or preterm newborns (defined as newborns with gestational age ≥37 weeks or <37 weeks, respectively); (2) included a diagnosis of EOS, defined as culture-proven sepsis for primary analysis and as either clinical or culture-proven sepsis for secondary analysis; and (3) assessed presepsin values during the initial workup for suspected EOS. Exclusion criteria were studies that (1) did not include EOS cases; (2) lacked data on presepsin sensitivity and/or specificity; and (3) were case reports, commentaries, or reviews. Two independent reviewers performed the study selection.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers performed data extraction and quality assessment. Quality assessment was performed using the Quality Assessment for Studies of Diagnostic Accuracy 2 tool, and data were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
The outcomes of interest for both the primary and secondary analyses were presepsin sensitivity, specificity, and diagnostic odds ratio for the diagnosis of EOS.
RESULTS
A total of 12 studies of 245 (4.9%) met inclusion criteria for the primary analysis. Twenty-three studies of 245 (9.4%) met the inclusion criteria for the secondary analysis. In the primary analysis, among 12 studies and 828 newborns of any gestational age, pooled sensitivity and specificity were 0.93 (95% CI, 0.86-0.95) and 0.91 (95% CI, 0.85-0.95), respectively; pooled diagnostic odds ratio was 131.69 (95% CI, 54.93-310.94). Subgroup analysis showed that presepsin specificity was associated with the inclusion of only EOS or all neonatal sepsis. Presepsin accuracy was not associated with gestational age, measurement with chemiluminescence enzyme immunoassay or enzyme-linked immunosorbent assay testing, country where the study was performed, or risk of bias judgment. In the secondary analysis, among 23 studies and 1866 newborns, accuracy was significantly associated with only test type.
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that presepsin was an accurate biomarker of EOS. Clinical trials are warranted to assess its usefulness and safety to reduce early antibiotic exposure, particularly in preterm newborns.
Topics: Biomarkers; Humans; Infant; Infant, Newborn; Infant, Premature; Lipopolysaccharide Receptors; Neonatal Sepsis; Peptide Fragments; Sepsis
PubMed: 35639395
DOI: 10.1001/jamapediatrics.2022.1647 -
Pharmacological Research Apr 2023Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell... (Meta-Analysis)
Meta-Analysis Review
Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.
Topics: Humans; Adult; Receptors, Chimeric Antigen; T-Lymphocytes; Hematologic Neoplasms; Chronic Disease; Multiple Myeloma; Recurrence; Cell- and Tissue-Based Therapy
PubMed: 36963592
DOI: 10.1016/j.phrs.2023.106742 -
Addiction (Abingdon, England) Feb 2018Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the... (Meta-Analysis)
Meta-Analysis
Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate.
BACKGROUND AND AIMS
Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication.
DESIGN
Systematic review with direct and network meta-analysis of double-blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non-abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data.
SETTING
Thirty-two RCTs.
PARTICIPANTS
A total of 6036 patients.
MEASUREMENTS
The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes.
FINDINGS
No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = -0.19, 95% confidence interval (CI) = -0.29, -0.10; I = 0%], baclofen (SMD = -1.00, 95% CI = -1.80, -0.19; one study) and topiramate (SMD = -0.77, 95% CI = -1.12, -0.42; I = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor.
CONCLUSIONS
There is currently no high-grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes.
Topics: Acamprosate; Alcoholism; Baclofen; Naltrexone; Narcotic Antagonists; Network Meta-Analysis; Topiramate; Treatment Outcome
PubMed: 28940866
DOI: 10.1111/add.13974 -
Journal For Immunotherapy of Cancer Mar 2023Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events. As oncological indications for ICIs widen, their rare side effects... (Review)
Review
Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events. As oncological indications for ICIs widen, their rare side effects become increasingly visible in clinical practice and impact therapy decisions.Here, we report a rare case of early-onset, mild cytokine release syndrome (CRS) in a patient who received ICIs for a metastasized renal cell carcinoma, which led to treatment discontinuation.We further provide a systematic review of the literature of CRS and related life-threatening side effects of ICI treatment, such as hemophagocytic lymphohistiocytosis (HLH). We searched Medline, Embase and the Web of Science Core Collection from inception to October 2021 for reports on CRS, cytokine storm, macrophage activation syndrome, HLH, and related hyperinflammatory disorders in patients with solid cancers receiving ICIs. We found n=1866 articles, which were assessed for eligibility independently by two examiners. Of those, n=49 articles reporting on n=189 individuals were eligible for review. We found that the median time from last infusion to the occurrence of CRS/HLH was approximately nine days, while the onset of symptoms varied from immediately after infusion to one month after treatment. Most patients were treated with either corticosteroids or the anti-interleukin 6 (IL-6) antibody tocilizumab, and although the majority of patients recovered, a few cases were fatal. Concomitant IL-6 and ICI treatment were reported as beneficial for both the antitumoral effect and for limiting side effects. Data from international pharmacovigilance databases underscored that ICI-related CRS and HLH are rare events, but we identified significant differences in reported frequencies, which might suggest substantial under-reporting.The results from this first systematic review of CRS/HLH due to ICI therapy highlight that life-threatening systemic inflammatory complications of ICIs are rare and might be associated with fatal outcome in approximately 10% of patients. Limited data support the use of IL-6 inhibitors in combination with ICIs to augment the antitumoral effect and reduce hyperinflammation.
Topics: Humans; Immune Checkpoint Inhibitors; Interleukin-6; Drug-Related Side Effects and Adverse Reactions; Cytokine Release Syndrome; Lymphohistiocytosis, Hemophagocytic; Kidney Neoplasms
PubMed: 36878533
DOI: 10.1136/jitc-2022-005841 -
Therapeutic Advances in... 2023More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage... (Review)
Review
BACKGROUND
More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis are currently limited.
OBJECTIVES
The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts.
DESIGN
Systematic review.
DATA SOURCES AND METHODS
PubMed, article references, and Clinicaltrials.gov up to June 30, 2022. Meta-analyses published within the last 2 years were also reviewed.
RESULTS
We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary objectives. Intravenous racemic ketamine was superior to control drugs (placebo or midazolam) within the first 72 h, in spite of large placebo effects. Adverse events were minor and transient. In contrast, intranasal esketamine did not differ from placebo in large-scale studies. Limitations, clinical considerations, and opportunities for future research include the following points: large placebo effects when studying suicidal ideation reduction; small concerns about blinding quality due to dissociative effects; no studies on the risk/prevention of suicidal acts and mortality; lack of studies beyond affective disorders; no studies in adolescents and older people; lack of knowledge of long-term side effects, notably liability for abuse; no robust predictive markers; limited understanding of the mechanisms of ketamine on suicidal ideas; need for improved assessment of suicidal ideation in clinical trials; need for studies in outpatient settings, emergency room, and liaison consultation; need for research on ketamine administration; limited knowledge on the positive and negative effects of concomitant treatments.
CONCLUSION
Overall, there is compelling evidence for a favorable short-term benefit-risk balance with intravenous racemic ketamine but not intranasal esketamine. The place of ketamine will have to be defined within a multimodal care strategy for suicidal patients. Caution remains necessary for clinical use, and pharmacovigilance will be essential.
PubMed: 36776623
DOI: 10.1177/20451253231151327 -
BioDrugs : Clinical Immunotherapeutics,... Feb 2018The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern. (Review)
Review
BACKGROUND
The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern.
OBJECTIVES
The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps.
METHODS
A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies.
RESULTS
The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups.
CONCLUSIONS
There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching.
Topics: Biosimilar Pharmaceuticals; Humans
PubMed: 29344876
DOI: 10.1007/s40259-017-0256-z -
PloS One 2020The objective of this review is to evaluate the existing evidence about the knowledge, attitude, and perceptions (KAP) of healthcare students towards pharmacovigilance...
OBJECTIVE
The objective of this review is to evaluate the existing evidence about the knowledge, attitude, and perceptions (KAP) of healthcare students towards pharmacovigilance and adverse drug reactions reporting (ADRs).
METHODS
A systematic literature search was conducted using MEDLINE, CINAHL, EMBASE, ERIC, and Cochrane Database of Systematic Reviews via OVID. This review restricted the search to studies published in English from inception until December 2019.
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary outcome was healthcare students' knowledge, attitude, and perceptions of pharmacovigilance.
RESULTS
Of the 664 articles identified, twenty-nine studies were included in the review. Overall, healthcare students vary in their knowledge and attitude towards pharmacovigilance and ADRs reporting. There was inconsistency in measuring KAP between the studies and the main drawback in the literature is lacking validated KAP measures.
CONCLUSIONS
In summation, optimal KAP assessment can be achieved through developing a standard validated measure. Our future healthcare providers should have basics pharmacovigilance knowledge in order to rationally reporting ADRs and preventing serious health problems.
Topics: Adverse Drug Reaction Reporting Systems; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Pharmacovigilance; Students, Health Occupations
PubMed: 32433649
DOI: 10.1371/journal.pone.0233393 -
Biomarker Insights 2023The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years,... (Review)
Review
BACKGROUND
The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs).
OBJECTIVE
The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area.
DESIGN
This is a systematic review of the literature.
DATA SOURCES AND METHODS
Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)-E16 guidance.
RESULTS
Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories.
CONCLUSION
Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs.
PubMed: 37077840
DOI: 10.1177/11772719231164528 -
International Journal of Cardiology.... Feb 2023The scope of this systematic review is to update the existing body of evidence regarding the cost-effectiveness of transcatheter aortic valve implantation, stratified... (Review)
Review
OBJECTIVE
The scope of this systematic review is to update the existing body of evidence regarding the cost-effectiveness of transcatheter aortic valve implantation, stratified across all risk categories, and to assess their methodological quality.
METHODS
A systematic review was performed including published cost-effectiveness analyses of heart valve implantations. The quality was assessed with the Quality of Health Economics Tool.
RESULTS
We identified 33 economic evaluations of transcatheter aortic heart valve implantations. Results were not consistent, ranging from dominant to dominating. Moreover, the models were sensitive to an array of variables. The methodological quality of the studies was good.
CONCLUSION
This systematic review led to inconclusive and inconsistent results pertinent to the economic profile of TAVI technology. It also highlighted areas which merit further research regarding the pillars of cost-effectiveness analysis such as modeling, the extrapolation of available data and the uncertainty of the evidence. A thorough assessment of the patient should proceed any decision-making.
PubMed: 36747880
DOI: 10.1016/j.ijcha.2023.101173 -
PloS One 2016Spontaneous or voluntary reporting of suspected adverse drug reactions (ADRs) is one of the vital roles of all health professionals. In India, under-reporting of ADRs by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Spontaneous or voluntary reporting of suspected adverse drug reactions (ADRs) is one of the vital roles of all health professionals. In India, under-reporting of ADRs by health professionals is recognized as one of the leading causes of poor ADR signal detection. Therefore, reviewing the literature can provide a better understanding of the status of knowledge, attitude and practice (KAP) of Pharmacovigilance (PV) activities by health professionals.
METHODS
A systematic review was performed through Pubmed, Scopus, Embase and Google Scholar scientific databases. Studies pertaining to KAP of PV and ADR reporting by Indian health professionals between January 2011 and July 2015 were included in a meta-analysis.
RESULTS
A total of 28 studies were included in the systematic review and 18 of them were selected for meta-analysis. Overall, 55.6% (95% CI 44.4-66.9; p<0.001) of the population studied were not aware of the existence of the Pharmacovigilance Programme in India (PvPI), and 31.9% (95% CI 16.3-47.4; p<0.001) thought that "all drugs available in the market are safe". Furthermore, 28.7% (95% CI 16.4-40.9; p<0.001) of them were not interested in reporting ADRs and 74.5%, (95% CI 67.9-81.9; p<0.001) never reported any ADR to PV centers.
CONCLUSION
There was an enormous gap of KAP towards PV and ADR reporting, particularly PV practice in India. There is therefore an urgent need for educational awareness, simplification of the ADR reporting process, and implementation of imperative measures to practice PV among healthcare professionals. In order to understand the PV status, PvPI should procedurally assess the KAP of health professionals PV activities in India.
Topics: Drug Therapy; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; India
PubMed: 27010447
DOI: 10.1371/journal.pone.0152221