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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and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu(®), Roche) treatment on mortality in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 -
The Journal of Infectious Diseases Nov 2023HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes... (Meta-Analysis)
Meta-Analysis
Geographic and Population Distributions of Human Immunodeficiency Virus (HIV)-1 and HIV-2 Circulating Subtypes: A Systematic Literature Review and Meta-analysis (2010-2021).
BACKGROUND
HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes (clades) across regions and populations is crucial. In this study, a systematic review of the past decade was conducted to characterize HIV-1/HIV-2 subtypes.
METHODS
A comprehensive search was performed in PubMed, EMBASE, and CABI Global Health, yielding 454 studies from 91 countries.
RESULTS
Globally, circulating recombinant forms (CRFs)/unique recombinant forms (URFs) accounted for 29% of HIV-1 strains, followed by subtype C (23%) and subtype A (17%). Among studies reporting subtype breakdowns in key populations, 62% of HIV infections among men who have sex with men (MSM) and 38% among people who inject drugs (PWIDs) were CRF/URFs. Latin America and the Caribbean exhibited a 25% increase in other CRFs (excluding CRF01_AE or CRF02_AG) prevalence between 2010-2015 and 2016-2021.
CONCLUSIONS
This review underscores the global distribution of HIV subtypes, with an increasing prevalence of CRFs and a lower prevalence of subtype C. Data on HIV-2 were limited. Understanding subtype diversity is crucial for vaccine development, which need to elicit immune responses capable of targeting various subtypes. Further research is needed to enhance our knowledge and address the challenges posed by HIV subtype diversity.
Topics: Male; Humans; HIV Infections; Homosexuality, Male; HIV-1; HIV-2; Genetic Variation; Phylogeny; Sexual and Gender Minorities; Prevalence; Genotype
PubMed: 37592824
DOI: 10.1093/infdis/jiad327 -
Journal of Internal Medicine Jul 2023Although a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be...
BACKGROUND
Although a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be ruled out. The aim of this study was to describe the clinical characteristics of ICI-induced CLS through a systematic review and to assess a potential safety signal.
METHODS
Medline/PubMed, Embase, and Reactions Weekly were screened, and a global disproportionality study was performed using the World Health Organization pharmacovigilance database through January 15, 2023. A signal of disproportionate reporting was defined as a Bayesian information component (IC) with a 95% credibility interval (CrI) lower boundary that exceeds 0.
RESULTS
A total of 47 cases of ICI-associated CLS were included, 14 from the systematic review (of 61 screened articles) and 33 from VigiBase (of 34,058,481 reports of adverse drug reactions). The median time to CLS onset from the start of ICI was 12 weeks (interquartile range 8-49, n = 24). A total of 57% (8/14) of patients experienced an immune-related adverse event (irAE) before CLS. A fatal outcome was reported in 23% (7/31) of patients. A significant overreporting of CLS was found with ICIs compared with all other drugs (IC 2.4, 95% CrI from 1.8 to 2.8).
CONCLUSION
This study showed a significant signal of disproportionality reporting for ICI-induced CLS, characterized by a long time to onset, and compared with the idiopathic form of the disease with a less abrupt onset and a less consistent hemoconcentration pattern.
Topics: Humans; Immune Checkpoint Inhibitors; Pharmacovigilance; Capillary Leak Syndrome; Bayes Theorem; Antineoplastic Agents, Immunological; Retrospective Studies; Drug-Related Side Effects and Adverse Reactions
PubMed: 37038359
DOI: 10.1111/joim.13641 -
BMC Musculoskeletal Disorders Oct 2013Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA.
METHODS
Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal.
RESULTS
Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo.
CONCLUSION
Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However, haematological, liver function tests and lipoproteins should be monitored. Long-term efficacy and pharmacovigilance studies are recommended.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Janus Kinase 3; Piperidines; Pyrimidines; Pyrroles; Treatment Outcome
PubMed: 24139404
DOI: 10.1186/1471-2474-14-298 -
Frontiers in Endocrinology 2022Despite patients with thyroid dysfunction show obvious abnormal hemostatic indicators in the peripheral blood, the current research on whether and how subclinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite patients with thyroid dysfunction show obvious abnormal hemostatic indicators in the peripheral blood, the current research on whether and how subclinical hypothyroidism (SCH) influence hemostatic function (the coagulation and fibrinolytic system) still remains controversial.
OBJECTIVE
We conducted this study to evaluate how SCH influence on the coagulation and fibrinolytic system in human body.
METHODS
Prior to March 2022, Web of Science, Embase, PubMed, WanFang, CNKI data and reference lists were searched to identify eligible researches. Two of us independently extracted the data and evaluated study quality. The effect size is represented by standard mean difference (SMD). Both fixed and random-effects models were used where appropriate. Review Manager 5.3 and STATA 16.0 were used to analyze the eligible data.
RESULTS
1325 patients from twelve observational studies were involved in our research. Our study revealed that SCH changed the heamostatic balance towards hypercoagulable and hypofibrinolytic conditions accompanied by an increase in tissue fibrinogen, plasminogen activator and plasminogen activator inhibitor-1. By contrast, there was no statistically difference in acivated partial thromboplastin time (APTT) and D-Dimer in SCH group compared with that in control subjects.
CONCLUSIONS
Our study confirmed that SCH is related with a prothrombotic state, as reflected by changes in both coagulation and fibrinolysis. It is highly recommended for screening cardiovascular risk factors in combination with an adequate evaluation of SCH state.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/#recordDetails] PROSPERO [CRD42021275313].
Topics: Blood Coagulation; Fibrinolysis; Hemostatics; Humans; Hypothyroidism; Thyroid Diseases
PubMed: 35574019
DOI: 10.3389/fendo.2022.861746 -
Therapeutics and Clinical Risk... 2021Malaria is one of the infectious diseases with substantial risks for pregnant women, the fetus and the newborn child. Thus, prevention and treatment of malaria with safe... (Review)
Review
INTRODUCTION
Malaria is one of the infectious diseases with substantial risks for pregnant women, the fetus and the newborn child. Thus, prevention and treatment of malaria with safe and effective drugs is of paramount importance. Pregnant women are mostly excluded from clinical trials, and systematic approaches of pharmacovigilance in pregnancy are limited. This means the safety and efficacy of antimalarial agents during pregnancy are unclear.
PURPOSE
This study was designed to carry out a systematic review and aggregate data meta-analysis of literature published on efficacy and safety of artemisinin-based combination therapy (ACT) for uncomplicated malaria in pregnant women.
METHODS
A search of literature published between 1998 to 2020 on efficacy and safety of artemisinin-based combination therapy (ACT) in pregnant women was made using Cochrane Library, Medline and the Malaria in Pregnancy Consortium Library. Data were extracted independently by two reviewers, and any discrepancies were resolved by consensus. Meta-analysis was carried out using Open Meta-Analyst software. Random effects model was applied, and the heterogeneity of studies was evaluated using Higgins I.
RESULTS
Twenty-four studies that fulfilled the inclusion criteria were included in the final assessment. Overall, days 28 to 63 malaria treatment success rate was 96.1%. Overall days 28 to 63 cure rates for AL, AS+AQ, AS+MQ, DHA+PQ, AS+ATQ+PG and AS+SP were 95.1%, 92.2%, 97.0%,94.3%, 96.5% and 97.4%, respectively. Comparison of ACTs with non-ACTs revealed that the risk of treatment failure was substantially lower in patients treated with ACTs than with non-ACTs (risk ratio 0.20, 95% C.I. 0.09-0.43). The overall prevalences of miscarriage, stillbirth and congenital anomalies were 0.3%, 2.1% and 1.0%, respectively, and found to be comparable among various ACTs. There was comparable tolerability across ACTs during pregnancy.
CONCLUSION
ACTs demonstrated a high cure rate, safety and tolerability against infection in pregnant women. The higher treatment success and comparable tolerability could be used as an input for decision makers to support the continued usage of ACTs for treatment of uncomplicated falciparum malaria in pregnant women.
PubMed: 35221688
DOI: 10.2147/TCRM.S336771 -
JGH Open : An Open Access Journal of... Jun 2019Perianal fistulas in Crohn's disease (CD) represent a highly debilitating and difficult-to-treat condition. Given emerging supportive evidence, we conducted a systematic... (Review)
Review
Perianal fistulas in Crohn's disease (CD) represent a highly debilitating and difficult-to-treat condition. Given emerging supportive evidence, we conducted a systematic review and meta-analysis of all trials/observational studies to establish the safety and efficacy of local injections of mesenchymal stem cells (MSCs). The PRISMA-P statement was applied for planning and reporting, and MEDLINE, EMBASE, Web of Science, Cochrane, CINAHL, ClinicalTrials.gov database, and ECCO 2017 proceedings were searched for published observational studies and one-arm and randomized clinical trials (RCTs). Safety was assessed in terms of acute local/systemic events, long-term events, and relatedness with MSC treatment. Efficacy was evaluated in terms of external and/or radiological closure of fistula tracks. After a review of 211 citations, 23 studies, including 696 participants, were evaluated. Four were RCTs with a total of 483 patients. Overall, fistula closure occurred in 80% of MSC-treated patients. In RCTs, this rate was 64% in the MSC arm and 37% in the control arm (relative risk (RR) = 1.54). Radiological response occurred in 83% of MSC-treated patients. Treatment-related adverse events occurred in 1% of MSC-treated patients, with severe treatment-related adverse events reaching 0% over a median follow-up of 6 months. In RCTs, treatment-related adverse events occurred in 13% in the MSC arm and 24% in the control arm (RR = 0.65). The relapse rate was 0. These results suggest that a local MSC injection is safe and efficacious. Further clinical trials with standardized end-points are required to ensure the timely implementation of this new therapy in the management of perianal CD.
PubMed: 31276044
DOI: 10.1002/jgh3.12141 -
International Journal of Cancer Nov 2016Cancer-associated thromboembolism is a substantial problem in clinical practice. An increase in the level of fibrinopeptide A (a substance associated with... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of the risk of severe and life-threatening thromboembolism in cancer patients receiving anti-EGFR monoclonal antibodies (cetuximab or panitumumab).
Cancer-associated thromboembolism is a substantial problem in clinical practice. An increase in the level of fibrinopeptide A (a substance associated with hypercoagulable states) has been observed in humans exposed to fluorouracil. Anti-EGFR monoclonal antibodies cetuximab and panitumumab, which are now widely used in patients with metastatic colorectal cancer, could prolong the uncovering of endothelial structures resulting from flouorouracil or other co-administered agents, thus favouring several factors leading to thromboembolism. We performed a systematic review and meta-analysis of randomised, controlled trials assessing whether cancer patients receiving anti-EGFR monoclonal antibodies cetuximab and panitumumab are at increased risk of thromboembolic events. We searched electronic databases (Medline, Embase, Web of Science, Central) and reference lists. Phase II/III randomised, controlled trials comparing standard anti-cancer regimens with or without anti-EGFR monoclonal antibodies and reporting serious venous thromboembolic events were included in the analysis. Seventeen studies (12,870 patients) were considered for quantitative analysis. The relative risk (RR) for venous thromboembolism (18 comparisons) was 1.46 (95% CI 1.26 to 1.69); the RR of pulmonary embolism, on the basis of eight studies providing nine comparisons, was 1.55 (1.20 to 2.00). Cancer patients receiving anti-EGFR monoclonal antibodies-containing regimens are approximately 1.5 times more likely to experience venous or pulmonary embolism, compared to those treated with the same regimens without anti-EGFR monoclonal antibodies. Clinicians should consider patient's baseline thromboembolic risk when selecting regimens that include cetuximab or panitumumab. Potential non-reporting of these important adverse events remains a concern. PROSPERO registration number is CRD42014009165.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; ErbB Receptors; Humans; Neoplasms; Panitumumab; Randomized Controlled Trials as Topic; Thromboembolism
PubMed: 27450994
DOI: 10.1002/ijc.30280 -
Journal of Asthma and Allergy 2023Strong associations between early antibiotic exposure and increased risk of childhood allergies have been established. Antibiotics have the potential to induce microbial... (Review)
Review
BACKGROUND
Strong associations between early antibiotic exposure and increased risk of childhood allergies have been established. Antibiotics have the potential to induce microbial dysbiosis that may be linked to allergic conditions. This review examines the limited available evidence on the associations between adult antibiotic use, microbial dysbiosis and atopic conditions.
METHODS
A systematic literature search was conducted using PubMed and Embase for relevant studies, published between 01-01-2000 and 08-17-2022. We searched for associations between antibiotic use, microbial dysbiosis, and allergic conditions in adults, defined as over 13 years of age for the purposes of this review.
RESULTS
Twenty-one studies were analyzed, with the inclusion of four narrative reviews as scarce relevant literature was found when stricter selection criteria were employed. Relevant studies predominantly focused on asthma. Significant microbial differences were observed in most measures between healthy subjects and subjects with allergic conditions. However, no system-wise and strain-wise associations were evident. Notably, at the phyla level, the Bacillota and Pseudomonadota phyla were associated with asthmatics, while the Actinobacteria phylum was linked to healthy controls. Asthmatics tends to reflect upregulation in the Bacillota and Pseudomonadota phyla in both airway and gut microbiomes.
CONCLUSION
No compelling evidence could be found between adult antibiotic exposure, consequent microbial dysbiosis, and allergic conditions in adults. Our review is limited by scarce literature and therefore remains inconclusive. However, potential implications of antibiotic use impacting on allergic conditions justify additional research and heightened pharmacovigilance in this area.
PubMed: 37822520
DOI: 10.2147/JAA.S401755 -
The World Allergy Organization Journal Jul 2022The change from prescription to over-the-counter (OTC) status of oral antihistamines may raise concerns about drug safety due to the possibility of misuse/abuse. In most... (Review)
Review
BACKGROUND
The change from prescription to over-the-counter (OTC) status of oral antihistamines may raise concerns about drug safety due to the possibility of misuse/abuse. In most European countries, oral antihistamines are available without prescription, whereas in Italy, only <10-tablet packs are available OTC.
OBJECTIVES
To evaluate the safety profile of fexofenadine after OTC switch in Italy in a real-world setting, and to compare its safety profile to that of other European countries where larger pack sizes are available. To compare the safety of fexofenadine, cetirizine, and loratadine in Italy. To examine safety/efficacy across Europe with a systematic review.
METHODS
This case-by-case analysis used the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) to extract data of the adverse events (AEs) related to fexofenadine, loratadine and cetirizine in Italy January 2010-June 2020. The year 2016 was taken as the index date (removal of prescription requirement) for evaluation of the reporting trend of AEs of fexofenadine in Italy and make a comparison pre/post-OTC switch. A comparison of AEs with other European countries where fexofenadine is sold OTC in large packs >20 tablets (Belgium, Portugal, Switzerland, Finland, Hungary) was made. The rate at which an AE related to oral antihistamines occurred was estimated by calculation of the reporting rate (number of cases/[defined daily dose/1000 inhabitants per day]) on the basis of IQVIA sales data using the Italian Institute of Statistics database. A systematic review of the literature was also performed.
RESULTS
There were 3760 reports of AEs with a suspected association with fexofenadine; of these, eight were reported from Italy. There was a slightly increasing trend per year, in line with a general reporting trend of other drugs. In European countries where fexofenadine is available, the impact of OTC switch on AE reporting activity was negligible: from 2016, the reporting rate increased slightly and then normalized at 3.01, an incidence value similar to that recorded before the OTC switch (3.7 in 2015). Of 22 studies included in the systematic review, 18 (82%) positively evaluated the OTC use of oral antihistamines, confirming an acceptable safety/tolerability profile.
CONCLUSION
There was no difference in number of AEs reported for fexofenadine pre/post-OTC switch, indicating a similar safety profile. Spontaneous reporting systems are a valuable source of real-world data and support the OTC provision of oral antihistamines in Europe and fexofenadine in Italy, in addition to supporting the use of larger pack sizes in Italy.
PubMed: 35833202
DOI: 10.1016/j.waojou.2022.100658