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Expert Review of Vaccines 2024This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV).
METHODS
We searched five databases for randomized controlled trials (RCTs) evaluating the effects of EVV on healthy adults. The primary outcomes were relative risk (RR) of sero-conversion or sero-response of EVV in healthy adults between the groups that received EVV and the controls.
RESULTS
Twenty-nine RCTs ( = 23573) were included. There was a significant difference in RR of sero-conversion of EVV (RR 13.18; 95% CI 11.28-15.41; I = 33%; < 0.01) between the two groups. There was a significant difference in RR of adverse events (AEs) of EVV (RR 1.49; 95% CI 1.27-1.74; I = 88%; < 0.01), although no difference in RR of serious AE (SAE) between the two groups. Subgroup analysis showed that there was no significant difference in RR of AEs for DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines, compared with controls.
CONCLUSIONS
The DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines are likely to be safe and immunogenic, tending to support the vaccination against Ebola disease. These findings should provide much-needed evidence for public health policy makers to develop preventive measures based on disease prevalence features and socio-economic conditions.
Topics: Adult; Humans; Ebola Vaccines; Randomized Controlled Trials as Topic; Hemorrhagic Fever, Ebola; Vaccination; Antibody Formation; Ebolavirus
PubMed: 38112249
DOI: 10.1080/14760584.2023.2296937 -
Advances in Clinical and Experimental... May 2024Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and... (Review)
Review
Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.
Topics: Humans; Vascular Calcification; Atherosclerosis; Animals; Wnt Signaling Pathway; Adaptor Proteins, Signal Transducing; Genetic Markers
PubMed: 37676098
DOI: 10.17219/acem/169567 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Multiple myeloma is a malignant cancerous condition that is characterized by abnormal plasma cell production and can lead to bone destruction due to increased...
Multiple myeloma is a malignant cancerous condition that is characterized by abnormal plasma cell production and can lead to bone destruction due to increased osteoclastic activity and decreased osteoblastic activity. Many therapeutic therapies are used to treat diseases, such as chemotherapy and radiotherapy. In recent years, anti-sclerostin antibody treatment has been under investigation for its effect on the multiple myeloma. The present study was conducted to assess the effective therapeutic use of anti-sclerostin antibody in the treatment of multiple myeloma. The literature search was conducted using PubMed, Google Scholar, ScienceDirect, and PubMed Central using the following MeSH terms: "multiple myeloma", "anti-sclerostin antibody", "ubiquitin-proteasome pathway", "proteasome inhibitor", "Wnt pathway". A total of 348 articles were screened. Twenty-five out of 348 were full-text articles assessed for eligibility, and four articles were used in this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the reporting of this systematic review. A total of four randomized control trials (RCT) were included and used in this systematic review. The anti-sclerostin antibodies were various other drugs, and it was found that the anti-sclerostin antibody was effective in preventing autoantibody formation, decreasing bone destruction, and increasing trabecular bone. Anti-sclerostin antibody was found to be effective in decreasing bone destruction by reducing osteoclastic activity and increasing osteoblastic activity associated with multiple myeloma.
PubMed: 37654355
DOI: 10.4103/jpbs.jpbs_560_22 -
Tremor and Other Hyperkinetic Movements... 2023Hand tremor is a common symptom of Parkinson's disease (PD). Tremors may be resistant to drug treatments. Therefore, Botulinum toxin (BoNT) could be a good alternative.... (Review)
Review
BACKGROUND
Hand tremor is a common symptom of Parkinson's disease (PD). Tremors may be resistant to drug treatments. Therefore, Botulinum toxin (BoNT) could be a good alternative. This study aimed to review and analyze studies on the efficacy and safety of BoNT injection in hand tremor intensity and upper limb function in patients with idiopathic PD.
METHODS
A comprehensive search was conducted for studies on the effect of local BoNT injections on tremors in PD patients from 1990 to December 2021. Electronic databases such as Cochrane Central Control Records, PubMed, Scopus, Web of Science, EMBASE, Google Scholar, Clinicaltrial.gov, ProQuest, Science Direct, CINAHL, and Psychoinfo were searched systematically.
RESULTS
Ten studies, comprising one double-blinded randomized clinical trial and nine pilot open-labeled studies with 131 participants, met eligibility criteria. The reported tremor intensity ranged from 1 to 3, and the average tremor duration of 5.93 ± 2.08 years. The injectable dose was 68-100 units of onabotulinum-toxin-A in each upper limb muscle, mostly wrist flexors. The results showed a decrease in unified Parkinson's disease rating scale (UPDRS)_20 and UPDRS_21 indices by 1.22 ± 1.1 and 1.20 ± 0.9, respectively, without causing severe side effects. The BoNT relative effectiveness in the forearm and arm muscles was reported 6-16 weeks after injection.
DISCUSSION
The kinematic, electromyography-guided, and electrical stimulation evaluations allow for accurate muscle localization and minimize the possibility of BoNT diffusion and antibody formation. More extensive randomized clinical trials with uniform measurement criteria are recommended to reduce bias and provide more accurate conclusions.
HIGHLIGHT
Tremor treatment in Parkinson's-disease (PD) is challenging. Drugs effect is temporary, and surgery is critical management. This study reviews the Botulinum-toxin injection efficacy in hand tremor intensity and upper limb function. The results showed a decrease in unified Parkinson's disease rating scale (UPDRS)_20 and UPDRS_21 by 1.22 ± 1.1 and 1.20 ± 0.9, respectively, 6-16 weeks after injection.
Topics: Humans; Parkinson Disease; Tremor; Upper Extremity; Forearm; Databases, Factual; Randomized Controlled Trials as Topic
PubMed: 37637849
DOI: 10.5334/tohm.773 -
Vaccine Jun 2023Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This... (Review)
Review
BACKGROUND
Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This systematic review aims to summarize which within-host methodology has been used to study and quantify antibody kinetics after infection or vaccination. In particular, we focus on data-driven and theory-driven mechanistic models.
MATERIALS
PubMed and Web of Science databases were used to identify eligible papers published until May 2022. Eligible publications included those studying mathematical models that measure antibody kinetics as the primary outcome (ranging from phenomenological to mechanistic models).
RESULTS
We identified 78 eligible publications, of which 8 relied on an Ordinary Differential Equations (ODEs)-based modelling approach to describe antibody kinetics after vaccination, and 12 studies used such models in the context of humoral immunity induced by natural infection. Mechanistic modeling studies were summarized in terms of type of study, sample size, measurements collected, antibody half-life, compartments and parameters included, inferential or analytical method, and model selection.
CONCLUSIONS
Despite the importance of investigating antibody kinetics and underlying mechanisms of (waning of) the humoral immunity, few publications explicitly account for this in a mathematical model. In particular, most research focuses on phenomenological rather than mechanistic models. The limited information on the age groups or other risk factors that might impact antibody kinetics, as well as a lack of experimental or observational data remain important concerns regarding the interpretation of mathematical modeling results. We reviewed the similarities between the kinetics following vaccination and infection, emphasising that it may be worth translating some features from one setting to another. However, we also stress that some biological mechanisms need to be distinguished. We found that data-driven mechanistic models tend to be more simplistic, and theory-driven approaches lack representative data to validate model results.
Topics: Antibody Formation; Vaccination; Immunity, Humoral; Models, Theoretical
PubMed: 37198016
DOI: 10.1016/j.vaccine.2023.04.030 -
The Cochrane Database of Systematic... May 2023Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with... (Review)
Review
BACKGROUND
Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review.
OBJECTIVES
To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding. Bisphosphonates versus placebo or no treatment Two RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty. There were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility. Different doses of bisphosphonate compared One 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment. Zinc versus placebo One trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment. Denosumab versus placebo Based on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD -2.40 cm, 95% CI -3.80 to -1.00). Strontium ranelate One trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD -0.70 cm (95% CI -1.30 to -0.10); we considered this measure representative of improved quality of life.
AUTHORS' CONCLUSIONS
Bisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD. We recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.
Topics: Adult; Child; Female; Male; Humans; Middle Aged; beta-Thalassemia; Alendronate; Pamidronate; Clodronic Acid; Denosumab; Osteoporosis; Diphosphonates; Fractures, Bone
PubMed: 37159055
DOI: 10.1002/14651858.CD010429.pub3 -
Biomolecules Feb 2023The deposition of amyloid-beta (Aβ) plaques in the brain is one of the primary pathological characteristics of Alzheimer's disease (AD). It can take place 20-30 years... (Review)
Review
The deposition of amyloid-beta (Aβ) plaques in the brain is one of the primary pathological characteristics of Alzheimer's disease (AD). It can take place 20-30 years before the onset of clinical symptoms. The imbalance between the production and the clearance of Aβ is one of the major causes of AD. Enhancing Aβ clearance at an early stage is an attractive preventive and therapeutic strategy of AD. Direct inhibition of Aβ production and aggregation using small molecules, peptides, and monoclonal antibody drugs has not yielded satisfactory efficacy in clinical trials for decades. Novel approaches are required to understand and combat Aβ deposition. Neurological dysfunction is a complex process that integrates the functions of different types of cells in the brain. The role of non-neurons in AD has not been fully elucidated. An in-depth understanding of the interactions between neurons and non-neurons can contribute to the elucidation of Aβ formation and the identification of effective drug targets. AD patient-derived pluripotent stem cells (PSCs) contain complete disease background information and have the potential to differentiate into various types of neurons and non-neurons in vitro, which may bring new insight into the treatment of AD. Here, we systematically review the latest studies on Aβ clearance and clarify the roles of cell interactions among microglia, astroglia and neurons in response to Aβ plaques, which will be beneficial to explore methods for reconstructing AD disease models using inducible PSCs (iPSCs) through cell differentiation techniques and validating the applications of models in understanding the formation of Aβ plaques. This review may provide the most promising directions of finding the clues for preventing and delaying the development of AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Neurons; Brain; Astrocytes
PubMed: 36830682
DOI: 10.3390/biom13020313 -
Influenza and Other Respiratory Viruses Jan 2023COVID-19 vaccine is critical in preventing SARS-CoV-2 infection and transmission. However, obesity's effect on immune responses to COVID-19 vaccines is still unknown. We... (Meta-Analysis)
Meta-Analysis Review
COVID-19 vaccine is critical in preventing SARS-CoV-2 infection and transmission. However, obesity's effect on immune responses to COVID-19 vaccines is still unknown. We performed a meta-analysis of the literature and compared antibody responses with COVID-19 vaccines among persons with and without obesity. We used Pubmed, Embase, Web of Science, and Cochrane Library to identify all related studies up to April 2022. The Stata.14 software was used to analyze the selected data. Eleven studies were included in the present meta-analysis. Five of them provided absolute values of antibody titers in the obese group and non-obese group. Overall, we found that the obese population was significantly associated with lower antibody titers (standardized mean difference [SMD] = -0.228, 95% CI [-0.437, -0.019], P < 0.001) after COVID-19 vaccination. Significant heterogeneity was present in most pooled analyses but was reduced after subgroup analyses. No publication bias was observed in the present analysis. The Trim and Fill method did not change the results in the primary analysis. The present meta-analysis suggested that obesity was significantly associated with decreased antibody responses to SARS-CoV-2 vaccines. Future studies should be performed to unravel the mechanism of response to the COVID-19 vaccine in obese individuals.
Topics: Humans; COVID-19 Vaccines; Antibody Formation; COVID-19; SARS-CoV-2; Vaccination; Obesity
PubMed: 36535669
DOI: 10.1111/irv.13078 -
British Journal of Cancer Nov 2022Patients living with cancer are at a significantly increased risk of morbidity and mortality after infection with severe acute respiratory syndrome coronavirus-2...
BACKGROUND
Patients living with cancer are at a significantly increased risk of morbidity and mortality after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This systematic review aims to investigate the current available evidence about the immunogenicity of SARS-CoV-2 booster vaccines in patients living with cancer.
METHODS
A systematic search was undertaken for studies published until March 1, 2022. A systematic narrative review was undertaken to include all studies that evaluated the efficacy of booster vaccines against SARS-CoV-2 in patients with cancer.
RESULTS
Fifteen studies encompassing 1205 patients with cancer were included. We found that a booster vaccine dose induced a higher response in patients with solid cancer as compared to haematological malignancies. Recent systemic anticancer therapy does not appear to affect seroconversion in solid organ malignancies, however, there is an association between B-cell depleting therapies and poor seroconversion in haematological patients.
CONCLUSIONS
Third booster vaccination induces an improved antibody response to SARS-CoV-2 in adults with haematological and solid cancer, relative to patients who only receive two doses. Access to vaccination boosters should be made available to patients at risk of poor immunological responses, and the provision of fourth doses may be of benefit to this vulnerable population.
REGISTRATION
PROSPERO number CRD42021270420.
Topics: Adult; Humans; Antibodies, Viral; Antibody Formation; COVID-19; COVID-19 Vaccines; Neoplasms; SARS-CoV-2; Vaccination; Viral Vaccines
PubMed: 36224402
DOI: 10.1038/s41416-022-01951-y -
Haematologica Feb 2023
Meta-Analysis
Topics: Adult; Humans; SARS-CoV-2; Antibody Formation; COVID-19; Hematologic Neoplasms; Vaccination; Antibodies, Viral
PubMed: 36172816
DOI: 10.3324/haematol.2022.281902