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International Journal of Molecular... Dec 2023Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that widely spread and share the same patterns of pro-inflammatory cytokines. This... (Review)
Review
Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that widely spread and share the same patterns of pro-inflammatory cytokines. This systematic review aims to evaluate the effects of non-surgical periodontal treatment (NSPT) on RA and, conversely, the impact of disease-modifying anti-rheumatic drugs (DMARDs) on periodontitis. PubMed, Embase, and Web of Science were searched using the MESH terms "periodontitis" and "rheumatoid arthritis" from January 2012 to September 2023. A total of 49 articles was included in the final analysis, 10 of which were randomized controlled trials. A total of 31 records concerns the effect of NSPT on parameters of RA disease activity, including a 28-joint disease activity score, anti-citrullinated protein antibodies, rheumatoid factor, C reactive protein, erythrocyte sedimentation rate, pro-inflammatory cytokines and acute phase proteins in serum, saliva, gingival crevicular fluid, and synovial fluid. A total of 18 articles investigated the effect of DMARDs on periodontal indexes and on specific cytokine levels. A quality assessment and risk-of-bias of the studies were also performed. Despite some conflicting results, there is evidence that RA patients and periodontitis patients benefit from NSPT and DMARDs, respectively. The limitations of the studies examined are the small samples and the short follow-up (usually 6 months). Further research is mandatory to evaluate if screening and treatment of periodontitis should be performed systematically in RA patients, and if the administration of DMARDs is useful in reducing the production of cytokines in the periodontium.
Topics: Humans; Antirheumatic Agents; Periodontitis; Arthritis, Rheumatoid; Rheumatoid Factor; Cytokines
PubMed: 38139057
DOI: 10.3390/ijms242417228 -
AIDS (London, England) Jul 2023People with HIV (PWH) experience a greater risk of morbidity and mortality following COVID-19 infection, and poorer immunological responses to several vaccines. We... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
People with HIV (PWH) experience a greater risk of morbidity and mortality following COVID-19 infection, and poorer immunological responses to several vaccines. We explored existing evidence regarding the immunogenicity, effectiveness, and safety of SARS-CoV-2 vaccines in PWH compared with controls.
METHODS
We conducted a systematic search of electronic databases from January 2020 until June 2022, in addition to conference databases, to identify studies comparing clinical, immunogenicity, and safety in PWH and controls. We compared results between those with low (<350 cells/μl) and high (>350 cells/μl) CD4 + T-cell counts where possible. We performed a meta-analysis of seroconversion and neutralization responses to calculate a pooled risk ratio as the measure of effect.
RESULTS
We identified 30 studies, including four reporting clinical effectiveness, 27 immunogenicity, and 12 reporting safety outcomes. PWH were 3% [risk ratio 0.97, 95% confidence interval (95% CI) 0.95-0.99] less likely to seroconvert and 5% less likely to demonstrate neutralization responses (risk ratio 0.95, 95% CI 0.91-0.99) following a primary vaccine schedule. Having a CD4 + T-cell count less than 350 cells/μl (risk ratio 0.91, 95% CI 0.83-0.99) compared with a CD4 + T-cell count more than 350 cells/μl, and receipt of a non-mRNA vaccine in PWH compared with controls (risk ratio 0.86, 95% CI 0.77-0.96) were associated with reduced seroconversion. Two studies reported worse clinical outcomes in PWH.
CONCLUSION
Although vaccines appear well tolerated in PWH, this group experience poorer immunological responses following vaccination than controls, particularly with non-mRNA vaccines and low CD4 + T-cell counts. PWH should be prioritized for mRNA COVID-19 vaccines, especially PWH with more advanced immunodeficiency.
Topics: Humans; Antibodies, Viral; COVID-19; COVID-19 Vaccines; HIV Infections; SARS-CoV-2; Vaccination
PubMed: 37070539
DOI: 10.1097/QAD.0000000000003579 -
PLoS Neglected Tropical Diseases Apr 2024Snakebite envenoming represents a significant and often neglected public health challenge, particularly in rural communities across tropical and subtropical regions. An... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Snakebite envenoming represents a significant and often neglected public health challenge, particularly in rural communities across tropical and subtropical regions. An estimated 1.2-5.5 million people are envenomed by snakebites annually. More than 125,000 of these bites are fatal, and 3-4 times as many results in disability/disfigurement. Despite its prevalence, collecting accurate epidemiological data on snakebite is challenging. This systematic review and meta-analysis collates global epidemiology data on snakebite morbidity and mortality.
METHODS
Medline, Embase, Cochrane and CINAHL Plus databases were searched for articles published between 2001-2022. Pooled incidence and mortality were obtained using random effects modelling, heterogeneity (I2) was tested, and sensitivity analyses performed. Newcastle-Ottawa Scale assessed study quality.
RESULTS
Out of the four databases, 5,312 articles were found. After removing duplicates, 3,953 articles were screened by title and abstract and 65 articles containing information on snakebite epidemiology, encompassing 663,460 snakebites, were selected for analysis. The people most at risk for snakebite were men (59%), engaged in agricultural labour (27.5%), and residing in rural areas (66.7%). More than half (57%) of the reported bites resulted in envenoming. Incidents occurred frequently in the summer season (38.5%), during daytime (56.7%), and bites were most often to the lower limb (56.4%). Envenoming severity was frequently mild (46.7%), treated in hospital (68.3%), and was treated with anti-venom (64.7%). The pooled global incidence and mortality was 69.4 /100,000 population (95%CI: 36.8 to 101.9) and 0.33/100,000 population (95%CI, 0.14 to 0.52) per year, respectively. Stratified by continents, Asia had the highest incidence of 130.7/100,000 population (95%CI: 48.3 to 213.1) while Europe has the lowest with 0.7/100,000 population (95%CI: -0.2 to 1.5). The highest mortality was reported in Asia at 0.96/100,000 population (95% CI: 0.22 to 1.70), and Africa 0.44/100,000 population (95%CI: -0.03 to 0.84). Incidence was highest among inhabitants of lower-middle-income countries 132.7/100,000 population (95%CI: 55.4 to 209.9) while mortality was highest in low-income countries at 0.85/100,000 population (95% CI: -0.06 to 2.31).
CONCLUSION
Incidence and mortality rates noted here highlight the global impact of snakebite and underscore the critical need to address the burden of snakebite envenoming. It also reveals that while reported snakebite incidence was higher in lower-middle-income countries, the burden of mortality was greatest among inhabitants of low-income countries, again emphasising the need for greater efforts to tackle this neglected tropical disease.
Topics: Male; Humans; Female; Snake Bites; Antivenins; Incidence; Asia; Prevalence
PubMed: 38574167
DOI: 10.1371/journal.pntd.0012080 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups.
METHODS
We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias.
RESULTS
Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61-0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43-0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group.
CONCLUSIONS
Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival.
Topics: Humans; Aged; Antilymphocyte Serum; Immunosuppressive Agents; Kidney Transplantation; Alemtuzumab; Antibodies; Graft Rejection; Lymphocytes; Transplant Recipients; Graft Survival
PubMed: 37774445
DOI: 10.1016/j.trre.2023.100795 -
The Journal of Medicine Access 2023Immunoglobulin replacement therapy (IgRT) benefits patients with primary immuno deficiency (PID) originating from the innate or polygenic defects in the immune system.... (Review)
Review
BACKGROUND
Immunoglobulin replacement therapy (IgRT) benefits patients with primary immuno deficiency (PID) originating from the innate or polygenic defects in the immune system. However, evidence supporting their therapeutic role is not as explicit in secondary immuno deficiency (SID) resulting from the treatment of haematological malignancies.
OBJECTIVES
This study aimed to (1) create a dataset of relevant research papers, which explore the use of IgRT in SID for analysis, (2) assess the risk of bias within this dataset and (3) study the characteristics of these papers.
DESIGN
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. In addition to the risk of bias, the study characteristics explored in this article included study design, study geographical location and year of publication.
DATA SOURCES AND METHODS
To identify studies relevant to the research question, EMBASE and PubMed databases were searched. The Population, Intervention, Comparison and Outcome (PICO) framework was used to assess study quality. Risk of bias and quality of studies were assessed in accordance with the study design. As one model was not appropriate to assess bias in all articles, several tools were used.
RESULTS
A total of 43 studies were identified from the literature search as relevant to the research objective. The most common study design was a retrospective case-control cohort study ( = 16/43), and randomised trials were among the least commonly used approaches ( = 1). Research in this area is occurring around the globe including the United States ( = 7), Italy ( = 7), China, India, Japan and throughout Europe. The annual number of papers in this area has varied from 2012 ( = 1) to 2021 ( = 7). The studies in this article demonstrated a varied risk of bias, with 9 of the 20 cohort studies scoring less than 5 out of 9 stars.
CONCLUSIONS
Randomised controlled trials are less frequently used to assess access and use of immunoglobulins. More commonly, a retrospective case-control cohort study was used which correlates with the higher risk of bias seen in the studies in this article. Most of the research concerning immunoglobulin use and access occurs in higher-income countries.
PubMed: 37846344
DOI: 10.1177/27550834231197315 -
Infection Dec 2023Tocilizumab, a monoclonal IL-6 receptor blocker, is an effective agent for severe-to-critical cases of COVID-19; however, its target patients for the optimum use need to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Tocilizumab, a monoclonal IL-6 receptor blocker, is an effective agent for severe-to-critical cases of COVID-19; however, its target patients for the optimum use need to be detailed. We performed a systematic review and meta-analysis to define its effect among severely ill but non-intubated cases with COVID-19.
METHODS
We searched PubMed, Scopus, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Medrxiv, and Biorxiv until February 13, 2022, for non-intubated cases, and included randomized-controlled trials (RCT) based on bias assessment. The primary outcomes were the requirement of invasive mechanical ventilation and mortality. Random effect and fixed-effect models were used. The heterogeneity was measured using the χ and I statistics, with χ p ≤ 0.05 and I ≥ 50% indicating the presence of significant heterogeneity. We registered the study to the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42021232575.
RESULTS
Among 261 articles, 11 RCTs were included. The pooled analysis of the 11 RCTs demonstrated that the rate of mortality was significantly lower in the tocilizumab group than in the control group (20.0% and 24.2%, OR: 0.84, 95% CI 0.73-0.96, and heterogeneity I = 0%. p = 0.82.). The mechanical ventilation rate was lower in the tocilizumab group than the control group (27% vs 35.2%, OR: 0.76, 95% CI 0.67-0.86, and heterogeneity I = 6%. p = 0.39).
CONCLUSION
Among non-intubated severe COVID-19 cases, tocilizumab reduces the risk of invasive mechanical ventilation and mortality compared to standard-of-care treatment.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; Antibodies, Monoclonal, Humanized; Respiration, Artificial
PubMed: 37162716
DOI: 10.1007/s15010-023-02047-2 -
Journal of Investigational Allergology... Dec 2023Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP.
METHODS
We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received.
RESULTS
Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell.
CONCLUSION
Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab.
Topics: Adult; Humans; Antibodies, Monoclonal; Nasal Polyps; Omalizumab; Smell; Rhinosinusitis; Chronic Disease; Sinusitis; Rhinitis; Quality of Life
PubMed: 37669083
DOI: 10.18176/jiaci.0939 -
Cureus Dec 2023Severe eosinophilic asthma (SEA) is characterized by persistent airway inflammation and frequent exacerbations despite standard treatments. Mepolizumab, a monoclonal... (Review)
Review
Severe eosinophilic asthma (SEA) is characterized by persistent airway inflammation and frequent exacerbations despite standard treatments. Mepolizumab, a monoclonal antibody that reduces eosinophil levels by targeting interleukin-5, has emerged as an add-on therapy for patients with SEA. This systematic review evaluated mepolizumab's efficacy and safety for treating SEA. A comprehensive literature search was conducted across major databases. Thirty-two studies with over 6,000 patients were included, comprising randomized controlled trials, open-label extensions, and real-world observational analyses. Study quality and risk of bias were assessed using standard tools. Meta-analysis was deemed inappropriate due to heterogeneity. Instead, a narrative synthesis was performed. Mepolizumab significantly reduced exacerbation rates by around 50% and improved symptoms and lung function compared to placebo in pivotal trials. Long-term open-label studies showed sustained reductions in exacerbations and stable lung function for up to 4.5 years. Real-world data demonstrated consistent 50%-90% exacerbation decreases across diverse patient populations over 6-24 months. Mepolizumab exhibited an acceptable safety profile, with mild injection site reactions and headaches as most common adverse events. While specific subgroups may show enhanced responses, mepolizumab displayed broad efficacy regardless of patient demographics or phenotypes. The extensive evidence provides robust support for mepolizumab as an efficacious and safe add-on treatment option for patients with severe, refractory eosinophilic asthma. Further high-quality comparative effectiveness research is warranted to optimize patient selection and positioning among emerging biologics.
PubMed: 38161547
DOI: 10.7759/cureus.49781 -
Journal of Cancer Research and Clinical... Jan 2024The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive... (Meta-Analysis)
Meta-Analysis
PURPOSE
The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive evaluation to inform clinical decision-making. We conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions.
METHODS
We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts from inception to June 1, 2023. NMA was performed to calculate and analyze progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events of grade 3 or higher (≥ 3 AEs).
RESULTS
Out of the 10,313 manuscripts retrieved, we included 28 RCTs involving 11,680 patients. Regarding PFS and ORR, the combination of trastuzumab with tyrosine kinase inhibitors (TKIs) was more favorable than dual-targeted therapy. If only using trastuzumab, combination chemotherapy is superior to monochemotherapy in terms of PFS. It is important to note that the addition of anthracycline did not result in improved PFS. For patients with hormone receptor-positive HER2-positive diseases, dual-targeted combined with endocrine therapy showed better benefit in terms of PFS compared to dual-targeted alone, but it did not reach statistical significance. The comprehensive analysis of PFS and ≥ 3 AEs indicates that monochemotherapy combined with dual-targeted therapy still has the optimal balance between efficacy and safety.
CONCLUSION
Monochemotherapy (Docetaxel) plus dual-target (Trastuzumab and Pertuzumab) therapy remains the optimal choice among all first-line treatment options for ABC. The combination of trastuzumab with TKIs (Pyrotinib) demonstrated a significant improvement in PFS and ORR, but further data are warranted to confirm the survival benefit.
Topics: Humans; Female; Network Meta-Analysis; Randomized Controlled Trials as Topic; Breast Neoplasms; Trastuzumab; Receptor, ErbB-2; Docetaxel; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38244085
DOI: 10.1007/s00432-023-05530-3 -
CVIR Endovascular Aug 2023Occult gastrointestinal bleeding (GIB) is a challenge for physicians to diagnose and treat. A systematic literature search of the PubMed and Embase databases was... (Review)
Review
Occult gastrointestinal bleeding (GIB) is a challenge for physicians to diagnose and treat. A systematic literature search of the PubMed and Embase databases was conducted up to January 1, 2023. Eligible studies included primary research studies with patients undergoing provocative mesenteric angiography (PMA) for diagnosis or localization of occult GIB. Twenty-seven articles (230 patients) were included in the review. Most patients (64.8%) presented with lower GIB. The average positivity rate for provocative angiography was 48.7% (58% with heparin and 46.7% in thrombolytics). Embolization was performed in 46.4% of patients, and surgical management was performed in 37.5%. Complications were rare. PMA can be an important diagnostic and treatment tool but studies with high-level evidence and standardized protocols are needed to establish its safety and optimal use.
PubMed: 37589781
DOI: 10.1186/s42155-023-00386-7