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JVS-vascular Science 2024Peripheral artery disease (PAD) impacts more than 200 million people worldwide. The understanding of the genetics of the disease and its clinical implications continue... (Review)
Review
BACKGROUND
Peripheral artery disease (PAD) impacts more than 200 million people worldwide. The understanding of the genetics of the disease and its clinical implications continue to evolve. This systematic review provides a comprehensive summary of all DNA variants that have been studied in association with the diagnosis and progression of PAD, with a meta-analysis of the ones replicated in the literature.
METHODS
A systematic review of all studies examining DNA variants associated with the diagnosis and progression of PAD was performed. Candidate gene and genome-wide association studies (GWAS) were included. A meta-analysis of 13 variants derived from earlier smaller candidate gene studies of the diagnosis of PAD was performed. The literature on the progression of PAD was limited, and a meta-analysis was not feasible because of the heterogeneity in the criteria used to characterize it.
RESULTS
A total of 231 DNA variants in 112 papers were studied for the association with the diagnosis of PAD. There were significant variations in the definition of PAD and the selection of controls in the various studies. GWAS have established 19 variants associated with the diagnosis of PAD that were replicated in several large patient cohorts. Only variants in intercellular adhesion molecule-1 (rs5498), IL-6 (rs1800795), and hepatic lipase (rs2070895) showed significant association with the diagnosis of PAD. However, these variants were not noted in the published GWAS.
CONCLUSIONS
Genetic research in the diagnosis of PAD has significant heterogeneity, but recent GWAS have demonstrated variants consistently associated with the disease. More research focusing on the progression of PAD is needed to identify patients at risk of adverse events and develop strategies that would improve their outcomes.
PubMed: 38314202
DOI: 10.1016/j.jvssci.2023.100133 -
International Journal of Medical... Nov 2023Lack of accurate and timely diagnosis of hepatitis poses obstacles to effective treatment, disease progression prevention, complication reduction, and life-saving... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lack of accurate and timely diagnosis of hepatitis poses obstacles to effective treatment, disease progression prevention, complication reduction, and life-saving interventions of patients. Utilizing machine learning can greatly enhance the achievement of timely and precise disease diagnosis. Therefore, we carried out this systematic review and meta-analysis to explore the performance of machine learning algorithms in predicting viral hepatitis.
METHODS
Using an extensive literature search in PubMed, Scopus, and Web of Science databases until June 15, 2023, English publications on hepatitis prediction using machine learning algorithms were included. Two authors independently extracted pertinent information from the selected studies. The PRISMA 2020 checklist was followed for study selection and result reporting. The risk of bias was checked using the International Journal of Medical Informatics (IJMEDI) checklist. Data were analyzed using the 'metandi' command in Stata 17.
RESULTS
Twenty-one original studies were included, covering 82 algorithms. Sixteen studies utilized five algorithms to predict hepatitis B. Ten studies used five algorithms for hepatitis C prediction. For hepatitis B prediction, the SVM algorithms demonstrated the highest sensitivity (90.0%; 95% confidence interval (CI): 77.0%-96.0%), specificity (94%; 95% CI: 90.0%-97.0%), and a diagnostic odds ratio (DOR) of 145 (95% CI: 37.0-559.0). In the case of hepatitis C, the KNN algorithms exhibited the highest sensitivity (80%; 95% CI:30.0%-97.0%), specificity (95%; 95% CI: 58.0%-99.0%), and DOR (72; 95% CI: 3.0-1644.0) for prediction.
CONCLUSION
SVM and KNN demonstrated superior performance in predicting hepatitis. The proper algorithm along with clinical practice could improve hepatitis prediction and management.
Topics: Humans; Hepatitis, Viral, Human; Machine Learning; Hepatitis C; Hepatitis B
PubMed: 37806178
DOI: 10.1016/j.ijmedinf.2023.105243 -
Cytokine Nov 2023Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main... (Meta-Analysis)
Meta-Analysis Review
Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main regulators of immune responses, play crucial roles in inflammatory diseases such as COPD. Moreover, certain genetic variations can alter cytokine expression, and changes in cytokine level or function can affect disease susceptibility. Therefore, investigating the association between genetic variations and disease progression can be useful for prevention and treatment. Several studies have explored the association between common genetic variations in cytokine genes and COPD susceptibility. In this study, we summarized the reported studies and, where possible, conducted a systematic review and meta-analysis to evaluate the genetic association between various cytokines and COPD pathogenesis. We extracted relevant articles from PubMed and Google Scholar databases using a standard systematic search strategy. We included a total of 183 studies from 78 separate articles that evaluated 50 polymorphisms in 12 cytokine genes in this study. Our analysis showed that among all reported cytokine polymorphisms (including TNF-α, TGF-β, IL1, IL1RN, IL4, IL4R, IL6, IL10, IL12, IL13, IL17, IL18, IL27, and IL33), only four variants, including TNF-α-rs1800629, TGF-β1-rs6957, IL13-rs1800925, and IL6-rs1800796, were associated with the risk of COPD development. This updated meta-analysis strongly supports the association of TNF-α-rs1800629, TGF-β1-rs6957, IL13-rs1800925, and IL6-rs1800796 variants with a high risk of COPD.
Topics: Humans; Polymorphism, Single Nucleotide; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Genetic Predisposition to Disease; Interleukin-13; Interleukin-6; Cytokines; Pulmonary Disease, Chronic Obstructive
PubMed: 37703677
DOI: 10.1016/j.cyto.2023.156352 -
Reviews in Medical Virology Nov 2023This study aimed to clarify the beneficial effect and the clinical application value of Paxlovid in the treatment of coronavirus disease-19 (COVID-19) through a... (Review)
Review
This study aimed to clarify the beneficial effect and the clinical application value of Paxlovid in the treatment of coronavirus disease-19 (COVID-19) through a systematic review. Databases including PubMed, Cochrane Library, Chinese Clinical Trial Registry, and ClinicalTrials.gov were systematically searched for interventional or observational studies on the efficacy and safety of Paxlovid in the treatment of SARS-COV-2. The relative and absolute effect sizes for the outcomes were calculated based on the data reported in the original intervention literature. The external applicability of the evidence was analysed in terms of clinical application scenarios, patient willingness, and cost utility. One interventional and three observational studies were conducted. Four studies published in 2022, had participation sample sizes ranging 1780-109,254. Based on the randomised controlled trial data, the risk of all-cause mortality, all-cause death, and hospitalisation was significantly reduced in the Paxlovid group. Serious adverse events were reduced during the study. Based on observational studies, Paxlovid can significantly reduce the risk of death and hospitalisation in older patients with COVID-19 (moderate certainty) and improve in-hospital disease progression, composite disease progression, and viral load (low certainty). Paxlovid did not improve the outcomes of death and hospitalisation (low certainty) in patients aged <65 years. As per the economic utility analysis, the economic cost of reducing one death dramatically decreased with increasing age. Early use of Paxlovid in the older adult population with COVID-19 is beneficial. However, in the setting of limited resources, Paxlovid should be prioritised for older patients.
Topics: Humans; Aged; COVID-19; SARS-CoV-2; Reproducibility of Results; Disease Progression
PubMed: 37578892
DOI: 10.1002/rmv.2476 -
Seminars in Ophthalmology Aug 2023To evaluate myopia progression during the novel coronavirus disease 2019 (COVID-19) pandemic and its risk factors. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate myopia progression during the novel coronavirus disease 2019 (COVID-19) pandemic and its risk factors.
METHODS
We searched PubMed, Scopus, and Web of Science to find literature until August 2022 related to COVID-19 pandemic and myopia progression. Outcomes of myopia progression included axial length (AL) and spherical equivalent (SE). Factors of screen time and outdoor activity time were analyzed.
RESULTS
Thirty-three studies were included in this meta-analysis. Compared to the same period before the COVID-19 pandemic, myopia prevalence increased (OR = 1.11; 95% CI, 1.05-1.18). The outcomes of SE decreased -0.61 diopter (95% CI, -0.98 to -0.23), and AL increased 0.42 mm (95% CI, 0.13-0.7). Mean screen time was increased 6.25 hours/day (95% CI, 4.84-7.66), and outdoor activity time was decreased -1.52 hours/day (95% CI, -3.20 to -0.15).
CONCLUSION
Establishing care policies is necessary to restrict behavioral changes and their consequences during the pandemic.
Topics: Humans; Pandemics; COVID-19; Myopia; Refraction, Ocular; Risk Factors; Disease Progression
PubMed: 36734046
DOI: 10.1080/08820538.2023.2168490 -
World Neurosurgery Aug 2023The optimal treatment algorithm for patients with degenerative lumbar spondylolisthesis has not been clarified. Part of the reason for this is that the natural history... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The optimal treatment algorithm for patients with degenerative lumbar spondylolisthesis has not been clarified. Part of the reason for this is that the natural history of degenerative spondylolisthesis (DS) has not been sufficiently studied. Comprehension of the natural history is essential for surgical decision making. We aimed to determine 1) the proportion of patients that develop de novo DS during follow-up; and 2) the proportion of patients with progression of preexistent DS by conducting a systematic review and meta-analysis of the literature.
METHODS
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Ovid, EMBASE, and the Cochrane Library were searched from their inception through April 2022. Demographic values of the study populations, grade of slip, rate of slippage before and after the follow-up period, and percentage of patients with slip in the populations at baseline and after follow-up were the extracted parameters.
RESULTS
Of the 1909 screened records, eventually 10 studies were included. Of these studies, 5 reported the development of de novo DS and 9 reported on the progression of preexistent DS. Proportions of patients developing de novo DS ranged from 12% to 20% over a period ranging from 4 to 25 years. The proportion of patients with progression of DS ranged from 12% to 34% over a period ranging from 4 to 25 years.
CONCLUSIONS
Systematic review and metanalysis of DS on the basis of radiologic parameters revealed both an increasing incidence over time and an increasing progression of the slip rate in up to a third of the patients older than 25 years, which is important for counseling patients and surgical decision making. Importantly, two thirds of patients did not experience slip progression.
Topics: Humans; Spondylolisthesis; Treatment Outcome; Decompression, Surgical; Spinal Fusion; Lumbar Vertebrae
PubMed: 37271258
DOI: 10.1016/j.wneu.2023.05.112 -
JAMA Ophthalmology May 2024Effects of genetic variants on primary angle-closure disease remained uncertain. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Effects of genetic variants on primary angle-closure disease remained uncertain.
OBJECTIVE
To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression.
DATA SOURCES
Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen.
STUDY SELECTION
Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression.
DATA EXTRACTION AND SYNTHESIS
PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics.
MAIN OUTCOMES AND MEASURES
SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized.
RESULTS
Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease-associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified.
CONCLUSIONS AND RELEVANCE
This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.
Topics: Glaucoma, Angle-Closure; Humans; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Genetic Predisposition to Disease; Intraocular Pressure
PubMed: 38546604
DOI: 10.1001/jamaophthalmol.2024.0363 -
Interactive Journal of Medical Research Jul 2023Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease globally. Obesity, metabolic diseases, and exposure to some environmental... (Review)
Review
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease globally. Obesity, metabolic diseases, and exposure to some environmental agents contribute to NAFLD. NAFLD is commonly considered a precursor for some types of cancers. Since the leading causes of death in people with NAFLD are cardiovascular disease and extrahepatic cancers, it is important to understand the mechanisms of the progression of NAFLD to control its progression and identify its association with extrahepatic cancers. Thus, this review aims to estimate the global prevalence of NAFLD in association with the risk of extrahepatic cancers.
OBJECTIVE
We aimed to determine the prevalence of various cancers in NAFLD patients and the association between NAFLD and cancer.
METHODS
We searched PubMed, ProQuest, Scopus, and Web of Science from database inception to March 2022 to identify eligible studies reporting the prevalence of NAFLD and the risk of incident cancers among adult individuals (aged ≥18 years). Data from selected studies were extracted, and meta-analysis was performed using random effects models to obtain the pooled prevalence with the 95% CI. The quality of the evidence was assessed with the Newcastle-Ottawa Scale.
RESULTS
We identified 11 studies that met our inclusion criteria, involving 222,523 adults and 3 types of cancer: hepatocellular carcinoma (HCC), breast cancer, and other types of extrahepatic cancer. The overall pooled prevalence of NAFLD and cancer was 26% (95% CI 16%-35%), while 25% of people had NAFLD and HCC (95% CI 7%-42%). NAFLD and breast cancer had the highest prevalence out of the 3 forms of cancer at 30% (95% CI 14%-45%), while the pooled prevalence for NAFLD and other cancers was 21% (95% CI 12%-31%).
CONCLUSIONS
The review suggests that people with NAFLD may be at an increased risk of cancer that might not affect not only the liver but also other organs, such as the breast and bile duct. The findings serve as important evidence for policymakers to evaluate and recommend measures to reduce the prevalence of NAFLD through lifestyle and environmental preventive approaches.
TRIAL REGISTRATION
PROSPERO CRD42022321946; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=321946.
PubMed: 37467012
DOI: 10.2196/40653 -
The Cochrane Database of Systematic... Oct 2023Immune checkpoint inhibitors are increasingly important in the treatment algorithm for locally advanced and metastatic bladder cancer. Numerous ongoing studies are... (Review)
Review
BACKGROUND
Immune checkpoint inhibitors are increasingly important in the treatment algorithm for locally advanced and metastatic bladder cancer. Numerous ongoing studies are investigating these agents as first- and second-line therapies, both alone and in combination with chemotherapy or in a maintenance therapy setting.
OBJECTIVES
To assess the effects of immune checkpoint inhibitors compared to chemotherapy as first- and second-line treatment of advanced or metastatic urothelial carcinoma.
SEARCH METHODS
We performed a comprehensive search including the Cochrane Library, MEDLINE, Embase, three other databases, several trial registers, other sources of gray literature, and conference proceedings, with no restrictions on language of publication. We limited the search period to run from 2000 until August 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) using immunotherapy versus chemotherapy and would have considered non-randomized trials in the absence of randomized trial data. Participants had locally advanced inoperable (cT4b or N+, or both) or metastatic (M1) (or both) urothelial carcinoma of the bladder or upper urinary tract. We excluded studies of people in whom immunotherapy was used in combination with chemotherapy or in a surveillance setting.
DATA COLLECTION AND ANALYSIS
Two review authors independently classified studies for inclusion and abstracted data from included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence on a per-outcome basis.
MAIN RESULTS
We included five RCTs and identified seven single-armed studies. The RCTs included 3572 participants comparing immunotherapy versus chemotherapy for the treatment of locally advanced and metastatic bladder cancer. First-line therapy Immunotherapy probably has little to no effect on the risk of death from any cause when used as first-line therapy compared to chemotherapy (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.87 to 1.07; I = 0%; 3 studies, 2068 participants; moderate-certainty evidence). This corresponds to 750 deaths per 1000 participants with chemotherapy and 11 fewer (45 fewer to 26 more) deaths per 1000 participants with immunotherapy at 36 months. Immunotherapy probably has little to no effect on health-related quality of life (mean difference (MD) 4.10, 95% CI 3.83 to 4.37; 1 study, 393 participants; moderate-certainty evidence), when assuming a minimal clinically important difference (MCID) of at least 6 points (using the Functional Assessment of Cancer Therapy - Bladder [FACT-BL] tool; scale 0 to 156 with higher scores representing better quality of life). Immunotherapy probably reduces adverse events grade 3 to 5 (RR 0.47, 95% CI 0.29 to 0.75; I = 97%; 3 studies, 2046 participants; moderate-certainty evidence). This corresponds to 908 grade 3 to 5 adverse events per 1000 participants with chemotherapy, with 481 fewer (644 fewer to 227 fewer) grade 3 to 5 adverse events per 1000 participants with immunotherapy. We found no evidence for the outcome time to death from bladder cancer. Immunotherapy probably increases the risk of time to disease progression (HR 1.33, 95% CI 1.17 to 1.50; I = 0%; 2 studies, 1349 participants; moderate-certainty evidence). This corresponds to 660 events per 1000 participants with chemotherapy and 102 more (57 more to 152 more) events per 1000 participants with immunotherapy at 36 months. Immunotherapy may reduce discontinuations due to adverse effects (RR 0.47, 95% CI 0.20 to 1.10; I = 94%; 3 studies, 2046 participants; low-certainty evidence). This corresponds to 338 discontinuations per 1000 participants with chemotherapy and 179 fewer (271 fewer to 34 more) discontinuations per 1000 participants with immunotherapy. Second-line therapy Immunotherapy may reduce the risk of death from any cause when used as second-line therapy (HR 0.72, 95% CI 0.63 to 0.81; I = 0%; 2 studies, 1473 participants; low-certainty evidence). This corresponds to 920 deaths per 1000 participants with chemotherapy (vinflunine, paclitaxel, docetaxel) and 59 fewer (95 fewer to 28 fewer) deaths per 1000 participants with immunotherapy at 36 months. Immunotherapy may have little to no effect on health-related quality of life when compared to chemotherapy (MD 4.82, 95% CI -3.11 to 12.75; I = 85%; 2 studies, 727 participants; low-certainty evidence), assuming an MCID of at least 10 points (using the EORTC QLQ tool; scale 0 to 100 with higher scores representing better quality of life). Immunotherapy may reduce adverse events grade 3 to 5 in participants undergoing second-line therapy (RR 0.89, 95% CI 0.81 to 0.97; I = 9%; 2 studies, 1423 participants; low-certainty evidence). This corresponds to 630 grade 3 to 5 adverse events per 1000 participants with chemotherapy and 76 fewer (126 fewer to 25 fewer) grade 3 to 5 adverse events per 1000 participants with immunotherapy. We found no evidence for the outcome of time to death from bladder cancer. We are very uncertain if immunotherapy reduces the risk of disease progression (HR 0.99, 95% CI 0.84 to 1.16; I = 0%; 2 studies, 1473 participants; very low-certainty evidence). Immunotherapy may reduce discontinuations due to adverse events in participants undergoing second-line therapy (RR 0.35, 95% CI 0.17 to 0.72; I = 69%; 2 studies, 1473 participants; low-certainty evidence). This corresponds to 110 discontinuations per 1000 participants with chemotherapy and 72 fewer (91 fewer to 31 fewer) discontinuations per 1000 participants with immunotherapy.
AUTHORS' CONCLUSIONS
Compared to chemotherapy, immunotherapy for treating advanced or metastatic urothelial carcinoma probably has little to no effect on the risk of death from any cause when used as first-line therapy. Still, it may reduce the risk of death from any cause when used as second-line therapy. Health-related quality of life for participants receiving first- and second-line therapy does not appear to be affected by immunotherapy. Immunotherapy probably reduces or may reduce adverse events grade 3 to 5 when used as first- and second-line therapy, respectively.
Topics: Humans; Carcinoma, Transitional Cell; Disease Progression; Immune Checkpoint Inhibitors; Immunotherapy; Systematic Reviews as Topic; Urinary Bladder Neoplasms
PubMed: 37811690
DOI: 10.1002/14651858.CD013774.pub2 -
Journal of Psychiatric Research Aug 2023Gene-environment interaction (G × E) refers to the change of genetic effects under the participation of environmental factors resulting in differences in genetic... (Review)
Review
BACKGROUND
Gene-environment interaction (G × E) refers to the change of genetic effects under the participation of environmental factors resulting in differences in genetic expression. G × E has been studied in the occurrence and development of many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD).
AIM
A systematic review was conducted to investigate the role of G × E plays in OCD. This review explored the relationship between G × E and the susceptibility to OCD occurrence, disease progression, and treatment response.
METHODS
This systematic literature search was performed using Web of Science, PubMed, Cochrane Library, and CNKI. Seven studies were selected, which included seven genes (BDNF, COMT, MAO, 5-HTT, SMAD4, PGRN, and SLC1A1) polymorphisms, polygenic risk score (PRS), and two environmental factors (childhood trauma and stressful life events).
RESULTS
Information from this systematic review indicated that G × E increased the susceptibility to OCD, played a crucial role in the clinical characteristics, and had an inconsistent impact on treatment response of OCD.
FUTURE DIRECTIONS
The multi-omics studies and the inclusion of G × E in future GWAS studies of OCD should be drawn more attention, which may contribute to a deeper understanding of the etiology of OCD as well as guide therapeutic interventions for the disease.
Topics: Humans; Gene-Environment Interaction; Genotype; Genetic Predisposition to Disease; Obsessive-Compulsive Disorder; Polymorphism, Genetic
PubMed: 37390623
DOI: 10.1016/j.jpsychires.2023.06.004