-
Communications Medicine Jan 2024Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D).
BACKGROUND
Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D).
METHODS
We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies.
RESULTS
Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort.
CONCLUSIONS
Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.
PubMed: 38253823
DOI: 10.1038/s43856-023-00429-z -
Journal of Pregnancy 2024Studies focusing on safety outcomes typically require large populations to comprehensively characterise the patient groups exposed to the medicines under investigation.... (Review)
Review
PURPOSE
Studies focusing on safety outcomes typically require large populations to comprehensively characterise the patient groups exposed to the medicines under investigation. However, there is often less information for subpopulations, such as pregnant or breastfeeding women, particularly when new medicines are considered. It is important to understand what information can be obtained from drug utilization studies (DUS) involving pregnant women in the early years postmarketing to provide supportive information for safety studies. The aims of this literature review are to (1) identify and review DUS for new medicines in pregnancy and breastfeeding and (2) list and summarise key information items to be reported in a DUS for new medicines in pregnancy.
METHODS
To identify postmarketing DUS of new prescription medicines or enantiomers in pregnancy, a systematic literature review was undertaken in PubMed and Embase between January 2015 and June 2022. In addition, the complete database of the ENCePP EU PAS Register was systematically searched to June 2022.
RESULTS
We identified 11 published DUS on new medicines in pregnancy from the ENCePP EU PAS Register and none from other sources. No studies on breastfeeding were identified. The 11 identified publications reported the medicine's use for the first 3 to 5 years after marketing approval. No reports assessed utilization in the first 3 years of approval. It was usual to issue interim reports annually (7 studies). All studies concerned conditions managed in ambulatory care (primary care and outpatient facilities) and included some primary care prescribing. Most ( = 8) only had prescribing/dispensing data available at individual level for ambulatory care; outpatient prescribing was included in three of these studies Three studies held a limited amount of in-hospital prescribing data. A DUS can confirm at an early stage whether there are sufficient exposed pregnancies in available data sources to ensure a safety study is powered to detect a difference in the prevalence of adverse pregnancy or infant outcomes or if additional data from other databases are needed. A DUS may also help address methodological considerations such as selection of comparators. DUS can be performed embedded in a DUS in the general population, in a cohort of women of childbearing age, or in a cohort of pregnant women.
CONCLUSION
This review summarises key aspects of a DUS for new medicines in pregnancy. DUS for new medicines in pregnancy should be planned before marketing, scheduled for the first 3 to 5 years after release, with annual interim/progress reports, and reported in peer-reviewed journals. By offering detailed information on data sources, exposure timing, prevalence and location, coprescribing, comorbidities, coexposures, and demographics, a DUS will offer a firm foundation for safety studies and will help to contextualize spontaneous reporting of serious adverse events.
Topics: Pregnancy; Infant; Humans; Female; Pregnant Women; Ambulatory Care; Breast Feeding; Databases, Factual; Drug Utilization
PubMed: 38250012
DOI: 10.1155/2024/8862801 -
Diagnostics (Basel, Switzerland) Jan 2024Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by the progressive replacement of the normal myocardium by fibroadipocytic... (Review)
Review
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by the progressive replacement of the normal myocardium by fibroadipocytic tissue. The importance of an early diagnosis is supported by a higher risk of sudden cardiac death in the pediatric population. We reviewed the literature on diagnosis, risk stratification, and prognosis in the pediatric population with ARVC. In case reports which analyzed children with ARVC, the most common sign was ventricular tachycardia, frequently presenting as dizziness, syncope, or even cardiac arrest. Currently, there is no gold standard for diagnosing ARVC in children. Nevertheless, genetic analysis may provide a proper diagnosis tool for asymptomatic cases. Although risk stratification is recommended in patients with ARVC, a validated prediction model for risk stratification in children is still lacking; thus, it is a matter of further research. In consequence, even though ARVC is a relatively rare condition in children, it negatively impacts the survival and clinical outcomes of the patients. Therefore, appropriate and validated diagnostic and risk stratification tools are crucial for the early detection of children with ARVC, ensuring a prompt therapeutic intervention.
PubMed: 38248052
DOI: 10.3390/diagnostics14020175 -
Environmental Research Apr 2024Ambient PM exposure has been recognized as a major health risk and related to aging, cardiovascular, respiratory and neurologic diseases, and cancer. However, underlying...
Ambient PM exposure has been recognized as a major health risk and related to aging, cardiovascular, respiratory and neurologic diseases, and cancer. However, underlying mechanism of epigenetic alteration and regulated pathways still remained unclear. The study on methylome effect of PM exposure was quite limited in Chinese population, and cohort-based study was absent. The study included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort. We estimated individual PM exposure level of short-medium-, medium- and long-term, based on a validated prediction model. We preformed epigenome-wide association studies to estimate the links between PM exposure and DNA methylation change, as well as stratification and sensitive analysis to examined the robustness of the association models. A systematic review was conducted to obtain the previously published CpGs and examined for replication. We also conducted comparison on the DNA methylation variation corresponding to different time windows. We further conducted gene function analysis and pathway enrichment analysis to reveal related biological response. We identified a total of 177 CpGs and 107 DMRs associated with short-medium-term PM exposure, at a strict genome-wide significance (P < 5 × 10). The effect sizes on most CpGs tended to cease with the exposure of extended time scale. Associated markers and aligned genes were related to aging, immunity, inflammation and carcinogenesis. Enriched pathways were mostly involved in cell cycle and cell division, signal transduction, inflammatory pathway. Our study is the first EWAS on PM exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways.
Topics: Humans; Air Pollutants; Particulate Matter; Epigenome; DNA Methylation; China
PubMed: 38246299
DOI: 10.1016/j.envres.2024.118276 -
Transplantation Reviews (Orlando, Fla.) Apr 2024Liver transplantation is a life-saving therapy for end-stage liver disease patients, but acute cellular rejection (ACR) and graft complications remain significant... (Review)
Review
BACKGROUND
Liver transplantation is a life-saving therapy for end-stage liver disease patients, but acute cellular rejection (ACR) and graft complications remain significant postoperative challenges. Early and accurate diagnosis is crucial for timely intervention and improved patient outcomes, but their diagnosis rely currently on invasive biopsy sampling, thus prompting the search for non-invasive Biomarkers. MicroRNA (miRNA) have emerged as promising biomarkers in various pathological conditions, and their potential utility in diagnosing acute cellular rejection after liver transplantation has gained significant interest.
METHODS
This systematic review of PubMed, Web of Science, and the ClinicalTrials.gov registry analyzes studies exploring miRNA as biomarkers for ACR and graft dysfunction in liver transplantation (PROSPERO ID CRD42023465278). The Cochrane Collaboration tool for assessing risk of bias was employed. Population data, identified miRNA and their dynamic regulation, as well as event prediction were compared. Data extraction and quality assessment were performed independently by two reviewers.
RESULTS
Thirteen studies were included in this systematic review. Various investigated miRNAs were upregulated in association with acute cellular rejection, like miR-122, miR-155, miR-181, miR-483-3p, and miR-885-5p, demonstrating great biomarker potential. Additionally, several studies conducted target gene analysis, revealing insights into cellular mechanisms linked to ACR. Moreover, various miRNA were also capable of predicting different organ complications following transplantation, expanding their versatility. Remaining challenges include the standardization of miRNA profiling, the need for functional validation, and the necessity for long-term studies.
CONCLUSION
The results highlight the potential of miRNA as specific, non-invasive biomarkers for ACR and graft dysfunction following liver transplantation. However, further research is needed to validate these findings and establish standardized diagnostic panels to incorporate them into clinical practice and explore miRNA-based therapies in the future.
Topics: Humans; MicroRNAs; Liver Transplantation; Biomarkers
PubMed: 38237243
DOI: 10.1016/j.trre.2024.100831 -
Frontiers in Cellular and Infection... 2023A number of mosquito-borne viruses (MBVs), such as dengue virus (DENV), zika virus (ZIKV), chikungunya (CHIKV), West Nile virus (WNV), and yellow fever virus (YFV) exert... (Review)
Review
BACKGROUND
A number of mosquito-borne viruses (MBVs), such as dengue virus (DENV), zika virus (ZIKV), chikungunya (CHIKV), West Nile virus (WNV), and yellow fever virus (YFV) exert adverse health impacts on the global population. and are the prime vectors responsible for the transmission of these viruses. The viruses have acquired a number of routes for successful transmission, including horizontal and vertical transmission. Transovarial transmission is a subset/type of vertical transmission adopted by mosquitoes for the transmission of viruses from females to their offspring through eggs/ovaries. It provides a mechanism for these MBVs to persist and maintain their lineage during adverse climatic conditions of extremely hot and cold temperatures, during the dry season, or in the absence of susceptible vertebrate host when horizontal transmission is not possible.
METHODS
The publications discussed in this systematic review were searched for using the PubMed, Scopus, and Web of Science databases, and websites such as those of the World Health Organization (WHO) and the European Centre for Disease Prevention and Control, using the search terms "transovarial transmission" and "mosquito-borne viruses" from 16 May 2023 to 20 September 2023.
RESULTS
A total of 2,391 articles were searched, of which 123 were chosen for full text evaluation, and 60 were then included in the study after screening and removing duplicates.
CONCLUSION
The present systematic review focuses on understanding the above diseases, their pathogenesis, epidemiology and host-parasite interactions. The factors affecting transovarial transmission, potential implications, mosquito antiviral defense mechanism, and the control strategies for these mosquito-borne viral diseases (MBVDs) are also be included in this review.
Topics: Animals; Female; Humans; Aedes; Mosquito Vectors; Mosquito-Borne Diseases
PubMed: 38235494
DOI: 10.3389/fcimb.2023.1304938 -
Genetics in Medicine : Official Journal... Apr 2024Rare genetic neurodevelopmental disorders associated with intellectual disability require lifelong multidisciplinary care. Clinical practice guidelines may support... (Review)
Review
PURPOSE
Rare genetic neurodevelopmental disorders associated with intellectual disability require lifelong multidisciplinary care. Clinical practice guidelines may support healthcare professionals in their daily practice, but guideline development for rare conditions can be challenging. In this systematic review, the characteristics and methodological quality of internationally published recommendations for this population are described to provide an overview of current guidelines and inform future efforts of European Reference Network ITHACA (Intellectual disability, TeleHealth, Autism, and Congenital Anomalies).
METHODS
MEDLINE, Embase, and Orphanet were systematically searched to identify guidelines for conditions classified as "rare genetic intellectual disability" (ORPHA:183757). Methodological quality was assessed using the Appraisal of Guidelines, Research, and Evaluation II tool.
RESULTS
Seventy internationally published guidelines, addressing the diagnosis and/or management of 28 conditions, were included. The methodological rigor of development was highly variable with limited reporting of literature searches and consensus methods. Stakeholder involvement and editorial independence varied as well. Implementation was rarely addressed.
CONCLUSION
Comprehensive, high-quality guidelines are lacking for many rare genetic neurodevelopmental disorders. Use and transparent reporting of sound development methodologies, active involvement of affected individuals and families, robust conflict of interest procedures, and attention to implementation are vital for enhancing the impact of clinical practice recommendations.
Topics: Humans; Intellectual Disability; Quality Improvement; Evidence-Based Medicine; Neurodevelopmental Disorders; Consensus
PubMed: 38224026
DOI: 10.1016/j.gim.2024.101071 -
Gynecologic and Obstetric Investigation 2024Refugee women are at an increased risk of developing postpartum depression (PPD) due to a combination of various psychosocial stressors. This systematic review aimed to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Refugee women are at an increased risk of developing postpartum depression (PPD) due to a combination of various psychosocial stressors. This systematic review aimed to outline the prevalence of PPD among refugee women and explore related risk factors and interventions currently in practice.
METHODS
A search was conducted using MEDLINE, Embase, PsycINFO, CINAHL, and Core Collection (Web of Science) for articles published until August 2022, yielding 1,678 records.
RESULTS
The prevalence of refugee and asylum-seeking women was 22.5% (n = 657/2,922), while the prevalence of non-refugee/asylum-seeking women with PPD was 17.5% (n = 400/2,285). Refugee/asylum-seeking women face a unique set of issues such as domestic abuse, separation and lack of support, stress, pre-migrational experiences, prior history of mental illness, low income, and discrimination. Refugee/asylum-seeking women may benefit from support groups, individual support, self-coping mechanisms, and familial support.
CONCLUSION
This review identifies that a higher prevalence of PPD in refugee and asylum-seeking women compared to other groups can potentially be attributed to the unique risk factors they face. This warrants the need for further research as studies on interventions for this condition are limited among this population.
Topics: Female; Humans; Depression, Postpartum; Refugees; Prevalence; Risk Factors
PubMed: 38219724
DOI: 10.1159/000535719 -
Med (New York, N.Y.) Jan 2024Synthetic lethality (SL) denotes a genetic interaction between two genes whose co-inactivation is detrimental to cells. Because more than 25 years have passed since SL...
BACKGROUND
Synthetic lethality (SL) denotes a genetic interaction between two genes whose co-inactivation is detrimental to cells. Because more than 25 years have passed since SL was proposed as a promising way to selectively target cancer vulnerabilities, it is timely to comprehensively assess its impact so far and discuss its future.
METHODS
We systematically analyzed the literature and clinical trial data from the PubMed and Trialtrove databases to portray the preclinical and clinical landscape of SL oncology.
FINDINGS
We identified 235 preclinically validated SL pairs and found 1,207 pertinent clinical trials, and the number keeps increasing over time. About one-third of these SL clinical trials go beyond the typically studied DNA damage response (DDR) pathway, testifying to the recently broadening scope of SL applications in clinical oncology. We find that SL oncology trials have a greater success rate than non-SL-based trials. However, about 75% of the preclinically validated SL interactions have not yet been tested in clinical trials.
CONCLUSIONS
Dissecting the recent efforts harnessing SL to identify predictive biomarkers, novel therapeutic targets, and effective combination therapy, our systematic analysis reinforces the hope that SL may serve as a key driver of precision oncology going forward.
FUNDING
Funded by the Samsung Research Funding & Incubation Center of Samsung Electronics, the Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Republic of Korea government (MSIT), the Kwanjeong Educational Foundation, the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), and Center for Cancer Research (CCR).
Topics: Humans; Medical Oncology; Neoplasms; Precision Medicine; Republic of Korea; Synthetic Lethal Mutations; United States; Clinical Trials as Topic
PubMed: 38218178
DOI: 10.1016/j.medj.2023.12.009 -
Cancers Dec 2023Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. While population-wide screening recommendations for PDAC in asymptomatic... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. While population-wide screening recommendations for PDAC in asymptomatic individuals are not achievable due to its relatively low incidence, pancreatic cancer surveillance programs are recommended for patients with germline causative variants in PDAC susceptibility genes or a strong family history. In this study, we sought to determine the prevalence and significance of germline alterations in major genes (, , , , , , , , , , , ) involved in PDAC susceptibility. We performed a systematic review of PubMed publications reporting germline variants identified in these genes in PDAC patients. Overall, the retrieved articles included 1493 PDAC patients. A high proportion of these patients ( = 1225/1493, 82%) were found to harbor alterations in genes (, , , ) involved in the homologous recombination repair (HRR) pathway. Specifically, the remaining PDAC patients were reported to carry alterations in genes playing a role in other cancer pathways (, , ; = 181/1493, 12.1%) or in the mismatch repair (MMR) pathway (, , , ; = 87/1493, 5.8%). Our findings highlight the importance of germline genetic characterization in PDAC patients for better personalized targeted therapies, clinical management, and surveillance.
PubMed: 38201484
DOI: 10.3390/cancers16010056