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Gynecologic Oncology Oct 2023Approximately 20% of ovarian cancers are due to an underlying germline pathogenic variant. While pathogenic variants in several genes have been well-established in the... (Review)
Review
OBJECTIVE
Approximately 20% of ovarian cancers are due to an underlying germline pathogenic variant. While pathogenic variants in several genes have been well-established in the development of hereditary ovarian cancer (e.g. BRCA1/2, RAD51C, RAD51D, BRIP1, mismatch repair genes), the role of partner and localizer of BRCA2 (PALB2) remains uncertain. We sought to utilize meta-analysis to evaluate the association between PALB2 germline pathogenic variants and ovarian cancer.
METHODS
We conducted a systematic review and meta-analysis. We searched key electronic databases to identify studies evaluating multigene panel testing in people with ovarian cancer. Eligible trials were subjected to meta-analysis.
RESULTS
Fifty-five studies met inclusion criteria, including 48,194 people with ovarian cancer and information available on germline PALB2 pathogenic variant status. Among people with ovarian cancer and available PALB2 sequencing data, 0.4% [95% CI 0.3-0.4] harbored a germline pathogenic variant in the PALB2 gene. The pooled odds ratio (OR) for carrying a PALB2 pathogenic variant among the ovarian cancer population of 20,474 individuals who underwent germline testing was 2.48 [95% CI 1.57-3.90] relative to 123,883 controls.
CONCLUSIONS
Our meta-analysis demonstrates that the pooled OR for harboring a PALB2 germline pathogenic variant among people with ovarian cancer compared to the general population is 2.48 [95% CI 1.57-3.90]. Prospective studies evaluating the role of germline PALB2 pathogenic variants in the development of ovarian cancer are warranted.
PubMed: 37651980
DOI: 10.1016/j.ygyno.2023.07.017 -
BMJ Open Dec 2023The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022.
STUDY ELIGIBILITY CRITERIA
We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant.
DATA EXTRACTION AND SYNTHESIS
Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach.
RESULTS
This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14-30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61-90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91-120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death.
CONCLUSION
The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies.
PROSPERO REGISTRATION NUMBER
CRD42023376698.
Topics: Humans; SARS-CoV-2; mRNA Vaccines; COVID-19; COVID-19 Vaccines
PubMed: 38128943
DOI: 10.1136/bmjopen-2023-076892 -
Obesity Reviews : An Official Journal... Jan 2024Obesity may track across generations, due to genetics and shared family environmental factors, or possibly intrauterine programming. However, many studies only assess... (Meta-Analysis)
Meta-Analysis Review
Obesity may track across generations, due to genetics and shared family environmental factors, or possibly intrauterine programming. However, many studies only assess associations between maternal body mass index (BMI) and offspring BMI in childhood. To determine whether maternal and paternal associations with offspring BMI differ and whether associations persist into adulthood, a systematic review and meta-analysis was done. PubMed, Embase, Web of Science, and Google Scholar (to October 2022) were searched. Observational studies reporting associations between maternal or paternal BMI and adult offspring BMI were included. Offspring BMIs were reported as continuous or categorical measures. Forty-six studies were included in the systematic review. Meta-analyses were conducted using random-effects models. Parental BMI was positively associated with offspring BMI in adulthood. The pooled mother-offspring standardized mean difference (SMD) was 0.23 (95% confidence interval [CI]: 0.20, 0.26), and father-offspring SMD was similar: 0.22 (95% CI: 0.19, 0.25) in adjusted models. Offspring of mothers with overweight or obesity had the same risk of higher BMI as offspring of fathers with overweight or obesity. If these associations are causal, they support interventions targeting all family members, rather than focusing solely on mothers, to obtain a healthy weight development among offspring.
Topics: Female; Adult; Humans; Body Mass Index; Overweight; Adult Children; Parents; Obesity; Mothers
PubMed: 37783229
DOI: 10.1111/obr.13644 -
Translational Vision Science &... Nov 2023This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV).
METHODS
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1.
RESULTS
Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%).
CONCLUSIONS
AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up.
TRANSLATIONAL RELEVANCE
This systematic review will help to inform and guide future clinical trials.
Topics: Humans; Retinal Degeneration; Dependovirus; Macular Degeneration; Retinitis Pigmentosa; Genetic Therapy
PubMed: 37982768
DOI: 10.1167/tvst.12.11.24 -
Ophthalmic & Physiological Optics : the... Jul 2024To synthesise evidence across studies on factors associated with pathologic myopia (PM) onset and progression based on the META-analysis for Pathologic Myopia (META-PM)... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To synthesise evidence across studies on factors associated with pathologic myopia (PM) onset and progression based on the META-analysis for Pathologic Myopia (META-PM) classification framework.
METHODS
Findings from six longitudinal studies (5-18 years) were narratively synthesised and meta-analysed, using odds ratio (OR) as the common measure of association. All studies adjusted for baseline myopia, age and sex at a minimum. The quality of evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation framework.
RESULTS
Five out of six studies were conducted in Asia. There was inconclusive evidence of an independent effect (or lack thereof) of ethnicity and sex on PM onset/progression. The odds of PM onset increased with greater axial length (pooled OR: 2.03; 95% CI: 1.71-2.40; p < 0.001), older age (pooled OR: 1.07; 1.05-1.09; p < 0.001) and more negative spherical equivalent refraction, SER (OR: 0.77; 0.68-0.87; p < 0.001), all of which were supported by an acceptable level of evidence. Fundus tessellation was found to independently increase the odds of PM onset in a population-based study (OR: 3.02; 2.58-3.53; p < 0.001), although this was only supported by weak evidence. There was acceptable evidence that greater axial length (pooled OR: 1.23; 1.09-1.39; p < 0.001), more negative SER (pooled OR: 0.87; 0.83-0.92; p < 0.001) and higher education level (pooled OR: 3.17; 1.36-7.35; p < 0.01) increased the odds of PM progression. Other baseline factors found to be associated with PM progression but currently supported by weak evidence included age (pooled OR: 1.01), severity of myopic maculopathy (OR: 3.61), intraocular pressure (OR: 1.62) and hypertension (OR: 0.21).
CONCLUSIONS
Most PM risk/prognostic factors are not supported by an adequate evidence base at present (an indication that PM remains understudied). Current factors for which an acceptable level of evidence exists (limited in number) are unmodifiable in adults and lack personalised information. More longitudinal studies focusing on uncovering modifiable factors and imaging biomarkers are warranted.
Topics: Humans; Myopia, Degenerative; Disease Progression; Risk Factors; Refraction, Ocular
PubMed: 38563652
DOI: 10.1111/opo.13312 -
Clinical Biochemistry Jan 2024Chronic kidney disease (CKD) affects over 0.5 billion people worldwide across their lifetimes. Despite a growingly ageing world population, an increase in all-age... (Review)
Review
Chronic kidney disease (CKD) affects over 0.5 billion people worldwide across their lifetimes. Despite a growingly ageing world population, an increase in all-age prevalence of kidney disease persists. Adult-onset forms of kidney disease often result from lifestyle-modifiable metabolic illnesses such as type 2 diabetes. Pediatric and adolescent forms of renal disease are primarily caused by morphological abnormalities of the kidney, as well as immunological, infectious and inherited metabolic disorders. Alterations in energy metabolism are observed in CKD of varying causes, albeit the molecular mechanisms underlying pathology are unclear. A systematic indexing of metabolites identified in plasma and urine of patients with kidney disease alongside disease enrichment analysis uncovered inborn errors of metabolism as a framework that links features of adult and pediatric kidney disease. The relationship of genetics and metabolism in kidney disease could be classified into three distinct landscapes: (i) Normal genotypes that develop renal damage because of lifestyle and / or comorbidities; (ii) Heterozygous genetic variants and polymorphisms that result in unique metabotypes that may predispose to the development of kidney disease via synergistic heterozygosity, and (iii) Homozygous genetic variants that cause renal impairment by perturbing metabolism, as found in children with monogenic inborn errors of metabolism. Interest in the identification of early biomarkers of onset and progression of CKD has grown steadily in the last years, though it has not translated into clinical routine yet. This systematic review indexes findings of differential concentration of metabolites and energy pathway dysregulation in kidney disease and appraises their potential use as biomarkers.
Topics: Adult; Adolescent; Humans; Child; Diabetes Mellitus, Type 2; Kidney; Renal Insufficiency, Chronic; Metabolomics; Biomarkers; Metabolism, Inborn Errors
PubMed: 38097032
DOI: 10.1016/j.clinbiochem.2023.110703 -
Reviews in Medical Virology Sep 2023Head and neck cancer, one of the most commonly prevalent malignancies globally is a complex category of tumours that comprises cancers of the oral cavity, pharynx, and... (Review)
Review
A systematic review on the molecular and clinical association between Human Papillomavirus and Human Immunodeficiency Virus co-infection in Head, Neck and Oral squamous cell carcinoma.
Head and neck cancer, one of the most commonly prevalent malignancies globally is a complex category of tumours that comprises cancers of the oral cavity, pharynx, and larynx. A specific subgroup of such cancers has been found with some unique chromosomal, therapeutic, and epidemiologic traits with the possibility of affecting via co-infection. About 25% of all head and neck cancers in the population are human papillomavirus infection (HPV)-associated, typically developing in the oropharynx, which comprises the tonsils. In the period of efficient combined antiviral treatment, HPV-positive oral cancers are also becoming a significant contributor to illness and fatality for Human Immunodeficiency Virus (HIV)-infected persons. Although the prevalence and historical background of oral HPV transmission are not thoroughly understood, it seems likely that oral HPV transmission is relatively frequent in HIV-infected people when compared to the overall population. Therefore, there is a need to understand the mechanisms leading to this co-infection, as there is very little research related to that. Hence, this study mainly focus on the therapeutical and biomedical analysis of HPV and HIV co-infection in the above-mentioned cancer, including oral squamous cell carcinoma.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Mouth Neoplasms; Human Papillomavirus Viruses; Papillomavirus Infections; Coinfection; Head and Neck Neoplasms; HIV Infections; HIV; Papillomaviridae
PubMed: 37280764
DOI: 10.1002/rmv.2462 -
Annals of Clinical Microbiology and... Aug 2023The emergence of multidrug-resistant (MDR) strains of genital pathogens, notably Mycoplasma genitalium and Ureaplasma spp., constitutes a significant global threat... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The emergence of multidrug-resistant (MDR) strains of genital pathogens, notably Mycoplasma genitalium and Ureaplasma spp., constitutes a significant global threat today. The present study aimed to evaluate the prevalence and trend of changes in MDR mycoplasma and ureaplasma strains.
METHODS
An exhaustive search was performed across the ISI Web of Science, PubMed, Scopus, ScienceDirect, and Google Scholar databases to accumulate relevant studies without restrictions until April 2023. We used event rate and corresponding 95% confidence intervals to determine the frequency of resistance-related mutations and examine the trend of antibiotic resistance changes.
RESULTS
The data from 27 studies, including 24,662 patients across 14 countries, were evaluated. Out of the total studies, 20 focused on M. genitalium infections, and five on Ureaplasma spp. The frequency of resistance-associated mutations to macrolides, tetracyclines, and fluoroquinolones in clinical strains of M. genitalium was 43.5%, 13.1%, and 18.6%, respectively. The prevalence of M. genitalium strains with double resistance and MDR was 11.0% and 17.4%, respectively. The incidence of both double-drug-resistant and MDR strains was higher in the World Health Organization (WHO) Western Pacific Region than in European and American populations. For Ureaplasma strains, resistance-associated mutations to macrolides, tetracyclines, and fluoroquinolones were 40.8%, 25.7%, and 90.3%, respectively. The rate of antibiotic resistance was higher in the African population compared to the European and WHO Western Pacific Regions. The rate of MDR Ureaplasma infections was 13.2%, with a higher incidence in the African population compared to the WHO Western Pacific and European regions.
CONCLUSION
The proliferation and spread of MDR Mycoplasma and Ureaplasma strains present a significant public health challenge. The situation is indeed alarming, and the rising trend of MDR M. genitalium and MDR Ureaplasma infections suggests that therapies involving macrolides and fluoroquinolones may become less effective.
Topics: Humans; Mycoplasma; Mycoplasma Infections; Ureaplasma Infections; Mycoplasma hominis; Anti-Bacterial Agents; Ureaplasma; Fluoroquinolones; Tetracyclines; Macrolides; Mutation; Prevalence
PubMed: 37563660
DOI: 10.1186/s12941-023-00627-6 -
Psychological Trauma : Theory,... Oct 2023Posttraumatic stress disorder (PTSD) is a severe and disabling condition that can lead to functional impairment and decreased productivity. The purpose of this...
INTRODUCTION
Posttraumatic stress disorder (PTSD) is a severe and disabling condition that can lead to functional impairment and decreased productivity. The purpose of this systematic review was to compile and evaluate existing research on PTSD in Lebanon and among Syrian refugees.
METHOD
We searched the databases OVID Medline, EMBASE, and PsycINFO for articles that used validated tools to report the screening or diagnosis of PTSD among our population of interest.
RESULTS
We included 102 articles out of a total of 10,367 screened manuscripts. We identified 24 studies discussing PTSD in the Lebanese population and 78 among Syrian refugees. A total of 90 studies described the epidemiological characteristics of PTSD while 12 assessed different treatment options. There was no significant difference in PTSD rates between males and females. We also identified several risks and protective factors for developing PTSD. The former included female gender, marriage, older age, and exposure to war.
CONCLUSION
PTSD among Lebanese individuals and Syrian refugees is multifactorial in nature, but commonly involves war-related events. There is a significant evidence gap regarding intervention strategies in this population group. Targeted, multidisciplinary, and holistic interventions are required. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Humans; Refugees; Lebanon; Syria; Stress Disorders, Post-Traumatic; Female; Male; Risk Factors
PubMed: 36689379
DOI: 10.1037/tra0001409 -
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