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Transplant Immunology Dec 2022Inactivated (killed) vaccines against COVID-19 have been widely used for the control of the pandemic condition. We performed a systematic and meta-analysis review of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Inactivated (killed) vaccines against COVID-19 have been widely used for the control of the pandemic condition. We performed a systematic and meta-analysis review of randomized, double-blind, placebo-controlled trials of the immunogenicity of inactivated vaccines against SARS-CoV-2 in healthy individuals.
METHODS
In the present study, all research and evidence were extracted from the available online databases. Two researchers randomly evaluated the assessment of the research sensitivity. Finally, after quality assessment and regarding the specific inclusion and exclusion criteria, the eligible articles were entered for meta-analysis. The heterogeneity between the results of the studies was measured using test statistics (Cochran's Q) and the I index. The forest plots illustrated the point and pooled estimates with 95% confidence intervals (crossed lines). All statistical analyses were performed using Comprehensive meta-Analysis V.2 software.
RESULTS
This meta-analysis included six primary studies investigating the immunogenicity of inactivated vaccines against SARS-CoV-2 in healthy individuals. According to the pooled prevalence (95% confidence interval), neutralizing antibody responses 28 days after receiving the second dose regarding different ages and micrograms per dose was 95.50% (CI: 93.2-97.1%). Our results showed that antibody levels were higher in the 6 μg group than in other groups. 98.3% (CI: 94.2-99.5%).
CONCLUSION
Since the rapid development of vaccinations has sparked widespread public anxiety regarding vaccine efficacy. Governments and unvaccinated individuals, particularly those with vaccination reluctance, will be interested in and benefit from the findings of this systematic study.
Topics: Humans; Vaccines, Inactivated; COVID-19 Vaccines; SARS-CoV-2; Antibodies, Viral; Viral Vaccines; COVID-19; Randomized Controlled Trials as Topic
PubMed: 36328249
DOI: 10.1016/j.trim.2022.101732 -
Frontiers in Medicine 2022β-hemoglobinopathies like sickle cell disease (SCD) and β-thalassemia are characterized by differing mutations in the hemoglobin subunit beta gene (HBB). These...
Using Clustered Regularly Interspaced Short Palindromic Repeats gene editing to induce permanent expression of fetal hemoglobin in β-thalassemia and sickle cell disease: A comparative meta-analysis.
β-hemoglobinopathies like sickle cell disease (SCD) and β-thalassemia are characterized by differing mutations in the hemoglobin subunit beta gene (HBB). These disorders vary in phenotypic presentation and severity, with more severe manifestations leading to transfusion dependence along with associated complications such as infection and iron overload. β-hemoglobinopathies symptoms rapidly worsen after birth as the levels of fetal hemoglobin (HbF) begin to decline. To reverse this decline, current treatment plans typically involve the use of pharmacological agents such as hydroxyurea to raise expression levels of HbF. However, these treatments only result in transient effects and must be consistently administered. Gene editing technologies such as CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR associated protein) offer the opportunity to create novel treatments which can raise HbF expression with potential permanent effects. Two gene targets, B-cell lymphoma/leukemia 11A gene (BCL11A) and the promoter regions of gamma globin genes (HBG1/2), have been identified to significantly increase HbF protein expression. In order to differentiate the effectiveness of BCL11A and HBG1/2 editing, a meta-analysis was performed by first identifying 119 studies for inclusion based on the search terms terms "β-Thalassemia," "beta-thal" "sickle cell disease," "SCD," and "CRISPR." Following application of exclusion and inclusion criteria, we performed analysis on 8 peer-reviewed published studies from 2018 to 2021 were included in the study. Forest plots were generated using R (version 4.1.2). Primary comparative analysis shows HBG1/2 had a significantly ( < 0.01)greater impact on induction of HbF expression compared to BCL11A. This analysis leads us to conclude that HBG1/2 merits further investigation as a possible gene editing target for treatment of SCD and β-thalassemia.
PubMed: 36250099
DOI: 10.3389/fmed.2022.943631 -
Journal of Oral Biology and... 2022The long passing time for tooth movement (TM) is one of the challenges in orthodontic. complications such as gingival recession, root resorption, and caries are common... (Review)
Review
INTRODUCTION
The long passing time for tooth movement (TM) is one of the challenges in orthodontic. complications such as gingival recession, root resorption, and caries are common in orthodontic. To address this, there is an increased tendency to find safe and effective methods to accelerating tooth movement. A surgical method such as micro-osteoperforations (MOP) accelerating the TM. The current meta-analysis aims to investigate the outcome of MOP in accelerating TM in animal studies.
METHODS
In the present meta-analysis, we evaluated 6 studies that focused on the effect of MOP on TM with the following keywords: (((MOP* OR micro-osteoperforations*) AND (("accelerating tooth movement " OR " tooth movement" AND " orthodontic tooth movement " OR " orthodontic ") until May 2021.
RESULTS
The results have shown there is significant difference in TM after using MOP (MD: 0.31, 95%CI: 0.20, 0.42, P < 0.00001, I2 = 76%). Subgroup analysis revealed that though experimental duration in both less than 4-week and more than 4-week, the TM were significant difference between MOP and controls. Besides, in both force subgroups including less than 100 g and more than 100g, the TM was a significant difference between MOP and controls.
CONCLUSION
This meta-analysis found that generally MOP has a positive effect on TM.
PubMed: 36212615
DOI: 10.1016/j.jobcr.2022.09.015 -
Blood Advances May 2023
Topics: Female; Humans; Pregnancy; Anemia, Sickle Cell; Pregnancy Complications, Hematologic
PubMed: 36198169
DOI: 10.1182/bloodadvances.2022007089 -
BMC Medicine Sep 2022Non-communicable diseases (NCDs) are a leading cause of maternal mortality and morbidity worldwide. The World Health Organization is developing new recommendations...
BACKGROUND
Non-communicable diseases (NCDs) are a leading cause of maternal mortality and morbidity worldwide. The World Health Organization is developing new recommendations focusing on the management of NCDs for pregnant, intrapartum, and postnatal women. Thus, to support the development of new guidelines and recommendations, we aimed to determine the availability, focus, and scope of recommendations of current guidelines for the management of NCDs during pregnancy, intrapartum, and postnatal period.
METHODS
PubMed, Global Index Medicus, TRIP, and Guideline International Network databases were searched on 31 May 2021, to identify any NCD-related guidelines published between 2011 and 2021 with no language or country restrictions. Websites of 165 professional organizations were also searched. Characteristics of included guidelines were analyzed, and recommendations were extracted from guidelines of five high-priority NCD conditions (diabetes, chronic hypertension, respiratory conditions, hemoglobinopathies and sickle cell disease, and mental and substance use disorders).
RESULTS
From 6026 citations and 165 websites, 405 guidelines were included of which 132 (33%) were pregnancy-specific and 285 (88%) were developed in high-income countries. Among pregnancy-specific guidelines, the most common conditions for which recommendations were provided were gestational diabetes, circulatory diseases, thyroid disorders, and hypertensive disorders of pregnancy. For the five high-priority conditions, 47 guidelines were identified which provided 1834 recommendations, largely focused on antenatal care interventions (62%) such as early detection, screening tools, pharmacological treatment, and lifestyle education. Postnatal recommendations largely covered postnatal clinical assessments, lifestyle education, and breastfeeding. Health system recommendations largely covered multidisciplinary care teams and strengthening referral pathways.
CONCLUSIONS
This study provides a robust assessment of currently available guidelines and mapping of recommendations on NCD management within maternal health services, which will inform the scope of the World Health Organization's future guideline development activities. This study identified a need to develop guidelines that consider NCDs holistically, with an integrated approach to antenatal, intrapartum, and postnatal care, and that are relevant for resource-limited contexts. Any such guidelines should consider what interventions are most essential to improving outcomes for women with NCDs and their newborns, and how variations in quality of NCD-related care can be addressed.
Topics: Diabetes, Gestational; Female; Global Health; Humans; Infant, Newborn; Noncommunicable Diseases; Postnatal Care; Pregnancy; World Health Organization
PubMed: 36123668
DOI: 10.1186/s12916-022-02508-9 -
Vox Sanguinis Nov 2022Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody testing. RBC alloimmunization to RBC antigens is a frequently encountered complication seen in chronically transfused patients. Genetic factors such as the human leukocyte antigen (HLA) are known to influence and regulate immune responses. HLAs are highly polymorphic and play an essential role in regulating immune responses, including RBC alloimmunization. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the association between HLA Class II allelic polymorphisms with the possible risk of developing RBC alloantibodies.
MATERIALS AND METHODS
Four databases were systematically searched for relevant studies between the years 2000 and 2021 following the PRISMA guidelines. Four articles met the eligibility and quality criterion, and three alleles, HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, that were found to be potentially associated with an increased risk in alloantibody formation were included.
RESULTS
The primary outcome measure was alloimmunization by RBC antigen exposure in multiply transfused SCD patients. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies.
CONCLUSION
A strategy to prevent RBC alloimmunization is genotyping for genetically susceptible SCD patients receiving multiple transfusions. Early identification of genetic variants that can potentially increase the risk of RBC alloimmunization could aid in the screening process and selection of phenotypically matched RBC units.
Topics: Humans; Isoantibodies; Anemia, Sickle Cell; Erythrocytes; Erythrocyte Transfusion; Anemia, Hemolytic, Autoimmune; Immunity
PubMed: 36102140
DOI: 10.1111/vox.13351 -
Medical Principles and Practice :... 2022The aim of this systematic review was to investigate whether sickle cell disease (SCD) protects against human immunodeficiency virus (HIV) infection by determining the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this systematic review was to investigate whether sickle cell disease (SCD) protects against human immunodeficiency virus (HIV) infection by determining the association between SCD and the incidence and virulence of HIV infection.
METHODS
This is a systematic review that used MEDLINE, PubMed, CINAHL, and Academic Search Complete as data sources. Articles describing the relationship of SCD with HIV infection were included in this review. The effect measures were converted to correlation coefficients and synthesized accordingly to examine the putative protective role of SCD against HIV infection. Independent full-text screening and data extraction were conducted on all eligible studies. The risk of bias was assessed using the mixed methods appraisal tool. We employed a random-effects model of meta-analysis to estimate the pooled prevalence. We computed Cochrane's Q statistics, I2, and prediction interval to quantify effect size heterogeneity.
RESULTS
SCD reduces the risk of HIV infection by 75% (odds ratio [OR] = 0.25; r = -0.36, p < 0.001; I2 = 71.65). There was no publication bias (Egger's t value = 0.411; p = 0.721). Similarly, risk of HIV virulence was reduced by 77% (OR = 0.23; r = -0.38; p < 0.001; I2 = 63.07). The mechanisms implicated in the protective influence of SCD include autosplenectomy, reduced CCR5 expression, and increased expression of heme and iron-regulated genes.
CONCLUSIONS
SCD appears to protect against HIV infection and slows HIV progression.
Topics: Humans; HIV Infections; Anemia, Sickle Cell; Prevalence
PubMed: 36096094
DOI: 10.1159/000526993 -
Health-related quality of life in hemoglobinopathies: A systematic review from a global perspective.Frontiers in Pediatrics 2022Sickle cell disease (SCD) and thalassemia are inherited blood disorders, which can lead to life-threatening events and chronic organ damage. Recent advances in...
BACKGROUND
Sickle cell disease (SCD) and thalassemia are inherited blood disorders, which can lead to life-threatening events and chronic organ damage. Recent advances in treatments have increased life expectancy, and hemoglobinopathies have become chronic illnesses with social and emotional impairments. Thus, health-related quality of life (HRQOL) assessment has a fundamental role in disease management and treatment, and generic and disease-specific questionnaires are reliable and validated measures to estimate disease burden. The heterogeneous distribution of treatment opportunities worldwide influences physical, social, and emotional disease perception.
OBJECTIVES
To review publications concerning HRQOL for SCD and thalassemia in different areas of the world in order to gather a global perspective of questionnaires used and outcomes evaluated.
METHODS
A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Medline databases were searched on 29 September 2021. Inclusion criteria were as follows: (1) studies of HRQOL assessment in SCD and thalassemia patients by using the PROMIS, the SF-36, the SCSES, the PedsQL-SCD, the PedsQOL generic core scale, the ASCQ-Me, and the TranQoL; and (2) every article type, including non-English studies. We excluded studies that were not limited to SCD or thalassemia and studies that were not specific to hemoglobinopathies, and not consistent with the topic of HRQOL assessment. We did not include the gray literature. A total of 102 out of 124 articles from PubMed, Cochrane Library, and Google Scholar were eligible for inclusion (66 SCD articles and 36 thalassemia articles). The quality of studies was assessed through Critical Appraisal tools for use in JBI Systematic Reviews. Data extraction was conducted using a standardized data collection form (authors, year and country of publication, study design, age and number of patients, HRQOL questionnaires, questionnaire language, and clinical outcomes).
RESULTS
The evaluation of HRQOL was conducted on all continents, but differences in the worldwide frequency of HRQOL assessment were observed. HRQOL of SCD patients was less investigated in Europe. HRQOL of thalassemia patients was less investigated in South-East Asia and Africa. Generic HRQOL questionnaires (PROMIS, SF-36, and PedsQL) were frequently adopted, while disease-specific ones (ASCQ-Me, SCSES for SCD, and TranQoL for thalassemia) were less used. Translation into local languages has been often performed.
CONCLUSION
Health-related quality of life is a complex outcome that has been increasingly incorporated in clinical research and clinical practice worldwide, although with regional differences. Disease-specific outcomes (pain for SCD and transfusion burden for thalassemia) and healthcare system characteristics, particularly in low-income countries, have an impact on HRQOL and should be considered in healthcare plans.
PubMed: 36090573
DOI: 10.3389/fped.2022.886674 -
The Cochrane Database of Systematic... Sep 2022Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea... (Review)
Review
BACKGROUND
Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising foetal haemoglobin (HbF). This is an update of a previously published Cochrane Review.
OBJECTIVES
The aims of this review are to determine through a review of randomised or quasi-randomised studies whether the use of hydroxyurea in people with SCD alters the pattern of acute events, including pain; prevents, delays or reverses organ dysfunction; alters mortality and quality of life; or is associated with adverse effects. In addition, we hoped to assess whether the response to hydroxyurea in SCD varies with the type of SCD, age of the individual, duration and dose of treatment, and healthcare setting.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. The date of the most recent search was 17 February 2022.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials (RCTs and quasi-RCTs), of one month or longer, comparing hydroxyurea with placebo or standard therapy in people with SCD.
DATA COLLECTION AND ANALYSIS
Authors independently assessed studies for inclusion, carried out data extraction, assessed the risk of bias and assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included nine RCTs recruiting 1104 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months. We judged the quality of the evidence for the first two comparisons below as moderate to low as the studies contributing to these comparisons were mostly large and well-designed (and at low risk of bias); however, the evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events, and the results are applicable only to individuals with HbSS and HbSβºthal genotypes. We judged the quality of the evidence for the third and fourth comparisons to be very low due to the limited number of participants, the lack of statistical power (both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes. Hydroxyurea versus placebo Five studies (784 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo; four recruited individuals with only severe disease and one recruited individuals with all disease severities. Hydroxyurea probably improves pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use) and life-threatening illness, but we found no difference in death rates (10 deaths occurred during the studies, but the rates did not differ by treatment group) (all moderate-quality evidence). Hydroxyurea may improve measures of HbF (low-quality evidence) and probably decreases neutrophil counts (moderate-quality evidence). There were no consistent differences in terms of quality of life and adverse events (including serious or life-threatening events) (low-quality evidence). There were fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups. Hydroxyurea and phlebotomy versus transfusion and chelation Two studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) contributed to this comparison. There were no consistent differences in terms of pain alteration, death or adverse events (low-quality evidence) or life-threatening illness (moderate-quality evidence). Hydroxyurea with phlebotomy probably increased HbF and decreased neutrophil counts (moderate-quality evidence), but there were more occurrences of acute chest syndrome and infections. Quality of life was not reported. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early. Hydroxyurea versus observation One study (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation. Pain alteration and quality of life were not reported. There were no differences in life-threatening illness, death (no deaths reported in either group) or adverse events (very low-quality evidence). We are uncertain if hydroxyurea improves HbF or decreases neutrophil counts (very low-quality evidence). Treatment regimens with and without hydroxyurea One study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea. Pain alteration, life-threatening illness and quality of life were not reported. There were no differences in death rates (no deaths reported in either group), adverse events or neutrophil levels (very low-quality evidence). We are uncertain if hydroxyurea improves HbF (very low-quality evidence).
AUTHORS' CONCLUSIONS
There is evidence to suggest that hydroxyurea may be effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSβºthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial Doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly with regard to preventing chronic complications of SCD, or recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with the HbSC genotype. Future studies should be designed to address such uncertainties.
Topics: Acute Chest Syndrome; Adult; Anemia, Sickle Cell; Antisickling Agents; Child; Hemoglobin, Sickle; Humans; Hydroxyurea; Pain; Stroke
PubMed: 36047926
DOI: 10.1002/14651858.CD002202.pub3 -
Ethiopian Journal of Health Sciences Jul 2022Pregnancy is a major concern among women with the sickle cell disease (SCD), and it is associated with increased adverse outcomes. The aim of the present meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pregnancy is a major concern among women with the sickle cell disease (SCD), and it is associated with increased adverse outcomes. The aim of the present meta-analysis is to report the fetomaternal outcomes in different sickle cell genotypes.
METHODS
In this systematic review and meta-analysis, a comprehensive search of databases and search engines such as PubMed, Scopus, Web of Science, ProQuest, Cochrane Library, Science Direct and Google Scholar were performed. Any observational studies that had compared at least one outcome such as maternal outcomes, fetal outcomes, and morbidity between two groups of pregnant women with different types of sickle cell genotypes and pregnant women without SCD were evaluated.
RESULTS
A total number of 9,827 pregnant women with SCD were examined. The results showed that pregnancy in SCD increased the risk of adverse outcomes for the mothers (including postpartum hemorrhage, prematurity, pregnancy-induced hypertension, pre-eclampsia, eclampsia, cesarean section, lower segment cesareansection, maternal death), fetus (including live births, low birth weight, intrauterine growth restriction, APGAR score at 5 min <7, stillbirth, neonatal death, perinatal mortality, acute fetal distress, intrauterine fetal death) and morbidity among the SCD(severe anemia, urinary tract infection, blood transfusion, painful crisis, acute chest syndrome, vaso-occlusive crises).
CONCLUSION
According to the results of this meta-analysis, pregnancy in the SCD is associated with an increased risk of maternal outcomes, fetal outcomes, and morbidity among SCD patients with different genotypes. Pregnancy in sickle cell hemoglobinopathies needs careful multidisciplinary management and cautious caring so as to decrease maternal and fetal morbidity and mortality.
Topics: Anemia, Sickle Cell; Cesarean Section; Female; Genotype; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome
PubMed: 35950054
DOI: 10.4314/ejhs.v32i4.23