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International Journal of Molecular... May 2023This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies,... (Review)
Review
This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies, leukodystrophies, lysosomal storage disorders and retinal dystrophies and extrapolated the key clinical findings to individuals with Rett syndrome (RTT). The PRISMA guidelines were used to search six databases during the last decade, followed by a thematic analysis to identify the emerging themes. Thematic analysis across the different disorders revealed four themes: (I) Therapeutic time window of gene therapy; (II) Administration and dosing strategies for gene therapy; (III) Methods of gene therapeutics and (IV) Future areas of clinical interest. Our synthesis of information has further enriched the current clinical evidence base and can assist in optimising gene therapy and gene editing studies in individuals with RTT, but it would also benefit when applied to other disorders. The findings suggest that gene therapies have better outcomes when the brain is not the primary target. Across different disorders, early intervention appears to be more critical, and targeting the pre-symptomatic stage might prevent symptom pathology. Intervention at later stages of disease progression may benefit by helping to clinically stabilise patients and preventing disease-related symptoms from worsening. If gene therapy or editing has the desired outcome, older patients would need concerted rehabilitation efforts to reverse their impairments. The timing of intervention and the administration route would be critical parameters for successful outcomes of gene therapy/editing trials in individuals with RTT. Current approaches also need to overcome the challenges of MeCP2 dosing, genotoxicity, transduction efficiencies and biodistribution.
Topics: Humans; Rett Syndrome; Gene Editing; Tissue Distribution; Methyl-CpG-Binding Protein 2; Brain; Genetic Therapy
PubMed: 37240368
DOI: 10.3390/ijms24109023 -
Health Expectations : An International... Apr 2023Increasing numbers of interventions are being developed to support self-management for children and young people (CYP) with sickle cell disease (SCD), but no systematic... (Review)
Review
BACKGROUND
Increasing numbers of interventions are being developed to support self-management for children and young people (CYP) with sickle cell disease (SCD), but no systematic review has systematically synthesized this evidence regarding their characteristics, effectiveness, acceptability and feasibility for all published intervention types.
METHODS
The Joanna Briggs Institute guidelines for mixed-method reviews were followed. A systematic search of eight databases and key journals was conducted from their inception to November 2021. Primary research of self-management interventions targeting CYP with SCD aged 8-24 years and reporting any health/social outcome and acceptability data were included. Design-specific standardized critical appraisal instruments were used. Two independent reviewers screened and appraised the articles. A third reviewer resolved disagreements.
RESULTS
Of 1654 articles identified, 38 studies were included. Methodological quality was moderate. Most studies evaluated SCD education, psycho-behavioural, psychosocial and skills training and/or social support interventions. They appear to demonstrate short-term improvements in knowledge, social functioning and medical adherence outcomes. Interventions that were multifaceted in content, combined technological platforms and in-person group-based formats and involved peers, family and care providers were more acceptable and effective. The long-term impact of interventions was limited, including CYP's involvement in the intervention development and implementation.
CONCLUSIONS
There is inconclusive evidence for any self-management programme. Nonetheless, support from family, peers and care providers appears to be important for self-management interventions' effectiveness and acceptability. Future research needs to prioritize CYP involvement in both intervention design and delivery, their wider social context and include CYP with SCD from non-Black backgrounds.
PATIENT AND PUBLIC CONTRIBUTION
Three young people with SCD recruited acted as the review advisors. They were formally trained in the review process and involved in every aspect of the review: the design, conduct and interpretation of the findings. CYP involvement in the interventions' development and implementation was analysed as part of the review. This systematic review was conducted as part of a wider research project titled: Understanding fatigue experiences of CYP with SCD to guide the co-development of a fatigue self-management intervention. Two of the young advisors involved in the review were also involved in the development of the project funding application.
Topics: Humans; Child; Adolescent; Self-Management; Self Efficacy; Anemia, Sickle Cell
PubMed: 36597596
DOI: 10.1111/hex.13692 -
Respiratory Investigation Jul 2022Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease that is characterized by poor airflow and airway inflammation. It is estimated that... (Review)
Review
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease that is characterized by poor airflow and airway inflammation. It is estimated that the global prevalence of COPD is about 13.1%. Anemia is associated with increased morbidity and hospitalization duration. In this systematic review, we investigate the association between all types of anemia and COPD progression.
METHODS
We systematically searched electronic databases, including Scopus, Medline/PubMed, EMBASE, Web of Sciences (WOS), and Cochrane Library, using the following mesh-standardized keywords: (((anemia∗ OR anaemia∗) OR "chronic anemia disease" [Mesh] OR "CAD" OR "iron deficiency anemia" OR" IDA" OR) AND ("COPD" [Mesh] OR "chronic obstructive pulmonary disease")) until February 2022.
RESULTS
Overall of 11,158 studies were included. Ultimately, 59 studies were included in the analysis. The most apparent findings from the analysis were that exacerbation of COPD, increased hospitalization, and increased long-term mortality were associated with anemia. Further analysis showed that iron deficiency (ID) is a common finding in COPD and is accompanied by an increase in the systolic pulmonary artery pressure.
CONCLUSION
Despite the comfortable control of anemia, the absence of treatment can be life-threatening in patients with COPD. Our systematic results showed significant homogeneity between studies on the increased mortality rate in anemic COPD, increased hospitalization, and decreased quality of life.
Topics: Anemia; Humans; Iron Deficiencies; Lung; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 35484075
DOI: 10.1016/j.resinv.2022.03.006 -
Journal of Community Genetics Dec 2023A large number of studies have reported that the prevalence of beta thalassemia carriers in India varies by ethnic groups. The objective of this study was to conduct a... (Review)
Review
A large number of studies have reported that the prevalence of beta thalassemia carriers in India varies by ethnic groups. The objective of this study was to conduct a systematic review of the published studies and conduct a meta-analysis to determine the prevalence of beta thalassaemia carriers in India. A PubMed database search using keywords "beta thalassaemia AND India" identified 1088 articles of which 69 articles were included in the review. Studies using diagnostic tests and methods recommended by the International Council for Standardization in Haematology were used for calculation of pooled prevalence. Pooled prevalence was calculated using a random effects model using Review Manager version 5.3. Studies had screened five categories of populations, that is, the general population; tribal groups, communities not belonging to tribal groups, persons with anemia, and persons referred with a suspicion of hemoglobinopathy. This heterogeneity contributed to a high pooled prevalence of beta thalassemia carriers of 8.23% (95% CI 7.36-9.10). Sub-group analysis however yielded 3.74% (95% CI 2.52-4.97) pooled prevalence of beta thalassemia carriers in the general population. It was 4.6% (95% CI 3.2-6.2) among tribal groups. Quality of prevalence studies was limited by methodological issues including non-random sampling methods, heterogeneity of population types screened, and lack of use of recommended diagnostic cut-offs. Prevalence of beta thalassemia carriers was similar in tribal populations and the general population, indicating the need to further investigate the prevalence of beta thalassemia carriers in tribal groups.
PubMed: 37861936
DOI: 10.1007/s12687-023-00683-7 -
American Journal of Hematology Jan 2020Children with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to conduct a systematic,... (Review)
Review
Children with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to conduct a systematic, PRISMA-based review of the literature, available clinical guidelines and practice recommendations. We also aimed to extract any valuable information for the "best of available-evidence"-based prevention of perioperative adverse events in children with SCD, and highlight the most urgent priorities in clinical research. As data sources, US National Library of Medicine, Medline, National Guideline Clearinghouse, International Guideline Network, TRIP databases were searched for any content until January 2019. We also included institutional, consortia and expert group guidelines. Included were reports/guidelines in English, French, German, and Italian. Excluded were reports on obstetrical and fetal management. We identified 202 reports/guidelines fulfilling the criteria outlined above. A majority focused on visceral, cardiovascular and orthopedic surgery procedures, and only five were multicenter randomized controlled trials and two prospective randomized studies. After grading of the quality of the evidence, the extracted data was summarized into clinical recommendations for daily practice. Additionally, we designed a risk-grading algorithm to identify contexts likely to be associated with adverse outcomes. In conclusion, we provide a systematic PRISMA-based review of the existing literature and ancillary practice and delineate a set of clinical recommendations and priorities for research.
Topics: Anemia, Sickle Cell; Child; Humans; Perioperative Care; Practice Guidelines as Topic; Risk Assessment
PubMed: 31456233
DOI: 10.1002/ajh.25626 -
Hemoglobin Sep 2021As a cause of chronic blood transfusions, iron overload is an important issue in β-thalassemia (β-thal) patients that leads to multiple organ dysfunctions. This is an... (Meta-Analysis)
Meta-Analysis Review
As a cause of chronic blood transfusions, iron overload is an important issue in β-thalassemia (β-thal) patients that leads to multiple organ dysfunctions. This is an updated meta-analysis conducted to summarize the existing evidence of the prevalence of hypothyroidism (HT) among patients with transfusion-dependent (TDT) and non transfusion-dependent β-thal (NTDT) and for the first time we meta-analyzed the relationship between ferritin level and HT. This systematic review and meta-analysis were done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We searched databases including Web of Science (ISI), Scopus, PubMed, Embase, and Scholar. The quality of the included studies was assessed based on the Newcastle-Ottawa scale (NOS) checklist. Meta-analysis was done using Stata statistical software. The pooled prevalence of total HT, subclinical HT, and overt HT among β-thal patients was 13.25 [95% confidence interval (95% CI): 10.29-16.21; 11.84, 95% CI: 8.43-15.25 and 12.46, 95% CI: 1.05-23.87], respectively. The prevalence of total HT was 16.22% (95% CI: 12.36-20.08) in TDT and 7.22% (95% CI: 3.66-10.78) in NTDT patients. Serum ferritin (SF) levels were significantly lower in euthyroid compared to hypothyroid patients [standard mean difference (SMD) -2.15 (95% CI: -3.08, -1.21, value <0.001]. The prevalence of HT was higher in TDT compared to NTDT patients. Moreover, our results showed a significant association of high serum ferritin (SF) levels with hypothyroidism in β-thal patients. Both of these findings highlight the importance of prevention measures and timely diagnosis and management of iron overload in β-thal patients.
Topics: Cross-Sectional Studies; Ferritins; Humans; Hypothyroidism; Iron Overload; Prevalence; beta-Thalassemia
PubMed: 34806533
DOI: 10.1080/03630269.2021.2003382 -
Pediatric Blood & Cancer Jun 2023Pain is the clinical hallmark of sickle cell disease (SCD) leading to hospitalization, psychological sequelae and a decreased health-related quality of life. The aim of... (Review)
Review
BACKGROUND
Pain is the clinical hallmark of sickle cell disease (SCD) leading to hospitalization, psychological sequelae and a decreased health-related quality of life. The aim of this systematic literature review is to evaluate the efficacy of non-pharmacological interventions in reducing sickle cell related pain in children with SCD.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive literature search up until October 2022 was performed to identify studies that investigated the efficacy of non-pharmacological interventions on (1) pain frequency and/or intensity, and (2) analgesic and health service use in children with SCD until the age of 21. Both randomized controlled trials (RCTs) and quasi-experimental designed (QED) studies were considered for inclusion.
RESULTS
Ten articles (five RCTs and five QED studies) with 422 participants were included. They investigated cognitive behavioural therapy (CBT) (n = 5), biofeedback (n = 2), massage (n = 1), virtual reality (n = 1) and yoga (n = 1). The majority of the interventions were psychological (n = 7) and were performed in the outpatient clinic (n = 6). CBT and biofeedback significantly reduced frequency and/or intensity of SCD-related pain in outpatient settings, while virtual reality and yoga significantly reduced pain in inpatient settings. Biofeedback also significantly reduced analgesic use. None of the included articles reported reduced health service use.
CONCLUSION
Non-pharmacological interventions may be effective in reducing pain in paediatric patients with SCD. However, due to the heterogeneity of the included studies a quantitative analysis could not be performed. Awaiting further supporting evidence, healthcare providers should consider implementing these interventions as valuable part of a comprehensive pain management strategy plan.
Topics: Child; Humans; Pain Management; Pain; Analgesics; Anemia, Sickle Cell; Cognitive Behavioral Therapy
PubMed: 36994864
DOI: 10.1002/pbc.30315 -
The Cochrane Database of Systematic... Nov 2020Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second...
BACKGROUND
Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal haemoglobin polymerisation leading to a symptomatic disorder. Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review.
OBJECTIVES
The objectives of this review are: - to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease; - to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries, Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 September 2020.
SELECTION CRITERIA
All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting.
DATA COLLECTION AND ANALYSIS
No trials of gene therapy for sickle cell disease were found.
MAIN RESULTS
No trials of gene therapy for sickle cell disease were reported.
AUTHORS' CONCLUSIONS
No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.
Topics: Anemia, Sickle Cell; Genetic Therapy; Humans
PubMed: 33251574
DOI: 10.1002/14651858.CD007652.pub7 -
Journal of Periodontal Research Aug 2023Previous studies have evaluated the association between sickle cell disease (SCD) and periodontal disease; however, their effect on the periodontal parameters remains... (Meta-Analysis)
Meta-Analysis Review
Previous studies have evaluated the association between sickle cell disease (SCD) and periodontal disease; however, their effect on the periodontal parameters remains unclear. This systematic review aimed to investigate whether individuals with sickle cell disease (SCD) increase the risks of periodontal disease more than those without. For the selection of eligible studies, an electronic search was conducted in the MEDLINE/PubMed, Web of Science, Cochrane Library, and Scopus databases. The meta-analysis was based on the inversion of variance using the mean difference (MD) of the continuous outcomes. The quality assessment of included studies was performed using the JBI Critical Appraisal Tools. In total, 13 studies and 2381 participants were included in the qualitative analysis, while 9 studies were considered for the meta-analysis. The meta-analysis indicated that patients with SCD present similar Plaque Index, Clinical Attachment Level, Bleeding on Probing, and Probing Depth when compared to healthy patients (p > .05). However, the Gingival Index was higher for patients with SCD (p = .0002; MD: 0.20). Compared to healthy patients, patients with SCD did not have an increase in periodontal parameters, except for the gingival index. However, further well-designed studies are recommended to reassess the association between SCD and periodontal diseases.
Topics: Humans; Periodontal Diseases; Anemia, Sickle Cell
PubMed: 37237445
DOI: 10.1111/jre.13129 -
European Journal of Haematology Apr 2023Iron overload in patients with thalassemia represents a serious complication by affecting numerous organ systems. This meta-analysis aims to establish an evidence... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Iron overload in patients with thalassemia represents a serious complication by affecting numerous organ systems. This meta-analysis aims to establish an evidence regarding the effect of amlodipine on cardiac iron overload in thalassemia patients.
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials (RCTs). The primary outcomes were cardiac T2* and myocardial iron concentration (MIC). Secondary outcomes were liver iron concentration (LIC), risk of Gastrointestinal (G.I.) upset and risk of lower limb edema. We used Hedges' g to pool continuous outcomes, while odds ratio was used for dichotomous outcomes.
RESULTS
Seven RCTs were eligible for this systematic review and meta-analysis, comprising of 233 patients included in the analysis. Amlodipine had a statistically significant lower MIC (Hedges' g = -0.82, 95% confidence interval [CI] [-1.40, -0.24], p < .001) and higher cardiac T2* (Hedges' g = 0.36, 95% CI [0.10, 0.62], p = .03). Amlodipine was comparable to standard chelation therapy in terms of the risk of lower limb edema and GI upset.
CONCLUSION
Our meta-analysis found that amlodipine significantly increases cardiac T2* and decreases MIC, hence decreasing the incidence of cardiomyopathy-related iron overload in thalassemia patients.
Topics: Humans; Calcium Channel Blockers; Siderosis; beta-Thalassemia; Thalassemia; Iron; Iron Overload; Amlodipine; Iron Chelating Agents
PubMed: 36565288
DOI: 10.1111/ejh.13919