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Health and Quality of Life Outcomes Feb 2024Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically... (Review)
Review
Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2-92.2% for deferiprone and 90-100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.
Topics: Humans; Iron Chelating Agents; Deferasirox; Deferiprone; Deferoxamine; Quality of Life; Pyridones; Benzoates; Triazoles; Thalassemia; Chelation Therapy; Ferritins; Outcome Assessment, Health Care
PubMed: 38302961
DOI: 10.1186/s12955-023-02221-y -
Indian Journal of Psychiatry Nov 2023Mood disorders are among the common mental disorders worldwide. Because of the persistence of cytomegalovirus (CMV) in the body and nervous system, this virus can be... (Review)
Review
Mood disorders are among the common mental disorders worldwide. Because of the persistence of cytomegalovirus (CMV) in the body and nervous system, this virus can be activated when the immune system is weakened and continues to exert its destructive effects throughout life. This study aimed to investigate the seroprevalence and association of human cytomegalovirus with mood disorders. Eligible articles were extracted using online international databases Science Direct, Medline, Web of Science, Scopus, and Google Scholar between 2000 and 2023. After quality assessment and specific inclusion and exclusion criteria, a total of eight eligible articles were included in the meta-analysis. Our finding showed that the seropositivity of CMV in mood disorders was 51.6% (95% CI; 42.8-60.4). There were statistical differences between mood disorders and control groups regarding the seropositivity of CMV 1.327% (95% CI; 13.27-10.45). The results of the publication bias using the Egger test confirmed no publication bias in each sub-group. The results of this meta-analysis study demonstrated that CMV infection might have associations with the incidence of mood disorders. Furthermore, we found that there were statistical differences between mood disorders and control groups regarding the seropositivity of CMV.
PubMed: 38249142
DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_672_23 -
Blood Advances Feb 2024Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia... (Meta-Analysis)
Meta-Analysis
Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia intermedia (TI). Pregnancy is associated with adverse maternal and neonatal outcomes, frequency of which has not been well delineated. This systematic review aims to provide risk estimates of maternal and fetal outcomes in TM and TI and explore pregnancy's impact on iron homeostasis. Fifteen studies (429 participants, 684 pregnancies) were included. Meta-analysis revealed a higher thrombosis risk in TI (3.7%) compared to TM (0.92%), unchanged from prepregnancy. Heart failure risks in the earlier years appeared similar (TM 1.6% vs TI 1.1%), and maternal mortality in TM was 3.7%, but with current management, these risks are rare. Gestational diabetes and pre-eclampsia occurred in 3.9% and 11.3% of TM pregnancies, respectively. Caesarean section rates were 83.9% in TM and 67% in TI. No significant difference in stillbirth, small for gestational age neonates, or preterm birth incidence between TM and TI was observed. In TM pregnancies, red cell requirements significantly increased (from 102 to 139 ml/kg/year, P = 0.001), and 70% of TI pregnancies required blood transfusions. As expected, increased transfusion alongside chelation cessation led to a significant increase in serum ferritin during pregnancy (TM by 1005 ng/mL; TI by 332 ng/mL, P < 0.0001). Deterioration in iron status was further reflected by an increase in liver iron concentration (from 4.6 to 11.9 mg/g dry weight, P < 0.0001), and myocardial T2-star (T2∗) magnetic resonance imaging decreased (from 36.2 ± 2.5 ms to 31.1 ms) during pregnancy. These findings emphasize the elevated maternal risk of iron-related cardiomyopathy during pregnancy and labor, stressing the importance of cardiac monitoring and postpartum chelation therapy resumption.
Topics: Humans; Infant, Newborn; Pregnancy; Female; beta-Thalassemia; Iron; Pregnancy Outcome; Cesarean Section; Premature Birth
PubMed: 38181780
DOI: 10.1182/bloodadvances.2023011636 -
Journal of Reproduction & Infertility 2023Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in... (Review)
Review
BACKGROUND
Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in maternal plasma. However, despite increased sensitivity, it has a number of limitations that may complicate of its results interpretation. Therefore, elucidating factors affecting fetal fraction, as a critical limitation, guides its clinical application.
METHODS
In this report, systematic search was carried out through PubMed, Web of Science, and Scopus databases until February 11, 2022 by using keywords consist of "noninvasive prenatal screening", "NIPT", "noninvasive prenatal", "cell free DNA" and "fetal fraction". The articles were screened for eligibility criteria before data extraction.
RESULTS
A total of 39 eligible studies, most published between 2010 and 2020, were included. Based on the results of studies, a negative correlation between maternal age and BMI/body weight with fetal fraction was found. Furthermore, LDL, cholesterol, triglyceride level, metformin, heparin and enoxaparin therapy, hemoglobin-related hemoglobinopathies, and physical activity showed to have negative associations. Interestingly, it seems the ethnicity of patients from South and East Asia has a correlation with fetal fraction compared to Caucasians. Positive correlation was observed between gestational age, free β-hCG, PAPP-A, living in high altitude, and twin pregnancy.
CONCLUSION
Considering each factor, there was significant inconsistency and controversy regarding their impact on outcomes. Indeed, multiple factors can influence the accuracy of NIPS results, and it is worth noting that the impact of these factors may vary depending on the individual's ethnic background. Therefore, it is important to recognize that NIPS remains a screening test, and comprehensive pre- and post-NIPS counseling should be conducted as part of standard clinical practice.
PubMed: 38164433
DOI: 10.18502/jri.v24i4.14149 -
Medicina (Kaunas, Lithuania) Dec 2023: Pain management poses a significant challenge for patients experiencing vaso-occlusive crisis (VOC) in sickle cell disease (SCD). While opioid therapy is highly...
: Pain management poses a significant challenge for patients experiencing vaso-occlusive crisis (VOC) in sickle cell disease (SCD). While opioid therapy is highly effective, its efficacy can be impeded by undesirable side effects. Local regional anesthesia (LRA), involving the deposition of a perineural anesthetic, provides a nociceptive blockade, local vasodilation and reduces the inflammatory response. However, the effectiveness of this therapeutic approach for VOC in SCD patients has been rarely reported up to now. The objective of this study was to assess the effectiveness of a single-shot local regional anesthesia (LRA) in reducing pain and consequently enhancing the management of severe vaso-occlusive crisis (VOC) in adults with sickle cell disease (SCD) unresponsive to conventional analgesic therapy. : We first collected consecutive episodes of VOC in critical care (ICU and emergency room) for six months in 2022 in a French University hospital with a large population of sickle cell patients in the West Indies population. We also performed a systematic review of the use of LRA in SCD. The primary outcome was defined using a numeric pain score (NPS) and/or percentage of change in opioid use. : We enrolled nine SCD adults (28 years old, 4 females) for ten episodes of VOC in whom LRA was used for pain management. Opioid reduction within the first 24 h post block was -75% (50 to 96%). Similarly, the NPS decreased from 9/10 pre-block to 0-1/10 post-block. Five studies, including one case series with three patients and four case reports, employed peripheral nerve blocks for regional anesthesia. In general, local regional anesthesia (LRA) exhibited a reduction in pain and symptoms, along with a decrease in opioid consumption post-procedure. : LRA improves pain scores, reduces opioid consumption in SCD patients with refractory pain, and may mitigate opioid-related side effects while facilitating the transition to oral analgesics. Furthermore, LRA is a safe and effective procedure.
Topics: Adult; Female; Humans; Pain Management; Retrospective Studies; Analgesics, Opioid; Volatile Organic Compounds; Pain; Analgesics; Anemia, Sickle Cell
PubMed: 38138299
DOI: 10.3390/medicina59122196 -
Journal of Health Care For the Poor and... 2023People of African descent and those identifying as Black and/or Latino experience a disproportionate burden of sickle cell disease (SCD), a chronic, serious blood...
People of African descent and those identifying as Black and/or Latino experience a disproportionate burden of sickle cell disease (SCD), a chronic, serious blood condition. Caregivers of children with chronic medical conditions report worse mental health than others. Disease-associated stressors can affect caregivers of children with SCD. We conducted a systematic review to summarize the prevalence of mental health symptoms in caregivers of children with SCD and to see if symptoms were associated with the child's SCD. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched PubMed, PsycINFO, and Embase, identifying 1,322 records of which 40 met criteria for inclusion in this review. Findings suggest caregivers experience mental health problems, and poorer mental health was associated with worse child SCD-related outcomes and treatment adherence. Efforts should be made to routinely screen SCD caregiver mental health and to refer accordingly.
Topics: Adolescent; Child; Humans; Anemia, Sickle Cell; Caregivers; Mental Health; Treatment Adherence and Compliance
PubMed: 38015138
DOI: No ID Found -
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 -
JAMA Network Open Oct 2023Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood.
OBJECTIVE
To assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations.
DATA SOURCES
PubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications.
STUDY SELECTION
At least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls.
DATA EXTRACTION AND SYNTHESIS
Data relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted.
MAIN OUTCOMES AND MEASURES
Outcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity.
RESULTS
The 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10-95 to 6.19 × 10-5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10-7 to 6.00 × 10-4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas.
CONCLUSIONS AND RELEVANCE
The findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.
Topics: Humans; Fetal Hemoglobin; alpha-Thalassemia; Anemia, Sickle Cell; Genotype; Genetic Variation
PubMed: 37851445
DOI: 10.1001/jamanetworkopen.2023.37484 -
Cureus Aug 2023Sickle cell anemia is a hemoglobinopathy that causes complications such as Vaso-Occlusive Crisis (VOC), stroke, priapism, Acute Chest Syndromes (ACS), and bone infarcts... (Review)
Review
Sickle cell anemia is a hemoglobinopathy that causes complications such as Vaso-Occlusive Crisis (VOC), stroke, priapism, Acute Chest Syndromes (ACS), and bone infarcts due to blood vessel occlusion, resulting in hypoxia, ischemia, and inflammation. Preventing these incidents improves the quality of life and lowers mortality rates in Sickle Cell Disease (SCD) patients. This systematic review aims to describe the drugs, their mechanisms of action, dosages, changes in hemoglobin parameters, decrease in VOCs, delay the time for the next VOC, decrease in the length of hospital stay, and side effects associated with these drugs. This review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. For this review, we searched the PubMed, Google Scholar, and Cochrane databases and screened them for full free texts published in English and studied in humans in the last five years beginning in 2018. Randomized clinical trials (RCT), observational studies, meta-analyses, systemic reviews, and traditional reviews were all included in the search. According to the type of study, quality assessment tools are used, and eight papers are chosen. Full-text articles from these papers are studied, analyzed, and tabulated. We discussed seven interventions that are used to treat sickle cell disease. Voxelotor, crizanlizumab, L-glutamate, long-term blood transfusions, Zinc (Zn), Niprisan®, and Ciklavit* were found to reduce the number and severity of VOC. We discovered that VOCs containing L -glutamate reduced the length of hospitalization. Magnesium (Mg) did not affect the number and severity of VOCs. This review includes a few articles for the study. Future papers on this subject should include a large sample size and many papers. More clinical trials are required to evaluate the dosages and outcomes of using these drugs in combination to prevent VOCs.
PubMed: 37664256
DOI: 10.7759/cureus.42785 -
Ontario Health Technology Assessment... 2023We conducted a health technology assessment to evaluate the safety, effectiveness, and cost-effectiveness of carrier screening programs for cystic fibrosis (CF), fragile...
BACKGROUND
We conducted a health technology assessment to evaluate the safety, effectiveness, and cost-effectiveness of carrier screening programs for cystic fibrosis (CF), fragile X syndrome (FXS), hemoglobinopathies and thalassemia, and spinal muscular atrophy (SMA) in people who are considering a pregnancy or who are pregnant. We also evaluated the budget impact of publicly funding carrier screening programs, and patient preferences and values.
METHODS
We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias tool and the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS), and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted cost-effectiveness analyses comparing preconception or prenatal carrier screening programs to no screening. We considered four carrier screening strategies: 1) universal screening with standard panels; 2) universal screening with a hypothetical expanded panel; 3) risk-based screening with standard panels; and 4) risk-based screening with a hypothetical expanded panel. We also estimated the 5-year budget impact of publicly funding preconception or prenatal carrier screening programs for the given conditions in Ontario. To contextualize the potential value of carrier screening, we spoke with 22 people who had sought out carrier screening.
RESULTS
We included 107 studies in the clinical evidence review. Carrier screening for CF, hemoglobinopathies and thalassemia, FXS, and SMA likely results in the identification of couples with an increased chance of having an affected pregnancy (GRADE: Moderate). Screening likely impacts reproductive decision-making (GRADE: Moderate) and may result in lower anxiety among pregnant people, although the evidence is uncertain (GRADE: Very low).We included 21 studies in the economic evidence review, but none of the study findings were directly applicable to the Ontario context. Our cost-effectiveness analyses showed that in the short term, preconception or prenatal carrier screening programs identified more at-risk pregnancies (i.e., couples that tested positive) and provided more reproductive choice options compared with no screening, but were associated with higher costs. While all screening strategies had similar values for health outcomes, when comparing all strategies together, universal screening with standard panels was the most cost-effective strategy for both preconception and prenatal periods. The incremental cost-effectiveness ratios (ICERs) of universal screening with standard panels compared with no screening in the preconception period were $29,106 per additional at-risk pregnancy detected and $367,731 per affected birth averted; the corresponding ICERs in the prenatal period were about $29,759 per additional at-risk pregnancy detected and $431,807 per affected birth averted.We estimated that publicly funding a universal carrier screening program in the preconception period over the next 5 years would require between $208 million and $491 million. Publicly funding a risk-based screening program in the preconception period over the next 5 years would require between $1.3 million and $2.7 million. Publicly funding a universal carrier screening program in the prenatal period over the next 5 years would require between $128 million and $305 million. Publicly funding a risk-based screening program in the prenatal period over the next 5 years would require between $0.8 million and $1.7 million. Accounting for treatment costs of the screened health conditions resulted in a decrease in the budget impact of universally provided carrier screening programs or cost savings for risk-based programs.Participants value the perceived potential positive impact of carrier screening programs such as medical benefits from early detection and treatment, information for reproductive decision-making, and the social benefit of awareness and preparation. There was a strong preference expressed for thorough, timely, unbiased information to allow for informed reproductive decision-making.
CONCLUSIONS
Carrier screening for CF, FXS, hemoglobinopathies and thalassemia, and SMA is effective at identifying at-risk couples, and test results may impact preconception and reproductive decision-making.The cost-effectiveness and budget impact of carrier screening programs are uncertain for Ontario. Over the short term, carrier screening programs are associated with higher costs, and also higher chances of detecting at-risk pregnancies compared with no screening. The 5-year budget impact of publicly funding universal carrier screening programs is larger than that of risk-based programs. However, accounting for treatment costs of the screened health conditions results in a decrease in the total additional costs for universal carrier screening programs or in cost savings for risk-based programs.The people we spoke with who had sought out carrier screening valued the potential medical benefits of early detection and treatment, particularly the support and preparation for having a child with a potential genetic condition.
Topics: Child; Female; Humans; Pregnancy; Cystic Fibrosis; Fragile X Syndrome; Hemoglobinopathies; Muscular Atrophy, Spinal; Technology Assessment, Biomedical; Thalassemia
PubMed: 37637488
DOI: No ID Found