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The Cochrane Database of Systematic... Nov 2023Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead... (Review)
Review
BACKGROUND
Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018.
OBJECTIVES
To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 μg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions.
AUTHORS' CONCLUSIONS
The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis.
Topics: Child; Humans; beta-Thalassemia; Calcium Channel Blockers; Iron Overload; Iron; Cardiomyopathies; Amlodipine; Iron Chelating Agents; Ferritins; Edema
PubMed: 37975597
DOI: 10.1002/14651858.CD011626.pub3 -
Osteoporosis International : a Journal... Jun 2021Thalassemia is a chronic congenital disease characterized by a combination of endocrine and metabolic disorders. Bone disease is a very common complication related to... (Review)
Review
Thalassemia is a chronic congenital disease characterized by a combination of endocrine and metabolic disorders. Bone disease is a very common complication related to the poor absorption of calcium, the secondary chronic renal disease with low vitamin D, as well as multiple endocrine risk factors. The aim of this systematic review was to estimate the prevalence of vitamin D deficiency in thalassemia, as well as its association with osteoporosis/low bone mass. A systematic review was carried out using PubMed/Medline, Cochrane, and EBSCO databases. The methodological quality of the included studies was assessed with the validated Newcastle-Ottawa Quality Assessment Scale adapted for cross-sectional studies and cohort studies respectfully and the Cochrane Collaboration for clinical trials. After application of predetermined exclusion criteria compatible with the PICOS process, a total of 12 suitable articles were identified. The prevalence of vitamin D deficiency varied considerably. Only five of the reviewed studies examined the correlation between vitamin D levels and BMD of which just three showed a statistically significant positive association of mild/moderate grade. Vitamin D deficiency is a common comorbidity in patients with thalassemia. However, both its prevalence and its severity vary considerably in different populations, and existing evidence is insufficient to conclude whether vitamin D supplementation is also associated with BMD improvement in this special population group.
Topics: Bone Density; Cross-Sectional Studies; Health Status; Humans; Vitamin D; Vitamin D Deficiency; Vitamins; beta-Thalassemia
PubMed: 33423084
DOI: 10.1007/s00198-021-05821-w -
The Cochrane Database of Systematic... Dec 2022Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with... (Review)
Review
BACKGROUND
Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review.
OBJECTIVES
The aim of the review is to determine whether the use of inhaled, short-acting bronchodilators for acute chest syndrome reduces morbidity and mortality in people with sickle cell disease and to assess whether this treatment causes adverse effects.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2004) and Embase (1981 to 2004) and ongoing trial registries (28 September 2022). Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 25 July 2022.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials. Trials using quasi-randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline.
DATA COLLECTION AND ANALYSIS
We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease.
MAIN RESULTS
We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease.
AUTHORS' CONCLUSIONS
If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease.
Topics: Humans; Acute Chest Syndrome; Bronchodilator Agents; Anemia, Sickle Cell; Bronchi; Asthma
PubMed: 36458811
DOI: 10.1002/14651858.CD003733.pub5 -
Journal of Clinical Psychology in... Jun 2020The objective of this systematic review was to assess the relationship between pain (frequency/intensity/duration, impairment, coping) and emotional functioning in...
The objective of this systematic review was to assess the relationship between pain (frequency/intensity/duration, impairment, coping) and emotional functioning in pediatric Sickle Cell Disease, and evaluate the state of the literature. Studies were included if they met each of the following criteria: (a) primarily pediatric sample of youth or young adults up to age 21 years with SCD, (b) examined emotional functioning including anxiety and/or depressive and/or internalizing symptoms, and/or affect, (c) examined pain intensity/frequency/duration and/or pain-related impairment and/or pain coping as it relates to emotional functioning, as defined above. Using the established guidelines for systematic reviews, we searched PsycINFO, PubMED, and CINAHL databases for studies published through June 2018. Screening resulted in 33 studies meeting inclusion criteria. Study data were extracted and evaluated for scientific merit, resulting in four studies being removed. 29 studies were included in the final synthesis. Studies provide strongest evidence of a relationship between increased pain frequency and higher depressive and anxiety symptoms. There are moderate-to-strong associations between pain-related impairment and depressive symptoms, and small-to-strong associations between pain-related impairment and anxiety. When examining pain-coping strategies, maladaptive cognitive strategies show the strongest association with emotional functioning. There is a need for more adequately powered, prospective studies based on theoretical frameworks in order to advance our understanding of the relationship between pain and emotional functioning in pediatric SCD.
Topics: Adaptation, Psychological; Adolescent; Anemia, Sickle Cell; Anxiety; Child; Emotions; Female; Humans; Male; Pain; Prospective Studies; Young Adult
PubMed: 31414278
DOI: 10.1007/s10880-019-09647-x -
Current Pharmaceutical Design 2023Several successful attempts have been recorded with PD-L1 blockade via atezolizumab monotherapy or combination therapy with chemotherapy in patients with metastatic... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Atezolizumab Monotherapy or Combined Therapy with Chemotherapy in Patients with Metastatic Triple-negative Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
INTRODUCTION
Several successful attempts have been recorded with PD-L1 blockade via atezolizumab monotherapy or combination therapy with chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). Due to the lack of a large-scale study, we present a meta-analysis aimed at evaluating the safety and efficacy of this promising strategy in patients with mTNBC.
METHODS
A comprehensive literature search was conducted using electronic databases to identify eligible RCTs. Twelve studies, including 2479 mTBNC patients treated with atezolizumab monotherapy or in combination with chemotherapy, were included up to January 2022. The PRISMA checklist protocol and the I2 statistic were applied for quality assessment and heterogeneity tests of the selected trials, respectively. Fixed and random-effects models were estimated based on the heterogeneity tests, and statistical analysis was performed using CMA.
RESULTS
Our pooled findings demonstrated that the median overall survival (OS) and progression-free survival (PFS) were 16.526 and 5.814 months in mTNBC patients, respectively. Furthermore, when comparing efficacy indicators between PD-L1-positive and PD-L1-negative groups, mTNBC patients with PD-L1 had better OS, PFS, and ORR than PD-L1-negative patients. Also, the immune-related adverse event incident for alopecia was higher (51.9%) than other complications across atezolizumab therapy.
CONCLUSION
Moreover, the pooled analysis indicated that the overall rate of lung metastasis following atezolizumab therapy was 42.8%, which was higher than the rates of metastasis in bone (26.9%), brain (5.4%), and lymph node (6.5%). Atezolizumab showed a manageable safety profile and had promising and durable anti-tumor efficacy in TMBC patients. Higher PD-L1 expression may be closely correlated with better clinical efficacy.
Topics: Humans; B7-H1 Antigen; Triple Negative Breast Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37921135
DOI: 10.2174/0113816128270102231016110637 -
Clinical Therapeutics Feb 2020β-Thalassemia is an inherited blood disorder characterized by reduced or no production of adult hemoglobin. Systematic identification of the burden of β-thalassemia...
PURPOSE
β-Thalassemia is an inherited blood disorder characterized by reduced or no production of adult hemoglobin. Systematic identification of the burden of β-thalassemia with contemporary treatments is lacking in published literature. Thus, a gap exists in understanding the baseline burden on which to assess future treatments. Therefore, a systematic literature review (SLR) was performed to assess management and outcomes in patients with transfusion-dependent β-thalassemia (TDT) who received long-term transfusion regimens.
METHODS
Searches of MEDLINE, EMBASE, and 5 conference websites were conducted to identify clinical-practice studies in Italy, France, Germany, Greece, the United States, and the United Kingdom, published since January 2007. The review found 135 articles meeting the SLR criteria.
FINDINGS
Among patients carrying 2 β-thalassemia mutations, 64%-89% underwent regular transfusions at intervals of between 2 and 4 weeks. Transfusion-associated complications that were reported included iron overload, transfusion reactions, alloimmunization, and infections. Analyses of 42, 25, and 73 studies reporting liver iron concentration (median, 8.5 mg/g of dry weight [dw]; interquartile range [IQR], 4.5-11.0 mg/g dw), cardiac * magnetic resonance imaging (median, 27.4 ms; IQR, 26.0-30.2 ms), and serum ferritin (median, 1465.0 ng/mL; IQR, 1238.2-1797.0 ng/mL), respectively, showed wide ranges in iron levels and a general trend toward improved iron control in recent years. Adverse transfusion reactions and alloimmunization were reported in ~50% and 10%-20% in patients, respectively. Rates of transfusion-transmitted infections were highly variable by study but were lower in more recent cohorts. Complications stemming from iron overload and underlying disease captured in this SLR included cardiac disease, liver disease, and endocrine and musculoskeletal disorders. Approximately 10% of patients were diagnosed with heart failure, with rates ranging from 2.9% to 20.9% across 6 studies. Other significant complications reported with β-thalassemia included pain (25%-69%), psychiatric disorders (25%-30%), and reduced health-related quality of life. Despite substantial improvements in survival, patients with TDT remained at an increased risk for early mortality.
IMPLICATIONS
Consistent with improvements in transfusion practices and iron monitoring and management, outcomes in patients with TDT have improved. However, iron overload and disease-associated complications remain a challenge in this population. This review supports the burden of disease affecting patients with β-thalassemia and provides a baseline health status against which to assess future improvements in care.
Topics: Blood Transfusion; Cost of Illness; Humans; beta-Thalassemia
PubMed: 31882227
DOI: 10.1016/j.clinthera.2019.12.003 -
Iranian Journal of Medical Sciences Jan 2022Patients with beta-thalassemia (BT) are susceptible to psychological disorders such as depression. The present study was conducted to estimate the pooled prevalence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with beta-thalassemia (BT) are susceptible to psychological disorders such as depression. The present study was conducted to estimate the pooled prevalence of depression among patients with BT in Iran.
METHODS
Domestic and international databases were searched for relevant articles published from 1991 until June 2019. We searched international databases such as Scopus, ISI, and Embase; Iranian databases such as SID, Magiran, and IranDoc; and Google Scholar and PubMed search engines. The MeSH keywords used were "depression", "mental health", "depressive disorder", "thalassemia", "beta-thalassemia major", "prevalence", "epidemiology", and "Iran". Relevant cross-sectional or cohort studies were included in the analysis. Cochran's test and the index were used to assess heterogeneity. The pooled prevalence and its 95% confidence interval (CI) were calculated using "metaprop" commands in Stata 14. In cases, where the statistic was greater than 50%, the random-effects model was used.
RESULTS
Eighteen eligible studies were included. The pooled prevalence of depression was 42% (95% CI: 33% to 52%), whereas the pooled prevalence of mild, moderate, severe, and extremely severe depression was 16% (95% CI: 11% to 22%), 13% (95% CI: 9% to 18%), 13% (95% CI: 9% to 17%), and 3% (95% CI: 0% to 8%), respectively. The pooled prevalence of depression in moderate- and high-quality studies was 45% (95% CI: 29% to 61%), and 39% (95% CI: 27% to 51%), respectively.
CONCLUSION
The high prevalence of depression highlights the urgent need for the establishment of interventions for the prevention, early detection, and treatment of depression among Iranian patients with BT.
Topics: Cross-Sectional Studies; Depression; Humans; Iran; Prevalence; beta-Thalassemia
PubMed: 35017773
DOI: 10.30476/ijms.2020.85941.1557 -
Hematology (Amsterdam, Netherlands) Dec 2020Although dental caries has been widely reported in individuals with sickle cell disease (SCD), there is still controversial in the literature regarding the association... (Meta-Analysis)
Meta-Analysis
Although dental caries has been widely reported in individuals with sickle cell disease (SCD), there is still controversial in the literature regarding the association between SCD and dental caries. The aim of this systematic review was to investigate whether individuals with SCD have more dental caries than individuals with non-SCD. PubMed and Embase databases were searched for eligible studies. The parameters of the permanent decayed, missing and filled teeth (DMFT) index and the permanent decayed, missing and filled surface (DMFS) index were considered as outcome measures. The overall meta-analyses of the DMFT and DMFS index and various subgroup analyses (caries components, age, and genotypes) of DMFT index were performed to calculate the weighted mean differences (WMD) between patients with SCD and non-SCD individuals. A total of 9 studies covering 1478 individuals were included in this meta-analysis. The results of overall meta-analyses indicated that the scores of the DMFT and DMFS index were not significantly different between patients with SCD and non-SCD participants. The results of subgroup analyses by caries components, age, and genotypes showed no significant difference in most items. The result of the missing teeth was significantly lower in patients with SCD than in non-SCD individuals (WMD, -0.14; 95% confidence interval [CI], -0.25 to -0.03; = 0.01). The results revealed that compared with non-SCD individuals, patients with SCD did not suffer from worse dental caries. Considering the limitations, further well-designed studies are necessary to reveal the association between SCD and dental caries.
Topics: Anemia, Sickle Cell; Dental Caries; Dental Health Surveys; Genotype; Humans
PubMed: 32783601
DOI: 10.1080/16078454.2020.1748927 -
Hematology. American Society of... Dec 2022Pregnancy in women with sickle cell disease (SCD) is a life-threatening condition. In both high- and low-income countries, there is an 11-fold increased risk of maternal...
Pregnancy in women with sickle cell disease (SCD) is a life-threatening condition. In both high- and low-income countries, there is an 11-fold increased risk of maternal death and a 4-fold increased risk of perinatal death. We highlight the epidemiology of SCD-specific and obstetric complications commonly seen during pregnancy in SCD and propose definitions for acute pain and acute chest syndrome (ACS) episodes during pregnancy. We conducted a systematic review of the recent obstetric and hematology literature using full research articles published within the last 5 years that reported outcomes in pregnant women with SCD. The prevalence of acute pain episodes during pregnancy ranged between 4% and 75%. The prevalence of ACS episodes during pregnancy ranged between 4% and 13%. The estimated prevalence of pulmonary thromboembolism in women with SCD during pregnancy is approximately 0.5 to 1%. ACS is the most common cause of death and is often preceded by acute pain episodes. The most crucial time to develop these complications in pregnancy is during the third trimester and postpartum period. In a pooled analysis from studies in low- and middle-income settings, maternal death in women with SCD is approximately 2393 and 4300 deaths per 100 000 live births with and without multidisciplinary care, respectively. In comparison, in the US and northern Europe, the general maternal mortality rate is approximately 23.8 and 8 deaths per 100 000 live births, respectively. A multidisciplinary SCD obstetrics care approach reduces maternal and perinatal morbidity and mortality in low- and middle-income countries.
Topics: Female; Pregnancy; Humans; Acute Chest Syndrome; Maternal Death; Acute Pain; Maternal Mortality; Anemia, Sickle Cell; Pulmonary Embolism
PubMed: 36485167
DOI: 10.1182/hematology.2022000376 -
Annals of Medicine Dec 2022Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no...
INTRODUCTION
Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents.
METHODS
This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria.
RESULTS
Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report ( = 15/36, 41.7%), and pill count ( = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills ( = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in "categories" with different levels of adherence ( = 29) or "quantitatively" as a percentage of medication taken out of those prescribed ( = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis.
CONCLUSIONS
Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients.Key messagesPredictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort.Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes.Inadequate adherence to ICT is associated with increased lifetime health costs.There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients.
Topics: Adolescent; Chelation Therapy; Child; Humans; Iron; Iron Overload; Patient Compliance; Thalassemia
PubMed: 35103514
DOI: 10.1080/07853890.2022.2028894