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Frontiers in Medicine 2023Sickle cell disease is the most common hemoglobinopathy among humans. As the condition promotes susceptibility to infections, chronic inflammation, and...
UNLABELLED
Sickle cell disease is the most common hemoglobinopathy among humans. As the condition promotes susceptibility to infections, chronic inflammation, and hypercoagulability disorders, several international agencies have included individuals with this disease in the COVID-19 risk group for severe outcomes. However, available information about the subject is not properly systematized yet. This review aimed to understand and summarize the scientific knowledge about the impact of SARS-CoV-2 infection in patients with sickle cell disease. Searches were performed in the Medline, PubMed, and Virtual Health Library databases based on descriptors chosen according to the Medical Subject Headings. We analyzed studies published between 2020 and October 2022, developed with qualitative, quantitative, or mixed methodology, and written in English, Spanish, or Portuguese. The search resulted in 90 articles organized into six categories. There is disagreement in the literature about how different aspects related to sickle cell disease, such as chronic inflammation status, hypercoagulability, hemolytic anemia, use of hydroxyurea, and access to medical care interference with the clinical course of COVID-19. These topics deserve further investigation. It is evident, however, that the infection may manifest in an atypical way and act as a trigger for the development of sickle cell-specific complications, such as acute chest syndrome and vaso-occlusive crises, conditions that are associated with great morbidity and mortality. Therefore, healthcare professionals must be aware of the different forms of presentation of COVID-19 among these individuals. Specific guidelines and therapeutic protocols, as well as public policies for sickle cell individuals, must be considered.
SYSTEMATIC REVIEW REGISTRATION
This review (https://doi.org/10.17605/OSF.IO/NH4AS) and the review protocol (https://osf.io/3y649/) are registered in the Open Science Framework platform.
PubMed: 37200963
DOI: 10.3389/fmed.2023.1144226 -
Journal of the American Academy of... May 2023Primary spinal infections (PSIs) are a group of infectious diseases characterized by inflammation of the end plate-disk unit or its surroundings. PSI is considered more...
PURPOSE
Primary spinal infections (PSIs) are a group of infectious diseases characterized by inflammation of the end plate-disk unit or its surroundings. PSI is considered more prevalent and aggressive among patients with chronic immunocompromised states. Association of PSIs, immunocompromising cancers, and hemoglobinopathies has not been systematically analyzed. We conducted a systematic review to study characteristics, clinical presentation, and mortality of patients with PSI in the setting of hematologic disease.
METHODS
A systematic literature search in PubMed, Web of Science, and Scopus was conducted in April 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included retrospective case series and individual case reports.
RESULTS
On careful review, 28 articles published between 1970 and 2022 were selected. These studies featured 29 patients who met inclusion criteria (mean age 29 years, age range 1.5 to 67 years; 63.3% male). Lumbar infection was the most common location (65.5%), with Salmonella (24.1%) as the main causative microorganism. Neurologic compromise was present in 41% of patients, and surgical intervention occurred in 48.3%. Average antibiotic duration was 13 weeks. The postoperative complication rate was 21.4%, with a mortality of 6.9%.
CONCLUSION
PSI in patients with hematologic disease, while having shorter periods to diagnosis, presents increased rates of neurologic deficit, surgical intervention, and complications.
Topics: Humans; Male; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Female; Retrospective Studies; Aggression; Anti-Bacterial Agents; Bone Plates; Hemoglobinopathies
PubMed: 37159278
DOI: 10.5435/JAAOSGlobal-D-22-00178 -
The Cochrane Database of Systematic... May 2023Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with... (Review)
Review
BACKGROUND
Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review.
OBJECTIVES
To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding. Bisphosphonates versus placebo or no treatment Two RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty. There were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility. Different doses of bisphosphonate compared One 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment. Zinc versus placebo One trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment. Denosumab versus placebo Based on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD -2.40 cm, 95% CI -3.80 to -1.00). Strontium ranelate One trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD -0.70 cm (95% CI -1.30 to -0.10); we considered this measure representative of improved quality of life.
AUTHORS' CONCLUSIONS
Bisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD. We recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.
Topics: Adult; Child; Female; Male; Humans; Middle Aged; beta-Thalassemia; Alendronate; Pamidronate; Clodronic Acid; Denosumab; Osteoporosis; Diphosphonates; Fractures, Bone
PubMed: 37159055
DOI: 10.1002/14651858.CD010429.pub3 -
The Pediatric Infectious Disease Journal Aug 2023Osteomyelitis is a condition that disproportionately affects those with sickle cell anemia (SCA). Despite the frequency of osteomyelitis in this population, there are...
BACKGROUND
Osteomyelitis is a condition that disproportionately affects those with sickle cell anemia (SCA). Despite the frequency of osteomyelitis in this population, there are reports of increasing life expectancy and rates of Staphylococcus aureus infections, which contrasts the belief that Salmonella is the most common organism identified. The purpose of this systematic review is to determine the most commonly identified organism and identify whether age is associated with the development of Salmonella osteomyelitis in homozygous sickle cell patients.
METHODS
A search of PubMed, EMBASE Cochrane and databases was performed for studies of all levels of evidence pertaining to osteomyelitis in SCA. Reasons for exclusion included non-English language, case reports, literature reviews, isolated septic arthritis without bony involvement and isolated oral-facial bony involvement.
RESULTS
The most common pathogen cultured was nontyphoid Salmonella , which occurred in 117 of 192 (60.9%) of cases identified. This was followed by S. aureus 41 of 192 (21.8%) and other enteric bacteria 14 of 192 (7.2%). Subgroup analysis demonstrated differences at the age of initial presentation with Salmonella cohort at 6.8 years and S. aureus cohort at 22.1 years ( P = 0.0001). On geographic analysis, African countries had an older average age of diagnosis at 13.1 years with decreased rates of Salmonella infections and increased rates of infections from other organisms compared with the US, Middle East and Europe.
CONCLUSIONS
This systematic review suggests that Salmonella is most commonly identified in patients with SCA (HbSS phenotype) especially those <12 years old presenting with acute osteomyelitis. Sub-Saharan African countries had later ages of diagnosis compared with the US, Middle East and Europe with bacterial profiles that favors a diagnosis of chronic osteomyelitis and missed acute initial presentation. Therefore, age of presentation is likely a surrogate for geographic and socioeconomic factors such as availability of medical screening and treatment.
Topics: Humans; Staphylococcus aureus; Salmonella Infections; Anemia, Sickle Cell; Salmonella; Osteomyelitis
PubMed: 37079601
DOI: 10.1097/INF.0000000000003937 -
British Journal of Haematology Jun 2023Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves... (Review)
Review
Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves destruction of both donor and recipient red blood cells (RBCs). As the epidemiology and underlying pathophysiology have yet to be definitively elucidated, recognition can be challenging. We systematically reviewed PubMed and EMBASE to identify all cases of post-transfusion hyperhaemolysis and characterized the epidemiological, clinical and immunohaematological characteristics and treatments of HHS. We identified 51 patients (33 females and 18 males), including 31 patients with SCD (HbSS, HbSC and HbS/β-thalassaemia). The median haemoglobin nadir (3.9 g/dL) occurred a median of 10 days post-transfusion. 32.6% and 45.7% of patients had a negative indirect anti-globulin test and a negative direct anti-globulin test, respectively. The most common therapies included corticosteroids and intravenous immune globulin. 66.0% of patients received ≥1 supportive transfusion, which was associated with a longer median hospital stay/time to recovery (23 days vs. 15 days; p = 0.015) compared to no supportive transfusion. These findings illustrate that HHS that often results in marked anaemia 10 days post-transfusion is not restricted to patients with haemoglobinopathies, and additional transfused RBCs may be associated with a longer time-to-recovery.
Topics: Male; Female; Humans; Transfusion Reaction; Anemia, Sickle Cell; Blood Transfusion; Erythrocytes; Hemoglobin SC Disease; Syndrome
PubMed: 37074146
DOI: 10.1111/bjh.18825 -
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 -
Reviews in Medical Virology Jul 2023Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We... (Meta-Analysis)
Meta-Analysis Review
Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta-analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID-19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59-1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77-1.7), p < 0.00001), angiopoietin-2 (Ang-2) (1.06 (0.6-1.51), p < 0.0001), E-selectin (1.09 (0.55-1.63), p < 0.0001), P-selectin (0.59 (0.24-0.94), p = 0.001), syndecan-1 (0.99 (0.6-1.37), p < 0.00001), mid-regional pro-adrenomedullin (MR-proADM) (1.52 (1.35-1.68), p < 0.00001), vascular endothelial growth factor (0.27 (0.02-0.53), p = 0.03), soluble fms-like tyrosine kinase-1 (sFLT-1) (1.93 (0.65-3.21), p = 0.03) and lower levels of ADAMTS13 antigen (-0.69 (-0.9 to -0.47) p < 0.00001) and activity (-0.84 (-1.06 to -0.61) p < 0.0000). Plasminogen activator inhibitor-1 and tissue plasminogen activator levels were not different between the two groups (p < 0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID-19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR-proADM, vWF, syndecan-1 and sFLT-1 showed a significant association with poor outcome in these patients.
Topics: Humans; Tissue Plasminogen Activator; Syndecan-1; COVID-19; Vascular Endothelial Growth Factor A; von Willebrand Factor; Biomarkers
PubMed: 36943015
DOI: 10.1002/rmv.2442 -
AIDS Research and Human Retroviruses Jul 2023Epidemiological data demonstrate the greater severity of SARS-CoV-2 infection in HIV patients along with the more hospitalization, and mortality rates. Thus, this... (Meta-Analysis)
Meta-Analysis
Epidemiological data demonstrate the greater severity of SARS-CoV-2 infection in HIV patients along with the more hospitalization, and mortality rates. Thus, this meta-analysis aimed to assess the possible differences in hospitalization, mortality, and the CD4 T cell counts between COVID-19/HIV co-infected patients and the control group. The relevant studies were obtained from online databases such as Science Direct, PubMed, Scopus, Web of Science, and Google Scholar using Mesh and Non-Mesh keywords and the meta-analysis was conducted according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols checklist. Then, the Newcastle-Ottawa scale (NOS) checklist was used to assess the quality of selected studies. According to the random effect models, the odds ratios of hospitalization, mortality, and CD4 T cell counts were estimated. The odds ratios of hospitalization and mortality rates in COVID-19 patients with HIV were 1.67 (confidence interval [CI]: 0.76 to 3.71) and 0.80 (CI: 0.57 to 1.11), respectively, compared to that of the COVID-19 group. In this meta-analysis, there was no statistically significant difference in the rates of hospitalization, mortality, and CD4 T cell counts between COVID-19 patients with HIV and the control group. The similarity between the studied groups could be attributed to factors such as the rarity of COVID-19/HIV co-infection patients and the presence of random error, administration of antiretroviral therapy in HIV patients, and early hospitalization time in COVID-19/HIV co-infected patients.
Topics: Humans; HIV Infections; COVID-19; CD4-Positive T-Lymphocytes; SARS-CoV-2; Comorbidity; Hospitalization; CD4 Lymphocyte Count
PubMed: 36924275
DOI: 10.1089/AID.2022.0076 -
Pediatric Blood & Cancer Jun 2023This study aimed to synthesize the evidence on the effects of disease-modifying agents for managing sickle cell disease (SCD) in children and adolescents by means of a... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of pharmacological interventions for managing sickle cell disease complications in children and adolescents: Systematic review with network meta-analysis.
This study aimed to synthesize the evidence on the effects of disease-modifying agents for managing sickle cell disease (SCD) in children and adolescents by means of a systematic review with network meta-analyses, surface under the cumulative ranking curve (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) (CRD42022328471). Eightteen randomized controlled trials (hydroxyurea [n = 7], l-arginine [n = 3], antiplatelets [n = 2], immunotherapy/monoclonal antibodies [n = 2], sulfates [n = 2], docosahexaenoic acid [n = 1], niprisan [n = 1]) were analyzed. SUCRA and SMAA demonstrated that hydroxyurea at higher doses (30 mg/kg/day) or at fixed doses (20 mg/kg/day) and immunotherapy/monoclonal antibodies are more effective for preventing vaso-occlusive crisis (i.e., lower probabilities of incidence of this event; 14, 25, and 30%, respectively), acute chest syndrome (probabilities ranging from 8 to 30%), and needing of transfusions (11-31%), while l-arginine (100-200 mg/kg) and placebo were more prone to these events. Therapies were overall considered safe; however, antiplatelets and sulfates may lead to more severe adverse events. Although the evidence was graded as insufficient and weak, hydroxyurea remains the standard of care for this population, especially if a maximum tolerated dose schedule is considered.
Topics: Child; Adolescent; Humans; Hydroxyurea; Antisickling Agents; Network Meta-Analysis; Anemia, Sickle Cell; Antibodies, Monoclonal
PubMed: 36916826
DOI: 10.1002/pbc.30294 -
The Cochrane Database of Systematic... Mar 2023Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia are at risk of iron overload. Iron overload can lead to iron toxicity in... (Review)
Review
BACKGROUND
Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands, which can be prevented and treated with iron-chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and wellbeing, which may affect adherence.
OBJECTIVES
To identify and assess the effectiveness of different types of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) and interventions specific to different age groups, to improve adherence to iron chelation therapy compared to another listed intervention, or standard care in people with SCD or thalassaemia.
SEARCH METHODS
We searched CENTRAL (Cochrane Library), MEDLINE, PubMed, Embase, CINAHL, PsycINFO, ProQuest Dissertations & Global Theses, Web of Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (13 December 2021). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (1 August 2022).
SELECTION CRITERIA
For trials comparing medications or medication changes, only randomised controlled trials (RCTs) were eligible for inclusion. For studies including psychological and psychosocial interventions, educational interventions, or multi-component interventions, non-randomised studies of interventions (NRSIs), controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion.
DATA COLLECTION AND ANALYSIS
For this update, two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 19 RCTs and one NRSI published between 1997 and 2021. One trial assessed medication management, one assessed an education intervention (NRSI) and 18 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral chelating agents, deferiprone and deferasirox. We rated the certainty of evidence as very low to low across all outcomes identified in this review. Four trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL. We identified nine comparisons of interest. 1. Deferiprone versus deferoxamine We are uncertain whether or not deferiprone affects adherence to iron chelation therapy (four RCTs, unpooled, very low-certainty evidence), all-cause mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.18 to 1.21; 3 RCTs, 376 participants; very low-certainty evidence), or serious adverse events (SAEs) (RR 1.43, 95% CI 0.83 to 2.46; 1 RCT, 228 participants; very low-certainty evidence). Adherence was reported as "good", "high" or "excellent" by all seven trials, though the data could not be analysed formally: adherence ranged from 69% to 95% (deferiprone, mean 86.6%), and 71% to 93% (deferoxamine, mean 78.8%), based on five trials (474 participants) only. 2. Deferasirox versus deferoxamine We are uncertain whether or not deferasirox affects adherence to iron chelation therapy (three RCTs, unpooled, very low-certainty evidence), although medication adherence was high in all trials. We are uncertain whether or not there is any difference between the drug therapies in serious adverse events (SAEs) (SCD or thalassaemia) or all-cause mortality (thalassaemia). 3. Deferiprone versus deferasirox We are uncertain if there is a difference between oral deferiprone and deferasirox based on a single trial in children (average age 9 to 10 years) with any hereditary haemoglobinopathy in adherence, SAEs and all-cause mortality. 4. Deferasirox film-coated tablet (FCT) versus deferasirox dispersible tablet (DT) One RCT compared deferasirox in different tablet forms. There may be a preference for FCTs, shown through a trend for greater adherence (RR 1.10, 95% CI 0.99 to 1.22; 1 RCT, 88 participants), although medication adherence was high in both groups (FCT 92.9%; DT 85.3%). We are uncertain if there is a benefit in chelation-related AEs with FCTs. We are uncertain if there is a difference in the incidence of SAEs, all-cause mortality or sustained adherence. 5. Deferiprone and deferoxamine combined versus deferiprone alone We are uncertain if there is a difference in adherence, though reporting was usually narrative as triallists report it was "excellent" in both groups (three RCTs, unpooled). We are uncertain if there is a difference in the incidence of SAEs and all-cause mortality. 6. Deferiprone and deferoxamine combined versus deferoxamine alone We are uncertain if there is a difference in adherence (four RCTs), SAEs (none reported in the trial period) and all-cause mortality (no deaths reported in the trial period). There was high adherence in all trials. 7. Deferiprone and deferoxamine combined versus deferiprone and deferasirox combined There may be a difference in favour of deferiprone and deferasirox (combined) in rates of adherence (RR 0.84, 95% CI 0.72 to 0.99) (one RCT), although it was high (> 80%) in both groups. We are uncertain if there is a difference in SAEs, and no deaths were reported in the trial, so we cannot draw conclusions based on these data (one RCT). 8. Medication management versus standard care We are uncertain if there is a difference in QoL (one RCT), and we could not assess adherence due to a lack of reporting in the control group. 9. Education versus standard care One quasi-experimental (NRSI) study could not be analysed due to the severe baseline confounding.
AUTHORS' CONCLUSIONS
The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects, though often follow-up was not good (high dropout over longer trials), with adherence based on a per protocol analysis. Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation. Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy. Due to lack of evidence this review cannot comment on intervention strategies for different age groups.
Topics: Child; Humans; Anemia, Sickle Cell; Chelating Agents; Chelation Therapy; Deferoxamine; Drug-Related Side Effects and Adverse Reactions; Iron; Thalassemia
PubMed: 36877640
DOI: 10.1002/14651858.CD012349.pub3