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CNS Neuroscience & Therapeutics Feb 2024Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have examined the efficacy of using the iron-chelating agent Deferiprone (DFP) for patients with PD. We conducted this meta-analysis to summarize and synthesize evidence from published randomized controlled trials about the efficacy of DFP for PD patients.
METHODS
A comprehensive literature search of four electronic databases was performed, spanning until February 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan software. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS-III).
RESULTS
Three RCTs with 431 patients were included in this analysis. DFP did not significantly improve UPDRS-III score compared to placebo (Standardized mean difference -0.06, 95% CI [-0.69, 0.58], low certainty evidence). However, it significantly reduced iron accumulation in the substantia nigra, putamen, and caudate as measured by T2*-weighted MRI (with high certainty evidence).
CONCLUSION
Current evidence does not support the use of DFP in PD patients. Future disease-modification trials with better population selection, adjustment for concomitant medications, and long-term follow up are recommended.
Topics: Humans; Deferiprone; Parkinson Disease; Iron Chelating Agents; Iron; Substantia Nigra
PubMed: 38334258
DOI: 10.1111/cns.14607 -
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 -
Cureus Nov 2023Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an... (Review)
Review
Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an optimal chelating regimen. Deferasirox (DFX) and deferiprone (DFP) are two oral iron chelators, and combination usage demonstrated effectiveness as an alternative to monotherapies in patients with a limited response to monotherapy. The present systematic review aimed to assess the evidence regarding the outcomes of combined DFP and DFX in iron-overloaded patients. An online search was conducted in PubMed, Scopus, Web of Science, and CENTRAL databases. Interventional and observational studies that assessed the outcomes of combined DFP and DFX in iron-overloaded patients were included. Eleven studies (12 reports) were considered in this meta-analysis. The studies included dual iron chelation strategies for a number of diagnoses. Single-arm studies (n =7) showed a reduction of serum ferritin, which reached the level of statistical significance in three studies. Likewise, most studies reported a numerical reduction in liver iron concentration (LIC) and increased cardiac MRI-T2* values after chelating therapy. Alternatively, comparative studies showed no significant difference in post-treatment serum ferritin between DFX plus DFP and DFX/DFP plus deferoxamine (DFO). The adherence to combination therapy was good to average in nearly 66.7-100% of the patients across four studies. One study reported a poor adherence rate. The combined regimen was generally tolerable, with no reported incidence of serious adverse events among the included studies. In conclusion, the DFP and DFX combination is a safe and feasible option for iron overload patients with a limited response to monotherapy.
PubMed: 38058350
DOI: 10.7759/cureus.48276 -
Therapeutic Advances in Rare Disease 2022The rare inherited autosomal recessive disease Friedreich ataxia (FA) causes progressive neurodegenerative changes and disability in patients. A systematic literature... (Review)
Review
OBJECTIVES
The rare inherited autosomal recessive disease Friedreich ataxia (FA) causes progressive neurodegenerative changes and disability in patients. A systematic literature review (SLR) was carried out to understand and summarize the published efficacy and safety of therapeutic interventions in this disease.
METHODS
Database searches were carried out in MEDLINE, Embase, and Cochrane by two independent reviewers. In addition, trial registries and conference proceedings were hand-searched.
RESULTS
Thirty-two publications were deemed eligible according to PICOS criteria. Twenty-four publications detail randomized controlled trials. The most frequently identified therapeutic intervention was idebenone ( = 11), followed by recombinant erythropoietin ( = 6), omaveloxolone ( = 3), and amantadine hydrochloride ( = 2). Other therapeutic interventions were investigated in one publication: A0001, CoQ10, creatine, deferiprone, interferon-γ-1b, the L-carnitine levorotatory form of 5-hydroxytryptophan, luvadaxistat, resveratrol, RT001, and vatiquinone (EPI-743). These studies included patients from 8 to 73 years old, and disease duration varied from 4.7 to 19 years. Disease severity as per the mean GAA1 and GAA2 allele repeat length ranged from 350 to 930 and 620 to 987 nucleotides, respectively. Most frequently reported efficacy outcomes were the International Cooperative Ataxia Rating Scale (ICARS, = 10), the Friedreich Ataxia Rating Scale (modified FARS and FARS-neuro, = 12), the Scale for Assessment and Rating of Ataxia (SARA, = 7), and the Activities of Daily Living scale (ADL, = 8). Each of these assesses the severity of disability in FA patients. In many studies, patients with FA deteriorated according to these severity scales regardless of treatment, or inconclusive results were found. Generally, these therapeutic interventions were well-tolerated and safe. Serious adverse events were atrial fibrillation ( = 1), craniocerebral injury ( = 1), and ventricular tachycardia ( = 1).
CONCLUSION
Identified literature showed a considerable unmet need for therapeutic interventions that halt or slow the deteriorating nature of FA. Novel efficacious drugs should be investigated that aim to improve symptoms or slow disease progression.
PubMed: 37180421
DOI: 10.1177/26330040221139872 -
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 -
Cerebellum (London, England) Jun 2021Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural...
Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural hearing loss and pyramidal signs. There is no proven treatment and patients experience slow progression of symptoms. Iron-chelating agents have been suggested as a therapeutic option and deferiprone is suited as it crosses the blood-brain barrier. However, deferiprone is reported to have a 1-2% risk of agranulocytosis. We performed a systematic review on treatment of infratentorial superficial siderosis with deferiprone based on PRISMA guidelines. Studies were included if in English or an English language translation was available, were about human subjects and referred to patients with ataxia. Studies were excluded if they did not possess an English translation, included animal studies or did not have ataxia. Studies were excluded if they discussed cerebral amyloid angiopathy or siderosis of other regions. Eleven papers were included. We identified 69 patients. Seventeen patients (25%) discontinued the drug. The most encountered adverse effect was anaemia (21.7%). Neutropaenia was observed in 8.7% and agranulocytosis in 5.8% of patients. Clinically, response varied, and stability or improvement was seen across neurological domains in 6 studies while 5 showed a mixed response. On imaging, 13 (28.9%) patients improved, 24 (53.3%) stabilised and 8 (17.8%) deteriorated. A prospective international centralised register of patients should be developed to inform the design and conduct of a multicentre, placebo-controlled, randomised clinical trial to evaluate the efficacy of deferiprone. The evidence from this systematic review is that deferiprone is a promising intervention.
Topics: Animals; Deferiprone; Hemosiderin; Humans; Iron Chelating Agents; Randomized Controlled Trials as Topic; Siderosis
PubMed: 33409768
DOI: 10.1007/s12311-020-01222-7 -
Mediterranean Journal of Hematology and... 2019Deferoxamine (DFO) or Deferiprone (DFP) or Deferasirox (DFX) monotherapy and DFO and DFP combination therapy (DFO+DFP) were four commonly implemented now chelation... (Review)
Review
BACKGROUND
Deferoxamine (DFO) or Deferiprone (DFP) or Deferasirox (DFX) monotherapy and DFO and DFP combination therapy (DFO+DFP) were four commonly implemented now chelation regimens for the iron overloaded of β-thalassemia major. This systematic review aims to determine the cost-effectiveness of four chelation regimens and provide evidence for the rational use of chelation regimens for β-thalassemia major therapy in the clinic.
METHODS
A systematic literature search in MEDLINE, EMBASE, the Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, VIP Data, and WanFang Data was conducted in April 2018. In addition, a manual search was performed. Two researchers, working independently, selected the papers, extracted the data, and assessed the methodological quality of the included documents. Each included paper was evaluated using a checklist developed by Drummond .
RESULTS
The number of records was initially 968, and eight papers met the final eligibility criteria. All the included eight papers were cost-utility analyses, and their methodological quality was fair. In these eight papers, nineteen studies were present. Nine studies of DFX versus DFO had contradictory results. Out of the nineteen studies, three studies of DFX versus DFP established that using DFP was cost-effective. Three studies of DFP versus DFO proved that using DFP was cost-effective. One survey of DFO+DFP versus DFO found that using DFO was cost-effective. One study of DFO+DFP versus DFP found that using DFP was cost-effective. Moreover, there were two studies of DFO+DFP versus DFX, but we cannot be sure which one of two chelation regimens was cost-effective.
CONCLUSION
In brief, DFP is cost-effective, followed by DFO or DFX, when an iron chelator is to be used alone for β-thalassemia iron overload treatment. All studies that compared DFO+DFP with DFO (or DFP) monotherapy established that the DFO+DFP was not cost-effective. Existing studies about DFO+DFP versus DFX could not prove which one of two chelation regimens was cost-effective. However, due to the low number of DFO+DFP versus DFO (or DFP or DFX) monotherapy studies, more extensive, high-quality research is required for further analysis and confirmation of our findings. Moreover, the cost-effectiveness is not an absolute issue when in different countries (regions) the results are opposite for other countries (regions). As a result, the local/national context had a substantial influence on the results of the pharmacoeconomic evaluation.
PubMed: 31308912
DOI: 10.4084/MJHID.2019.036 -
The Cochrane Database of Systematic... May 2018Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia (who are transfusion-dependent or non-transfusion-dependent) are at risk of iron... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia (who are transfusion-dependent or non-transfusion-dependent) 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 well-being, which may affect adherence.
OBJECTIVES
To identify and assess the effectiveness of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) to improve adherence to iron chelation therapy in people with SCD or thalassaemia.
SEARCH METHODS
We searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, Psychology and Behavioral Sciences Collection, Web of Science Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (01 February 2017). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (12 December 2017).
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-RCTs, controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Three authors independently assessed trial eligibility, risk of bias and extracted data. The quality of the evidence was assessed using GRADE.
MAIN RESULTS
We included 16 RCTs (1525 participants) published between 1997 and 2017. Most participants had β-thalassaemia major; 195 had SCD and 88 had β-thalassaemia intermedia. Mean age ranged from 11 to 41 years. One trial was of medication management and 15 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral-chelating agents, deferiprone and deferasirox.We rated the quality of evidence as low to very low across all outcomes identified in this review.Three trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL.Deferiprone versus deferoxamineWe are uncertain whether deferiprone increases adherence to iron chelation therapy (four trials, very low-quality evidence). Results could not be combined due to considerable heterogeneity (participants' age and different medication regimens). Medication adherence was high (deferiprone (85% to 94.9%); deferoxamine (71.6% to 93%)).We are uncertain whether deferiprone increases the risk of agranulocytosis, risk ratio (RR) 7.88 (99% confidence interval (CI) 0.18 to 352.39); or has any effect on all-cause mortality, RR 0.44 (95% CI 0.12 to 1.63) (one trial; 88 participants; very low-quality evidence).Deferasirox versus deferoxamineWe are uncertain whether deferasirox increases adherence to iron chelation therapy, mean difference (MD) -1.40 (95% CI -3.66 to 0.86) (one trial; 197 participants; very-low quality evidence). Medication adherence was high (deferasirox (99%); deferoxamine (100%)). We are uncertain whether deferasirox decreases the risk of thalassaemia-related serious adverse events (SAEs), RR 0.95 (95% CI 0.41 to 2.17); or all-cause mortality, RR 0.96 (95% CI 0.06 to 15.06) (two trials; 240 participants; very low-quality evidence).We are uncertain whether deferasirox decreases the risk of SCD-related pain crises, RR 1.05 (95% CI 0.68 to 1.62); or other SCD-related SAEs, RR 1.08 (95% CI 0.77 to 1.51) (one trial; 195 participants; very low-quality evidence).Deferasirox film-coated tablet (FCT) versus deferasirox dispersible tablet (DT)Deferasirox FCT may make little or no difference to adherence, RR 1.10 (95% CI 0.99 to 1.22) (one trial; 173 participants; low-quality evidence). Medication adherence was high (FCT (92.9%); DT (85.3%)).We are uncertain if deferasirox FCT increases the incidence of SAEs, RR 1.22 (95% CI 0.62 to 2.37); or all-cause mortality, RR 2.97 (95% CI 0.12 to 71.81) (one trial; 173 participants; very low-quality evidence).Deferiprone and deferoxamine combined versus deferiprone alone We are uncertain if deferiprone and deferoxamine combined increases adherence to iron chelation therapy (very low-quality evidence). Medication adherence was high (deferiprone 92.7% (range 37% to 100%) to 93.6% (range 56% to 100%); deferoxamine 70.6% (range 25% to 100%).Combination therapy may make little or no difference to the risk of SAEs, RR 0.15 (95% CI 0.01 to 2.81) (one trial; 213 participants; low-quality evidence).We are uncertain if combination therapy decreases all-cause mortality, RR 0.77 (95% CI 0.18 to 3.35) (two trials; 237 participants; very low-quality evidence).Deferiprone and deferoxamine combined versus deferoxamine aloneDeferiprone and deferoxamine combined may have little or no effect on adherence to iron chelation therapy (four trials; 216 participants; low-quality evidence). Medication adherence was high (deferoxamine 91.4% to 96.1%; deferiprone: 82.4%)Deferiprone and deferoxamine combined, may have little or no difference in SAEs or mortality (low-quality evidence). No SAEs occurred in three trials and were not reported in one trial. No deaths occurred in two trials and were not reported in two trials.Deferiprone and deferoxamine combined versus deferiprone and deferasirox combinedDeferiprone and deferasirox combined may improve adherence to iron chelation therapy, RR 0.84 (95% CI 0.72 to 0.99) (one trial; 96 participants; low-quality evidence). Medication adherence was high (deferiprone and deferoxamine: 80%; deferiprone and deferasirox: 95%).We are uncertain if deferiprone and deferasirox decreases the incidence of SAEs, RR 1.00 (95% CI 0.06 to 15.53) (one trial; 96 participants; very low-quality evidence).There were no deaths in the trial (low-quality evidence).Medication management versus standard careWe are uncertain if medication management improves health-related QoL (one trial; 48 participants; very low-quality evidence). Adherence was only measured in one arm of the trial.
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.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: Adolescent; Adult; Anemia, Sickle Cell; Benzoates; Chelation Therapy; Child; Deferasirox; Deferiprone; Deferoxamine; Humans; Iron Chelating Agents; Iron Overload; Patient Compliance; Pyridones; Quality of Life; Randomized Controlled Trials as Topic; Triazoles; beta-Thalassemia
PubMed: 29737522
DOI: 10.1002/14651858.CD012349.pub2 -
American Journal of Hematology Jul 2018Red blood cell transfusions have become standard of care for the prevention of life-threatening anemia in patients with β-thalassemia and sickle cell disease (SCD)....
Red blood cell transfusions have become standard of care for the prevention of life-threatening anemia in patients with β-thalassemia and sickle cell disease (SCD). However, frequent transfusions can lead to accumulation of iron that can result in liver cirrhosis, diabetes mellitus, arthritis, arrhythmias, cardiomyopathy, heart failure, and hypogonadotropic hypogonadism. Iron chelation therapy has been shown to reduce serum ferritin levels and liver iron content, but limitations of trial design have prevented any demonstration of improved survival. The objective of this systematic review was to investigate the impact of iron chelation therapy on overall and event-free survival in patients with β-thalassemia and SCD. Eighteen articles discussing survival in β-thalassemia and 3 in SCD were identified. Overall iron chelation therapy resulted in better overall survival, especially if it is instituted early and compliance is maintained. Comparative studies did not show any significant differences between available iron chelation agents, although there is evidence that deferiprone is better tolerated than deferoxamine and that compliance is more readily maintained with the newer oral drugs, deferiprone and deferasirox. Iron chelation therapy, particularly the second-generation oral agents, appears to be associated with improved overall and event-free survival in transfusion-dependent patients with β-thalassemia and patients with SCD.
Topics: Anemia, Sickle Cell; Blood Transfusion; Deferiprone; Deferoxamine; Humans; Iron Chelating Agents; Medication Adherence; Survival Analysis; beta-Thalassemia
PubMed: 29635754
DOI: 10.1002/ajh.25103 -
Neurology Mar 2018To systematically review evidence regarding ataxia treatment.
Comprehensive systematic review summary: Treatment of cerebellar motor dysfunction and ataxia: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.
OBJECTIVE
To systematically review evidence regarding ataxia treatment.
METHODS
A comprehensive systematic review was performed according to American Academy of Neurology methodology.
CONCLUSIONS
For patients with episodic ataxia type 2, 4-aminopyridine 15 mg/d probably reduces ataxia attack frequency over 3 months (1 Class I study). For patients with ataxia of mixed etiology, riluzole probably improves ataxia signs at 8 weeks (1 Class I study). For patients with Friedreich ataxia or spinocerebellar ataxia (SCA), riluzole probably improves ataxia signs at 12 months (1 Class I study). For patients with SCA type 3, valproic acid 1,200 mg/d possibly improves ataxia at 12 weeks. For patients with spinocerebellar degeneration, thyrotropin-releasing hormone possibly improves some ataxia signs over 10 to 14 days (1 Class II study). For patients with SCA type 3 who are ambulatory, lithium probably does not improve signs of ataxia over 48 weeks (1 Class I study). For patients with Friedreich ataxia, deferiprone possibly worsens ataxia signs over 6 months (1 Class II study). Data are insufficient to support or refute the use of numerous agents. For nonpharmacologic options, in patients with degenerative ataxias, 4-week inpatient rehabilitation probably improves ataxia and function (1 Class I study); transcranial magnetic stimulation possibly improves cerebellar motor signs at 21 days (1 Class II study). For patients with multiple sclerosis-associated ataxia, the addition of pressure splints possibly has no additional benefit compared with neuromuscular rehabilitation alone (1 Class II study). Data are insufficient to support or refute use of stochastic whole-body vibration therapy (1 Class III study).
Topics: Ataxia; Cerebellar Diseases; Humans
PubMed: 29440566
DOI: 10.1212/WNL.0000000000005055