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Archives of Plastic Surgery May 2023Hemoglobinopathies such as sickle cell disease (SCD) are traditionally considered a relative contraindication to free tissue transfer, due to concerns that erythrocyte...
Hemoglobinopathies such as sickle cell disease (SCD) are traditionally considered a relative contraindication to free tissue transfer, due to concerns that erythrocyte sickling will increase the risk of microvascular thrombosis and flap failure. This article describes a case report with the successful use of free tissue transfer in a patient with SCD and provides a systematic literature review on free tissue transfer in SCD. A retrospective chart review was performed of a patient with SCD who underwent free tissue transfer at the authors' institution. A systematic literature review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using the keywords "free tissue transfer," "free flap," or "microsurgery" and "sickle cell" on PubMed, Ovid/Medline, and Scopus. A 29-year-old male with delayed presentation of an electrical burn to the face and scalp underwent wound closure with a free anterolateral thigh flap. Key management principles included red blood cell transfusion to keep hemoglobin S under 30% and hemoglobin greater than 10 g/dL, maintenance of hydration, normothermia, adequate analgesia, and postoperative anticoagulation. Systematic literature review identified 7 articles describing 13 cases of free tissue transfer in 10 patients with SCD, with combined complete free flap success in 10 of the 13 flaps. Free tissue transfer can be successfully performed in patients with SCD. However, evidence on the optimal management of this unique patient population in the perioperative period after free tissue transfer is limited to case reports in the literature.
PubMed: 37256042
DOI: 10.1055/s-0043-1763260 -
International Journal of Molecular... May 2023This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies,... (Review)
Review
This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies, leukodystrophies, lysosomal storage disorders and retinal dystrophies and extrapolated the key clinical findings to individuals with Rett syndrome (RTT). The PRISMA guidelines were used to search six databases during the last decade, followed by a thematic analysis to identify the emerging themes. Thematic analysis across the different disorders revealed four themes: (I) Therapeutic time window of gene therapy; (II) Administration and dosing strategies for gene therapy; (III) Methods of gene therapeutics and (IV) Future areas of clinical interest. Our synthesis of information has further enriched the current clinical evidence base and can assist in optimising gene therapy and gene editing studies in individuals with RTT, but it would also benefit when applied to other disorders. The findings suggest that gene therapies have better outcomes when the brain is not the primary target. Across different disorders, early intervention appears to be more critical, and targeting the pre-symptomatic stage might prevent symptom pathology. Intervention at later stages of disease progression may benefit by helping to clinically stabilise patients and preventing disease-related symptoms from worsening. If gene therapy or editing has the desired outcome, older patients would need concerted rehabilitation efforts to reverse their impairments. The timing of intervention and the administration route would be critical parameters for successful outcomes of gene therapy/editing trials in individuals with RTT. Current approaches also need to overcome the challenges of MeCP2 dosing, genotoxicity, transduction efficiencies and biodistribution.
Topics: Humans; Rett Syndrome; Gene Editing; Tissue Distribution; Methyl-CpG-Binding Protein 2; Brain; Genetic Therapy
PubMed: 37240368
DOI: 10.3390/ijms24109023 -
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 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 -
The Cochrane Database of Systematic... Feb 2023Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains... (Review)
Review
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life-long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence-based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.
OBJECTIVES
To assess different methods for treating dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.
MAIN RESULTS
We included one parallel-design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full-mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years. There is very low-certainty evidence from this trial that full-mouth ultrasonic scaling plus photodynamic therapy compared to full-mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia. We found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.
AUTHORS' CONCLUSIONS
Although the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review. This review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.
Topics: Male; Female; Humans; Thalassemia; Gingivitis
PubMed: 36732291
DOI: 10.1002/14651858.CD012969.pub3 -
The Cochrane Database of Systematic... Jan 2023Non-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of... (Review)
Review
BACKGROUND
Non-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDβT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use.
OBJECTIVES
To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDβT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 21 August 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDβT, quality of life and adverse events.
MAIN RESULTS
We included seven RCTs involving 291 people with NTDβT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved. HbF inducer against placebo or usual care Three HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI -0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001. Adverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP. HbF inducer versus another HbF inducer Four studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence). Different doses of the same HbF inducer Two studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD -2.39 g/dL, 95% CI -2.80 to -1.98; very low-certainty evidence; HbF: MD -10.20%, 95% CI -16.28% to -4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects. A combination of HbF inducers versus a single HbF inducer Two studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported. Hydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD -0.74 g/dL, 95% CI -1.45 to -0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions. We are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group. None of the comparisons reported the outcome of HbF.
AUTHORS' CONCLUSIONS
We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDβT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing.
Topics: Humans; beta-Thalassemia; Fetal Hemoglobin; Hydroxyurea; Resveratrol; Blood Transfusion
PubMed: 36637054
DOI: 10.1002/14651858.CD013767.pub2 -
The Indian Journal of Medical Research Aug 2022Sickle cell disease (SCD) constitutes frequently inherited haemoglobin disorders and poses a significant health burden in India. Hydroxyurea (HU), the most commonly used...
BACKGROUND & OBJECTIVES
Sickle cell disease (SCD) constitutes frequently inherited haemoglobin disorders and poses a significant health burden in India. Hydroxyurea (HU), the most commonly used drug, has shown promising results in the clinical management of SCD. The present systematic review was undertaken to assess the efficacy and toxicity of HU in Indian sickle cell patients.
METHODS
A systematic review of studies on HU therapy was conducted to identify the application of HU and its outcome(s) across India. PubMed, Scopus and Cochrane Library was used as data sources for various studies on the efficacy and toxicity of HU therapy for treatment for SCD in India published between January 2001 and October 2021. Two authors independently extracted the data on study design, patient characteristics and therapeutic outcomes of HU in order to determine the study quality of the present review.
RESULTS
Overall, 14 studies were included for a systematic analysis. Of these 11 were prospective, two cross-sectional and one double-blind randomized controlled trial. Low-dose HU (10 mg/kg/day) was found to reduce the rates of vaso-occlusive crisis and hospitalization as well as decreased the requirement of blood transfusion in SCD patients. The foetal haemoglobin (HbF) level was recorded in 13 (80%) studies all of whom reported an elevation in the HbF levels, with a mean increase in per cent HbF from 15.8 to 21.4 per cent across studies. The common adverse events were reversible, mild-to-moderate cytopenia and anaemia.
INTERPRETATION & CONCLUSIONS
The findings of the present review suggest that there is still insufficient information presently to determine the long-term or major adverse effects on organ damage, fertility as well as pregnancy on the use of HU therapy for SCD. Long-term multi-centric studies are thus required to address these problems.
Topics: Humans; Hydroxyurea; Antisickling Agents; Cross-Sectional Studies; Prospective Studies; Anemia, Sickle Cell; Randomized Controlled Trials as Topic
PubMed: 36629190
DOI: 10.4103/ijmr.ijmr_3447_21 -
Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.BMC Pregnancy and Childbirth Jan 2023Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past...
BACKGROUND
Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research.
METHODS
We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality.
RESULTS
We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks.
CONCLUSION
These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.
Topics: Female; Humans; Pregnancy; Erythroblastosis, Fetal; Hydrops Fetalis; Hemolysis; Blood Transfusion, Intrauterine; Fetus
PubMed: 36611144
DOI: 10.1186/s12884-022-05329-z