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.
OBJECTIVE: To assess the learning curve of a dual attending surgeon strategy in severe adolescent idiopathic scoliosis patients.
SUMMARY OF BACKGROUND DATA: The advantages of a dual attending surgeon strategy in improving the perioperative outcome in scoliosis surgery had been reported. However, the learning curve of this strategy in severe scoliosis had not been widely studied.
METHODS: A total of 105 patients with adolescent idiopathic scoliosis with Cobb angle of 90° or greater, who underwent posterior spinal fusion using a dual attending surgeon strategy were recruited. Primary outcomes were operative time, total blood loss, allogeneic blood transfusion requirement, length of hospital stay from time of operation and perioperative complications. Cases were sorted chronologically into group 1: cases 1 to 35, group 2: cases 36 to 70, and group 3: case 71 to 105. Mean operative time (≤193.3 min), total blood loss (≤1612.2 mL), combination of both and allogeneic blood transfusion were the selected criteria for receiver operating characteristic analysis of the learning curve.
RESULTS: The mean Cobb angle was 104.5° ± 12.3°. The operative time, total blood loss, and allogeneic blood transfusion requirement reduced significantly for group 1 (220.6 ± 54.8 min; 2011.3 ± 881.8 mL; 12 cases) versus group 2 (183.6 ± 36.7 min; 1481.6 ± 1035.5 mL; 3 cases) and group 1 versus group 3 (175.6 ± 38.4 min; 1343.7 ± 477.8 mL; 3 cases) (P blood loss) (area under the curve 0.740; P blood loss when comparing group 1 versus group 2 and group 1 versus group 3. The cut-off point for the learning curve was 57 cases when the preset criteria were fulfilled (≤193.3 min operative time and ≤1612.2 mL of total blood loss).Level of Evidence: 4.
Purpose: To report the perioperative and radiological outcomes of single-stage posterior passive correction and fusion (SSPPCF) in adolescent patients who present with congenital scoliosis.
Overview of Literature: The surgical treatment for congenital scoliosis is complex. There is no definitive guide on surgical options for skeletally matured adolescent patients who have congenital scoliosis.
Methods: Patients with congenital scoliosis who underwent SSPPCF using a pedicle screw system were reviewed. We identified the following three surgical indications: (1) hemivertebra or wedge vertebra over the thoracic or thoracolumbar region with structural lumbar curves, (2) hemivertebra or wedge vertebra at the lumbar region with significant pelvic obliquity or sacral slanting, and (3) mixed or complex congenital scoliosis. The demographic, perioperative, and radiographic data of these patients were collected.
Results: Thirty-four patients were reviewed. The mean patient age was 14.6±3.4 years. There were 13 hemivertebrae, three wedged vertebrae, two butterfly vertebrae, three hemivertebrae with butterfly vertebra, eight unsegmented bars, and five multiple complex lesions. The average surgical duration was 219.4±68.8 minutes. The average blood loss was 1,208.4±763.5 mL. Seven patients required allogeneic blood transfusion. The mean hospital stay duration was 6.1±2.5 days. The complication rate was 11.8% (4/34): one patient had severe blood loss, one had rod breakage, and two had distal adding-on. The Cobb angle reduced from 65.9°±17.4° to 36.3°±15.3° (p<0.001) with a correction rate (CR) of 44.8%±17.4%. The regional kyphotic angle decreased from 39.9°±20.5° to 27.5°±13.9° (p=0.001) with a CR of 19.3%±49.6%. Radiographic parameters (radiographic shoulder height, clavicle angle, T1 tilt, cervical axis, pelvic obliquity, coronal balance, and apical vertebral translation) showed significant improvement postoperatively.
Conclusions: SSPPCF was a feasible option for adolescent patients with congenital scoliosis who were skeletally matured.
METHODS: The total lifetime cost per TDT patient (TC1) is the sum of lifetime healthcare cost (TC2) and lifetime patient and family healthcare expenditure (TC3). TC2 was simulated using the Markov model, taking into account all costs subsidized by the government, and TC3 was estimated through a cross-sectional health survey approach. A survey was performed using a two-stage sampling method in 13 thalassaemia centres covering all regions in Malaysia.
RESULTS: A TDT patient is expected to incur TC2 of USD 561,208. ICT was the main driver of cost and accounted for 56.9% of the total cost followed by blood transfusion cost at 13.1%. TC3 was estimated to be USD 45,458. Therefore, the estimated TC1 of a TDT patient was USD 606,665. Sensitivity analyses showed that if all patients were prescribed oral ICT deferasirox for their lifetime, the total healthcare cost would increase by approximately 65%. Frequency of visits to health facilities for blood transfusion/routine monitoring and patients who were prescribed desferrioxamine were observed to be factors affecting patient and family monthly expenses.
CONCLUSION: The lifetime cost per TDT patient was USD 606,665, and this result may be useful for national health allocation planning. An estimation of the economic burden will provide additional information to decision makers on implementing prevention interventions to reduce the number of new births and medical service reimbursement.
Methods: The initial part of this study is a descriptive cross-sectional study involving data collection from all requests sent for group, screen, and hold (GSH) and group and cross match (GXM) tests from 2011 to 2017. The association between sociodemographic, workplace, and experience factors with near-miss events amongst HO was analyzed with a case-control study using logistic regression.
Results: We reported 83 near-miss events with a prevalence of 0.034% (95% confidence interval 0.027-0.042). The rate of near-miss events was one in every 2916 requests. The mean reporting rate was 11.9 events per year. Clinical near miss predominated at 89.2% compared to 10.8% laboratory near miss. Mislabeled events (33.7%) were more than miscollected events (10.8%). HO were implicated with most events (83.1%). Most events were predominantly in the medical and obstetrics and gynecology wards amounting to 31.3% each. We found a significant association between the ages of HO with near-miss events.
Conclusions: The prevalence of near-miss events in our hospital was relatively low. Our study has shown areas for improvement include improving sampling practices in clinical areas, adequate training of laboratory technicians, and providing proper transfusion education. Interventions such as encouraging compliance to guidelines and training in clinical and laboratory areas to minimize the risk of mistransfusion should be considered.
METHODS: A cross-sectional survey using the EQ-5D-3L instrument was conducted between May to September 2018 across various public hospitals in Malaysia. Using a multi-stage sampling, patients diagnosed with TDT and receiving iron chelating therapy were sampled. The findings on the EQ-5D-3L survey were converted into utility values using local tariff values. A two-part model was used to examine and derive the HSUVs associated with the treatment and complications of iron overload in TDT.
RESULTS: A total of 585 patients were surveyed. The unadjusted mean (SD) EQ-5D-3L utility value for TDT patients were 0.893 (0.167) while mean (SD) EQ VAS score was 81.22 (16.92). Patients who had more than two iron overload complications had a significant decline in HRQoL. Patients who were on oral monotherapy had a higher utility value of 0.9180 compared to other regimen combinations.
CONCLUSION: Lower EQ-5D-3L utility values were associated with patients who developed iron overload complications and were on multiple iron chelating agents. Emphasizing compliance to iron chelating therapy to prevent the development of complications is crucial in the effort to preserve the HRQoL of TDT patients.
Methods: Donated blood units were assessed for the presence or absence of HBV, HCV, and HIV using two screening method: serology and NAT. Reactive blood samples were then subjected to serological confirmatory and NAT discriminatory assays.
Results: A total of 9669 donors were recruited from September 2017 to June 2018. Among these, 36 donors were reactive either for HBV, HCV, or HIV by serological testing and eight by NAT screening. However, only 10 (three for HBV and seven for HCV) donors tested positive using serological testing and five (two for HBV and three for HCV) by NAT discriminatory assays. Note that all five NAT positive donors detected in the NAT discriminatory assays were confirmed to be serologically reactive. Therefore, the prevalence of HBV, HCV, and HIV was 0.03%, 0.1%, and 0.0%, respectively, in our donor pool.
Conclusions: Both serological and NAT screening and confirmatory assays should be used routinely to reduce the risk of infection transmission via the transfusion of blood and blood components.
Methods: We conducted a cross-sectional study over one year from January to December 2018 in the Transfusion Medicine Unit, Hospital Universiti Sains Malaysia. A total of 249 samples were recruited from CKD patients who received a blood transfusion (at least one-pint), which only match for ABO and Rh(D) antigen. The serum was screened for the presence of the RBC antibody using the gel agglutination technique (Diamed gel cards). Samples with positive antibody screening were subjected to antibody identification.
Results: Of the 249 transfused CKD patients, 31 (12.4%) developed RBC immunization. Thirty (12%) were alloimmunized, and one (0.4%) was autoimmunized. Anti-Mia was the most common antibody (n = 14, 46.7%) among alloantibodies, followed by anti-E (n = 7, 23.3%). There was a significant association between pregnancy history with the development of antibodies whereas, no significant association was found between sociodemographic background, stage of CKD, hemodialysis status, underlying medical illness, and number of packed cell transfusions with the development of RBC antibodies.
Conclusions: One-eighth of our patient cohort had RBC alloimmunization, and the risk was increased in patients with a history of pregnancy. We propose Rhesus RBC phenotyping and to supply blood match Rhesus antigen in CKD patients, especially patients of reproductive age.
OBJECTIVE: To investigate whether menses affect intraoperative blood loss in female adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF) surgeries.
SUMMARY OF BACKGROUND DATA: There were concerns whether patients having menses will have higher intraoperative blood loss if surgery were to be done during this period.
METHODS: This study included 372 females who were operated between May 2016 to May 2019. Fifty-five patients had menses during surgery (Group 1, G1) and 317 patients did not have menses during surgery (Group 2, G2). Propensity score matching (PSM) analysis with one-to-one, nearest neighbor matching technique and with a match tolerance of 0.001 was used. The main outcome measures were intraoperative blood loss (IBL), volume of blood salvaged, transfusion rate, preoperative hemoglobin, preoperative platelet, preoperative prothrombin time, preoperative activated partial thromboplastin time (APTT), international normalized ratio (INR), and postoperative hemoglobin. Postoperative Cobb angle and correction rate were also documented.
RESULTS: At the end of PSM analysis, 46 patients from each group were matched and balanced. The average operation duration for G1 was 140.8 ± 43.0 minutes compared with 143.1 ± 48.3 minutes in G2 (P = 0.806). The intraoperative blood loss for G1 was 904.3 ± 496.3 mL and for G2 was 907.9 ± 482.8 mL (P = 0.972). There was no significant difference in terms of normalized blood loss (NBL), volume of blood salvaged during surgery, preoperative hemoglobin, postoperative hemoglobin, hemoglobin drift, estimated blood volume (EBV), IBL per EBV and IBL per level fused (P > 0.05). No postoperative complications were encountered in both groups. On average, the postoperative hospital stay was 3.5 ± 0.8 days for both groups (P = 0.143).
CONCLUSION: Performing corrective surgery during the menstrual phase in female AIS patients is safe without risk of increased blood loss.
LEVEL OF EVIDENCE: 4.
METHODOLOGY: This is a retrospective cohort study recruiting all kidney transplant recipients in South Australia from January 2010 till December 2018. Following that, the incidence of blood transfusion within one week post-operatively were traced (transfusion group). The outcomes were compared with all other transplant recipients (non-transfusion group). Recipient's demographic, donor characteristics and immunological risk profiles were obtained from the transplant unit database, while the biopsy report, history of blood transfusion, latest serum creatinine and follow-up status was gathered from the electronic medical system (OASIS). The HLA-DSA and HLA-Ab results were collected from the NOMS database. Finally, the survival data were merged with the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for South Australia recipients graft survival.
RESULTS: A total of 699 patients were eligible for analysis. The mean age was 50.64 ± 13.23 years old. There were more elderly (>65 years old) and females who needed transfusion. The majority had glomerulonephritis as the primary disease. There was no statistical difference in donor characteristics, cold ischemic time and immunological risk between the transfusion and non-transfusion group. There was no difference in the development of de novo HLA-DSA, HLA-Ab and rejection episodes between the group and the results were consistent in a model adjusted for all potential confounders. Median graft survival in days between the transfusion vs non-transfusion group was 1845 IQR (961,2430) and 1250 IQR (672,2013).
CONCLUSION: Blood transfusion under strong immunosuppressive cover within a one-week post-operative period is safe with no significant association with the development of de novo HLA-DSA, HLA-Ab or clinical rejection.
DESIGN: Data were extracted from the Malaysian Thalassaemia Registry, a web-based system accessible to enrolled users through www.mytalasemia.net.my.
SETTING: The Malaysian Thalassaemia Registry data was recorded from reports obtained from 110 participating government and university hospitals in Malaysia.
PARTICIPANTS: The patients were those attending the 110 participating hospitals for thalassaemia treatment.
INTERVENTION: Data were collected from the Malaysian Thalassaemia Registry from 2007 until the fourth quarter of 2018.
PRIMARY OUTCOME MEASURE: 7984 out of 8681 patients with thalassaemia registered in the Malaysian Thalassaemia Registry were reported alive.
RESULTS: Majority of the patients were reported in the state of Sabah (22.72%); the largest age group affected was 5.0-24.9 years old (64.45%); the largest ethnic group involved was Malay (63.95%); and the major diagnosis was haemoglobin E/β-thalassaemia (34.37%). From the 7984 patients, 56.73% were on regular blood transfusions and 61.72% were on chelation therapy. A small fraction (14.23%) has undergone splenectomy, while the percentage of patients with severe iron overload (serum ferritin ≥5000 µg/L) reduced over time. However, cardiac complications are still the main cause of death in patients with thalassaemia.
CONCLUSION: Data gathered into the registry can be used to understand the progression of the disorder, to monitor iron overload management and to improve the outcomes of treatment, to enhance preventive strategies, reduce healthcare burden and improve the quality of life. Sustainability of the Malaysian Thalassaemia Registry is important for surveillance of thalassaemia management in the country and help the national health authorities to develop more effective policies.
OBJECTIVE: To compare the perioperative outcome between after-hours and daytime surgery carried out by a dedicated spinal deformity team for severe Idiopathic Scoliosis (IS) patients with Cobb angle ≥ 90°.
SUMMARY OF BACKGROUND DATA: There were concerns that after-hours corrective surgeries in severe IS have higher morbidity compared to daytime surgeries.
METHODS: Seventy-one severe IS patients who underwent single-staged Posterior Spinal Fusion (PSF) were included. Surgeries performed between 08:00H and 16:59H were classified as "daytime" group and surgeries performed between 17:00H and 06:00H were classified as "after-hours" group. Perioperative outcome parameters were average operation start time and end time, operation duration, intraoperative blood loss, intraoperative hemodynamic parameters, preoperative and postoperative hemoglobin, blood transfusion rate, total patient-controlled anesthesia (PCA) morphine usage, length of postoperative hospitalization, and complications. Radiological variables assessed were preoperative and postoperative Cobb angle, side bending flexibility, number of fusion levels, number of screws used, Correction Rate, and Side Bending Correction Index.
RESULTS: Thirty patients were operated during daytime and 41 patients were operated after-hours. The mean age was 16.1 ± 5.8 years old. The mean operation start time for daytime group was 11:31 ± 2:45H versus 19:10 ± 1:24H for after-hours group. There were no significant differences between both groups in the operation duration, intraoperative blood loss, intraoperative hemodynamic parameters, postoperative hemoglobin, hemoglobin drift, transfusion rate, length of postoperative hospitalization, postoperative Cobb angle, Correction Rate, and Side Bending Correction Index. There were four complications (1 SSEP loss, 1 massive blood loss, and 2 superficial wound infections) with no difference between daytime and after-hours group.
CONCLUSION: After-hours elective spine deformity corrective surgeries in healthy ambulatory patients with severe IS performed by a dedicated spinal deformity team using dual attending surgeon strategy were as safe as those performed during daytime.
LEVEL OF EVIDENCE: 4.