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.
MATERIALS AND METHODS: Major electronic databases were searched for randomized-controlled trials comparing carbetocin with oxytocin. Only trials involving cesarean deliveries were included. Non-randomized trials, non-cesarean deliveries, studies which did not directly compare carbetocin to oxytocin and studies which did not analyze the intended outcomes were excluded. Outcomes analysed were postpartum hemorrhage, additional use of uterotonic and transfusion requirement.
RESULTS: Seven studies involving 2012 patients were included in the meta-analysis. There was a significant reduction in the rates of postpartum hemorrhage (RR 0.79; 95% CI 0.66 to 0.94; p = 0.009), use of additional uterotonics (RR 0.57; 95% CI 0.49 to 0.65; p
OBJECTIVE: To evaluate the perioperative outcome of dual attending surgeon strategy for severe adolescent idiopathic scoliosis (AIS) patients with Cobb angle more than or equal to 90°.
SUMMARY OF BACKGROUND DATA: The overall complication rate for AIS remains significant and is higher in severe scoliosis. Various operative strategies had been reported for severe scoliosis. However the role of dual attending surgeon strategy in improving the perioperative outcome in severe scoliosis has not been investigated.
METHODS: The patients were stratified into two groups, Cobb angles 90° to 100° (Group 1) and more than 100° (Group 2). Demographic, intraoperative, preoperative, and postoperative day 2 data were collected. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay postsurgery, and documentation of any perioperative complications.
RESULTS: Eighty-five patients were recruited. The mean age for the whole cohort was 16.2 ± 5.2 years old. The mean age of Group 1 was 16.7 ± 5.7 and Group 2 was 15.6 ± 4.8 years old. The majority of the patients in both groups were Lenke 2 curves with the average Cobb angle of 93.9 ± 3.0° in Group 1 and 114.2 ± 10.2° in Group 2. The average operative time was 198.5 ± 47.5 minutes with an average blood loss of 1699.5 ± 939.3 mL. The allogeneic blood transfusion rate was 17.6%. The average length of stay postoperation was 71.6 ± 22.5 hours. When comparing the patients between Group 1 and Group 2, the operating time, total blood loss, allogeneic transfusion rate showed significant intergroup differences. Five complications were documented (one intraoperative seizure, one massive blood loss, one intraoperative loss of somatosensory evoked potential (SSEP) signal, and two superficial wound breakdown).
CONCLUSION: Dual attending surgeon strategy in severe AIS more than or equal to 90° demonstrated an average operative time of 199 minutes, intraoperative blood loss of 1.7 L, postoperative hospital stay of 71.6 hours, and a complication rate of 5.9% (5/85 patients). Curves with Cobb angle more than 100° lead to longer operating time, greater blood loss, and allogeneic transfusion rate.
LEVEL OF EVIDENCE: 4.
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.
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.
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.
METHODS: We reviewed all patients with TDT who had ≥ 8 blood transfusions per year. Patients who had a history of stem cell transplantation, concurrent autoimmune diseases or were newly diagnosed to have TDT were excluded. Standard diagnostic criteria were used in the diagnosis of various endocrine dysfunctions.
RESULTS: Of the 82 patients with TDT, 65% had at least one endocrine dysfunction. Short stature was the commonest (40.2%), followed by pubertal disorders (14.6%), hypoparathyroidism (12.3%), vitamin D deficiency (10.1%), hypocortisolism (7.3%), diabetes mellitus (5.2%) and overt hypothyroidism (4.9%). Subclinical hypothyroidism and pre-diabetes mellitus were seen in 13.4% and 8.6% of the patients, respectively. For children aged < 10 years, the prevalence of both thyroid dysfunction and hypoparathyroidism was 9.1%.
CONCLUSION: Two-thirds of children with TDT experienced at least one endocrine dysfunction. Thyroid dysfunction and hypoparathyroidism may be missed if endocrine screening is only performed in children with TDT > 10 years of age. Close monitoring for endocrine dysfunction and hormonal therapy is essential to prevent long-term adverse outcomes.