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Facial Plastic Surgery & Aesthetic... 2020There is controversy surrounding the management of orbital roof fractures. Guidelines with regard to when to operate and type of reconstruction are lacking....
There is controversy surrounding the management of orbital roof fractures. Guidelines with regard to when to operate and type of reconstruction are lacking. Categorizing these data will help clinicians make informed decisions about the management of orbital roof fractures and avoid preventable complications. To perform a systematic review evaluating underlying causes, associated complications, and management of orbital roof fractures including reconstructive options in the general population of children and adults. A systematic review using the PubMed, EmBase, Cochrane, and MEDLINE databases identified relevant studies for inclusion. Studies were included from 1987 to 2017. Demographics, symptoms, management, reconstruction, and outcomes were reported following preferred reporting items for systematic reviews and meta-analyses guidelines. Inclusion criteria included articles discussing management of traumatic orbital roof fractures across all ages. Included studies were assessed for level of evidence. Forty-seven studies encompassing 526 patients met inclusion criteria. There were 28 case reports, 15 retrospective case series and 4 retrospective cohort studies. The most common etiologies were motor vehicle accidents (39.5%), falls (30.3%), and assault (11.8%). Periorbital ecchymosis, exophthalmos, and dystopia were the most common initial symptoms. In total, 60.0% of patients underwent surgical repair and 40% of patients were managed conservatively. The most common surgical approach was bicoronal (94.8%), followed by a superolateral orbital rim approach and transpalpebral (5.1%). A variety of grafting materials were utilized, including titanium miniplates (46.2%), bone graft (37.7%), porous polyethylene (2.8%), and silastic implants (2.8%). Overall patients undergoing surgery were adults with clinical symptoms including exophthalmos, diplopia, and gaze restriction as well as patients with dura exposure. Most patients undergoing surgery were those with concomitant fractures. The most common fractures among the surgical patients were frontal bone (32.2%), ethmoid (25.2%), and zygomaticomaxillary complex/zygoma (12.2%). Management of orbital roof fractures varies based on individual clinical features including the presence of exophthalmos, gaze restriction, and concomitant injuries such as dural tears. Surgically, bicoronal approaches were performed most commonly along with reconstruction utilizing titanium miniplates. Conservative management was more common among the pediatric population. This systematic review demonstrates both conservative and surgical measures can lead to positive outcomes in appropriately selected patients.
Topics: Evidence-Based Medicine; Humans; Orbital Fractures; Practice Patterns, Physicians'; Plastic Surgery Procedures
PubMed: 32779938
DOI: 10.1089/fpsam.2020.0029 -
EJVES Vascular Forum 2023Calcification of vascular grafts, including polyethylene terephthalate (PET) and expanded polytetrafluoroethylene (ePTFE) grafts may contribute to graft failure, but is... (Review)
Review
OBJECTIVE
Calcification of vascular grafts, including polyethylene terephthalate (PET) and expanded polytetrafluoroethylene (ePTFE) grafts may contribute to graft failure, but is under reported. The aim of this study was to review the literature to assess whether vascular graft calcification is deleterious to vascular graft outcomes.
DATA SOURCES
The Medline and Embase databases were searched.
REVIEW METHODS
A systematic literature search according to PRISMA Guidelines was performed using a combined search strategy of MeSH terms. The MeSH terms used were "calcification, physiologic", "calcinosis", "vascular grafting", "blood vessel prosthesis", "polyethylene terephthalates", and "polytetrafluoroethylene".
RESULTS
The systematic search identified 17 cases of PET graft calcification and 73 cases of ePTFE graft calcification over a 35 year period. All cases of PET graft calcification were reported in grafts explanted for graft failure. The majority of cases of ePTFE graft calcification were unexpectedly noted in grafts used during cardiovascular procedures and subsequently removed.
CONCLUSION
Calcification of synthetic vascular grafts is under reported but can compromise the long term performance of the grafts. More data, including specific analysis of radiological findings as well as explant analysis are needed to obtain a more sensitive and specific analysis of the prevalence and incidence of vascular graft calcification and the impact of calcification on synthetic graft outcomes.
PubMed: 37416860
DOI: 10.1016/j.ejvsvf.2023.05.013 -
Cancer Treatment Reviews Jul 2023Although platinum-based chemotherapy (CT) is considered the standard treatment for relapsed platinum-sensitive ovarian cancer, there is currently no standard treatment... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Although platinum-based chemotherapy (CT) is considered the standard treatment for relapsed platinum-sensitive ovarian cancer, there is currently no standard treatment for these patients. We compared the effectiveness of modern and older therapies in relapsed platinum-sensitive, BRCA-wild type, and ovarian cancers using a network meta-analysis (NMA).
METHODS
A systematic search of PubMed, EMBASE, and Cochrane Library was performed up to October 31, 2022. Randomized controlled trials (RCT) that compared different second-line approaches were included. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS).
RESULTS
In total, 17 RCTs (n = 9405) comparing various strategies were included. The risk of death was significantly decreased with carboplatin + pegylated liposomal doxorubicin + bevacizumab compared to platinum-based doublet CT (hazard ratio [HR] = 0.59, 95%CI 0.35, 1). Various strategies, including secondary cytoreduction followed by platinum-based CT, carboplatin + pegylated liposomal doxorubicin + bevacizumab, and platinum-based CT with bevacizumab or cediranib, were better than platinum-based doublets alone for PFS.
CONCLUSIONS
This NMA showed that carboplatin + pegylated liposomal doxorubicin + bevacizumab seems to increase the efficacy of standard second-line CT. These strategies can be considered when treating patients with relapsed platinum-sensitive ovarian cancer without BRCA mutations. This study provides systematic comparative evidence for the efficacy of different second-line therapies for relapsed ovarian cancer.
Topics: Humans; Female; Network Meta-Analysis; Bevacizumab; Carboplatin; Neoplasm Recurrence, Local; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Doxorubicin; Platinum; Polyethylene Glycols; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37201444
DOI: 10.1016/j.ctrv.2023.102571 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
Journal of Functional Biomaterials Apr 2023The majority of patients strongly favor the use of aligners in the present time, especially with the advancement in esthetic dentistry. Today's market is flooded with... (Review)
Review
The majority of patients strongly favor the use of aligners in the present time, especially with the advancement in esthetic dentistry. Today's market is flooded with aligner companies, many of which share the same therapeutic ethos. We therefore carried out a systematic review and network meta-analysis to evaluate research that had looked at various aligner materials and attachments and their effect on orthodontic tooth movement in relevant studies. A total of 634 papers were discovered after a thorough search of online journals using keywords such as "Aligners", "Orthodontics", "Orthodontic attachments", "Orthodontic tooth movement", and "Polyethylene" across databases such as PubMed, Web of Science, and Cochrane. The authors individually and in parallel carried out the database investigation, removal of duplicate studies, data extraction, and bias risk. The statistical analysis demonstrated that the type of aligner material had a significant impact on orthodontic tooth movement. The low level of heterogeneity and significant overall effect further support this finding. However, there was little effect of attachment size or shape on tooth mobility. The examined materials were primarily concerned with influencing the physical/physicochemical characteristics of the appliances and not tooth movement directly. Invisalign (Inv) had a higher mean value than the other types of materials that were analyzed, which suggested a potentially greater impact on orthodontic tooth movement. However, its variance value indicated that there was also greater uncertainty associated with the estimate compared to some of the other plastics. These findings could have important implications for orthodontic treatment planning and aligner material selection. Registration: This review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42022381466).
PubMed: 37103299
DOI: 10.3390/jfb14040209 -
Digestive Diseases and Sciences Dec 2023The rate of adequate cleansing (ACR) and complete examinations (CR) are key quality indicators in capsule colonoscopy (CC) and pan-intestinal capsule endoscopy (PCE). (Meta-Analysis)
Meta-Analysis
BACKGROUND
The rate of adequate cleansing (ACR) and complete examinations (CR) are key quality indicators in capsule colonoscopy (CC) and pan-intestinal capsule endoscopy (PCE).
AIMS
To evaluate the efficacy of bowel preparation protocols regarding ACR and CR.
METHODS
We conducted a systematic review and meta-analysis, search terms regarding colon capsule preparation, publication date from 2006/01, and date of search 2021/12, in six bibliographic databases. Multiple steps of the cleansing protocol were assessed: diet, adjunctive laxatives, purgative solution, use of prokinetic agents, and "booster". The meta-analytical frequency of ACR and CR was estimated, and subgroup analyses performed. Strategies associated with higher ACR and CR were explored using meta-analytical univariable and multivariable regression models.
RESULTS
Twenty-six observational studies and five RCTs included (n = 4072 patients). The pooled rate of ACR was 72.5% (95% C.I. 67.8-77.5%; I = 92.4%), and the pooled rate of CR was 83.0% (95% C.I. 78.7-87.7%; I = 96.5%). The highest ACR were obtained using a low-fibre diet [78.5% (95% C.I. 72.0-85.6%); I = 57.0%], adjunctive laxatives [74.7% (95% C.I. 69.8-80.1%); I = 85.3%], and split dose < 4L polyethylene glycol (PEG) as purgative [77.5% (95% C.I. 68.4-87.8%); I = 47.3%]. The highest CR were observed using routine prokinetics prior to capsule ingestion [84.4% (95% C.I. 79.9-89.2%); I = 89.8%], and sodium phosphate (NaP) as "booster" [86.2% (95% C.I. 82.3-90.2%); I = 86.8%]. In univariable models, adjunctive laxatives were associated with higher ACR [OR 1.81 (95% C.I. 1.13; 2.90); p = 0.014]. CR was higher with routine prokinetics [OR 1.86 (95% C.I. 1.13; 3.05); p = 0.015] and split-dose PEG purgative [OR 2.03 (95% C.I. 1.01; 4.09), p = 0.048].
CONCLUSIONS
Main quality outcomes (ACR, CR) remain suboptimal for CC and PCE. Despite considerable heterogeneity, our results support low-fibre diet, use of adjunctive sennosides, split dose < 4L PEG, and routine prokinetics, while NaP remains the most consistent option as booster.
Topics: Humans; Cathartics; Laxatives; Capsule Endoscopy; Colonoscopy; Polyethylene Glycols
PubMed: 37833441
DOI: 10.1007/s10620-023-08133-7 -
Scientific Reports Nov 2023Polyethylene glycol loxenatide (PEX168) is a novel glucagon-like peptide-1 receptor agonist with a longer half-life developed by modifying the chemical structure of... (Meta-Analysis)
Meta-Analysis
Polyethylene glycol loxenatide (PEX168) is a novel glucagon-like peptide-1 receptor agonist with a longer half-life developed by modifying the chemical structure of exenatide. This study aims to assess the efficacy and safety of PEX168 and determine the best dose. We searched PubMed, Scopus, Cochrane Library, and Web of Science databases from inception to April 25, 2023, for randomized controlled trials (RCTs) comparing PEX168 therapy alone or in combination with metformin versus other therapies. We used the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CI). Six RCTs, including 1248 participants, were included. PEX168 added to metformin was significantly better than metformin alone regarding fasting blood glucose (MD = -1.20, 95% CI (-1.78, - 0.62), p < 0.0001), HbA1c (MD = -1.01, 95% CI (-1.48, - 0.53), p < 0.0001), and postprandial glycemia (MD = -1.94, 95% CI (-2.99, - 0.90), p = 0.0003). Similarly, for glycemic control, PEX168 monotherapy was superior to placebo (P < 0.05). No significant effects were noticed in terms of triglycerides, low-density lipoprotein, or high-density lipoprotein (p > 0.05). Body weight was significantly reduced in obese diabetic patients receiving PEX168 compared to the control group (MD = -5.46, 95% CI (-7.90, - 3.01), p < 0.0001) but not in non-obese patients (MD = 0.06, 95% CI (-0.47, 0.59), p = 0.83). People who received PEX168 alone or with metformin showed more common gastrointestinal adverse effects, especially nausea and vomiting (p < 0.05). PEX168 100, 200, and 300 ug monotherapy demonstrated comparable safety and diabetes control to metformin, but when combined with metformin, PEX168 100 and 200 ug showed significant effects on diabetes control; however, only the latter showed a significantly higher incidence of nausea and vomiting (p < 0.05). PEX168 could be a viable option for treating diabetic patients whose metformin control is inadequate or who cannot tolerate metformin. PEX168 at 100 ug in combination with metformin was found to be safe and more effective compared to metformin; however, due to the small number of trials included, these findings should be interpreted with caution, and additional trials are required.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Metformin; Nausea; Randomized Controlled Trials as Topic; Vomiting
PubMed: 37923756
DOI: 10.1038/s41598-023-46274-x -
Digestive Endoscopy : Official Journal... Jul 2022We conducted a systematic review and meta-analysis of population-based studies to explore pooled prevalence and magnitude of electrolyte changes after bowel preparation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND STUDY AIMS
We conducted a systematic review and meta-analysis of population-based studies to explore pooled prevalence and magnitude of electrolyte changes after bowel preparation for colonoscopy based on the most recent guidelines.
PATIENTS AND METHODS
PubMed and Cochrane were queried for population-based studies examining changes in electrolyte values after bowel preparation, published by July 1, 2021. We report prevalences of serum hypokalemia, hyponatremia, hyperphosphatemia, and hypocalcemia after bowel preparation and changes in mean electrolyte values after vs. before bowel preparation using sodium phosphate (NaP) and polyethylene glycol (PEG).
RESULTS
Thirteen studies met the inclusion criteria; 2386 unique patients were included. Overall, hypokalemia was found in 17.2% (95% CI 6.7, 30.9) in the NaP group vs. 4.8% (95% CI 0.27, 13.02) in the PEG group. The magnitude of potassium decrease after NaP bowel preparation was significantly increased compared to PEG (mean difference -0.38; 95% CI -0.49 to -0.27, P < 0.001). No study reported on major complications.
CONCLUSIONS
Hypokalemia was found in 17.2% of patients after bowel preparation with NaP and in 4.8% of patients with PEG, a finding that is clinically relevant with respect to choosing the type of bowel preparation. The magnitude of the potassium decrease after NaP was significantly higher compared to PEG. These data provide the evidence that supports the recommendation of the European Society of Gastrointestinal Endoscopy against routine use of NaP for bowel preparation.
Topics: Cathartics; Colonoscopy; Electrolytes; Humans; Hypokalemia; Polyethylene Glycols; Potassium
PubMed: 35037327
DOI: 10.1111/den.14237 -
The Journal of Craniofacial SurgeryEar reconstruction is 1 of the most technically challenging sub-specialties of craniofacial and reconstructive plastic surgery. The reconstructive ear must not only... (Review)
Review
Ear reconstruction is 1 of the most technically challenging sub-specialties of craniofacial and reconstructive plastic surgery. The reconstructive ear must not only fulfil the requirement of being aesthetically pleasing but must also have good vascularity with a low complication rate. Several ear reconstructive techniques have been developed such as the autologous ear reconstruction technique using costal cartilage and ear reconstruction with high-density porous polyethylene or Medpor (Porex Surgical, Inc, College Park, GA). Autologous ear reconstructive techniques have advantages of durability and low infection rates however are associated with poorer aesthetic outcomes such as poor projection of the ear. Medpor has advantages of a more consistent three-dimensional definition without the need to harvest costochondral cartilage and create a donor site. However, due to its alloplastic material properties, Medpor has historically been reported as having a higher rate of extrusion and infection. This is the first systematic review to compare the outcomes of both techniques. The 6 studies that were reviewed were analyzed against 3 evaluative criteria: aesthetic outcome, complication rate, and convenience of intervention. This is so a comprehensive, evidence-based decision can be made by the surgeon and patient when ear reconstruction is required. The results showed heterogeneity in data and a lack of detailed descriptions of the assessment for aesthetic outcomes and convenience, hence were inconclusive. The results however showed that there were more complications with Medpor framework with 15% of total cases resulting in either extrusion or infection compared to 2% of autologous ear reconstruction framework.
Topics: Ear, External; Esthetics, Dental; Humans; Polyethylene; Polyethylenes; Plastic Surgery Procedures
PubMed: 34643598
DOI: 10.1097/SCS.0000000000008130 -
The Cochrane Database of Systematic... May 2023Asparaginase has played a crucial role in the improvement of survival in children with acute lymphoblastic leukaemia (ALL), which is the commonest cancer among children.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asparaginase has played a crucial role in the improvement of survival in children with acute lymphoblastic leukaemia (ALL), which is the commonest cancer among children. Survival rates have steadily increased over decades since the introduction of asparaginase to ALL therapy, and overall survival rates reach 90% with the best contemporary protocols. Currently, polyethylene glycolated native Escherichia coli-derived L-asparaginase (PEG-asparaginase) is the preferred first-line asparaginase preparation. Besides its clinical benefits, PEG-asparaginase is well known for severe toxicities. Agreement on the optimal dose, treatment duration, and frequency of administration has never been reached among clinicians.
OBJECTIVES
Primary objective To assess the effect of the number of PEG-asparaginase doses on survival and relapse in children and adolescents with ALL. Secondary objectives To assess the association between the number of doses of PEG-asparaginase and asparaginase-associated toxicities (e.g. hypersensitivity, thromboembolism, pancreatitis and osteonecrosis). To undertake a network meta-analysis at dose-level in order to generate rankings of the number of doses of PEG-asparaginase used in the treatment for ALL, according to their benefits (survival and relapse) and harms (toxicity).
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, Web of Science databases and three trials registers in November 2021, together with reference checking, citation searching and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing different PEG-asparaginase treatment regimens in children and adolescents (< 18 years of age) with first-line ALL treated with multiagent chemotherapy including PEG-asparaginase.
DATA COLLECTION AND ANALYSIS
Using a standardised data collection form, two review authors independently screened and selected studies, extracted data, assessed risk of bias for each outcome using a standardised tool (RoB 2.0) and assessed the certainty of evidence for each outcome using the GRADE approach. Primary outcomes included overall survival, event-free survival and leukaemic relapse. Secondary outcomes included asparaginase-associated toxicities (hypersensitivity, thromboembolism, pancreatitis, sinusoidal obstruction syndrome and osteonecrosis as well as overall asparaginase-associated toxicity). We conducted the review and performed the analyses in accordance with the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We included three RCTs in the review, and identified an additional four ongoing studies. We judged outcomes of two RCTs to be at low risk of bias in all the Cochrane risk of bias (RoB 2) domains. We rated the remaining study as having some concerns regarding bias. Due to concerns about imprecision, we rated all outcomes as having low- to moderate-certainty evidence. One study compared intermittent PEG-asparaginase treatment (eight doses of PEG-asparaginase, 1000 IU/m, intramuscular (IM) administration) versus continuous PEG-asparaginase treatment (15 doses of PEG-asparaginase, 1000 IU/m, IM) in 625 participants with non-high risk ALL aged 1.0 to 17.9 years. We found that treatment with eight doses probably results in little to no difference in event-free survival compared to treatment with 15 doses (RR 1.01, 95% CI 0.97 to 1.06; moderate-certainty evidence). Compared to treatment with 15 doses, treatment with eight doses may result in either no difference or a slight reduction in hypersensitivity (RR 0.64, 95% CI 0.21 to 1.93; low-certainty evidence), thromboembolism (RR 0.55, 95% CI 0.22 to 1.36; low-certainty evidence) or osteonecrosis (RR 0.68, 95% CI 0.35 to 1.32; low-certainty evidence). Furthermore, we found that treatment with eight doses probably reduces pancreatitis (RR 0.31, 95% CI 0.12 to 0.75; moderate-certainty evidence) and asparaginase-associated toxicity (RR 0.53, 95% CI 0.35 to 0.78; moderate-certainty evidence) compared to treatment with 15 doses. One study compared low-risk standard treatment with additional PEG-asparaginase (six doses, 2500 IU/m, IM) versus low-risk standard treatment (two doses, 2500 IU/m, IM) in 1857 participants aged one to nine years old with standard low-risk ALL. We found that, compared to treatment with two doses, treatment with six doses probably results in little to no difference in overall survival (RR 0.99, 95% CI 0.98 to 1.00; moderate-certainty evidence) and event-free survival (RR 1.01, 95% CI 0.99 to 1.04; moderate-certainty evidence), and may result in either no difference or a slight increase in osteonecrosis (RR 1.65, 95% CI 0.91 to 3.00; low-certainty evidence). Furthermore, we found that treatment with six doses probably increases hypersensitivity (RR 12.05, 95% CI 5.27 to 27.58; moderate-certainty evidence), pancreatitis (RR 4.84, 95% CI 2.15 to 10.85; moderate-certainty evidence) and asparaginase-associated toxicity (RR 4.49, 95% CI 3.05 to 6.59; moderate-certainty evidence) compared to treatment with two doses. One trial compared calaspargase (11 doses, 2500 IU/m, intravenous (IV)) versus PEG-asparaginase (16 doses, 2500 IU/m, IV) in 239 participants aged one to 21 years with standard- and high-risk ALL and lymphoblastic lymphoma. We found that treatment with 11 doses of calaspargase probably results in little to no difference in event-free survival compared to treatment with 16 doses of PEG-asparaginase (RR 1.06, 95% CI 0.97 to 1.16; moderate-certainty evidence). However, treatment with 11 doses of calaspargase probably reduces leukaemic relapse compared to treatment with 16 doses of PEG-asparaginase (RR 0.32, 95% CI 0.12 to 0.83; moderate-certainty evidence). Furthermore, we found that treatment with 11 doses of calaspargase results in either no difference or a slight reduction in hypersensitivity (RR 1.17, 95% CI 0.64 to 2.13; low-certainty evidence), pancreatitis (RR 0.85, 95% CI 0.47 to 1.52; low-certainty evidence), thromboembolism (RR 0.83, 95% CI 0.48 to 1.42; low-certainty evidence), osteonecrosis (RR 0.63, 95% CI 0.15 to 2.56; low-certainty evidence) and asparaginase-associated toxicity (RR 1.00, 95% CI 0.71 to 1.40; low-certainty evidence) compared to treatment with 16 doses of PEG-asparaginase.
AUTHORS' CONCLUSIONS
We were not able to conduct a network meta-analysis, and could not draw clear conclusions because it was not possible to rank the interventions. Overall, we found that different numbers of doses of PEG-asparaginase probably result in little to no difference in event-free survival across all studies. In two studies, we found that a higher number of PEG-asparaginase doses probably increases pancreatitis and asparaginase-associated toxicities.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Asparaginase; Neoplasm Recurrence, Local; Network Meta-Analysis; Pancreatitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Systematic Reviews as Topic; Thromboembolism; Recurrence
PubMed: 37260073
DOI: 10.1002/14651858.CD014570.pub2