-
Expert Review of Hematology 2024To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM).
METHODS
Published clinical trials were searched in the Cochrane Library, PubMed, EMBASE to February 2023. The literature was screened and evaluated according to the inclusion criteria, and the data were analyzed by a random effect model. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and full grade or ≥ 3 adverse events (AEs) were the outcomes.
RESULTS
This study included 31 clinical trials, which included 4776 patients. The pooled ORR of the doublet regimens was 33.3% (95%CI: 27-39%) and the triplet regimens was 66% (95%CI: 58-74%). Among the 25 included studies, the median PFS was 8.29 months (95%CI: 7.27-9.31), and nine studies reported median OS of 19.43 months (95%CI: 14.56-24.30). In terms of safety, the most common hematologic AEs of grade ≥ 3 were neutropenia (41%) and anemia (20%); Non-hematologic AEs were pneumonia (14%) and infection/febrile neutropenia (14%).
CONCLUSIONS
Pomalidomide combined treatment regimens have shown good clinical efficacy, especially in pomalidomide + dexamethasone combined with other drugs. In terms of safety, it's important to pay attention to the likelihood of hematological adverse events when used clinically.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO: CRD42023420644.
Topics: Multiple Myeloma; Humans; Thalidomide; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Recurrence; Treatment Outcome
PubMed: 38421372
DOI: 10.1080/17474086.2024.2326219 -
Frontiers in Pediatrics 2024Prolonged mechanical ventilation, commonly used to assist preterm newborns, increases the risk of developing bronchopulmonary dysplasia (BPD). In recent decades, studies... (Review)
Review
INTRODUCTION
Prolonged mechanical ventilation, commonly used to assist preterm newborns, increases the risk of developing bronchopulmonary dysplasia (BPD). In recent decades, studies have demonstrated that systemic corticosteroids play a significant role in the prevention and management of BPD. In this systematic review of randomized controlled trials (RCTs), we evaluated the association between the administration of systemic corticosteroids in preterm infants and its long-term outcomes, such as neurodevelopment, growth, extubation rate, and related adverse effects.
METHODS
We conducted an electronic search in Medline, Scopus, and PubMed using the following terms: "premature infants" and "corticosteroids." We considered all RCTs published up to June 2023 as eligible. We included all studies involving preterm newborns treated with systemic corticosteroids and excluded studies on inhaled corticosteroids.
RESULTS
A total of 39 RCTs were evaluated. The influence of steroids administered systemically during the neonatal period on long-term neurological outcomes remains unknown, with no influence observed for long-term growth. The postnatal administration of systemic corticosteroids has been found to reduce the timing of extubation and improve respiratory outcomes. Dexamethasone appears to be more effective than hydrocortisone, despite causing a higher rate of systemic hypertension and hyperglycemia. However, in the majority of RCTs analyzed, there were no differences in the adverse effects related to postnatal corticosteroid administration.
CONCLUSION
Dexamethasone administered during the neonatal period appears to be more effective than hydrocortisone in terms of respiratory outcomes; however, caution should be taken when administering dexamethasone. Data derived from current evidence, including meta-analyses, are inconclusive on the long-term effects of the administration of systemic steroids in preterm infants or the possibility of neurodevelopmental consequences.
PubMed: 38419972
DOI: 10.3389/fped.2024.1344337 -
The Cochrane Database of Systematic... Feb 2024Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced... (Review)
Review
BACKGROUND
Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced mouth opening. OSF has a significant impact on eating and swallowing, affecting quality of life. There is an increased risk of oral malignancy in people with OSF. The main risk factor for OSF is areca nut chewing, and the mainstay of treatment has been behavioural interventions to support habit cessation. This review is an update of a version last published in 2008.
OBJECTIVES
To evaluate the benefits and harms of interventions for the management of oral submucous fibrosis.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 5 September 2022.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) of adults with a biopsy-confirmed diagnosis of OSF treated with systemic, locally delivered or topical drugs at any dosage, duration or delivery method compared against placebo or each other. We considered surgical procedures compared against other treatments or no active intervention. We also considered other interventions such as physiotherapy, ultrasound or alternative therapies.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. participant-reported resumption of normal eating, chewing and speech; 2. change or improvement in maximal mouth opening (interincisal distance); 3. improvement in range of jaw movement; 4. change in severity of oral/mucosal burning pain/sensation; 5.
ADVERSE EFFECTS
Our secondary outcomes were 6. quality of life; 7. postoperative discomfort or pain as a result of the intervention; 8. participant satisfaction; 9. hospital admission; 10. direct costs of medication, hospital bed days and any associated inpatient costs for the surgical interventions. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included 30 RCTs (2176 participants) in this updated review. We assessed one study at low risk of bias, five studies at unclear risk of bias and 24 studies at high risk of bias. We found diverse interventions, which we categorised according to putative mechanism of action. We present below our main findings for the comparison 'any intervention compared with placebo or no active treatment' (though most trials included habit cessation for all participants). Results for head-to-head comparisons of active interventions are presented in full in the main review. Any intervention versus placebo or no active treatment Participant-reported resumption of normal eating, chewing and speech No studies reported this outcome. Interincisal distance Antioxidants may increase mouth opening (indicated by interincisal distance (mm)) when measured at less than three months (mean difference (MD) 3.11 mm, 95% confidence interval (CI) 0.46 to 5.77; 2 studies, 520 participants; low-certainty evidence), and probably increase mouth opening slightly at three to six months (MD 8.83 mm, 95% CI 8.22 to 9.45; 3 studies, 620 participants; moderate-certainty evidence). Antioxidants may make no difference to interincisal distance at six-month follow-up or greater (MD -1.41 mm, 95% CI -5.74 to 2.92; 1 study, 90 participants; low-certainty evidence). Pentoxifylline may increase mouth opening slightly (MD 1.80 mm, 95% CI 1.02 to 2.58; 1 study, 106 participants; low-certainty evidence). However, it should be noted that these results are all less than 10 mm, which could be considered the minimal change that is meaningful to someone with oral submucous fibrosis. The evidence was very uncertain for all other interventions compared to placebo or no active treatment (intralesional dexamethasone injections, pentoxifylline, hydrocortisone plus hyaluronidase, physiotherapy). Burning sensation Antioxidants probably reduce burning sensation visual analogue scale (VAS) scores at less than three months (MD -30.92 mm, 95% CI -31.57 to -30.27; 1 study, 400 participants; moderate-certainty evidence), at three to six months (MD -70.82 mm, 95% CI -94.39 to -47.25; 2 studies, 500 participants; moderate-certainty evidence) and at more than six months (MD -27.60 mm, 95% CI -36.21 to -18.99; 1 study, 90 participants; moderate-certainty evidence). The evidence was very uncertain for the other interventions that were compared to placebo and measured burning sensation (intralesional dexamethasone, vasodilators). Adverse effects Fifteen studies reported adverse effects as an outcome. Six of these studies found no adverse effects. One study evaluating abdominal dermal fat graft reported serious adverse effects resulting in prolonged hospital stay for 3/30 participants. There were mild and transient general adverse effects to systemic drugs, such as dyspepsia, abdominal pain and bloating, gastritis and nausea, in studies evaluating vasodilators and antioxidants in particular.
AUTHORS' CONCLUSIONS
We found moderate-certainty evidence that antioxidants administered systemically probably improve mouth opening slightly at three to six months and improve burning sensation VAS scores up to and beyond six months. We found only low/very low-certainty evidence for all other comparisons and outcomes. There was insufficient evidence to make an informed judgement about potential adverse effects associated with any of these treatments. There was insufficient evidence to support or refute the effectiveness of the other interventions tested. High-quality, adequately powered intervention trials with a low risk of bias that compare biologically plausible treatments for OSF are needed. It is important that relevant participant-reported outcomes are evaluated.
Topics: Adult; Humans; Oral Submucous Fibrosis; Pentoxifylline; Drug-Related Side Effects and Adverse Reactions; Vasodilator Agents; Abdominal Pain; Antioxidants; Dexamethasone
PubMed: 38415846
DOI: 10.1002/14651858.CD007156.pub3 -
BMJ Open Feb 2024Postoperative nausea and vomiting (PONV) is a leading perioperative morbidity outcome following general anaesthesia. This systematic review aims to identify, appraise...
OBJECTIVES
Postoperative nausea and vomiting (PONV) is a leading perioperative morbidity outcome following general anaesthesia. This systematic review aims to identify, appraise and summarise the evidence synthesis studies of prophylactic interventions that reduce the incidence of paediatric PONV, thereby highlighting knowledge gaps and avenues of future research.
DESIGN
Systematic review using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews 2) tool and the ROBIS (Risk Of Bias In Systematic reviews) tool.
DATA SOURCES
Seven major databases, including MEDLINE and EMBASE, from inception to 23 September 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Evidence synthesis studies of only randomised controlled trials that explored prophylactic interventions for PONV in children undergoing general anaesthesia.
DATA EXTRACTION AND SYNTHESIS
Following screening process by two reviewers, data were extracted from all eligible studies, including demographic parameters and details of interventions. Eligible studies were categorised into 'pharmacological' and 'non-pharmacological' groups and high-risk surgical groups of 'strabismus' and 'tonsillectomy' for qualitative synthesis.
RESULTS
There were 20 evidence synthesis reviews (17 meta-analyses, 2 systematic reviews, 1 network meta-analysis): 14 investigated pharmacological PONV prophylaxis in children, 5 investigated non-pharmacological interventions, 1 studied both pharmacological and non-pharmacological interventions. Monotherapy pharmacological prophylaxis agents, for example, dexamethasone (relative risk (RR) 0.49, 95% CI 0.41 to 0.58), 5-hydroxytryptamine (5-HT) antagonists (OR 0.12, 95% CI 0.07 to 0.20) and α-adrenoreceptor agonists (dexmedetomidine: RR 0.33, 95% CI 0.21 to 0.54), are more effective than placebo. A combination of pharmacological agents provided superior efficacy to monotherapy, particularly dexamethasone and 5-HT antagonists (RR 0.21, 95% credible interval 0.15 to 0.28). Acustimulation practice was consistently favourable in preventing PONV compared with placebo (RR 0.36, 95% CI 0.25 to 0.52).
CONCLUSION
Monotherapy pharmacological prophylaxis is more effective than placebo in reducing the incidence of paediatric PONV, with the efficacy increased further by using combination pharmacotherapy. Further research must compare multiple treatment arms of pharmacological and non-pharmacological prophylaxes for PONV to identify the optimal multimodal prophylaxis regimen.
PROSPERO REGISTRATION NUMBER
CRD42021236698.
Topics: Child; Humans; Antiemetics; Dexamethasone; Incidence; Postoperative Nausea and Vomiting; Serotonin; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 38388499
DOI: 10.1136/bmjopen-2022-070775 -
Cureus Jan 2024Post-dural puncture headache (PDPH) is occasionally an inevitable side effect of neuraxial anesthesia, which can happen after spinal anesthesia or if an accidental dural... (Review)
Review
Post-dural puncture headache (PDPH) is occasionally an inevitable side effect of neuraxial anesthesia, which can happen after spinal anesthesia or if an accidental dural puncture (ADP) happens during epidural anesthesia. The treatment and prevention options for PDPH differ widely from one institution to another. The management of PDPH is heterogeneous in many institutions because of the absence of clear guidelines and protocols for the management of PDPH. This study aimed to summarize all articles published during the past decade that discussed the treatment or prevention of PDPH. From 2013 to 2023, 345 publications were filtered for all treatment and prevention approaches used for PDPH patients. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines were followed for conducting this systematic review, and 38 articles were included for analysis and review. Existing data come from small randomized clinical trials and retrospective or prospective cohort studies. This review supports the effect of oral pregabalin and intravenous aminophylline in both treatment and prevention. Intravenous mannitol, intravenous hydrocortisone, triple prophylactic regimen, and neostigmine plus atropine combination showed effective and beneficial outcomes. On the other hand, neither neuraxial morphine nor epidural dexamethasone showed promising results. Consequently, the use of neuraxial morphine or epidural dexamethasone for the prevention of PDPH remains questionable. Regarding the posture of the patient and its consequences on the incidence of the headache, lateral decubitus is better than a sitting position, and a prone position is better than a supine position. Smaller non-cutting needles play a role in avoiding PDPH. Minimally invasive nerve blocks, including sphenopalatine ganglion or greater occipital nerves, are satisfyingly effective. Epidural blood patches remain the more invasive but the gold standard and ultimate solution in patients resisting medical therapy. This study highlights the need for larger research to define the best approach to prevent and treat PDPH.
PubMed: 38361721
DOI: 10.7759/cureus.52330 -
Frontiers in Oncology 2024Since no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD)...
BACKGROUND
Since no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD) in the frontline treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM), this study systematically reviewed the clinical studies regarding immunotherapy with daratumumab and RVD regimen in the treatment of TIE-NDMM to explore the optimization direction of the best first-line therapy.
METHODS
The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to collect studies on regimens containing daratumumab or RVD/RVD-lite for TIE-NDMM. Pooled and meta-analysis was then performed to compare the overall response rate (ORR), stringent complete remission (sCR) and CR rate, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate between daratumumab-containing immunotherapy regimen and RVD/RVD-lite regimen by using R 4.3.1 software.
RESULTS
Nine prospective clinical trials were included, including 1795 TIE-NDMM or NDMM without intent for immediate ASCT. Among them, 938 patients were treated with daratumumab-based immunotherapy and 857 with RVD/RVD-lite regimens. Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P<0.01). The median PFS of the daratumumab-based and RVD/RVD-lite groups were 52.6 months and 35.1 months respectively (HR 0.77, 95%CI, 0.66-0.90). The median OS of both groups was not reached, and there were no significant differences in OS between the two groups (HR 1.03, 95%CI, 0.86-1.23). The therapy discontinuation rate led by adverse events was significantly higher in the RVD/RVD-lite group than in the daratumumab-based regimen group for the TIE-NDMM (16% vs. 7%, P=0.03).
CONCLUSION
This meta-analysis suggests that daratumumab-containing immunotherapy is superior to RVD in the depth of treatment efficacy, progression-free survival, and lower treatment-related discontinuation rates. Limited by the lack of head-to-head clinical trials, this conclusion needs to be verified by concurrent cohort studies.
PubMed: 38333688
DOI: 10.3389/fonc.2024.1286029 -
Cureus Jan 2024Diabetic macular edema (DME) is a significant condition linked to diabetes that can result in visual loss. In recent times, there has been a notable change in the desire... (Review)
Review
Comparative Efficacy of Anti-vascular Endothelial Growth Factor (Anti-VEGF) Agents and Corticosteroids in Managing Diabetic Retinopathy-Associated Diabetic Macular Edema: A Meta-Analysis and Comprehensive Systematic Review.
Diabetic macular edema (DME) is a significant condition linked to diabetes that can result in visual loss. In recent times, there has been a notable change in the desire for treatment, with a shift toward anti-vascular endothelial growth factor (anti-VEGF) therapy and intravitreal steroids while moving away from conventional laser therapies. This comprehensive meta-analysis explicitly compares the efficacy of two therapies for DME: anti-VEGF therapy and corticosteroid. We conducted a thorough search using PubMed and Google Scholar to identify publications that compare the effects of anti-VEGF therapy and corticosteroid implants on DME. Using Review Manager 5.0 (RevMan), we incorporated data from nine research studies, which involved a total of 877 people. The group was split into two factions: 453 patients were administered corticosteroids, while 466 patients underwent treatment with anti-VEGF therapy. Our investigation demonstrated that both corticosteroid and anti-VEGF therapy positively improved the best-corrected visual acuity (BCVA) and reduced the central macular thickness (CMT). Nevertheless, comparing the mean BCVA on the logarithm of the minimum angle of resolution (logMAR) scale revealed no statistically significant changes between the two treatments. This indicates considerable inconsistency, as evidenced by the weighted mean difference (WMD) of -0.13 (-0.41, 0.16) with a -value of 0.39 and an value of 99%. In addition, both treatments improved BCVA compared to the initial measurement. However, there was no statistically significant benefit for corticosteroid over anti-VEGF therapy, as indicated by the WMD of 0.03 (-0.07, 0.13) with a -value of 0.55 and an value of 80%. The examination of the average CMT also yielded findings that lacked statistical significance, displaying a significant amount of variation (WMD -36.37, 95% confidence interval [-127.52, 54.78], = 0.43, = 98%). Remarkably, there were no significant alterations among the anti-VEGF therapy group despite a rise in CMT from the initial measurement. The main conclusion drawn from our research is that corticosteroid demonstrates encouraging immediate enhancements in BCVA and CMT. However, anti-VEGF therapy seems to provide more significant long-term advantages. Nevertheless, it is crucial to acknowledge that the corticosteroid group had a greater susceptibility to acquiring elevated intraocular pressure (IOP) and the possibility of glaucoma.
PubMed: 38333510
DOI: 10.7759/cureus.51910 -
Frontiers in Pharmacology 2023This review of systematic reviews evaluated the effectiveness and safety of the preemptive use of anti-inflammatory and analgesic drugs in the management of...
This review of systematic reviews evaluated the effectiveness and safety of the preemptive use of anti-inflammatory and analgesic drugs in the management of postoperative pain, edema, and trismus in oral surgery. The databases searched included the Cochrane Library, MEDLINE, EMBASE, Epistemonikos, Scopus, Web of Science, and Virtual Health Library, up to March 2023. Pairs of reviewers independently selected the studies, extracted the data, and rated their methodological quality using the AMSTAR-2 tool. All of the 19 studies reviewed had at least two critical methodological flaws. Third molar surgery was the most common procedure ( = 15) and the oral route the most frequent approach ( = 14). The use of betamethasone (10, 20, and 60 mg), dexamethasone (4 and 8 mg), methylprednisolone (16, 20, 40, 60, 80, and 125 mg), and prednisolone (10 and 20 mg) by different routes and likewise of celecoxib (200 mg), diclofenac (25, 30, 50, 75, and 100 mg), etoricoxib (120 mg), ibuprofen (400 and 600 mg), ketorolac (30 mg), meloxicam (7.5, 10, and 15 mg), nimesulide (100 mg), and rofecoxib (50 mg) administered by oral, intramuscular, and intravenous routes were found to reduce pain, edema, and trismus in patients undergoing third molar surgery. Data on adverse effects were poorly reported. Further randomized clinical trials should be conducted to confirm these findings, given the wide variety of drugs, doses, and routes of administration used.
PubMed: 38328575
DOI: 10.3389/fphar.2023.1303382 -
Journal of Maxillofacial and Oral... Feb 2024The proponents of local route of Dexamethasone (DXM) administration for impacted mandibular 3rd molar (MM3) surgeries claim advantages over the traditional systemic... (Review)
Review
The Local Route of Administration of Dexamethasone in Impacted Mandibular Third Molar Surgery: A Systematic Review and Meta-analysis of Randomised Controlled Trials and a Critical Narrative Review on the Claimed Advantages of the Local Route.
INTRODUCTION
The proponents of local route of Dexamethasone (DXM) administration for impacted mandibular 3rd molar (MM3) surgeries claim advantages over the traditional systemic routes. This systematic review and meta-analysis were aimed to determine whether the route of perioperative administration of DXM influences the inflammatory outcomes of MM3 surgeries.
METHODOLOGY
An electronic database search over a 25 year period of randomised trials of DXM in MM3 surgeries was conducted. The mean differences or standardised mean differences were extracted and pooled using the fixed or random-effects model.
RESULTS
Of the sixteen selected trials, four were considered for a meta-analysis. There were no statistically significant differences in the inflammatory outcomes between the local and systemic routes of DXM.
CONCLUSION
The claimed advantages of the local route of DXM do not appear to be scientifically valid. Clinical trials supported with DXM plasma measurements are needed to confirm the absence of a systemic effect when DXM is administered locally.
PubMed: 38312984
DOI: 10.1007/s12663-023-02011-5 -
BMJ Open Respiratory Research Jan 2024Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired pneumonia (CAP). We aimed to investigate the efficacy and safety of different corticosteroids on patients who were hospitalised for severe CAP.
METHODS
We performed a systematic search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to May 2023. The primary outcome was all-cause mortality. Data analysis was performed using a random-effects model.
RESULTS
A total of 10 RCTs comprising 1962 patients were included. Corticosteroids were associated with a lower rate of all-cause mortality (risk ratio (RR), 0.70 (95% CI 0.54 to 0.90); I=0.00%). When stratified into different corticosteroid types, hydrocortisone was associated with an approximately 50% lower mortality risk (RR, 0.48 (95% CI 0.32 to 0.72); I=0.00%). However, dexamethasone, methylprednisolone or prednisolone were not associated with an improvement in mortality. Furthermore, hydrocortisone was associated with a reduction in the rate of mechanical ventilation, acute respiratory distress syndrome, shock and duration of intensive care unit stay. These trends were not observed for dexamethasone, methylprednisolone or prednisolone. Corticosteroids were not associated with an increased risk of adverse events including gastrointestinal bleeding, secondary infection or hyperglycaemia.
CONCLUSIONS
The use of hydrocortisone, but not other types of corticosteroids, was associated with a reduction in mortality and improvement in pneumonia outcomes among patients hospitalised with severe CAP.PROSPERO registration numberCRD42023431360.
Topics: Humans; Hydrocortisone; Adrenal Cortex Hormones; Methylprednisolone; Community-Acquired Infections; Pneumonia; Dexamethasone
PubMed: 38262670
DOI: 10.1136/bmjresp-2023-002141