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Health Technology Assessment... Jan 2024Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus).
OBJECTIVES
To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib).
DATA SOURCES
Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review.
METHODS
A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources.
RESULTS
Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost.
CONCLUSIONS
The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations.
FUTURE WORK AND LIMITATIONS
The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42021266219.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in ; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.
Topics: Child; Adult; Adolescent; Humans; Child, Preschool; Dermatitis, Atopic; Cyclosporine; State Medicine; Treatment Outcome; Cost-Benefit Analysis; Eczema; Antibodies, Monoclonal; Purines; Heterocyclic Compounds, 3-Ring; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38343072
DOI: 10.3310/LEXB9006 -
The Cochrane Database of Systematic... Jun 2020Hyperkalaemia is a common electrolyte abnormality caused by reduced renal potassium excretion in patients with chronic kidney diseases (CKD). Potassium binders, such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hyperkalaemia is a common electrolyte abnormality caused by reduced renal potassium excretion in patients with chronic kidney diseases (CKD). Potassium binders, such as sodium polystyrene sulfonate and calcium polystyrene sulfonate, are widely used but may lead to constipation and other adverse gastrointestinal (GI) symptoms, reducing their tolerability. Patiromer and sodium zirconium cyclosilicate are newer ion exchange resins for treatment of hyperkalaemia which may cause fewer GI side-effects. Although more recent studies are focusing on clinically-relevant endpoints such as cardiac complications or death, the evidence on safety is still limited. Given the recent expansion in the available treatment options, it is appropriate to review the evidence of effectiveness and tolerability of all potassium exchange resins among people with CKD, with the aim to provide guidance to consumers, practitioners, and policy-makers.
OBJECTIVES
To assess the benefits and harms of potassium binders for treating chronic hyperkalaemia among adults and children with CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 10 March 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating potassium binders for chronic hyperkalaemia administered in adults and children with CKD.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed risks of bias and extracted data. Treatment estimates were summarised by random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD), with 95% confidence interval (CI). Evidence certainty was assessed using GRADE processes.
MAIN RESULTS
Fifteen studies, randomising 1849 adult participants were eligible for inclusion. Twelve studies involved participants with CKD (stages 1 to 5) not requiring dialysis and three studies were among participants treated with haemodialysis. Potassium binders included calcium polystyrene sulfonate, sodium polystyrene sulfonate, patiromer, and sodium zirconium cyclosilicate. A range of routes, doses, and timing of drug administration were used. Study duration varied from 12 hours to 52 weeks (median 4 weeks). Three were cross-over studies. The mean study age ranged from 53.1 years to 73 years. No studies evaluated treatment in children. Some studies had methodological domains that were at high or unclear risks of bias, leading to low certainty in the results. Studies were not designed to measure treatment effects on cardiac arrhythmias or major GI symptoms. Ten studies (1367 randomised participants) compared a potassium binder to placebo. The certainty of the evidence was low for all outcomes. We categorised treatments in newer agents (patiromer or sodium zirconium cyclosilicate) and older agents (calcium polystyrene sulfonate and sodium polystyrene sulfonate). Patiromer or sodium zirconium cyclosilicate may make little or no difference to death (any cause) (4 studies, 688 participants: RR 0.69, 95% CI 0.11, 4.32; I = 0%; low certainty evidence) in CKD. The treatment effect of older potassium binders on death (any cause) was unknown. One cardiovascular death was reported with potassium binder in one study, showing that there was no difference between patiromer or sodium zirconium cyclosilicate and placebo for cardiovascular death in CKD and HD. There was no evidence of a difference between patiromer or sodium zirconium cyclosilicate and placebo for health-related quality of life (HRQoL) at the end of treatment (one study) in CKD or HD. Potassium binders had uncertain effects on nausea (3 studies, 229 participants: RR 2.10, 95% CI 0.65, 6.78; I = 0%; low certainty evidence), diarrhoea (5 studies, 720 participants: RR 0.84, 95% CI 0.47, 1.48; I = 0%; low certainty evidence), and vomiting (2 studies, 122 participants: RR 1.72, 95% CI 0.35 to 8.51; I = 0%; low certainty evidence) in CKD. Potassium binders may lower serum potassium levels (at the end of treatment) (3 studies, 277 participants: MD -0.62 mEq/L, 95% CI -0.97, -0.27; I = 92%; low certainty evidence) in CKD and HD. Potassium binders had uncertain effects on constipation (4 studies, 425 participants: RR 1.58, 95% CI 0.71, 3.52; I = 0%; low certainty evidence) in CKD. Potassium binders may decrease systolic blood pressure (BP) (2 studies, 369 participants: MD -3.73 mmHg, 95%CI -6.64 to -0.83; I = 79%; low certainty evidence) and diastolic BP (one study) at the end of the treatment. No study reported outcome data for cardiac arrhythmias or major GI events. Calcium polystyrene sulfonate may make little or no difference to serum potassium levels at end of treatment, compared to sodium polystyrene sulfonate (2 studies, 117 participants: MD 0.38 mEq/L, 95% CI -0.03 to 0.79; I = 42%, low certainty evidence). There was no evidence of a difference in systolic BP (one study), diastolic BP (one study), or constipation (one study) between calcium polystyrene sulfonate and sodium polystyrene sulfonate. There was no difference between high-dose and low-dose patiromer for death (sudden death) (one study), stroke (one study), myocardial infarction (one study), or constipation (one study). The comparative effects whether potassium binders were administered with or without food, laxatives, or sorbitol, were very uncertain with insufficient data to perform meta-analysis.
AUTHORS' CONCLUSIONS
Evidence supporting clinical decision-making for different potassium binders to treat chronic hyperkalaemia in adults with CKD is of low certainty; no studies were identified in children. Available studies have not been designed to measure treatment effects on clinical outcomes such as cardiac arrhythmias or major GI symptoms. This review suggests the need for a large, adequately powered study of potassium binders versus placebo that assesses clinical outcomes of relevance to patients, clinicians and policy-makers. This data could be used to assess cost-effectiveness, given the lack of definitive studies and the clinical importance of potassium binders for chronic hyperkalaemia in people with CKD.
Topics: Aged; Cause of Death; Chelating Agents; Chelation Therapy; Chronic Disease; Humans; Hyperkalemia; Middle Aged; Polymers; Polystyrenes; Potassium; Quality of Life; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Silicates
PubMed: 32588430
DOI: 10.1002/14651858.CD013165.pub2 -
Critical Care (London, England) May 2020The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed.
METHODS
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated.
RESULTS
We identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74-0.87) and 0.88 (95% CI 0.82-0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96-7.50), the pooled negative LR was 0.26 (95% CI 0.19-0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00-51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72-0.91) and 0.77 (95% CI 0.64-0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06-4.86) and 0.25 (95% CI 0.14-0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74-32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1-2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51-13.33).
CONCLUSION
The FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.
Topics: Acute Kidney Injury; Disease Progression; Exercise Test; Furosemide; Humans; Predictive Value of Tests; Renal Replacement Therapy; Severity of Illness Index
PubMed: 32381019
DOI: 10.1186/s13054-020-02912-8 -
The Journal of Headache and Pain Jul 2023Menstrual migraine is a subtype of migraine disease that is typically more disabling, longer-lasting, and more challenging to treat. The purpose of this network... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Menstrual migraine is a subtype of migraine disease that is typically more disabling, longer-lasting, and more challenging to treat. The purpose of this network meta-analysis (NMA) is to compare the relative efficacy of treatments for menstrual migraine.
METHODS
We systematically searched databases, including PubMed, EMBASE, and Cochrane, and included all eligible randomized controlled trials in the study. We conducted the statistical analysis using Stata version 14.0, based on the frequentist framework. We used the Cochrane Risk of Bias tool for randomized trials version 2 (RoB2) to assess the risk of bias of the included studies.
RESULTS
This network meta-analysis included 14 randomized controlled trials with 4601 patients. For short-term prophylaxis, frovatriptan 2.5 mg twice daily had the highest probability of effectiveness [OR = 1.87 (95% CI: 1.48 to 2.38)] compared to placebo. For acute treatment, the results showed that sumatriptan 100 mg [OR = 4.32 (95% CI: 2.95 to 6.34)] was the most effective treatment compared to placebo.
CONCLUSIONS
These findings suggest that frovatriptan 2.5 mg twice daily was best for short-term prevention, sumatriptan 100 mg were best for acute treatment. More high-quality randomized trials are required to determine the most effective treatment.
Topics: Humans; Sumatriptan; Network Meta-Analysis; Migraine Disorders; Tryptamines
PubMed: 37400775
DOI: 10.1186/s10194-023-01625-x -
Dermatology (Basel, Switzerland) 2021Atopic dermatitis (AD) is a widely acquired, relapsing inflammatory skin disease. Biologics are now widely used in patients with moderate-to-severe AD.
BACKGROUND
Atopic dermatitis (AD) is a widely acquired, relapsing inflammatory skin disease. Biologics are now widely used in patients with moderate-to-severe AD.
OBJECTIVE
This work aims to summarize both label and off-label biologics on AD treatment in phase II and phase III stages, and compile evidence on the efficacy of the most-studied biologics.
METHODS
We conducted a comprehensive literature search through PubMed, EMBASE, and ClinicalTrials.gov to identify all documented biological therapies for AD. The criteria were further refined to focus on those treatments with the highest evidence level for AD with at least one randomized clinical trial supporting their use. Only studies or articles published in English were enrolled in this study.
FINDINGS
Primary searches identified 525 relevant articles and 27 trials. Duplicated articles and papers without a full text were excluded. Only completed trials were enrolled. We included 28 randomized controlled trials, 4 unpublished trials, 2 observational studies, and 1 meta-analysis. Eight kinds of biologics, including IL-4/IL-13 inhibitors, JAK inhibitors, anti-IL-13 antibodies, anti-IL-22 antibodies, anti-IL-33 antibodies, thymic stromal lymphopoietin inhibitor (TSLP), OX40 antibodies, and H4R-antagonists were included in this work. Dupliumab, as the most widely used and investigated biologic, was reported in 1 meta-analysis and 4 trials exploring its long-term use and application in both adults and pediatric patients. Besides dupilumab, four other IL-4/IL-13 inhibitors recruited were all randomized, clinical trials at phase 2-3 stage. Six different kinds of JAK inhibitors were summarized with strong evidence revealing their significant therapeutic effects on AD. There were 3 trials for nemolizumab, an anti-IL-13 antibody, all of which were in the phase 2 clinical trial stage. Results showed nemolizumab could be another alternative therapy for moderate-to-severe AD with long-term efficiency and safety.
CONCLUSION
The biological therapies with the most robust evidence on efficacy and long-term safety for AD treatment include dupilumab, barcitinib, abrocitinib, and delgocitinib. Most of the biologics mentioned in this review were still at the exploratory stage. This review will help practitioners advise patients seeking suitable biological therapies and offer experimental study directions for treatment.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azetidines; Biological Products; Carbamates; Clinical Trials as Topic; Dermatitis, Atopic; Dermatologic Agents; Heterocyclic Compounds, 3-Ring; Humans; Nitriles; Piperidines; Protein Kinase Inhibitors; Purines; Pyrazoles; Pyrimidines; Pyrroles; Sulfonamides
PubMed: 33735876
DOI: 10.1159/000514535 -
American Journal of Men's Health 2023Lower urinary tract symptoms (LUTS) secondary to benign prostrate hyperplasia (BPH) are common geriatric diseases, and its incidence rises with age. The treatment of BPH... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-Analysis of the Efficacy and Safety of Tamsulosin Plus Tadalafil Compared With Tamsulosin Alone in Treating Males With Lower Urinary Tract Symptoms Secondary to Benign Prostrate Hyperplasia.
Lower urinary tract symptoms (LUTS) secondary to benign prostrate hyperplasia (BPH) are common geriatric diseases, and its incidence rises with age. The treatment of BPH and LUTS is becoming a burden for health care. The meta-analysis was performed to evaluate the efficacy and safety of combination therapy (tamsulosin plus tadalafil) compared with tamsulosin alone in treatment of males with LUTS/BPH. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were utilized to conduct this study. There were several databases available for literature retrieval, including Medline, Embase, PubMed, Scopus, Web of Science databases, and Cochrane Controlled Trials Register. To improve the comprehensiveness of the search, related references were also searched. Finally, six randomized controlled trials including 441 patients were included. The combination therapy had significant improvements in total International Prostate Symptom Score ( < .0001), quality of life score ( = .003), maximum urine flow rate ( < .00001), and International Index of Erectile Function ( < .00001) compared with the tamsulosin monotherapy, but there was no obvious difference in postvoid residual volume ( = .06). In terms of safety, the combination group had comparable rates of discontinuation due to adverse events ( = .19) than the monotherapy group except for pain symptoms ( < .0001). The combination of tamsulosin and tadalafil provided a preferable therapeutic effect compared with the tamsulosin alone in treating males with BPH/LUTS, and both therapy regimens were well tolerated by the patients.
Topics: Male; Humans; Aged; Tamsulosin; Tadalafil; Prostatic Hyperplasia; Hyperplasia; Quality of Life; Erectile Dysfunction; Drug Therapy, Combination; Treatment Outcome; Lower Urinary Tract Symptoms; Randomized Controlled Trials as Topic
PubMed: 36842963
DOI: 10.1177/15579883231155096 -
Frontiers in Immunology 2024Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined...
BACKGROUND
Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.
METHODS
Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).
RESULTS
Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).
CONCLUSION
Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Nasopharyngitis; Pruritus; Acne Vulgaris; Headache; Herpes Zoster; Immunoglobulin A; Purines; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38464512
DOI: 10.3389/fimmu.2024.1342810 -
Arquivos de Neuro-psiquiatria Jun 2023Chronic low back pain (CLBP) is a global health problem, and gabapentin and pregabalin are often used in the treatment of patients without associated radiculopathy or...
BACKGROUND
Chronic low back pain (CLBP) is a global health problem, and gabapentin and pregabalin are often used in the treatment of patients without associated radiculopathy or neuropathy. Therefore, determining their efficacy and safety is of enormous value.
OBJECTIVE
To examine the efficacy and safety of using gabapentin and pregabalin for CLBP without radiculopathy or neuropathy.
METHODS
We performed a search on the CENTRAL, MEDLINE, EMBASE, LILACS, and Web of Science data bases for clinical trials, cohorts, and case-control studies that evaluated patients with CLBP without radiculopathy or neuropathy for at least eight weeks. The data were extracted and inserted into a previously-prepared Microsoft Excel spreadsheet; the outcomes were evaluated using the Cochrane RoB 2 tool, and the quality of evidence, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
RESULTS
Of the 2,230 articles identified, only 5 were included, totaling 242 participants. In them, pregabalin was slightly less efficacious than amitriptyline, the combination of tramadol/acetaminophen, and celecoxib, and pregabalin added to celecoxib showed no benefit when compared to celecoxib alone (very low evidence for all). On the other hand, although one study with gabapentin did not support its use in a general sample of patients with low back pain, another found a reduction in the pain scale and improved mobility (moderate evidence). No serious adverse events were observed in any of the studies.
CONCLUSION
Quality information to support the use of pregabalin or gabapentin in the treatment of CLBP without radiculopathy or neuropathy is lacking, although results may suggest gabapentin as a viable option. More data is needed to fill this current gap in knowledge.
Topics: Humans; Radiculopathy; Gabapentin; Pregabalin; Low Back Pain; Celecoxib
PubMed: 37379868
DOI: 10.1055/s-0043-1764414 -
BMC Neurology Jun 2023Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs. (Meta-Analysis)
Meta-Analysis
The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs.
METHODS
We searched online databases like PubMed, Cochrane Library, Scopus, and Web of Science till June 2022 for RCTs that compared metoclopramide alone with placebo or active drugs. The main outcomes were the mean change in headache score and complete headache relief. The secondary outcomes were the rescue medications need, side effects, nausea and recurrence rate. We qualitatively reviewed the outcomes. Then, we performed the network meta-analyses (NMAs) when it was possible. which were done by the Frequentist method using the MetaInsight online software.
RESULTS
Sixteen studies were included with a total of 1934 patients: 826 received metoclopramide, 302 received placebo, and 806 received other active drugs. Metoclopramide was effective in reducing headache outcomes even for 24 h. The intravenous route was the most chosen route in the included studies and showed significant positive results regarding headache outcomes; however, the best route whether intramuscular, intravenous, or suppository was not compared in the previous studies. Also, both 10 and 20 mg doses of metoclopramide were effective in improving headache outcomes; however, there was no direct comparison between both doses and the 10 mg dose was the most frequently used dosage. In NMA of headache change after 30 min or 1 h, metoclopramide effect came after granisetron, ketorolac, chlorpromazine, and Dexketoprofen trometamol. Only granisetron's effect was significantly higher than metoclopramide's effect which was only significantly higher than placebo and sumatriptan. In headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide which was higher than other medications and showed significantly higher effects only with placebo. In rescue medication, metoclopramide's effect was only non-significantly lower than prochlorperazine and chlorpromazine while its effect was higher than other drugs and showed higher significant effects only than placebo and valproate. In the recurrence rate, studies showed no significant difference between metoclopramide and other drugs. Metoclopramide significantly decreased nausea more than the placebo. Regarding side effects, metoclopramide showed a lower incidence of mild side effects than pethidine and chlorpromazine and showed a higher incidence of mild side effects than placebo, dexamethasone, and ketorolac. The reported extrapyramidal symptoms with metoclopramide were dystonia or akathisia.
CONCLUSION
A dose of 10 mg IV Metoclopramide was effective in relieving migraine attacks with minimal side effects. Compared to other active drugs, it only showed a lower significant effect compared with granisetron regarding headache change while it showed significantly higher effects only with placebo in both rescue medication needs and headache-free symptoms and valproate in only rescue medication need. Also, it significantly decreased headache scores more than placebo and sumatriptan. However, more studies are needed to support our results.
Topics: Humans; Metoclopramide; Sumatriptan; Network Meta-Analysis; Prochlorperazine; Chlorpromazine; Granisetron; Valproic Acid; Ketorolac; Randomized Controlled Trials as Topic; Migraine Disorders; Nausea; Headache
PubMed: 37291500
DOI: 10.1186/s12883-023-03259-7 -
The Cochrane Database of Systematic... Jun 2023Hypertonic saline enhances mucociliary clearance and may lessen the destructive inflammatory process in the airways. This is an update of a previously published review. (Review)
Review
BACKGROUND
Hypertonic saline enhances mucociliary clearance and may lessen the destructive inflammatory process in the airways. This is an update of a previously published review.
OBJECTIVES
To investigate efficacy and tolerability of nebulised hypertonic saline treatment in people with cystic fibrosis (CF) compared to placebo or other treatments that enhance mucociliary clearance.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also searched ongoing trials databases. Most recent search: 25 April 2022.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials assessing hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with CF (any age or disease severity).
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed all identified trials and data, and assessed trial quality. We assessed the certainty of the evidence using GRADE. For cross-over trials we stipulated a one-week washout period. We planned to use results from a paired analysis in the review, but this was only possible in one trial. For other cross-over trials, we chose to treat the trials as if they were parallel.
MAIN RESULTS
We included 24 trials (1318 participants, aged one month to 56 years); we excluded 29 trials, two trials are ongoing and six are awaiting classification. We judged 15 of the 24 included trials to have a high risk of bias due to participants' ability to discern the taste of the solutions. Hypertonic saline 3% to 7% versus placebo (stable disease) We are uncertain whether the regular use of nebulised hypertonic saline in stable lung disease leads to an improvement in forced expiratory volume in one second (FEV) % predicted at four weeks, (mean difference (MD) 3.30%, 95% confidence interval (CI) 0.71 to 5.89; 4 trials, 246 participants; very low-certainty evidence). In preschool children we found no difference in lung clearance index (LCI) at four weeks, but a small improvement after 48 weeks of treatment with hypertonic saline compared to isotonic saline (MD -0.60, 95% CI -1.00 to -0.19; 2 trials, 192 participants). We are also uncertain whether hypertonic saline made a difference to mucociliary clearance, pulmonary exacerbations or adverse events compared to placebo. Hypertonic saline versus control (acute exacerbation) Two trials compared hypertonic saline to control, but only one provided data. There may be little or no difference in lung function measured by FEV % predicted after hypertonic saline compared to isotonic saline (MD 5.10%, 95% CI -14.67 to 24.87; 1 trial, 130 participants). Neither trial reported any deaths or measures of sputum clearance. There were no serious adverse events. Hypertonic saline versus rhDNase Three trials compared a similar dose of hypertonic saline to recombinant deoxyribonuclease (rhDNase); two trials (61 participants) provided data for inclusion in the review. We are uncertain whether there was an effect of hypertonic saline on FEV % predicted after three weeks (MD 1.60%, 95% CI -7.96 to 11.16; 1 trial, 14 participants; very low-certainty evidence). At three months, rhDNase may lead to a greater increase in FEV % predicted than hypertonic saline (5 mL twice daily) at 12 weeks in participants with moderate to severe lung disease (MD 8.00%, 95% CI 2.00 to 14.00; low-certainty evidence). We are uncertain whether adverse events differed between the two treatments. No deaths were reported. Hypertonic saline versus amiloride One trial (12 participants) compared hypertonic saline to amiloride but did not report on most of our outcomes. The trial found that there was no difference between treatments in measures of sputum clearance (very low-certainty evidence). Hypertonic saline compared with sodium-2-mercaptoethane sulphonate (Mistabron®) One trial (29 participants) compared hypertonic saline to sodium-2-mercaptoethane sulphonate. The trial did not measure our primary outcomes. There was no difference between treatments in any measures of sputum clearance, courses of antibiotics or adverse events (very low-certainty evidence). Hypertonic saline versus mannitol One trial (12 participants) compared hypertonic saline to mannitol, but did not report lung function at relevant time points for this review; there were no differences in sputum clearance, but mannitol was reported to be more 'irritating' (very low-certainty evidence). Hypertonic saline versus xylitol Two trials compared hypertonic saline to xylitol, but we are uncertain whether there is any difference in FEV % predicted or median time to exacerbation between groups (very low-certainty evidence). No other outcomes were reported in the review. Hypertonic saline 7% versus hypertonic saline 3% We are uncertain whether there was an improvement in FEV % predicted after treatment with 7% hypertonic saline compared with 3% (very low-certainty evidence).
AUTHORS' CONCLUSIONS
We are very uncertain if regular use of nebulised hypertonic saline by adults and children over the age of 12 years with CF results in an improvement in lung function after four weeks (three trials; very low-certainty evidence); there was no difference seen at 48 weeks (one trial; low-certainty evidence). Hypertonic saline improved LCI modestly in children under the age of six years. Evidence from one small cross-over trial in children indicates that rhDNase may lead to better lung function than hypertonic saline at three months; qualifying this, we highlight that while the study did demonstrate that the improvement in FEV was greater with daily rhDNase, there were no differences seen in any of the secondary outcomes. Hypertonic saline does appear to be an effective adjunct to physiotherapy during acute exacerbations of lung disease in adults. However, for the outcomes assessed, the certainty of the evidence ranged from very low to low at best, according to the GRADE criteria. The role of hypertonic saline in conjunction with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy now needs to be considered, and future research needs to focus on this aspect.
Topics: Adult; Child; Child, Preschool; Humans; Administration, Inhalation; Amiloride; Cystic Fibrosis; Mannitol; Saline Solution, Hypertonic; Sodium; Xylitol; Infant; Adolescent; Young Adult; Middle Aged
PubMed: 37319354
DOI: 10.1002/14651858.CD001506.pub5