scholarly journals Fidaxomicin as first line: What will it cost in the USA and Canada?

2021 ◽  
Author(s):  
Devangi Patel ◽  
Julien Senecal ◽  
Brad Spellberg ◽  
Andrew M Morris ◽  
Lynora Saxinger ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cost Saving ◽  
Average Cost ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Healthcare Systems ◽  
Controlled Trials ◽  
First Line ◽  
Medication Costs ◽  
Canadian Healthcare

Importance: Recent changes in the Infectious Diseases and Healthcare Epidemiology Societies of America (IDSA-SHEA) guidelines for managing Clostridioides difficile infections (CDI) have placed fidaxomicin as first-line treatment for CDI. Objective: To estimate the net cost of first line fidaxomicin as compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving. Data sources: We identified all randomized controlled trials comparing fidaxomicin with vancomycin through the 2021 IDSA-SHEA guideline update. Medication costs were obtained from wholesale prices (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through two systematic reviews using PubMed. Study selection: For fidaxomicin efficacy, we included double-blind and placebo-controlled trials. For the systematic review of recurrence costs, studies were included if they were primary research articles, had a cost-analysis of CDI, included cases of recurrent CDI, and were calculated with cost parameters from American or Canadian healthcare systems. Studies were excluded if the population was solely pediatric or hospitalized. Data extraction and Synthesis: For the efficacy meta-analysis, data was pooled using a random effects model. For the costs review, literature screening was performed by 2 independent reviewers. The mean cost across identified studies was adjusted to 2021 dollars. Main Outcomes and Measures: The primary outcome of the meta-analysis was CDI recurrence at day 40. The primary outcome of the systematic review was the average cost of a CDI recurrence in the American and Canadian healthcare systems. The objective was to estimate the net cost per recurrence prevented and the price point below which fidaxomicin would be cost saving. Results: At current drug pricing, the estimated additional cost of a 10-day course of fidaxomicin compared to vancomycin in order to prevent one recurrence was $46,178USD (95%CI $36,942-$69,267) and $13,760CAD (95%CI $11,008-$20,640), respectively. The estimated mean systemic cost of a CDI recurrence was $14,506USD and $8,588CAD, respectively. When priced below $1550USD and $800CAD, fidaxomicin was likely to become cost saving. Conclusions and Relevance: The increased drug expenditure on fidaxomicin will not be offset through recurrence prevention unless fidaxomicin price is re-negotiated.

Comparative efficacy and acceptability of psychotherapies for panic disorder with or without agoraphobia: systematic review and network meta-analysis of randomised controlled trials

2021 ◽  
pp. 1-13
Author(s):  
Davide Papola ◽  
Giovanni Ostuzzi ◽  
Federico Tedeschi ◽  
Chiara Gastaldon ◽  
Marianna Purgato ◽  
...  
Keyword(s):  
Systematic Review ◽  
Panic Disorder ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Psychodynamic Therapy ◽  
Controlled Trials ◽  
First Line ◽  
Short Term ◽  
Randomised Controlled

Background Psychotherapies are the treatment of choice for panic disorder, but which should be considered as first-line treatment is yet to be substantiated by evidence. Aims To examine the most effective and accepted psychotherapy for the acute phase of panic disorder with or without agoraphobia via a network meta-analysis. Method We conducted a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the most effective and accepted psychotherapy for the acute phase of panic disorder. We searched MEDLINE, Embase, PsycInfo and CENTRAL, from inception to 1 Jan 2021 for RCTs. Cochrane and PRISMA guidelines were used. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO (CRD42020206258). Results We included 136 RCTs in the systematic review. Taking into consideration efficacy (7352 participants), acceptability (6862 participants) and the CINeMA confidence in evidence appraisal, the best interventions in comparison with treatment as usual (TAU) were cognitive–behavioural therapy (CBT) (for efficacy: standardised mean differences s.m.d. = −0.67, 95% CI −0.95 to −0.39; CINeMA: moderate; for acceptability: relative risk RR = 1.21, 95% CI −0.94 to 1.56; CINeMA: moderate) and short-term psychodynamic therapy (for efficacy: s.m.d. = −0.61, 95% CI −1.15 to −0.07; CINeMA: low; for acceptability: RR = 0.92, 95% CI 0.54–1.54; CINeMA: moderate). After removing RCTs at high risk of bias only CBT remained more efficacious than TAU. Conclusions CBT and short-term psychodynamic therapy are reasonable first-line choices. Studies with high risk of bias tend to inflate the overall efficacy of treatments. Results from this systematic review and network meta-analysis should inform clinicians and guidelines.

Vacuum Therapy and Internal Drainage as the First-Line Endoscopic Treatment for Post-Bariatric Leaks: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-8
Author(s):  
Issaree Laopeamthong ◽  
Thanita Akethanin ◽  
Wisit Kasetsermwiriya ◽  
Suphakarn Techapongsatorn ◽  
Amarit Tansawet
Keyword(s):  
Systematic Review ◽  
Fixed Effects ◽  
Primary Outcome ◽  
Clinical Success ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Data Availability ◽  
Vacuum Therapy ◽  
Internal Drainage ◽  
First Line

<b><i>Introduction:</i></b> Several endoscopic methods can be employed to manage post-bariatric leaks. However, endoluminal vacuum therapy (EVT) and endoscopic internal drainage (EID) are relatively new methods, and studies regarding these methods are scarce. We performed a systematic review of the literature and a meta-analysis to evaluate the efficacy of EVT and EID. <b><i>Methods:</i></b> Databases were searched for eligible studies. The clinical success of leak closure was the primary outcome of interest. A proportional meta-analysis was performed for pooling the primary outcome using a fixed-effects model. A meta-analysis or descriptive analysis of other outcomes was performed based on the data availability. <b><i>Results:</i></b> Data from 3 EVT and 10 EID studies (<i>n</i> = 279) were used for evidence synthesis. The leak closure rates (95% confidence interval [CI]) of EVT and EID were 85.2% (75.1%–95.4%) and 91.6% (88.1%–95.2%), respectively. The corresponding mean treatment durations (95% CI) were 28 (2.4–53.6) and 78.4 (50.1–106.7) days, respectively. However, data about other outcomes were extremely limited; thus, a pooled analysis could not be performed. <b><i>Conclusions:</i></b> Both EVT and EID were effective when used as the first-line treatment for post-bariatric leaks. However, larger studies must be conducted to compare the efficacy of the 2 interventions.

Effect of High-Flow Nasal Cannula Oxygen Therapy Versus Conventional Oxygen Therapy and Noninvasive Ventilation on Reintubation Rate in Adult Patients After Extubation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2017 ◽  
Vol 33 (11) ◽  
pp. 609-623 ◽  
Author(s):  
Hua-Wei Huang ◽  
Xiu-Mei Sun ◽  
Zhong-Hua Shi ◽  
Guang-Qiang Chen ◽  
Lu Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Noninvasive Ventilation ◽  
Oxygen Therapy ◽  
Primary Outcome ◽  
Meta Analysis ◽  
High Flow ◽  
Adult Patients ◽  
Controlled Trials ◽  
High Flow Nasal Cannula ◽  
Randomized Controlled

Purpose: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of high-flow nasal cannula (HFNC) on reintubation in adult patients. Procedures: Ovid Medline, Embase, and Cochrane Database of Systematic Reviews were searched up to November 1, 2016, for RCTs comparing HFNC versus conventional oxygen therapy (COT) or noninvasive ventilation (NIV) in adult patients after extubation. The primary outcome was reintubation rate, and the secondary outcomes included complications, tolerance and comfort, time to reintubation, length of stay, and mortality. Dichotomous outcomes were presented as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as weighted mean difference and 95% CIs. The random effects model was used for data pooling. Findings: Seven RCTs involving 2781 patients were included in the analysis. The HFNC had a similar reintubation rate compared to either COT (RR, 0.58; 95% CI, 0.21-1.60; P = .29; 5 RCTs, n = 1347) or NIV (RR, 1.11; 95% CI, 0.88-1.40; P = .37; 2 RCTs, n = 1434). In subgroup of critically ill patients, the HFNC group had a significantly lower reintubation rate compared to the COT group (RR, 0.35; 95% CI, 0.19-0.64; P = .0007; 2 RCTs, n = 632; interaction P = .07 compared to postoperative subgroup). Qualitative analysis suggested that HFNC might be associated with less complications and improved patient’s tolerance and comfort. The HFNC might not delay reintubation. Trial sequential analysis on the primary outcome showed that required information size was not reached. Conclusion: The evidence suggests that COT may still be the first-line therapy in postoperative patients without acute respiratory failure. However, in critically ill patients, HFNC may be a potential alternative respiratory support to COT and NIV, with the latter often associating with patient intolerance and requiring a monitored setting. Because required information size was not reached, further high-quality studies are required to confirm these results.

scholarly journals Exercise for premenstrual syndrome: a systematic review and meta-analysis of randomised controlled trials

BJGP Open ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. bjgpopen20X101032 ◽  
Author(s):  
Emma Pearce ◽  
Kate Jolly ◽  
Laura L Jones ◽  
Gemma Matthewman ◽  
Mandana Zanganeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Premenstrual Syndrome ◽  
Randomised Controlled Trials ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Current Evidence ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Exercise Interventions ◽  
Randomised Controlled

BackgroundExercise is recommended as a treatment for premenstrual syndrome (PMS) in clinical guidelines, but this is currently based on poor-quality trial evidence.AimTo systematically review the evidence for the effectiveness of exercise as a treatment for PMS.Design & settingThis systematic review searched eight major databases, including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), and two trial registries from inception until April 2019.MethodRandomised controlled trials (RCTs) comparing exercise interventions of a minimum of 8-weeks duration with non-exercise comparator groups in women with PMS were included. Mean change scores for any continuous PMS outcome measure were extracted from eligible trials and standardised mean differences (SMDs) were calculated where possible. Random-effects meta-analysis of the effect of exercise on global PMS symptoms was the primary outcome. Secondary analyses examined the effects of exercise on predetermined clusters of psychological, physical, and behavioural symptoms.ResultsA total of 436 non-duplicate returns were screened, with 15 RCTs eligible for inclusion (n = 717). Seven trials contributed data to the primary outcome meta-analysis (n = 265); participants randomised to an exercise intervention reported reduced global PMS symptom scores (SMD = -1.08; 95% confidence interval [CI] = -1.88 to -0.29) versus comparator, but with substantial heterogeneity (I2 = 87%). Secondary results for psychological (SMD = -1.67; 95% CI = -2.38 to -0.96), physical (SMD = -1.62; 95% CI = -2.41 to -0.83) and behavioural (SMD = -1.94; 95% CI = -2.45 to -1.44) symptom groupings displayed similar findings. Most trials (87%) were considered at high risk of bias.ConclusionBased on current evidence, exercise may be an effective treatment for PMS, but some uncertainty remains.

scholarly journals Risk of Serious Infections with Carfilzomib in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1841-1841 ◽  
Author(s):  
Somedeb Ball ◽  
Tapas Ranjan Behera ◽  
Sariya Wongsaengsak ◽  
Nuvneet Khandelwal ◽  
Rajshekhar Chakraborty
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Relative Risk ◽  
Respiratory Tract ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Serious Infections ◽  
Combination Regimens

Introduction: Infections are an important cause of morbidity and mortality in multiple myeloma [MM]. Infections can be a result of the underlying disease or toxicity of anti-myeloma therapy or both. Proteasome inhibitors [PI] are associated with a risk of infection due to several mechanisms including decreased cytotoxic T-cell and natural killer cell proliferation, inhibition of dendritic cell function, and suppression of polyclonal immunoglobulins. Carfilzomib is an irreversible PI, with a higher potency compared to bortezomib in preclinical studies. Although infections are frequently reported as adverse events with carfilzomib-based combination regimens, definitive data on increased infection risk with carfilzomib is lacking. Hence, we conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to estimate the relative risk of serious infections associated with the use of carfilzomib-based regimens in MM. Methods: A systematic electronic search was performed in Ovid MEDLINE, Ovid EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov with appropriate search terms through March 20, 2019. We included RCTs comparing carfilzomib-based regimens with non-carfilzomib based regimens in MM. Primary outcome of our analysis was to estimate the relative risk of serious infections with carfilzomib. Data on primary outcome was obtained from ClinicalTrials.gov records of the included studies. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method of the random-effects model by Der Simonian and Laird. Heterogeneity of effect size was quantified using I2 statistic. Publication bias was assessed by the Egger's regression test. All statistical analyses were performed with Review Manager (RevMan Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration). Results: A total of 3,683 unique records were screened, among which, four RCTs including a total of 2954 patients (1486 in carfilzomib arm and 1468 in control arm) were included in the final analysis. Characteristics of studies included in the analysis are summarized in table 1. All but one study (CLARION) were conducted in relapsed/refractory MM. Carfilzomib was administered twice weekly in all trials, with dose ranging from 20/27 to 20/56 mg/m2. The median duration of treatment ranged from 16 to 88 weeks. Other than FOCUS trial which had single-agent carfilzomib, all had carfilzomib-based combination regimens in the intervention arm, namely, carfilzomib-dexamethasone, carfilzomib-lenalidomide-dexamethasone, and carfilzomib-melphalan-prednisone. The risk of total serious infections was significantly elevated with carfilzomib-based regimens compared to other agents [pooled RR 1.40, 95% CI: 1.17 - 1.69, p = 0.0003, I2 = 57%, figure 1]. In the carfilzomib arm, 65% of all serious infections involved the respiratory tract, and 38% were serious pneumonia. Patients on carfilzomib-based regimens were at a significantly higher risk of serious respiratory tract infections (RTI) in comparison with those on other treatments [pooled RR 1.30, 95% CI: 1.12 - 1.50, p = 0.0004, I2 = 0%, figure 2]. However, there was no significant difference in the incidence of serious pneumonia between carfilzomib and control groups [pooled RR 1.14, 95% CI: 0.92 - 1.41, p = 0.23, I2 = 15%, figure 3]. None to substantial levels of heterogeneity were noted across trials, depending on the type of analysis. Subgroup analysis based on carfilzomib dose (≤ 27 vs. >27 mg/m2) and treatment setting (relapsed/refractory vs. newly diagnosed) did not reveal any statistically significant subgroup effect. There was no publication bias among studies. Conclusion: In our meta-analysis, carfilzomib is associated with a 40% increased relative risk of serious infections in patients with MM. The most common site of infection is the respiratory tract. Although carfilzomib leads to a higher risk of serious RTIs, the risk of serious pneumonia was not significantly different compared to controls. These findings will assist clinicians with risk-benefit assessment prior to initiation of carfilzomib-based regimens. Future studies should investigate patient-related and disease-related risk factors for serious infections and the utility of prophylactic antibiotic or intravenous immunoglobulin in high-risk patients. Disclosures No relevant conflicts of interest to declare.

Comparing active immunotherapy efficacy of PD-L1 ≥ 50% NSCLC patients: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21139-e21139
Author(s):  
Yi Hu ◽  
Xiaochen Zhao ◽  
Yuezong Bai ◽  
Longgang Cui ◽  
Fan Zhang
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
The Difference ◽  
Nsclc Patients

e21139 Background: Several therapies based on immune checkpoint inhibitors (ICIs) have been approved as the 1L standard of care for PD-L1≥ 50% advanced non-small cell lung cancer (NSCLC). However, little is known about the difference in efficacy between different strategies. We conducted a systematic review and meta-analysis to help clinicians choose more reasonable treatment options. Methods: We searched PubMed, Cochrane library, Embase and major conference proceedings from January 2010 to December 2020 for randomized controlled trials that had available subgroup hazard ratios (HRs) for overall survival according to PD-L1≥ 50%. Only drugs met primary outcome or approved by FDA were included for analysis. The primary outcome was the difference in overall survival (OS). HRs and 95% CI were calculated for the pooled OS using a random-effects model. p<0.05 was considered as statistical difference. Results: A total of 10 randomized controlled trials were included for this meta-analysis. The pooled HR and 95% CI for monotherapy, ICI plus chemotherapy and ICI plus ICI were 0.64 (0.55, 0.74), 0.64 (0.51, 0.79) and 0.70 (0.55, 0.90), respectively. There was no statistical differences between ICI monotherapy and ICI plus chemotherapy (HR 1.00, 95% CI 0.77- 1.30), between ICI monotherapy and ICI plus ICI (HR 0.91, 95% CI 0.69- 1.22) or between ICI plus chemotherapy and ICI plus ICI (HR 0.91, 95% CI 0.66- 1.27). Conclusions: For PD-L1≥ 50% NSCLC patients, active ICI monotherapies showed no different efficacy when compared with ICI combination therapies.

P469Minimally interrupted versus uninterrupted non-vitamin K anticoagulants for atrial fibrillation ablation. a meta-analysis of randomized controlled trials

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
B Enache ◽  
H Del Castillo-Carnevali ◽  
O Lairez ◽  
M Postula
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Atrial Fibrillation Ablation ◽  
Controlled Trials ◽  
Minor Bleeding ◽  
Af Ablation ◽  
Randomized Controlled

Abstract Introduction More and more patients undergoing atrial fibrillation (AF) ablation are anticoagulated with direct oral anticoagulants (DOAC). In order to balance the peri-procedural risk of bleeding with the risk of stroke, an important clinical question is whether to continue an interrupted DOAC administration or minimal interrupt by skipping the last one or two doses before the procedure. Dealing with rare events, the randomized controlled trials (RCTs) looking at this question have not been sufficiently powered to give a definitive answer.  Purpose To do a systematic review of the literature comparing an uninterrupted DOAC strategy to minimally interrupted (1-2 doses) strategy in the setting of AF ablation in terms of peri-procedural stroke and bleeding. Methods PubMed, EMBASE, and Cochrane databases were searched for RCTs comparing a strategy of uninterrupted versus minimally interrupted DOAC administration for atrial fibrillation ablation. The primary endpoint was a composite of clinically significant adverse events: ischemic stroke, transient ischemic attack (TIA), systemic embolism, and major or minor bleeding events. A random-effects meta-analysis was performed on the resulting trials. The systematic review protocol was pre-registered in the PROSPERO database. The study selection process followed the PRISMA statement. Results After checking and removing duplicates, 188 articles were screened by reading the title and abstract. 8 of them were selected for a full text screening.  Because 3 were not randomized, finally, 5 RCTs met the inclusion criteria. A total of 1 769 patients were included in the meta-analysis, and the sample size of the individual RCTs ranged from 97 to 846 patients. The overall prevalence of paroxysmal AF varied from 54% to 100%. The mean age of patients ranged from 63,5 to 70 years, and 21,6% to 32,8% of the trial populations were women. Comorbidities, such as hypertension, dyslipidemia, and diabetes, were common. Most patients had CHA2DS2-VASc &lt; 3; range from 1,7 to 2,7We found consistently low rates of strokes, TIAs, systemic embolisms and bleedings across all trials and both arms (RR = 0.98, 95% CI 0.69 – 1.38, I-squared = 0%, p = 0.874).  Conclusion We found no evidence in favor of a difference between uninterrupted and interrupted administration of NOACs regarding the primary outcome of clinical thromboembolic and bleeding. Abstract Figure. Meta-analysis of the primary outcome

scholarly journals 5-HT3 receptor antagonists for the prevention of perioperative shivering undergoing spinal anaesthesia: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e038293
Author(s):  
Qi-Hong Shen ◽  
Hui-Fang Li ◽  
Xuyan Zhou ◽  
Yaping Lu ◽  
Xiao-Zong Yuan
Keyword(s):  
Systematic Review ◽  
Spinal Anaesthesia ◽  
Randomised Controlled Trials ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Receptor Antagonists ◽  
Assessment Development ◽  
Different Types ◽  
Randomised Controlled

ObjectivePerioperative shivering (POS) is a common complication in patients undergoing spinal anaesthesia. The present study investigated the efficacy of 5-HT3 receptor antagonists in preventing POS following spinal anaesthesia.DesignSystematic review and meta-analysis.Data sourcesPubmed, Embase, the Web of Science and Cochrane Library were searched from database establishment on 31 July 2019.Eligibility criteriaRandomised controlled trials that reported the effects of 5-HT3 receptor antagonists in the prevention of POS in patients after spinal anaesthesia.Data extraction and synthesisTwo reviewers independently extracted data. The primary outcome of the present study was the incidence of POS. The risk of bias for the included studies was assessed according to the Cochrane Handbook. The quality of primary outcome was evaluated by Grading of Recommendations Assessment, Development and Evaluation. Trial sequential analysis for the primary outcome was performed to reduce the type 1 error caused by repeated meta-analysis and the required information size was calculated.ResultsA total of 13 randomised controlled trials consisting of 1139 patients were included. The overall incidence of POS was significantly lower in the 5-HT3 receptor antagonists group (risk ratio 0.31; 95% CI 0.26 to 0.38; p<0.01; I2=0%). Subgroup analysis for different types of 5-HT3 receptor antagonists and timing of administration produced similar results. Also, patients had a lower incidence of postoperative nausea and vomiting after administrating 5-HT3 receptor antagonists. No statistically significant differences in drug-related adverse effects were observed. Grading of Recommendations Assessment, Development and Evaluation revealed a high level of evidence. The cumulative z-curve crossed the trial sequential monitoring boundary.ConclusionsThe present study revealed that prophylactic 5-HT3 receptor antagonists were an effective measure for reducing the incidence of POS in patients after spinal anaesthesia. However, further studies investigating the different types of surgeries are required.PROSPERO registration numberCRD42019148191.

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