SMART and as-needed therapies in mild-to-severe asthma: a network meta-analysis

To date, there are no network meta-analyses comparing the impact of as-needed treatments in asthma, including the single maintenance and reliever therapy (known as “SMART” or “MART”; for simplicity, SMART will be used hereafter) and the use of inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination exclusively on an as-needed basis. Therefore, we performed a systematic review and network meta-analysis concerning the efficacy and safety of SMART and as-needed therapies in asthma. Data from 32 096 asthmatic patients were extracted from 21 studies, lasting from 6 to 12 months. In adult mild-to-moderate asthmatic patients low-dose SMART and as-needed low-dose ICS/LABA combination were significantly (relative effect <0.78; p<0.05) more effective than the other as-needed therapies in reducing the risk of exacerbation, and both were ranked as the first treatment option reaching the first quartile of the surface under the cumulative ranking curve analysis (SUCRA). In adult moderate-to-severe asthmatic patients, low-dose to medium-dose SMART and high-dose ICS/LABA+as-needed short-acting β2-agonist were equally effective in reducing the risk of severe asthma exacerbation (p>0.05), although only low- to medium-dose SMART was ranked as the first treatment option (first SUCRA quartile). Overall, these treatments were well tolerated, and effective also on lung function and disease control. This study supports SMART and as-needed therapies as a suitable therapeutic option for asthma, by providing the most effective positioning of each specific treatment according to the disease severity.

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Do adjuvants add to the efficacy and tolerance of bowel preparations? A meta-analysis of randomized trials

Endoscopy ◽

10.1055/s-0043-119638 ◽

2017 ◽

Vol 50 (02) ◽

pp. 159-176 ◽

Cited By ~ 3

Author(s):

Sophie Restellini ◽

Omar Kherad ◽

Charles Menard ◽

Myriam Martel ◽

Alan Barkun

Keyword(s):

Randomized Trials ◽

Low Dose ◽

Meta Analysis ◽

High Dose ◽

Detection Rates ◽

Adenoma Detection ◽

Adenoma Detection Rates ◽

Split Dosing ◽

Bowel Preparations ◽

The Impact

Abstract Background and study aims Recommendations on adjuvant use with bowel preparations remain disparate. We performed a meta-analysis determining the clinical impact of adding an adjuvant to polyethylene glycol (PEG), sodium phosphate, picosulfate (PICO), or oral sulfate solutions (OSS)-based regimens. Methods Systematic searches were made of MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials from January 1980 to April 2016 that assessed preparations with or without adjuvants, given in split and non-split dosing, and PEG high- (> 3 L) or low-dose (≤ 2 L) regimens. Bowel cleansing efficacy was the primary outcome. Secondary outcomes included patient willingness to repeat the procedure, and polyp and adenoma detection rates. Results Of 3093 citations, 77 trials fulfilled the inclusion criteria. Overall, addition of an adjuvant compared with no adjuvant, irrespective of the type of preparation and mode of administration, yielded improvements in bowel cleanliness (odds ratio [OR] 1.23 [1.01 – 1.51]) without greater willingness to repeat (OR 1.40 [0.91 – 2.15]). Adjuvants combined with high-dose PEG significantly improved colon cleansing (OR 1.96 [1.32 – 2.94]). The odds for achieving adequate preparation with low-dose PEG with an adjuvant were not different to high-dose PEG alone (OR 0.95 [0.73 – 1.22]), but yielded improved tolerance (OR 3.22 [1.85 – 5.55]). However, split high-dose PEG yielded superior cleanliness to low-dose PEG with adjuvants (OR 2.53 [1.25 – 5.13]). No differences were noted for OSS and PICO comparisons, or for any products regarding polyp or adenoma detection rates. Conclusions Critical heterogeneity precludes firm conclusion on the impact of adjuvants with existing bowel preparations. Additional research is required to better characterize the methods of administration and resulting roles of adjuvants in an era of split-dosing.

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Efficacy of low or high-dose rituximab treatment in membranous nephropathy: a systematic review and meta-analysis

10.21203/rs.3.rs-408713/v1 ◽

2021 ◽

Author(s):

Naresh Kharbuja ◽

Min Wu ◽

Yu-Chen Han ◽

Dan Liu ◽

Bin Wang ◽

...

Keyword(s):

Membranous Nephropathy ◽

Low Dose ◽

Control Strategies ◽

Therapeutic Option ◽

Meta Analysis ◽

Biological Indicators ◽

High Dose ◽

Serious Adverse Events ◽

Protein Levels ◽

Significant Difference

Abstract Background: Rituximab (RTX) has emerged as a promising therapeutic option in patients with primary membranous nephropathy (MN). But the optimal dosing of RTX protocol has not been established. Recently, favorable outcomes even with low-dose of RTX has been described in MN patients. Thus, the aim of this meta-analysis is to compare the efficacy and safety between high-dose and low-dose RTX in patients with MN.Methods: After literature search, eligible studies were further classified into high-dose and low-dose groups according to the dosage of one cycle RTX therapy. A meta-analysis was performed to evaluate remission rates and changes in biological indicators in two groups. Results: Eight studies involving 588 patients were included in this meta-analysis. In comparison to the control groups (including cyclosporin, cyclophosphamide, chlorambucil, prednisone, non-immunosuppressive anti-proteinuria treatment), RTX significantly improved the complete remission (CR) rate. Furthermore, there is no significant difference between high-dose and low-dose RTX in inducing total remission (TR) and CR. Also, high-dose RTX did not significantly improve serum albumin, creatine and urinary protein levels when compared with the low-dose RTX group. However, high-dose RTX did reduce the serum PLA2R antibody titers in patients. Even the difference was not significant, there was a tendency for low-dose RTX to have less serious adverse events (SAEs) than high-dose RTX groups. Conclusion: RTX administration indicated a better efficacy than the control strategies for the treatment of primary MN. And a low-dose regimen of RTX was non-inferior to high-dose usage in inducing long-term TR up to 24 months and holds the superior tendency in preventing SAEs in MN patients.

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The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx113 ◽

2017 ◽

Vol 4 (3) ◽

Cited By ~ 8

Author(s):

Nikolaos Andreatos ◽

Myrto Eleni Flokas ◽

Anna Apostolopoulou ◽

Michail Alevizakos ◽

Eleftherios Mylonakis

Keyword(s):

Febrile Neutropenia ◽

Low Dose ◽

Meta Analysis ◽

Treatment Discontinuation ◽

High Dose ◽

First Line ◽

The Impact ◽

Dose Dependent ◽

Overall Mortality

Abstract Background Despite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting. Methods We searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016. Results Thirty-two trials, reporting on 5724 patients, were included. Clinical efficacy was similar between study arms (P = .698), but overall mortality was greater among cefepime-treated patients (risk ratio [RR] = 1.321; 95% confidence interval [CI], 1.035–1.686; P = .025). Also of note, this effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038–2.727; P = .035). Cefepime was also associated with increased mortality compared with carbapenems (RR = 1.668; 95% CI, 1.089–2.555; P = .019), a finding possibly influenced by cefepime dose, because carbapenems were compared with low-dose cefepime monotherapy in 5 of 9 trials. Treatment failure in clinically documented infections was also more frequent with cefepime (RR = 1.143; 95% CI, 1.004–1.300; P = .043). Toxicity-related treatment discontinuation was more common among patients that received high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in fewer adverse events, compared with alternative monotherapy (P = .009). Conclusions Cefepime demonstrated increased mortality compared with carbapenems, reduced efficacy in clinically documented infections, and higher rates of toxicity-related treatment discontinuation. The impact of cefepime dosing on these outcomes is important, because low-dose regimens were associated with lower toxicity at the expense of higher mortality.

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Comparison of the Efficacy and Safety of Different Doses of Linaclotide for Patients with Chronic Constipation: A Meta-Analysis and Bayesian Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9923879 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Jiao Yang ◽

YanChang Lei

Keyword(s):

Bayesian Analysis ◽

Chronic Constipation ◽

Dose Group ◽

Low Dose ◽

Meta Analysis ◽

Responder Rate ◽

High Dose Group ◽

High Dose ◽

Efficacy And Safety ◽

Medium Dose

Background. It is ambiguous whether a higher dose of linaclotide provides higher efficacy for chronic constipation (CC) patients. The meta-analysis aimed to assess the efficacy and safety of linaclotide doses ranging from 62.5 μg to 600 μg for CC patients. Methods. A comprehensive search was conducted, and STATA16 software was used for data analysis. Results. Seven studies with 4,107 patients were eligible. A significantly enhanced number of completely spontaneous bowel movement (CSBM) responders were found in the extremely low-dose group (OR: 2.94; 95% CI: 1.98–4.34; p < 0.001 ), the low-dose group (OR: 3.24; 95% CI: 2.44–4.31; p < 0.001 ), the medium-dose group (OR: 3.08; 95% CI: 1.46–6.50; p = 0.003 ), and high-dose group (OR: 4.79; 95% CI: 3.04–7.54; p < 0.001 ). Bayesian analysis showed the high-dose group obtained the maximum CSBM responder rate (OR: 4.94; 95% credible interval (CrI): 3.22–7.79; probability rank = 0.87) indirectly compared with extremely low-dose, low-dose, and medium-dose groups. However, no significant difference presented in the CSBM responder rate by pairwise comparisons of the different dose groups. Additionally, no more any adverse events occurred in the higher linaclotide dose group (RR: 0.91; 95% CrI: 0.60–1.38) indirectly compared with other dose groups. Conclusions. High dose of linaclotide could be more effective and safer for CC patients, which need more trials to confirm in the future.

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Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials

Hormone and Metabolic Research ◽

10.1055/a-1240-5058 ◽

2020 ◽

Vol 52 (12) ◽

pp. 841-849

Author(s):

Chunmei Xu ◽

Ping Wang ◽

Huikai Miao ◽

Tianyue Xie ◽

Xiaojun Zhou ◽

...

Keyword(s):

Fixed Effects ◽

Dose Group ◽

Low Dose ◽

Radioiodine Therapy ◽

Meta Analysis ◽

High Dose Group ◽

High Dose ◽

Fixed Effects Model ◽

Recombinant Human Thyrotropin

AbstractA potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

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Effectiveness of Valganciclovir 900mg Versus 450mg for Cytomegalovirus Prophylaxis in Renal Transplantation: A Systematic Review and Meta-Analysis

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3805b ◽

2017 ◽

Vol 20 ◽

pp. 168 ◽

Cited By ~ 3

Author(s):

Wang Xin ◽

Yang Hui ◽

Zhang Xiaodong ◽

Cui Xiangli ◽

Wang Shihui ◽

...

Keyword(s):

Renal Transplantation ◽

Acute Rejection ◽

Low Dose ◽

Opportunistic Infections ◽

Meta Analysis ◽

High Dose ◽

Renal Transplant Recipients ◽

Significant Difference ◽

Allograft Loss ◽

Cmv Disease

Objectives: Valganciclovir 900 mg/day is approved for cytomegalovirus (CMV) prophylaxis, but 450 mg/day is seems also effective. We systematically reviewed the efficacy and safety of low-dose versus high-dose valganciclovir prophylaxis in renal transplantation recipients. Methods: An electronic search was conducted up to November 29, 2016. The primary outcomes were incidences of CMV, CMV disease, mortality and opportunistic infection. The second outcomes were acute rejection, allograft loss, adverse drug reaction (ADR). Results: 7 cohort studies, all with high quality involving (1431 patients) were included. There was no significant difference of the incidence of following CMV disease (1271 patients, odds ratio [OR] 0.74, 95% confidence interval [CI], 0.38-1.43, p=0.36), acute rejection (1343 patients, OR 0.77, 95%CI 0.53-1.14, p=0.19), allograft loss (1271 patients, OR 0.64, 95%CI 0.31-1.35, p=0.24), mortality (1271 patients, OR 0.55, 95%CI 0.20-1.47, p=0.23) and opportunistic infections (OI) (985 patients, OR 0.76, 95%CI 0.52-1.10, p=0.14) between the low-dose and the high-dose valganciclovir prophylaxis. And no significant difference was observed for premature valganciclovir discontinuation (1010 patients, OR 0.81, 95%CI 0.52-1.25, p=0.33) and the incidence of leukopenia (1082 patients, OR 0.65, 95%CI 0.34-1.22, p=0.18) between the two regimens. Conclusion: 450 mg and 900 mg doses of valganciclovir are equipotent for CMV universal prophylaxis. CMV 450 mg prophylaxis should be used for renal transplant recipients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm8010045 ◽

2019 ◽

Vol 8 (1) ◽

pp. 45 ◽

Cited By ~ 17

Author(s):

Tamara Y. Milder ◽

Sophie L. Stocker ◽

Christina Abdel Shaheed ◽

Lucy McGrath-Cadell ◽

Dorit Samocha-Bonet ◽

...

Keyword(s):

Type 2 Diabetes ◽

Combination Therapy ◽

Low Dose ◽

Meta Analysis ◽

Sglt2 Inhibitor ◽

Cochrane Library ◽

High Dose ◽

Dose Combination ◽

Inhibitor Combination

Background: Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. Aims: To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. Methods: PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24–26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. Results: In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); −0.55% (−0.67, −0.43)) and weight (−2.00 kg (−2.34, −1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (−0.59% (−0.72, −0.46)) and weight (−0.57 kg (−0.89, −0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; −0.47 kg (−0.88, −0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. Conclusions: Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.

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