Moxifloxacin and gatifloxacin for initial therapy of tuberculosis: a meta-analysis of randomized clinical trials.
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ABSTRACT:
SUBMITTER: Ruan Q
PROVIDER: S-EPMC4777926 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundShortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.MethodsNewly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.ResultsOf 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.Conclusions4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.Trial registrationClinical Trials Registry of India CTRI/2012/10/003060.
| S-EPMC3700922 | biostudies-literature
Project description:Granulomas are complex lung lesions that are the hallmark of tuberculosis (TB). Understanding antibiotic dynamics within lung granulomas will be vital to improving and shortening the long course of TB treatment. Three fluoroquinolones (FQs) are commonly prescribed as part of multi-drug resistant TB therapy: moxifloxacin (MXF), levofloxacin (LVX) or gatifloxacin (GFX). To date, insufficient data are available to support selection of one FQ over another, or to show that these drugs are clinically equivalent. To predict the efficacy of MXF, LVX and GFX at a single granuloma level, we integrate computational modeling with experimental datasets into a single mechanistic framework, GranSim. GranSim is a hybrid agent-based computational model that simulates granuloma formation and function, FQ plasma and tissue pharmacokinetics and pharmacodynamics and is based on extensive in vitro and in vivo data. We treat in silico granulomas with recommended daily doses of each FQ and compare efficacy by multiple metrics: bacterial load, sterilization rates, early bactericidal activity and efficacy under non-compliance and treatment interruption. GranSim reproduces in vivo plasma pharmacokinetics, spatial and temporal tissue pharmacokinetics and in vitro pharmacodynamics of these FQs. We predict that MXF kills intracellular bacteria more quickly than LVX and GFX due in part to a higher cellular accumulation ratio. We also show that all three FQs struggle to sterilize non-replicating bacteria residing in caseum. This is due to modest drug concentrations inside caseum and high inhibitory concentrations for this bacterial subpopulation. MXF and LVX have higher granuloma sterilization rates compared to GFX; and MXF performs better in a simulated non-compliance or treatment interruption scenario. We conclude that MXF has a small but potentially clinically significant advantage over LVX, as well as LVX over GFX. We illustrate how a systems pharmacology approach combining experimental and computational methods can guide antibiotic selection for TB.
| S-EPMC5560534 | biostudies-literature
Project description:BackgroundRecent randomized controlled trials (RCTs) suggest that ablation is superior to antiarrhythmic drugs (AADs) as an initial therapy for paroxysmal atrial fibrillation (pAF) to prevent arrhythmia recurrences. We performed an updated meta-analysis of RCTs, to include recent data from cryoballoon-based ablation and to compare arrhythmia-free survival and adverse events between ablation and AADs.MethodsWe searched MEDLINE and EMBASE from inception to December 2020. We included RCT comparing patients with pAF undergoing ablation or receiving AADs as an initial therapy. We combined data using the random-effects model to calculate hazards ratio (HR) for arrhythmia-free survival and odds ratio (OR) for adverse events.ResultsFive studies from 2005 to 2020 involving 985 patients were included (495 patients and 490 patients underwent ablation and medication as initial therapy, respectively). Patients who underwent ablation had higher freedom from atrial tachyarrhythmias (ATs) during the 12-24 months follow-up period (pooled HR = 0.48, 95% CI: 0.40-0.59, P < .001). In a subgroup analysis of ablation method used, both cryoablation group (pooled HR = 0.49, 95% CI: 0.38-0.64, P < .001) and radiofrequency ablation group (pooled HR = 0.47, 95%CI: 0.35-0.64, P < .001) showed reduction in AT recurrence compared with AAD group. There were no differences in adverse events including cerebrovascular accident, pericardial effusion or tamponade, pulmonary vein stenosis, acute coronary syndrome, deep vein thrombosis and pulmonary embolism, and bradycardia requiring a pacemaker.ConclusionCatheter ablation (both cryoablation and radiofrequency ablation) is superior to AAD as an initial therapy for pAF in efficacy for reducing AT recurrences without a compromise in adverse events.
| S-EPMC8637078 | biostudies-literature
Project description:BackgroundThis aim of this study was to provide an updated meta-analysis comparing antibiotic therapy with appendicectomy in adults (16 years or older) with uncomplicated acute appendicitis.MethodsA search for randomized clinical trials comparing antibiotic therapy with appendicectomy in adults with uncomplicated acute appendicitis from inception to 3 October 2021 in MEDLINE, Embase and CENTRAL with no language constraints was performed. Studies were excluded if they included paediatric participants or those with complicated appendicitis. Data on complications of treatment, treatment efficacy (defined in the antibiotic group as not undergoing appendicectomy within 1 year of enrolment, versus surgery without complications or no negative histology in the appendicectomy group), readmissions, and length of stay (LOS) were presented.ResultsEight RCTs involving 3203 participants (1613 antibiotics/1590 appendicectomy; 2041 males/1162 females) were included. There was no significant benefit of antibiotic treatment on complication rates (risk ratio (RR) 0.66, 95 per cent c.i. 0.41 to 1.04). Antibiotics had a reduced treatment efficacy compared with appendicectomy (RR 0.75, 95 per cent c.i. 0.63 to 0.89). Antibiotic treatment at 1 year was successful in 1016 of 1613 (62.9 per cent) participants. There was a six-fold increase in hospital readmissions within 1 year of enrolment in participants receiving antibiotic treatment (RR 6.28, 95 per cent c.i. 2.87 to 13.74). There was no difference in index admission LOS (mean difference 0.15 days (95 per cent c.i. -0.05 to 0.35)).ConclusionsEarlier optimism regarding the benefits of antibiotic therapy for uncomplicated acute appendicitis does not persist at the same level now that further, large trials have been included. If antibiotic treatment is to be offered routinely as first-line therapy, patients should be counselled appropriately.
| S-EPMC9379374 | biostudies-literature
Project description:The aims of this systematic review were to study the analgesic effect of real acupuncture and to explore whether sham acupuncture (SA) type is related to the estimated effect of real acupuncture for musculoskeletal pain. Five databases were searched. The outcome was pain or disability immediately (?1 week) following an intervention. Standardized mean differences (SMDs) with 95% confidence intervals were calculated. Meta-regression was used to explore possible sources of heterogeneity. Sixty-three studies (6382 individuals) were included. Eight condition types were included. The pooled effect size was moderate for pain relief (59 trials, 4980 individuals, SMD -0.61, 95% CI -0.76 to -0.47; P?<?0.001) and large for disability improvement (31 trials, 4876 individuals, -0.77, -1.05 to -0.49; P?<?0.001). In a univariate meta-regression model, sham needle location and/or depth could explain most or all heterogeneities for some conditions (e.g., shoulder pain, low back pain, osteoarthritis, myofascial pain, and fibromyalgia); however, the interactions between subgroups via these covariates were not significant (P?<?0.05). Our review provided low-quality evidence that real acupuncture has a moderate effect (approximate 12-point reduction on the 100-mm visual analogue scale) on musculoskeletal pain. SA type did not appear to be related to the estimated effect of real acupuncture.
| S-EPMC4965798 | biostudies-other
Project description:BackgroundThe efficacy and safety of preoperative chemoradiation therapy (CRT) for advanced esophago-gastric adenocarcinoma are still in question, and the prognosis of these patients is poor.MethodsWe systematically searched electronic databases from January 1990 to July 2014. The primary outcome was overall survival. The secondary outcomes were a R0 resection rate, positive rate of lymph node metastasis, postoperative recurrence rate, pathological complete response (pCR) rate and perioperative mortality. Overall survival was measured with a hazard ratio (HR), while other secondary outcomes were measured with an odds ratio (OR).ResultsSeven randomized controlled trials (RCTs) including 1085 patients were searched and, of these, 869 had adenocarcinoma. Patients receiving preoperative CRT had a longer overall survival (HR 0.74; 95% confidence interval (CI) 0.63-0.88), higher likelihood of R0 resection and greater chance of pCR, while they had a lower likelihood of lymph node metastasis and postoperative recurrence. The difference of perioperative mortality was non-significant. In addition, the result of the comparison between preoperative CRT and preoperative chemotherapy (CT) in two RCTs was non-significant.ConclusionPatients with resectable esophago-gastric adenocarcinoma can gain a survival advantage from preoperative CRT. However, limited to the number of RCTs, the effect of adding radiotherapy to preoperative CT separately is still uncertain and more high-quality prospective trials are needed.
| S-EPMC4415228 | biostudies-literature
Project description:BackgroundStudies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality.MethodsWe searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy.ResultsOf 3071 reports identified, 12 studies (n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62-0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72-0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67-0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69-1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials.InterpretationThe cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.
| S-EPMC3050946 | biostudies-literature
Project description:Importance:The physical benefits of resistance exercise training (RET) are well documented, but less is known regarding the association of RET with mental health outcomes. To date, no quantitative synthesis of the antidepressant effects of RET has been conducted. Objectives:To estimate the association of efficacy of RET with depressive symptoms and determine the extent to which logical, theoretical, and/or prior empirical variables are associated with depressive symptoms and whether the association of efficacy of RET with depressive symptoms accounts for variability in the overall effect size. Data Sources:Articles published before August 2017, located using Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science. Study Selection:Randomized clinical trials included randomization to RET (n = 947) or a nonactive control condition (n = 930). Data Extraction and Synthesis:Hedges d effect sizes were computed and random-effects models were used for all analyses. Meta-regression was conducted to quantify the potential moderating influence of participant and trial characteristics. Main Outcomes and Measures:Randomized clinical trials used validated measures of depressive symptoms assessed at baseline and midintervention and/or postintervention. Four primary moderators were selected a priori to provide focused research hypotheses about variation in effect size: total volume of prescribed RET, whether participants were healthy or physically or mentally ill, whether or not allocation and/or assessment were blinded, and whether or not the RET intervention resulted in a significant improvement in strength. Results:Fifty-four effects were derived from 33 randomized clinical trials involving 1877 participants. Resistance exercise training was associated with a significant reduction in depressive symptoms with a moderate-sized mean effect ∆ of 0.66 (95% CI, 0.48-0.83; z = 7.35; P < .001). Significant heterogeneity was indicated (total Q = 216.92, df = 53; P < .001; I2 = 76.0% [95% CI, 72.7%-79.0%]), and sampling error accounted for 32.9% of observed variance. The number needed to treat was 4. Total volume of prescribed RET, participant health status, and strength improvements were not significantly associated with the antidepressant effect of RET. However, smaller reductions in depressive symptoms were derived from randomized clinical trials with blinded allocation and/or assessment. Conclusions and Relevance:Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant improvements in strength. Better-quality randomized clinical trials blinding both allocation and assessment and comparing RET with other empirically supported treatments for depressive symptoms are needed.
| S-EPMC6137526 | biostudies-other
Project description:High-intensity laser therapy (HILT) is one of the therapeutic approaches used in the treatment of musculoskeletal disorders (MSD). The main objective of this study was to examine the effectiveness of HILT for reducing pain and improving functionality in people with MSD. Ten databases were systematically searched for randomized trials published up to 28 February 2022. Randomized clinical trials (RCTs) assessing the effectiveness of HILT on MSD were included. The main outcome measures were pain and functionality. In total, 48 RCTs were included in the qualitative synthesis and 44 RCTs in the quantitative analysis. HILT showed a decrease on the pain VAS (mean difference (MD) = -1.3 cm; confidence interval (CI) 95%: -1.6 to -1.0) and an improvement in functionality (standardized mean difference (SMD) = -1.0; CI95%: -1.4 to -0.7), with low and moderate quality of evidence, respectively. A greater effect was observed when compared with control than with other conservative treatments, both on pain (χ2 = 20.6; p < 0.001) and functionality (χ2 = 5.1; p = 0.02). Differences in the effectiveness of HILT were found depending on the location (χ2 = 40.1 p < 0.001), with further improved functionality in MSD of the knee and shoulder. HILT is an effective treatment for improving pain, functionality, range of motion, and quality of life in people with MSD, although these findings must be treated with caution due to the high risk of bias in the studies. Further clinical trials should be well designed to lower the risk of bias.
| S-EPMC9963402 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is strongly associated with high morbidity and mortality of critically ill patients. In the last years several different biological markers with higher sensitivity and specificity for the occurrence of renal impairment have been developed in order to promptly recognize and treat AKI. Nonetheless, their potential role in improving patients' outcome remains unclear since the effectiveness of an "earlier" initiation of renal replacement therapy (RRT) is still debated. Since one large, high-quality randomized clinical trial has been recently pubblished, we decided to perform a meta-analysis of all the RCTs ever performed on "earlier" initiation of RRT versus standard RRT in critically ill patients with AKI to evaluate its effect on major outcomes.MethodsPertinent studies were independently searched in BioMedCentral, PubMed, Embase, and Cochrane Central Register of clinical trials. The following inclusion criteria were used: random allocation to treatment ("earlier" initiation of RRT versus later/standard initiation); critically ill patients.ResultsTen trials randomizing 2214 patients, 1073 to earlier initiation of RRT and 1141 to later initiation were included. No difference in mortality (43.3% (465 of 1073) for those receiving early RRT and 40.8% (466 of 1141) for controls, p = 0.97) and survival without dependence on RRT (3.6% (34 of 931) for those receiving early RRT and 4.2% (40 of 939) for controls, p = 0.51) were observed in the overall population. On the contrary, early initiation of RRT was associated with a significant reduction in hospital length of stay. No differences in occurrence of adverse events were observed.ConclusionsOur study suggests that early initiation of RRT in critically ill patients with AKI does not provide a clinically relevant advantage when compared with standard/late initiation.
| S-EPMC6492439 | biostudies-literature