scholarly journals Excluded versus included patients in a randomized controlled trial of infections caused by carbapenem-resistant Gram-negative bacteria: relevance to external validity

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vered Daitch ◽  
Mical Paul ◽  
George L. Daikos ◽  
Emanuele Durante-Mangoni ◽  
Dafna Yahav ◽  
...  

Abstract Background Population external validity is the extent to which an experimental study results can be generalized from a specific sample to a defined population. In order to apply the results of a study, we should be able to assess its population external validity. We performed an investigator-initiated randomized controlled trial (RCT) (AIDA study), which compared colistin-meropenem combination therapy to colistin monotherapy in the treatment of patients infected with carbapenem-resistant Gram-negative bacteria. In order to examine the study’s population external validity and to substantiate the use of AIDA study results in clinical practice, we performed a concomitant observational trial. Methods The study was conducted between October 1st, 2013 and January 31st, 2017 (during the RCTs recruitment period) in Greece, Israel and Italy. Patients included in the observational arm of the study have fulfilled clinical and microbiological inclusion criteria but were excluded from the RCT due to receipt of colistin for > 96 h, refusal to participate, or prior inclusion in the RCT. Non-randomized cases were compared to randomized patients. The primary outcome was clinical failure at 14 days of infection onset. Results Analysis included 701 patients. Patients were infected mainly with Acinetobacter baumannii [78.2% (548/701)]. The most common reason for exclusion was refusal to participate [62% (183/295)]. Non-randomized and randomized patients were similar in most of the demographic and background parameters, though randomized patients showed minor differences towards a more severe infection. Combination therapy was less common in non-randomized patients [31.9% (53/166) vs. 51.2% (208/406), p = 0.000]. Randomized patients received longer treatment of colistin [13 days (IQR 10–16) vs. 8.5 days (IQR 0–15), p = 0.000]. Univariate analysis showed that non-randomized patients were more inclined to clinical failure on day 14 from infection onset [82% (242/295) vs. 75.5% (307/406), p = 0.042]. After adjusting for other variables, non-inclusion was not an independent risk factor for clinical failure at day 14. Conclusion The similarity between the observational arm and RCT patients has strengthened our confidence in the population external validity of the AIDA trial. Adding an observational arm to intervention studies can help increase the population external validity and improve implementation of study results in clinical practice. Trial registration The trial was registered with ClinicalTrials.gov, number NCT01732250 on November 22, 2012.

2018 ◽  
Vol 10 (1) ◽  
pp. 2018030 ◽  
Author(s):  
Igor Stoma ◽  
Igor Karpov ◽  
Igor Iskrov ◽  
Svetlana Krivenko ◽  
Anatoly Uss ◽  
...  

BackgroundIntestinal colonization by MDR/XDR gram-negative bacteria leads to an increased risk of subsequent bloodstream infections (BSI) in patients receiving chemotherapy as a treatment for hematologic malignancies.ObjectivesThe objective of this study was to evaluate the efficacy of oral colistin in eradicating the intestinal carriage of MDR/XDR Gram-negative bacteria in patients with hematological malignancies.MethodsIn a tertiary hematology center adult patients with intestinal colonization by MDR/XDR Gram-negative bacteria were included in a randomized controlled trial (RCT) during a period from November 2016 to October 2017. Patients were treated with oral colistin for 14 days or observed with the primary outcome set as a decolonization on day 21 post-treatment. Secondary outcomes included treatment safety and changes in MICs of isolated microorganisms. ClinicalTrials.gov Identifier: NCT02966457.ResultsShort-time positive effect (61.3% vs 32.3%; OR 3.32; 95% CI 1.17–9.44; p=0.0241) was demonstrated on the day 14 of colistin treatment, without any statistical difference on day 21 post-treatment. The incidence of BSI in decolonization group was lower in the first 30 days after the intervention (3.2% vs 12.9%), but overall in the 90-day observation period it did not show any advantages comparing to control group (log-rank test; p=0.4721). No serious adverse effects or increase in resistance to colistin was observed.ConclusionsThis study suggests that in hematological patients the strategy of selective intestinal decolonization by colistin may be beneficial to decrease the rate of MDR/XDR Gram-negative intestinal colonization and the risk of BSI in the short-term period, having no long-term sustainable effects.


Author(s):  
Gro Grimnes ◽  
Soerajja Bhoelan ◽  
Kristian Hindberg ◽  
Mark Davids ◽  
Max Nieuwdorp ◽  
...  

Abstract Rationale Inflammation is present in several conditions associated with risk of venous thromboembolism. The gut microbiome might be a source of systemic inflammation and activation of coagulation, by translocation of lipopolysaccharides from gram-negative bacteria to the systemic circulation. Objective To investigate whether a vancomycin-induced shift of the gut microbiome in a gram-negative direction influences systemic inflammation and plasma factor (F) VIII procoagulant activity (FVIII:C). Methods and Results We performed a randomized controlled trial including 43 healthy volunteers aged 19 to 37 years. Twenty-one were randomized to 7 days of oral vancomycin intake and 22 served as controls. Feces and blood were sampled at baseline, the day after the end of intervention, and 3 weeks after intervention. Gut microbiome composition was assessed by amplicon sequencing. FVIII:C was measured using an activated partial thromboplastin time-based assay, cytokines were measured using multiplex technology, complement activation was measured using the enzyme-linked immunosorbent assay, and high-sensitivity C-reactive protein (CRP) was measured by an immunoturbidimetric assay. Vancomycin intake reduced gut microbiome diversity and increased the abundance of gram-negative bacteria. Change in FVIII:C in the intervention group was +4 IU/dL versus −6 IU/dL (p = 0.01) in the control group. A similar change was observed for log-transformed CRP (+0.21 mg/dL vs. −0.25 mg/dL, p = 0.04). The cytokines and complement activation markers remained similar in the two groups. Conclusion The found slight increases in FVIII:C and CRP levels might support the hypothesis that a vancomycin-induced gram-negative shift in the gut microbiome could induce increased systemic inflammation and thereby a procoagulant state.


2021 ◽  
Author(s):  
Kyoko Tanaka ◽  
Maoko Hayakawa ◽  
Chihiro Noda ◽  
Moemi Nakamura ◽  
Akio Nakamura ◽  
...  

Abstract Procedures and actions such as injections and immobilization cause pain and distress to children. In the pediatric field, there is a need for interventions and support to alleviate the pain and distress caused by such medical procedures. In recent years, the introduction of robots as a means of distraction has begun to be attempted. In this study, we conducted a non-randomized controlled trial to examine the effect of intervention using ‘aibo’, a dog-like robot which has artificial intelligence (AI), to promote distraction in children after vaccination. As a result, 57 children (32 in the intervention group) participated in the study. Results of a t-test with the control group showed that the intervention group using aibo had significantly less pain following the post-vaccination intervention than the control group using stuffed dog (Face Scale, t(55) = 2.582, p = .0125; Behavioral Observation Scale, t(55) = 2.772, p = .00759). The results support the hypothesis that the aibo intervention group will be less distressed and able to calm down more quickly after vaccination than the control group. Conclusion : AI-powered aibo interventions that allow for interactive interaction can be an effective distraction method during painful procedures such as vaccinations.


2018 ◽  
Vol 7 (8) ◽  
pp. 208 ◽  
Author(s):  
I-Ling Cheng ◽  
Yu-Hung Chen ◽  
Chih-Cheng Lai ◽  
Hung-Jen Tang

This meta-analysis aims to compare intravenous colistin monotherapy and colistin-based combination therapy against carbapenem-resistant gram-negative bacteria (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July 2018. Only randomized controlled trials (RCTs) evaluating colistin alone and colistin-based combination therapy in the treatment of carbapenem-resistant GNB infections were included. The primary outcome was all-cause mortality. Five RCTs including 791 patients were included. Overall, colistin monotherapy was associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89–1.20, I2 = 0%) for all-cause mortality compared with colistin-based combination therapy. The non-significant difference was also detected in infection-related mortality (RR, 1.23, 95% CI, 0.91–1.67, I2 = 0%) and microbiologic response (RR, 0.86, 95% CI, 0.72–1.04, I2 = 62%). In addition, no significant difference was observed in the subgroup analysis—high or low dose, with or without a loading dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination with rifampicin. Finally, colistin monotherapy was not associated with lower nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84–1.21, I2 = 0%). Based on the analysis of the five RCTs, no differences were found between colistin monotherapy and colistin-based combination therapy against carbapenem-resistant GNB infections, especially for A. baumannii infections.


2003 ◽  
Vol 21 (5) ◽  
pp. 836-842 ◽  
Author(s):  
Cathy A. Coyne ◽  
Ronghui Xu ◽  
Peter Raich ◽  
Kathy Plomer ◽  
Mark Dignan ◽  
...  

Purpose: Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population. This study hypothesized that use of an easy-to-read consent statement, when compared with a standard consent statement, will result in higher patient comprehension of the clinical treatment protocol, lower patient anxiety, higher patient satisfaction, and higher patient accrual. Methods: A randomized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups. Institutions were randomly assigned to administer either an easy-to-read consent statement or the standard consent statement to patients being recruited to participate in selected cancer treatment trials. Telephone interviews were conducted with a total of 207 patients to assess study outcomes. Results: Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm. Patient comprehension and state anxiety were not affected by the intervention. Accrual rates into the parent studies also did not differ significantly between the two study groups. Conclusion: Clinical trial informed consent statements can be modified to be easier to read without omitting critical information. Patient anxiety and satisfaction can be affected by the consent document. The generalizability of these study results is limited by the characteristics of the patient sample. Ninety percent of the sample were white women, and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64, indicating a literacy level at or above the ninth grade.


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