Statistical Considerations for Performing Multiple Tests in a Single Experiment. 2. Comparisons Among Several Therapies

O’Brien, Peter C.; Shampo, Marc A.

doi:10.1016/s0025-6196(12)62363-5

Cited by 34 publications

(10 citation statements)

References 5 publications

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“…The overall null hypothesis that no differences existed among any of the treatment groups was analyzed with the Kruskal-Wallis test to estimate the per-experiment type I error rate. Individual pairwise comparisons were performed only if the preliminary Kruskal-Wallis test indicated significant differences among treatment groups at the ␣ ϭ 0.05 level (36). The reported P values for individual treatment group comparisons therefore reflect the comparisonwise type 1 statistical error rate conditional on an experimentwise error rate of P Յ 0.05 (36).…”

Section: Methodsmentioning

confidence: 99%

“…Individual pairwise comparisons were performed only if the preliminary Kruskal-Wallis test indicated significant differences among treatment groups at the ␣ ϭ 0.05 level (36). The reported P values for individual treatment group comparisons therefore reflect the comparisonwise type 1 statistical error rate conditional on an experimentwise error rate of P Յ 0.05 (36). Differences between pairwise comparisons were considered significant at the ␣ ϭ 0.05 level.…”

Section: Methodsmentioning

confidence: 99%

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Effective treatment of cephalosporin-rifampin combinations against cryptic methicillin-resistant beta-lactamase-producing coagulase-negative staphylococcal experimental endocarditis

Brandt

Rouse

Tallan

et al. 1995

Antimicrob Agents Chemother

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The efficacy of cefazolin or cefpirome alone or combined with rifampin was compared with that of vancomycin alone or combined with rifampin in an experimental model of methicillin-resistant, ␤-lactamaseproducing, coagulase-negative staphylococcal endocarditis. Phenotypically, the mecA gene-positive strain used in vivo did not exhibit methicillin resistance by the agar dilution or disk susceptibility method but was resistant in vitro (oxacillin MIC, 64 g/ml) by the microtiter dilution method with 2% NaCl supplementation. Macrodilution broth susceptibilities at standard inocula failed to demonstrate cross-resistance of staphylococci to cefazolin (MIC, 8 g/ml) or cefpirome (MIC, 4 g/ml). In vivo, vancomycin and cefpirome had similar activities, and both regimens were more effective than was cefazolin alone. While the MIC of rifampin was low (0.031 g/ml), monotherapy with rifampin resulted in a bimodal distribution of outcomes due to the expected emergence of resistant mutants. The results in vitro of time-kill synergy studies using rifampin in combination with cefazolin or cefpirome varied with the antimicrobial concentrations tested and did not reliably predict activities in vivo of rifampin-beta-lactam combination therapies. Cefpirome, but not cefazolin or vancomycin, in combination with rifampin was synergistic in vivo. Cefpirome in combination with rifampin was more effective than was cefazolin in combination with rifampin. Both cephalosporin-rifampin regimens were significantly more effective than was cephalosporin or vancomycin monotherapy and were as effective as vancomycin combined with rifampin. These data support further evaluation of rifampin-beta-lactam combinations as possible alternative therapies to vancomycin-containing regimens for selected methicillin-resistant coagulasenegative staphylococcal infections.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effective treatment of cephalosporin-rifampin combinations against cryptic methicillin-resistant beta-lactamase-producing coagulase-negative staphylococcal experimental endocarditis

Brandt

Rouse

Tallan

et al. 1995

Antimicrob Agents Chemother

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“…Comparisons of two means used the unpaired Student's t test. In studies involving multiple comparisons, the threshold value for statistical significance was adjusted using the Bonferroni correction (28). Differences among groups of rats with respect to diabetes-free survival were analyzed by the KaplanMeier method using the log-rank statistic (29).…”

Section: Statisticsmentioning

confidence: 99%

A Regulatory CD4+ T Cell Subset in the BB Rat Model of Autoimmune Diabetes Expresses Neither CD25 Nor Foxp3

Hillebrands

Whalen

Visser

et al. 2006

The Journal of Immunology

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Biobreeding (BB) rats model type 1 autoimmune diabetes (T1D). BB diabetes-prone (BBDP) rats develop T1D spontaneously. BB diabetes-resistant (BBDR) rats develop T1D after immunological perturbations that include regulatory T cell (Treg) depletion plus administration of low doses of a TLR ligand, polyinosinic-polycytidylic acid. Using both models, we analyzed CD4+CD25+ and CD4+CD45RC− candidate rat Treg populations. In BBDR and control Wistar Furth rats, CD25+ T cells comprised 5–8% of CD4+ T cells. In vitro, rat CD4+CD25+ T cells were hyporesponsive and suppressed T cell proliferation in the absence of TGF-β and IL-10, suggesting that they are natural Tregs. In contrast, CD4+CD45RC− T cells proliferated in vitro in response to mitogen and were not suppressive. Adoptive transfer of purified CD4+CD25+ BBDR T cells to prediabetic BBDP rats prevented diabetes in 80% of recipients. Surprisingly, CD4+CD45RC−CD25− T cells were equally protective. Quantitative studies in an adoptive cotransfer model confirmed the protective capability of both cell populations, but the latter was less potent on a per cell basis. The disease-suppressing CD4+CD45RC−CD25− population expressed PD-1 but not Foxp3, which was confined to CD4+CD25+ cells. We conclude that CD4+CD25+ cells in the BBDR rat act in vitro and in vivo as natural Tregs. In addition, another population that is CD4+CD45RC−CD25− also participates in the regulation of autoimmune diabetes.

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“…For quantitative nonparametric analysis, samples with no growth on the lowest dilution ("sterile" vegetations) were assigned half of the value of the lowest detectable quantity of microorganisms. The overall null hypothesis that no differences in mean log1o CFU of staphylo- Wallis test (10). Pairwise comparisons of treatment groups were performed by the Wilcoxon rank sum test (10).…”

mentioning

confidence: 99%

“…The overall null hypothesis that no differences in mean log1o CFU of staphylo- Wallis test (10). Pairwise comparisons of treatment groups were performed by the Wilcoxon rank sum test (10). The MICs (in micrograms per milliliter) for the strain used in vivo were 0.5 for nafcillin, 0.5 for cefazolin, 1 for cefpirome, 0.015 for rifampin, and 1 for gentamicin.…”

mentioning

confidence: 99%

Failure of time-kill synergy studies using subinhibitory antimicrobial concentrations to predict in vivo antagonism of cephalosporin-rifampin combinations against Staphylococcus aureus

Brandt

Rouse

Tallan

et al. 1994

Antimicrob Agents Chemother

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Results of in vitro time-kill synergy studies using subinhibitory, inhibitory, or suprainhibitory concentrations of bactericidal agents were compared with treatment outcomes of experimental infective endocarditis due to a methicillin-susceptible strain of Staphylococcus aureus. For rifampin-cephalosporin combinations, in vitro synergy testing using recommended fractions of the MIC failed to predict antagonism in vivo while concentrations above the MIC corresponded with antagonism in vivo.

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Statistical Considerations for Performing Multiple Tests in a Single Experiment. 2. Comparisons Among Several Therapies

Cited by 34 publications

References 5 publications

Effective treatment of cephalosporin-rifampin combinations against cryptic methicillin-resistant beta-lactamase-producing coagulase-negative staphylococcal experimental endocarditis

Effective treatment of cephalosporin-rifampin combinations against cryptic methicillin-resistant beta-lactamase-producing coagulase-negative staphylococcal experimental endocarditis

A Regulatory CD4+ T Cell Subset in the BB Rat Model of Autoimmune Diabetes Expresses Neither CD25 Nor Foxp3

Failure of time-kill synergy studies using subinhibitory antimicrobial concentrations to predict in vivo antagonism of cephalosporin-rifampin combinations against Staphylococcus aureus

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