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Hierarchical statistical techniques are necessary to draw reliable conclusions from analysis of isolated cardiomyocyte studies.

ABSTRACT: Aims:It is generally accepted that post-MI heart failure (HF) changes a variety of aspects of sarcoplasmic reticular Ca2+ fluxes but for some aspects there is disagreement over whether there is an increase or decrease. The commonest statistical approach is to treat data collected from each cell as independent, even though they are really clustered with multiple likely similar cells from each heart. In this study, we test whether this statistical assumption of independence can lead the investigator to draw conclusions that would be considered erroneous if the analysis handled clustering with specific statistical techniques (hierarchical tests). Methods and results:Ca2+ transients were recorded in cells loaded with Fura-2AM and sparks were recorded in cells loaded with Fluo-4AM. Data were analysed twice, once with the common statistical approach (assumption of independence) and once with hierarchical statistical methodologies designed to allow for any clustering. The statistical tests found that there was significant hierarchical clustering. This caused the common statistical approach to underestimate the standard error and report artificially small P values. For example, this would have led to the erroneous conclusion that time to 50% peak transient amplitude was significantly prolonged in HF. Spark analysis showed clustering, both within each cell and also within each rat, for morphological variables. This means that a three-level hierarchical model is sometimes required for such measures. Standard statistical methodologies, if used instead, erroneously suggest that spark amplitude is significantly greater in HF and spark duration is reduced in HF. Conclusion:Ca2+ fluxes in isolated cardiomyocytes show so much clustering that the common statistical approach that assumes independence of each data point will frequently give the false appearance of statistically significant changes. Hierarchical statistical methodologies need a little more effort, but are necessary for reliable conclusions. We present cost-free simple tools for performing these analyses.

SUBMITTER: Sikkel MB

PROVIDER: S-EPMC5852514 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Hierarchical statistical techniques are necessary to draw reliable conclusions from analysis of isolated cardiomyocyte studies.

Sikkel Markus B MB Francis Darrel P DP Howard James J Gordon Fabiana F Rowlands Christina C Peters Nicholas S NS Lyon Alexander R AR Harding Sian E SE MacLeod Kenneth T KT

Cardiovascular research 20171201 14

<h4>Aims</h4>It is generally accepted that post-MI heart failure (HF) changes a variety of aspects of sarcoplasmic reticular Ca2+ fluxes but for some aspects there is disagreement over whether there is an increase or decrease. The commonest statistical approach is to treat data collected from each cell as independent, even though they are really clustered with multiple likely similar cells from each heart. In this study, we test whether this statistical assumption of independence can lead the in ...[more]

PMID: 29016722

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Project description:BackgroundWe aimed to compare the efficacy and safety of bivalirudin versus heparin as the anticoagulant in patients undergoing extracorporeal membrane oxygenation (ECMO).MethodsWe conducted a search in PubMed, Embase and the Cochrane Library for all the studies in which bivalirudin was compared to heparin as the anticoagulant for ECMO. Efficacy outcomes were defined as the time to reach therapeutic levels, time within therapeutic range (TTR), thrombotic events, circuit thrombosis, circuit exchanges. Safety outcomes were reported as heparin-induced thrombocytopenia (HIT), major bleeding events, minor bleeding events. Other outcomes included hospital length of stay (LOS), ICU LOS, mortality, 30-day mortality and in-hospital mortality.ResultsTen studies with 1091 patients were included for meta-analysis. A significant reduction in thrombotic events [OR 0.51, 95%CI 0.36,0.73, p = 0.0002, I2 = 0%], major bleeding events [OR 0.31, 95%CI 0.10,0.92, p = 0.04, I2 = 75%] and in-hospital mortality [OR 0.63, 95%CI 0.44,0.89, p = 0.009, I2 = 0%] treated with bivalirudin were found compared with heparin. There were no significant differences between groups regarding the time to reach therapeutic levels [MD 3.53, 95%CI -4.02,11.09, p = 0.36, I2 = 49%], TTR [MD 8.64, 95%CI -1.72,18.65, p = 0.10, I2 = 77%], circuit exchanges [OR 0.92, 95%CI 0.27,3.12, p = 0.90, I2 = 38%], HIT [OR 0.25, 95%CI 0.02,2.52, p = 0.24, I2 = 0%], minor bleeding events [OR 0.93, 95%CI 0.38,2.29, p = 0.87, I2 = 0%], hospital LOS [MD -2.93, 95%CI -9.01,3.15, p = 0.34, I2 = 45%], ICU LOS [MD -4.22, 95%CI -10.07,1.62, p = 0.16, I2 = 0%], mortality [OR 1.84, 95%CI 0.58,5.85, p = 0.30, I2 = 60%] and 30-day mortality [OR 0.75, 95%CI 0.38,1.48, p = 0.41, I2 = 0%].ConclusionBivalirudin probably be a potential choice for ECMO anticoagulation. However, based on the included studies' limitation, the superiority of bivalirudin over heparin for anticoagulation in the ECMO population still require further prospective randomized controlled studies before a definite conclusion.

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Hierarchical statistical techniques are necessary to draw reliable conclusions from analysis of isolated cardiomyocyte studies.

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Hierarchical statistical techniques are necessary to draw reliable conclusions from analysis of isolated cardiomyocyte studies.

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