Appropriate Clinical Monitoring as Prevention Against Untoward Side Effects of Prolonged Aminoglycoside Treatment in Patients Treated for Tuberculosis 公开

Choquette Deutschle, Amber (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/j9602144d?locale=zh
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Abstract

Background: The author examined the association between better clinical monitoring and the development of aminoglycoside toxicity among patients who received aminoglycosides as treatment for drug-resistant tuberculosis in a retrospective cohort study. Original data were obtained via chart abstraction for patients admitted to the tuberculosis unit of the University of Texas Health Science Center in Tyler, TX between 1985 and 2010. The toxicities of interest were ototoxicity (measured by serial audiometry) and nephrotoxicity (measured by serial serum creatinine determinations). Methods: Multivariate logistic regression was used to examine the effect of increased frequency of clinical monitoring on decreasing toxicity. Count of total audiograms and serum chemistries and total regimen changes were used as proxies for clinical monitoring. Stratified analysis, likelihood ratio test, and backward elimination methods were used to examine effect modification by risk factors previously established in literature, using corresponding interaction terms, while change-in-estimate was used to assess confounding. Results: In total, 541 observations within the original dataset were treated with aminoglycosides; 420 had information on nephrotoxicity development, and 93 had information on ototoxicity development. Forty-four percent of the ototoxicity dataset (n=93) developed ototoxicity (P=0.254) while 23 % of the nephrotoxicity dataset (n=420) developed nephrotoxicity (P<0.0001). Multivariate logistic regression showed significant associations between both aminoglycoside toxicities; ototoxicity and audiogram frequency (crude OR 1.35, 95% CI 1.16,1.58), and nephrotoxicity with creatinine measurement frequency and regimen change frequency (crude OR 1.41, 95% CI 1.29,1.54). Conclusion: While odds ratios were not in the expected direction, they do not completely contradict the original hypothesis due to use of the proxy variables and lack of a time component. Attending physicians might have noticed developing toxicities and ordered more toxicity measurements and dose changes to manage them rather than ordering more of these prior to the development of the toxicities

Table of Contents

INTRODUCTION 1
MATERIALS AND METHODS 4
Data 4
Statistical Analysis 4
RESULTS 7
Univariate descriptive statistics 7
Bivariate analysis 8
Multivariate logistic regression analysis 9
DISCUSSION 11
Strengths 13
Limitations 13
Future directions and public health importance 14
Conclusion 14
References 16
Tables 19
Table 1. Socio Demographic Characteristics of 541 Patients Treated with Aminoglycosides for Persistent Tuberculosis in Tyler, TX; 1985 - 2008 19
Table 2. Aminoglycoside Characteristics of 541 Patients Treated with Aminoglycosides for Persistent Tuberculosis in Tyler, Texas; 1985 through 2008 21
Table 3. Audiometry Related Characteristics of 541 Patients Treated with Aminoglycosides for Persistent Tuberculosis in Tyler, TX; 1985 - 2008 23
Table 4. Serum Creatinine Related Characteristics of 541 Patients Treated with Aminoglycosides for Persistent Tuberculosis in Tyler, TX; 1985 - 2008 24
Table 5. Crude Associations of Study among 541 Patients Treated with Aminoglycosides for Persistent Tuberculosis in Tyler, TX; 1985 - 2008 25

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