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Re: Antibiotic Prophylaxis for Infective Endocarditis: Ethical Care in the Era of Revised Guidelines
Urological Survey
Infection and Inflammation of the Genitourinary Tract Re: Antibiotic Prophylaxis for Infective Endocarditis: Ethical Care in the Era of Revised Guidelines D. S. Bach University of Michigan, Ann Arbor, Michigan Methodist Debakey Cardiovasc J 2010; 6: 48 –52.
Beginning in 1955, the American Heart Association recommended antibiotic prophylaxis among patients with certain structural heart diseases to decrease the likelihood of infective endocarditis (IE) following dental procedures. Over the ensuing 52 years, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines were revised to address gastrointestinal and genitourinary procedures and to modify the assessment of relative risks and specific regimens for prophylaxis. Throughout the various revisions, prophylaxis was recommended for individuals who were at increased risk of developing IE based on best evidence and consensus opinion, albeit in the absence of randomized controlled trials. In 2007, the AHA published a revised guideline statement dramatically restricting its recommendations for antibiotic prophylaxis against IE. In 2008, these views were incorporated in an ACC/AHA guideline update on the management of patients with heart valve disease. The revisions represent a dramatic shift in terms of the patients for whom antibiotic prophylaxis is recommended and the procedures for which it is recommended. What is striking about the new guidelines is that the change in recommendations was based not on new data, but on a change in philosophy despite the lack of new data. To some degree, the arguments for and against antibiotic prophylaxis become those of philosophy, ethics, and the role of evidence-based medicine. This manuscript attempts to briefly examine those arguments and discuss why the revised guidelines may fail to respect the ethical principles of beneficence and patient autonomy. Editorial Comment: This editorial presents serious food for thought on antibiotic prophylaxis for IE. In 2007 revisions to these recommendations excluded any gastrointestinal or urological procedures from needing prophylaxis as well as several heart conditions from requiring prophylaxis with dental procedures. This change in recommendations was made not because of new data, but because of new emphasis on existing data and the specific absence of randomized controlled trial (RCT) data. There are 2 large observational studies showing a 49% and 69% reduction in IE with prophylaxis. RCTs will probably never be performed because of sample size required. These guidelines interpret the absence of RCTs supporting the efficacy of prophylaxis as a priori evidence of absence of benefit. In this sense the revised guidelines serve as an excellent example of the dangers of evidencebased medicine—an absence of proof (of efficacy) is confused for proof of absence (of efficacy). They further emphasize that one of the risks of recommending prophylaxis is malpractice claims. There has not been a single reported case of anaphylaxis, although it theoretically exists. The author states, “That the current guidelines consider one patient’s adverse outcome more important than another’s fails to respect the principle of beneficence and fails to honor the physician’s responsibility to the individual patient. . . [it] is paternalistic not to inform a patient of conflicting opinions and simply prescribe no antibiotic prophylaxis based on incomplete data. . . [there is] no precedent in medicine to write practice guidelines with the specific goal of avoiding malpractice claims when they
0022-5347/11/1862-0545/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
Vol. 186, 545-549, August 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.04.035
www.jurology.com
545
546
INFECTION AND INFLAMMATION OF GENITOURINARY TRACT
are not followed, but respect for autonomy and truthfulness again dictate that individual patients should be made aware that recommended therapy is based (even in part) on this.” There seems to be a good argument for offering the patient at risk for IE the option of prophylaxis based on the arguments presented in this article. Richard E. Berger, M.D.
Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Systematic Review and Network Meta-Analysis T. Anothaisintawee, J. Attia, J. C. Nickel, S. Thammakraisorn, P. Numthavaj, M. McEvoy and A. Thakkinstian Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand JAMA 2011; 305: 78 – 86.
Context: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is common, but trial evidence is conflicting and therapeutic options are controversial. Objective: To conduct a systematic review and network meta-analysis comparing mean symptom scores and treatment response among ␣-blockers, antibiotics, anti-inflammatory drugs, other active drugs (phytotherapy, glycosaminoglycans, finasteride, and neuromodulators), and placebo. Data Sources: We searched MEDLINE from 1949 and EMBASE from 1974 to November 16, 2010, using the PubMed and Ovid search engines. Study Selection: Randomized controlled trials comparing drug treatments in CP/CPPS patients. Data Extraction: Two reviewers independently extracted mean symptom scores, quality-of-life measures, and response to treatment between treatment groups. Standardized mean difference and randomeffects methods were applied for pooling continuous and dichotomous outcomes, respectively. A longitudinal mixed regression model was used for network meta-analysis to indirectly compare treatment effects. Data Synthesis: Twenty-three of 262 studies identified were eligible. Compared with placebo, ␣-blockers were associated with significant improvement in symptoms with standardized mean differences in total symptom, pain, voiding, and quality-of-life scores of ⫺1.7 (95% confidence interval [CI], ⫺2.8 to ⫺0.6), ⫺1.1 (95% CI, ⫺1.8 to ⫺0.3), ⫺1.4 (95% CI, ⫺2.3 to ⫺0.5), and ⫺1.0 (95% CI, ⫺1.8 to ⫺0.2), respectively. Patients receiving ␣-blockers or anti-inflammatory medications had a higher chance of favorable response compared with placebo, with pooled RRs of 1.6 (95% CI, 1.1–2.3) and 1.8 (95% CI, 1.2–2.6), respectively. Contour-enhanced funnel plots suggested the presence of publication bias for smaller studies of ␣-blocker therapies. The network meta-analysis suggested benefits of antibiotics in decreasing total symptom scores (⫺9.8; 95% CI, ⫺15.1 to ⫺4.6), pain scores (⫺4.4; 95% CI, ⫺7.0 to ⫺1.9), voiding scores (⫺2.8; 95% CI, ⫺4.1 to ⫺1.6), and qualityof-life scores (⫺1.9; 95% CI, ⫺3.6 to ⫺0.2) compared with placebo. Combining ␣-blockers and antibiotics yielded the greatest benefits compared with placebo, with corresponding decreases of ⫺13.8 (95% CI, ⫺17.5 to ⫺10.2) for total symptom scores, ⫺5.7 (95% CI, ⫺7.8 to ⫺3.6) for pain scores, ⫺3.7 (95% CI, ⫺5.2 to ⫺2.1) for voiding, and ⫺2.8 (95% CI, ⫺4.7 to ⫺0.9) for quality-of-life scores. Conclusions: ␣-Blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo. Anti-inflammatory therapies have a lesser but measurable benefit on selected outcomes. However, beneficial effects of ␣-blockers may be overestimated because of publication bias. Editorial Comment: The large National Institutes of Health study showed that neither alpha-blockers nor antibiotics were effective in treating CPPS. Furthermore, it appeared that the combination of antibiotics and alpha-blockers was actually worse than either agent alone. Yet the authors of this meta-analysis suggest that “alpha-blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo.” The authors also state concerning their methods and assumptions, “These methods have limitations, however. Although all studies were randomized controlled trials, most studies were unclear in randomization sequence generations and, hence, selection bias or confounding might be present. Pooled results were often heterogeneous and the source of this difference was not apparent.” Given the
Infection and Inflammation of the Genitourinary Tract Re: Antibiotic Prophylaxis for Infective Endocarditis: Ethical Care in the Era of Revised Guidelines D. S. Bach University of Michigan, Ann Arbor, Michigan Methodist Debakey Cardiovasc J 2010; 6: 48 –52.
Beginning in 1955, the American Heart Association recommended antibiotic prophylaxis among patients with certain structural heart diseases to decrease the likelihood of infective endocarditis (IE) following dental procedures. Over the ensuing 52 years, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines were revised to address gastrointestinal and genitourinary procedures and to modify the assessment of relative risks and specific regimens for prophylaxis. Throughout the various revisions, prophylaxis was recommended for individuals who were at increased risk of developing IE based on best evidence and consensus opinion, albeit in the absence of randomized controlled trials. In 2007, the AHA published a revised guideline statement dramatically restricting its recommendations for antibiotic prophylaxis against IE. In 2008, these views were incorporated in an ACC/AHA guideline update on the management of patients with heart valve disease. The revisions represent a dramatic shift in terms of the patients for whom antibiotic prophylaxis is recommended and the procedures for which it is recommended. What is striking about the new guidelines is that the change in recommendations was based not on new data, but on a change in philosophy despite the lack of new data. To some degree, the arguments for and against antibiotic prophylaxis become those of philosophy, ethics, and the role of evidence-based medicine. This manuscript attempts to briefly examine those arguments and discuss why the revised guidelines may fail to respect the ethical principles of beneficence and patient autonomy. Editorial Comment: This editorial presents serious food for thought on antibiotic prophylaxis for IE. In 2007 revisions to these recommendations excluded any gastrointestinal or urological procedures from needing prophylaxis as well as several heart conditions from requiring prophylaxis with dental procedures. This change in recommendations was made not because of new data, but because of new emphasis on existing data and the specific absence of randomized controlled trial (RCT) data. There are 2 large observational studies showing a 49% and 69% reduction in IE with prophylaxis. RCTs will probably never be performed because of sample size required. These guidelines interpret the absence of RCTs supporting the efficacy of prophylaxis as a priori evidence of absence of benefit. In this sense the revised guidelines serve as an excellent example of the dangers of evidencebased medicine—an absence of proof (of efficacy) is confused for proof of absence (of efficacy). They further emphasize that one of the risks of recommending prophylaxis is malpractice claims. There has not been a single reported case of anaphylaxis, although it theoretically exists. The author states, “That the current guidelines consider one patient’s adverse outcome more important than another’s fails to respect the principle of beneficence and fails to honor the physician’s responsibility to the individual patient. . . [it] is paternalistic not to inform a patient of conflicting opinions and simply prescribe no antibiotic prophylaxis based on incomplete data. . . [there is] no precedent in medicine to write practice guidelines with the specific goal of avoiding malpractice claims when they
0022-5347/11/1862-0545/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
Vol. 186, 545-549, August 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.04.035
www.jurology.com
545
546
INFECTION AND INFLAMMATION OF GENITOURINARY TRACT
are not followed, but respect for autonomy and truthfulness again dictate that individual patients should be made aware that recommended therapy is based (even in part) on this.” There seems to be a good argument for offering the patient at risk for IE the option of prophylaxis based on the arguments presented in this article. Richard E. Berger, M.D.
Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Systematic Review and Network Meta-Analysis T. Anothaisintawee, J. Attia, J. C. Nickel, S. Thammakraisorn, P. Numthavaj, M. McEvoy and A. Thakkinstian Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand JAMA 2011; 305: 78 – 86.
Context: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is common, but trial evidence is conflicting and therapeutic options are controversial. Objective: To conduct a systematic review and network meta-analysis comparing mean symptom scores and treatment response among ␣-blockers, antibiotics, anti-inflammatory drugs, other active drugs (phytotherapy, glycosaminoglycans, finasteride, and neuromodulators), and placebo. Data Sources: We searched MEDLINE from 1949 and EMBASE from 1974 to November 16, 2010, using the PubMed and Ovid search engines. Study Selection: Randomized controlled trials comparing drug treatments in CP/CPPS patients. Data Extraction: Two reviewers independently extracted mean symptom scores, quality-of-life measures, and response to treatment between treatment groups. Standardized mean difference and randomeffects methods were applied for pooling continuous and dichotomous outcomes, respectively. A longitudinal mixed regression model was used for network meta-analysis to indirectly compare treatment effects. Data Synthesis: Twenty-three of 262 studies identified were eligible. Compared with placebo, ␣-blockers were associated with significant improvement in symptoms with standardized mean differences in total symptom, pain, voiding, and quality-of-life scores of ⫺1.7 (95% confidence interval [CI], ⫺2.8 to ⫺0.6), ⫺1.1 (95% CI, ⫺1.8 to ⫺0.3), ⫺1.4 (95% CI, ⫺2.3 to ⫺0.5), and ⫺1.0 (95% CI, ⫺1.8 to ⫺0.2), respectively. Patients receiving ␣-blockers or anti-inflammatory medications had a higher chance of favorable response compared with placebo, with pooled RRs of 1.6 (95% CI, 1.1–2.3) and 1.8 (95% CI, 1.2–2.6), respectively. Contour-enhanced funnel plots suggested the presence of publication bias for smaller studies of ␣-blocker therapies. The network meta-analysis suggested benefits of antibiotics in decreasing total symptom scores (⫺9.8; 95% CI, ⫺15.1 to ⫺4.6), pain scores (⫺4.4; 95% CI, ⫺7.0 to ⫺1.9), voiding scores (⫺2.8; 95% CI, ⫺4.1 to ⫺1.6), and qualityof-life scores (⫺1.9; 95% CI, ⫺3.6 to ⫺0.2) compared with placebo. Combining ␣-blockers and antibiotics yielded the greatest benefits compared with placebo, with corresponding decreases of ⫺13.8 (95% CI, ⫺17.5 to ⫺10.2) for total symptom scores, ⫺5.7 (95% CI, ⫺7.8 to ⫺3.6) for pain scores, ⫺3.7 (95% CI, ⫺5.2 to ⫺2.1) for voiding, and ⫺2.8 (95% CI, ⫺4.7 to ⫺0.9) for quality-of-life scores. Conclusions: ␣-Blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo. Anti-inflammatory therapies have a lesser but measurable benefit on selected outcomes. However, beneficial effects of ␣-blockers may be overestimated because of publication bias. Editorial Comment: The large National Institutes of Health study showed that neither alpha-blockers nor antibiotics were effective in treating CPPS. Furthermore, it appeared that the combination of antibiotics and alpha-blockers was actually worse than either agent alone. Yet the authors of this meta-analysis suggest that “alpha-blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo.” The authors also state concerning their methods and assumptions, “These methods have limitations, however. Although all studies were randomized controlled trials, most studies were unclear in randomization sequence generations and, hence, selection bias or confounding might be present. Pooled results were often heterogeneous and the source of this difference was not apparent.” Given the