Letters
lessening the opportunity to identify a treatment effect, and would have risked lack of generalization to the target population. We acknowledged previously that further follow-up of study participants may “reveal a [unexpected] lateappearing benefit to tadalafil” because a planned analysis at 24 months is a secondary end point of our trial. Other patient-reported outcomes research does not provide great optimism in this regard, however,2-4 with stability in the ED rate from 12 months to 24 months,2-4 or even up to 6 years after radiotherapy.3 Causes of ED unrelated to prostate cancer therapy (eg, advancing age, vascular disease) or use of androgen suppression subsequently are apt to lessen the effect of preventive or rehabilitative interventions in the long-term.4 We agree that many uncertainties exist about optimal PDE5-I dosing and treatment duration when this drug class is tested to prevent radiotherapy-related ED. Yet the development and conduct of our study was supported by the efficacy of tadalafil at 5-mg (vs 10-mg) once daily dosing,5 which aligned with usage approved by the US Food and Drug Administration and which was demonstrated also during the active 24week drug administration phase of our trial (Figure 2). We cannot know presently whether a longer treatment phase would yield other outcomes, but it is essential to consider the value of such an approach compared with on-demand PDE5-I use as treatment for ED. Although it may be sensible to further test the effect of PDE5-I administered prior to surgery, as proposed by Castiglione and colleagues, our study essentially did so with radiotherapy—tadalafil was started before vasogenic injury is thought to occur. We therefore cannot endorse a research strategy that would extend this hypothesis further in the context of radiotherapy. We encourage further research in this area, but cannot endorse use of a PDE5-I as a preventive measure until such an approach is found beneficial. Thomas M. Pisansky, MD Deborah W. Bruner, PhD, RN Richard E. Greenberg, MD Author Affiliations: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (Pisansky); Emory University, Atlanta, Georgia (Bruner); Fox Chase Cancer Center, Philadelphia, Pennsylvania (Greenberg). Corresponding Author: Thomas M. Pisansky, MD, Department of Radiation Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (pisansky.thomas @mayo.edu). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bruner reported receiving grant funding from the National Cancer Institute and Eli Lilly & Co; and travel support from the Community Clinical Oncology Program. No other disclosures were reported. Disclaimer: The views presented herein are those solely of the Radiation Therapy Oncology Group and of the authors, who accept no liability for the consequences of any actions taken on the basis of information provided. 1. Wang Y, Liu T, Rossi PJ, et al. Influence of vascular comorbidities and race on erectile dysfunction after prostate cancer radiotherapy. J Sex Med. 2013;10 (8):2108-2114. 2. Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008;358(12):12501261.
3. Siglin J, Kubicek GJ, Leiby B, Valicenti RK. Time of decline in sexual function after external beam radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2010;76(1):31-35. 4. Resnick MJ, Koyama T, Fan KH, et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med. 2013;368(5):436-445. 5. Porst H, Giuliano F, Glina S, et al. Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial. Eur Urol. 2006;50(2):351-359.
Statins and Ischemic Stroke To the Editor The report from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study1 indicated that the new equations for predicting atherosclerotic cardiovascular risk appeared to overestimate the risk of atherosclerotic events in the participants. This study affords an opportunity to assess a possible problem with the new Pooled Cohort risk equations. The accompanying Editorial2 emphasized underascertainment of events in the observational REGARDS study as a likely reason for apparent overestimation of risk and raised the possibility that statin therapy in participants may have reduced outcomes compared with the prediction by the equations. Another possibility should be considered: it may be an error to classify all ischemic strokes as hard atherosclerotic end points. Because the REGARDS study was designed to assess differences between blacks and other racial/ethnic groups, it may be possible to investigate this issue even though data on stroke subtypes were not collected. Strokes due to large artery atherosclerosis constitute only a subset of stroke subtypes, which also include cardioembolic stroke, infarctions due to hypertensive small vessel disease (lacunar infarctions), other causes such as vasculitis, and strokes of undetermined origin. Historical data from mainly white populations suggest that strokes due to large artery atherosclerosis account for approximately 20% of strokes.3 The Greater Cincinnati/Northern Kentucky Stroke Study4 showed that black participants were nearly twice as likely as whites to have strokes due to small vessel disease. Although the overall performance of the risk equations in the REGARDS study was similar between black and white participants, there was an indication that they performed less well in blacks: the Hosmer-Lemeshow χ2 for blacks was 11.8 (P = .16) vs 14 for whites (P = .08), and the C index was lower for blacks (0.69; 95% CI, 0.65-0.74) than for whites (0.74; 95% CI, 0.710.77). The risk equations were designed to identify which individuals would qualify for statin therapy under the new cholesterol-lowering guidelines2; however, statins may be more effective in preventing large artery stroke.5 It would be of interest to reanalyze the data to compare the performance of the equations in blacks and whites in the prediction of coronary events, which represent truly atherosclerotic events, with ischemic stroke. This would give an indication of the extent to which it may be erroneous to classify all ischemic strokes as atherosclerotic end points. J. David Spence, MD, FRCPC
jama.com
JAMA August 20, 2014 Volume 312, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Tulane University User on 05/16/2015
749
Letters
Author Affiliation: Robarts Research Institute, Western University, London, Ontario, Canada. Corresponding Author: J. David Spence, MD, FRCPC, Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, ON N6G 2V2, Canada ([email protected]). Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease pooled cohort risk equations. JAMA. 2014;311(14):1406-1415. 2. Krumholz HM. The new cholesterol and blood pressure guidelines: perspective on the path forward. JAMA. 2014;311(14):1403-1405. 3. Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke. 1999;30(12):2513-2516. 4. Schneider AT, Kissela B, Woo D, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites. Stroke. 2004;35(7):1552-1556. 5. Sillesen H, Amarenco P, Hennerici MG, et al; Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke. 2008;39(12):3297-3302.
In Reply Based on published studies,1-3 we think there are clear benefits for statins for the primary and secondary prevention of stroke. The Cholesterol Treatment Trialists’ Collaboration4 meta-analysis from 2010 showed a hazard ratio of 0.85 (95% CI, 0.80-0.90) for stroke per 1-mmol/L reduction of lowdensity lipoprotein cholesterol with statin use vs placebo; 0.80 (99% CI, 0.73-0.88) for ischemic stroke, 1.10 (99% CI, 0.861.42) for hemorrhagic stroke, and 0.88 (99% CI, 0.76-1.02) for unknown stroke type. Although heterogeneity between primary and secondary prevention trials was not reported, similar patterns appeared to be present for primary and secondary prevention trials. Trials of statin therapy have not reported results specific to ischemic stroke subtypes. Therefore, we cannot infer that the benefits of statins are present only for certain types of ischemic strokes (eg, large vessel vs small vessel vs cardioembolic). The hypothesis that statins have differential benefits on subtypes of ischemic stroke is an interesting and important question. However, investigation of subtypes of stroke was beyond the scope of the study we conducted. We think that it may be useful for future randomized trials to investigate whether statins reduce the risk of only certain subtypes of ischemic stroke. The goal of the REGARDS study analysis was to evaluate the validity of the American College of Cardiology (ACC)/ American Heart Association (AHA) Pooled Cohort risk equations in a population for whom the decision to initiate statins may be based on predicted atherosclerotic cardiovascular disease risk. For this reason, we chose to follow the definition of cardiovascular disease set forth in the ACC/AHA guideline on risk assessment5 and include all ischemic stroke outcomes. The performance of the ACC/AHA Pooled Cohort risk equations for coronary events per se is not known and determining the performance was beyond the scope of our study. Nonetheless, the excellent calibration of the Pooled Cohort risk equations when using a similar definition to that used in the ACC/AHA derivation is noteworthy and should 750
provide clinicians confidence when using these risk equations as part of the decision-making process surrounding the initiation of statins. Paul Muntner, PhD George Howard, DrPh Monika M. Safford, MD Author Affiliations: Department of Epidemiology, University of Alabama, Birmingham (Muntner); Department of Biostatistics, University of Alabama, Birmingham (Howard); Department of Medicine, University of Alabama, Birmingham (Safford). Corresponding Author: Paul Muntner, PhD, Department of Epidemiology, University of Alabama, 1665 University Blvd, Ste 230J, Birmingham, AL 35294 ([email protected]). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Muntner reported receiving grants and personal fees from Amgen outside the submitted work. Dr Safford reported receiving grants from Amgen and diaDexus outside the submitted work. No other disclosures were reported. 1. Ridker PM, Danielson E, Fonseca FA, et al; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. 2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7-22. 3. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344(8934):1383-1389. 4. Baigent C, Blackwell L, Emberson J, et al; Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. 5. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;129(25)(suppl 2):S49-S73.
Treatment for Opioid Use Disorder To the Editor The Viewpoint by Drs Olsen and Scharfstein1 addressed an important and timely topic, the stigma of opioid use disorder and its treatment. Olsen and Scharfstein appropriately emphasized the importance of medication-assisted treatment as a mainstay of intervention for and treatment of opioid addiction. However, while the therapeutic armamentarium for this disorder is limited, it is not as limited as Olsen and Scharfstein suggested. The authors emphasized 2 treatments in particular, methadone and buprenorphine. However, there is a third medication approved by the US Food and Drug Administration that also deserves mention, naltrexone. Naltrexone is a non– narcotic opioid antagonist available as both short-acting daily oral and extended-release once monthly injectable products. Extended-release naltrexone is specifically indicated for the prevention of relapse to opioid dependence following opioid detoxification as part of a comprehensive management program that includes psychosocial support.2 Given the heterogeneity of the needs of different patients, and the inherent complexities of opioid use disorder, awareness of the full array of therapeutic options is important. Jeffrey J. Stoddard, MD
JAMA August 20, 2014 Volume 312, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Tulane University User on 05/16/2015
jama.com
lessening the opportunity to identify a treatment effect, and would have risked lack of generalization to the target population. We acknowledged previously that further follow-up of study participants may “reveal a [unexpected] lateappearing benefit to tadalafil” because a planned analysis at 24 months is a secondary end point of our trial. Other patient-reported outcomes research does not provide great optimism in this regard, however,2-4 with stability in the ED rate from 12 months to 24 months,2-4 or even up to 6 years after radiotherapy.3 Causes of ED unrelated to prostate cancer therapy (eg, advancing age, vascular disease) or use of androgen suppression subsequently are apt to lessen the effect of preventive or rehabilitative interventions in the long-term.4 We agree that many uncertainties exist about optimal PDE5-I dosing and treatment duration when this drug class is tested to prevent radiotherapy-related ED. Yet the development and conduct of our study was supported by the efficacy of tadalafil at 5-mg (vs 10-mg) once daily dosing,5 which aligned with usage approved by the US Food and Drug Administration and which was demonstrated also during the active 24week drug administration phase of our trial (Figure 2). We cannot know presently whether a longer treatment phase would yield other outcomes, but it is essential to consider the value of such an approach compared with on-demand PDE5-I use as treatment for ED. Although it may be sensible to further test the effect of PDE5-I administered prior to surgery, as proposed by Castiglione and colleagues, our study essentially did so with radiotherapy—tadalafil was started before vasogenic injury is thought to occur. We therefore cannot endorse a research strategy that would extend this hypothesis further in the context of radiotherapy. We encourage further research in this area, but cannot endorse use of a PDE5-I as a preventive measure until such an approach is found beneficial. Thomas M. Pisansky, MD Deborah W. Bruner, PhD, RN Richard E. Greenberg, MD Author Affiliations: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (Pisansky); Emory University, Atlanta, Georgia (Bruner); Fox Chase Cancer Center, Philadelphia, Pennsylvania (Greenberg). Corresponding Author: Thomas M. Pisansky, MD, Department of Radiation Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (pisansky.thomas @mayo.edu). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bruner reported receiving grant funding from the National Cancer Institute and Eli Lilly & Co; and travel support from the Community Clinical Oncology Program. No other disclosures were reported. Disclaimer: The views presented herein are those solely of the Radiation Therapy Oncology Group and of the authors, who accept no liability for the consequences of any actions taken on the basis of information provided. 1. Wang Y, Liu T, Rossi PJ, et al. Influence of vascular comorbidities and race on erectile dysfunction after prostate cancer radiotherapy. J Sex Med. 2013;10 (8):2108-2114. 2. Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008;358(12):12501261.
3. Siglin J, Kubicek GJ, Leiby B, Valicenti RK. Time of decline in sexual function after external beam radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2010;76(1):31-35. 4. Resnick MJ, Koyama T, Fan KH, et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med. 2013;368(5):436-445. 5. Porst H, Giuliano F, Glina S, et al. Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial. Eur Urol. 2006;50(2):351-359.
Statins and Ischemic Stroke To the Editor The report from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study1 indicated that the new equations for predicting atherosclerotic cardiovascular risk appeared to overestimate the risk of atherosclerotic events in the participants. This study affords an opportunity to assess a possible problem with the new Pooled Cohort risk equations. The accompanying Editorial2 emphasized underascertainment of events in the observational REGARDS study as a likely reason for apparent overestimation of risk and raised the possibility that statin therapy in participants may have reduced outcomes compared with the prediction by the equations. Another possibility should be considered: it may be an error to classify all ischemic strokes as hard atherosclerotic end points. Because the REGARDS study was designed to assess differences between blacks and other racial/ethnic groups, it may be possible to investigate this issue even though data on stroke subtypes were not collected. Strokes due to large artery atherosclerosis constitute only a subset of stroke subtypes, which also include cardioembolic stroke, infarctions due to hypertensive small vessel disease (lacunar infarctions), other causes such as vasculitis, and strokes of undetermined origin. Historical data from mainly white populations suggest that strokes due to large artery atherosclerosis account for approximately 20% of strokes.3 The Greater Cincinnati/Northern Kentucky Stroke Study4 showed that black participants were nearly twice as likely as whites to have strokes due to small vessel disease. Although the overall performance of the risk equations in the REGARDS study was similar between black and white participants, there was an indication that they performed less well in blacks: the Hosmer-Lemeshow χ2 for blacks was 11.8 (P = .16) vs 14 for whites (P = .08), and the C index was lower for blacks (0.69; 95% CI, 0.65-0.74) than for whites (0.74; 95% CI, 0.710.77). The risk equations were designed to identify which individuals would qualify for statin therapy under the new cholesterol-lowering guidelines2; however, statins may be more effective in preventing large artery stroke.5 It would be of interest to reanalyze the data to compare the performance of the equations in blacks and whites in the prediction of coronary events, which represent truly atherosclerotic events, with ischemic stroke. This would give an indication of the extent to which it may be erroneous to classify all ischemic strokes as atherosclerotic end points. J. David Spence, MD, FRCPC
jama.com
JAMA August 20, 2014 Volume 312, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Tulane University User on 05/16/2015
749
Letters
Author Affiliation: Robarts Research Institute, Western University, London, Ontario, Canada. Corresponding Author: J. David Spence, MD, FRCPC, Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, ON N6G 2V2, Canada ([email protected]). Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease pooled cohort risk equations. JAMA. 2014;311(14):1406-1415. 2. Krumholz HM. The new cholesterol and blood pressure guidelines: perspective on the path forward. JAMA. 2014;311(14):1403-1405. 3. Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke. 1999;30(12):2513-2516. 4. Schneider AT, Kissela B, Woo D, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites. Stroke. 2004;35(7):1552-1556. 5. Sillesen H, Amarenco P, Hennerici MG, et al; Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke. 2008;39(12):3297-3302.
In Reply Based on published studies,1-3 we think there are clear benefits for statins for the primary and secondary prevention of stroke. The Cholesterol Treatment Trialists’ Collaboration4 meta-analysis from 2010 showed a hazard ratio of 0.85 (95% CI, 0.80-0.90) for stroke per 1-mmol/L reduction of lowdensity lipoprotein cholesterol with statin use vs placebo; 0.80 (99% CI, 0.73-0.88) for ischemic stroke, 1.10 (99% CI, 0.861.42) for hemorrhagic stroke, and 0.88 (99% CI, 0.76-1.02) for unknown stroke type. Although heterogeneity between primary and secondary prevention trials was not reported, similar patterns appeared to be present for primary and secondary prevention trials. Trials of statin therapy have not reported results specific to ischemic stroke subtypes. Therefore, we cannot infer that the benefits of statins are present only for certain types of ischemic strokes (eg, large vessel vs small vessel vs cardioembolic). The hypothesis that statins have differential benefits on subtypes of ischemic stroke is an interesting and important question. However, investigation of subtypes of stroke was beyond the scope of the study we conducted. We think that it may be useful for future randomized trials to investigate whether statins reduce the risk of only certain subtypes of ischemic stroke. The goal of the REGARDS study analysis was to evaluate the validity of the American College of Cardiology (ACC)/ American Heart Association (AHA) Pooled Cohort risk equations in a population for whom the decision to initiate statins may be based on predicted atherosclerotic cardiovascular disease risk. For this reason, we chose to follow the definition of cardiovascular disease set forth in the ACC/AHA guideline on risk assessment5 and include all ischemic stroke outcomes. The performance of the ACC/AHA Pooled Cohort risk equations for coronary events per se is not known and determining the performance was beyond the scope of our study. Nonetheless, the excellent calibration of the Pooled Cohort risk equations when using a similar definition to that used in the ACC/AHA derivation is noteworthy and should 750
provide clinicians confidence when using these risk equations as part of the decision-making process surrounding the initiation of statins. Paul Muntner, PhD George Howard, DrPh Monika M. Safford, MD Author Affiliations: Department of Epidemiology, University of Alabama, Birmingham (Muntner); Department of Biostatistics, University of Alabama, Birmingham (Howard); Department of Medicine, University of Alabama, Birmingham (Safford). Corresponding Author: Paul Muntner, PhD, Department of Epidemiology, University of Alabama, 1665 University Blvd, Ste 230J, Birmingham, AL 35294 ([email protected]). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Muntner reported receiving grants and personal fees from Amgen outside the submitted work. Dr Safford reported receiving grants from Amgen and diaDexus outside the submitted work. No other disclosures were reported. 1. Ridker PM, Danielson E, Fonseca FA, et al; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. 2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7-22. 3. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344(8934):1383-1389. 4. Baigent C, Blackwell L, Emberson J, et al; Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. 5. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;129(25)(suppl 2):S49-S73.
Treatment for Opioid Use Disorder To the Editor The Viewpoint by Drs Olsen and Scharfstein1 addressed an important and timely topic, the stigma of opioid use disorder and its treatment. Olsen and Scharfstein appropriately emphasized the importance of medication-assisted treatment as a mainstay of intervention for and treatment of opioid addiction. However, while the therapeutic armamentarium for this disorder is limited, it is not as limited as Olsen and Scharfstein suggested. The authors emphasized 2 treatments in particular, methadone and buprenorphine. However, there is a third medication approved by the US Food and Drug Administration that also deserves mention, naltrexone. Naltrexone is a non– narcotic opioid antagonist available as both short-acting daily oral and extended-release once monthly injectable products. Extended-release naltrexone is specifically indicated for the prevention of relapse to opioid dependence following opioid detoxification as part of a comprehensive management program that includes psychosocial support.2 Given the heterogeneity of the needs of different patients, and the inherent complexities of opioid use disorder, awareness of the full array of therapeutic options is important. Jeffrey J. Stoddard, MD
JAMA August 20, 2014 Volume 312, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Tulane University User on 05/16/2015
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