Letters
gram (eg, PubMed, diagnostic support, Google). The key to harnessing any software program’s potential is to have it detect, extract, and interpret the relevant variables from the electronic medical record (and other inputs) without interrupting physician workflow. Societies and organizations that shift from the business of generating guidelines to the business of delivering guidelines’ most relevant content at the right place and the right time, and in the most brain- and workflow-friendly way, will have the greatest potential to bring best practices to the bedside. I share Dr Ross’ optimism that well-designed software will have an increasing role in improving our diagnostic and therapeutic performance and therefore should garner increased attention and academic credit. Gurpreet Dhaliwal, MD Author Affiliations: Department of Medicine, University of California, San Francisco; Medical Service, San Francisco Veterans Affairs Medical Center, San Francisco, California. Corresponding Author: Gurpreet Dhaliwal, MD, Department of Medicine, University of California, San Francisco, San Francisco VA Medical Center, 4150 Clement St (111), San Francisco, CA 94131 ([email protected]).
tween antihypertensive medications and breast cancer risk. Moreover, long-term hypertension exposure could be associated with increased cancer risk as it is associated with cellular senescence, telomere shortening, and inhibition of apoptosis.4 However, in the study of Li et al,1 the authors did not separate the independent effects of the condition of hypertension itself (varying levels of severity) and treatment in the form of antihypertensive medications on the risk of breast cancer. Furthermore, the doseresponse relationship of antihypertensive medications exposure on subgroups of patients has yet not been explored in their study.1 The carcinogenic potential of antihypertensive medications has been debated for nearly 40 years.5 However, despite the apparent widespread use of antihypertensive drugs, the current data are limited. Many publications were not subjected to the usual stringency of phase 1 to 3 clinical trials, and most were not prospective or randomized. Do antihypertensive medications influence breast cancer risk? Prospective randomized clinical trials may provide the only way to overcome the selection and ascertainment bias and answer this question more accurately. Yi Ji, MD, PhD Siyuan Chen, MD, PhD
Conflict of Interest Disclosures: None reported. 1. Bond WF, Schwartz LM, Weaver KR, Levick D, Giuliano M, Graber ML. Differential diagnosis generators: an evaluation of currently available computer programs. J Gen Intern Med. 2012;27(2):213-219.
Author Affiliations: Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China (Ji); Intensive Care Unit, West China Hospital of Sichuan University, Chengdu, China (Chen).
2. Meyer AN, Payne VL, Meeks DW, Rao R, Singh H. Physicians’ diagnostic accuracy, confidence, and resource requests: a vignette study. JAMA Intern Med. 2013;173(21):1952-1958.
Corresponding Author: Yi Ji, MD, PhD, Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, 37 Guo-Xue-Xiang, Chengdu 610041, China ([email protected]).
3. Cook DA, Sorensen KJ, Wilkinson JM, Berger RA. Barriers and decisions when answering clinical questions at the point of care: a grounded theory study. JAMA Intern Med. 2013;173(21):1962-1969.
Conflict of Interest Disclosures: None reported.
Antihypertensive Medications and Breast Cancer Risk
2. Bangalore S, Kumar S, Kjeldsen SE, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol. 2011;12(1):65-82.
To the Editor We read with great interest the article published in JAMA Internal Medicine titled “Use of Antihypertensive Medications and Breast Cancer Risk Among Women Aged 55 to 74 Years” by Li et al.1 The study provided further evidence that long-term current use of calcium channel blockers is associated with an increased risk of breast cancer. Moreover, the data revealed that a reduction in breast cancer risk was associated with long-term use of angiotensin-converting enzyme inhibitors. We appreciate the authors’ extraordinary contribution, which provides us with a basis for further investigation of the effects of antihypertensive medications on breast cancer risk. Nonetheless, there are several major points that need further discussion with respect to this article. It has been well documented that host factors (eg, alcohol or tobacco use), confounding with other pharmacologic exposures (eg, aspirin), and comorbid medical conditions (eg, system inflammation or heart disease) are associated with cancer risk.2,3 In the study by Li et al,1 the authors used polytomous logistic regression to calculate odds ratios and their associated 95% confidence intervals to compare patients with breast cancer with controls. The models are adjusted for age, reference year, county, race/ethnicity, and recency of alcohol use (Tables 2, 3, and 4). However, many other important factors were not included in the analysis (eg, history of heart disease). This brings up the possibility that the current study is not likely to accurately establish the association be640
1. Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-1637.
3. Fung TT, Hu FB, Hankinson SE, Willett WC, Holmes MD. Low-carbohydrate diets, dietary approaches to stop hypertension-style diets, and the risk of postmenopausal breast cancer. Am J Epidemiol. 2011;174(6):652-660. 4. Hamet P, Richard L, Dam TV, et al. Apoptosis in target organs of hypertension. Hypertension. 1995;26(4):642-648. 5. Boston Collaborative Drug Surveillance Program. Reserpine and breast cancer. Lancet. 1974;2(7882):669-671.
To the Editor In their article, Li and colleagues1 assess the association between antihypertensive medication use and increased breast cancer risk in women aged 55 to 74 years. They conclude that only continued use of calcium channel blockers for 10 years or more was significantly associated with a higher risk of breast cancer. However, we query the lack of significant results in their study concerning β-blocker use and breast cancer risk. The potential effect of β-blocker use on the risk of cancer is an important issue, and we believe that the results deserve to be reported stratified by β-adrenergic receptor (AR) antagonist subtype. Published data indicate that β2-AR signaling plays the most prominent role in breast tumor regulation and that the relative effects of β1-selective and β1/β2-nonselective antagonists are different.2 In vitro, in vivo, and preclinical models show that propranolol (β 2 -AR) can specifically inhibit stress-
JAMA Internal Medicine April 2014 Volume 174, Number 4
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Ndsu Library Periodicals User on 05/25/2015
jamainternalmedicine.com
Letters
induced tumor growth and metastatic spread through antiangiogenic and immunostimulatory mechanisms. Accumulating clinical evidence suggests that β-AR antagonist, and propranolol in particular, may increase survival and decrease recurrence in patients with breast cancer.3 Barron et al2 have studied the associations between use of β2-AR (propranolol) or β1-selective antagonists (atenolol) and risk of breast cancer. They show that propranolol is associated with significantly less advanced disease at diagnosis and lowers breast cancer-specific mortality. Furthermore, Pasquier et al3 strongly suggest that propranolol with chemotherapy may improve the outcome of women with breast cancer. In contrast, a recent study found no protective effect of propranolol (which represented 16% of the β-blockers prescribed) and increased recurrence rates associated with metoprolol.4 Propranolol is also a new and emerging treatment for melanoma, multiple myeloma, pancreatic cancer, head and neck squamous cell carcinoma cell lines, or severe infantile haemangioma.5 It would thus be interesting to evaluate the risk of breast cancer according to the subtype of β-blockers and, in particular, nonselective β-blockers. Would it be possible for the authors of this article to provide breast cancer risk data according to the type of β-blockers? Justine Hugon-Rodin, MD Anne Gompel, MD, PhD Geneviève Plu-Bureau, MD, PhD Author Affiliations: Department of Gynecology and Endocrinology, Hôpital Universitaire Paris Centre, Paris-Descartes University, Paris, France (Hugon-Rodin, Gompel, Plu-Bureau). Corresponding Author: Geneviève Plu-Bureau, MD, Department of Gynecology and Endocrinology, Hôpital Universitaire Paris Centre, Paris-Descartes University, 53 Ave de l’Observatoire, Paris 75014, France ([email protected]). Conflict of Interest Disclosures: None reported. 1. Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-1637. 2. Barron TI, Sharp L, Visvanathan K. Beta-adrenergic blocking drugs in breast cancer: a perspective review. Ther Adv Med Oncol. 2012;4(3):113-125. 3. Pasquier E, Ciccolini J, Carre M, et al. Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment. Oncotarget. 2011;2(10):797-809.
were seen when we analyzed risks according to current use of β1selective blockers vs nonselective β-blockers. Specifically, current users of β1-selective blockers of any duration and for 10 years or more had ORs of 0.9 (95% CI, 0.7-1.2) and 1.2 (95% CI, 0.7-1.9), respectively, and current users of nonselective β-blockers of any duration and for 10 years or more had ORs of 0.8 (95% CI, 0.4-1.6) and 0.8 (95% CI, 0.3-2.4), respectively. However, 90% of control women who were current β-blocker users were users of a β1selective blocker (the other 10% were current users of nonselective β-blockers), limiting our power to detect differences in risk between β1-selective blockers vs nonselective β-blockers. Ji and Chen asked about the influence other potential confounders may have had on our risk estimates, specifically heart disease and duration of hypertension history. Adjustment for heart disease did not appreciably influence the magnitude or direction of any of the risk estimates reported in Table 2 of our article. Specifically, in Table 2, the risk estimate associated with current use of calcium channel blockers for 10 years or more (OR, 2.4 [95% CI, 1.2-4.9]) did not change after additional adjustment for history of heart disease (OR, 2.4 [95% CI, 1.2-5.0]). With respect to duration of hypertension history, we defined this as years between age at initial hypertension diagnosis and reference age. This variable is highly correlated with duration of antihypertensive use, and thus we only assessed its potential to confound current antihypertensive use risk estimates. None of our current use risk estimates reported in Table 2 were statistically significant, and additional adjustment for duration of hypertension history did not appreciably change the magnitude or direction of any of these estimates. We did not collect information on hypertension severity (how well hypertension was controlled), and our ascertainment of only self-reported dose information limited our ability to evaluate dose-response relationships. Christopher I. Li, MD, PhD Mei-Tzu C. Tang, PhD Kathleen E. Malone, PhD Author Affiliations: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington (Li, Tang, Malone). Corresponding Author: Christopher I. Li, MD, PhD, Translational Research Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-C308, Seattle, WA 98109-1024 ([email protected]). Conflict of Interest Disclosures: None reported.
4. Sørensen GV, Ganz PA, Cole SW, et al. Use of β-blockers, angiotensinconverting enzyme inhibitors, angiotensin II receptor blockers, and risk of breast cancer recurrence: a Danish nationwide prospective cohort study. J Clin Oncol. 2013;31(18):2265-2272.
1. Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-1637.
5. Monami M, Filippi L, Ungar A, et al. Further data on beta-blockers and cancer risk: observational study and meta-analysis of randomized clinical trials. Curr Med Res Opin. 2013;29(4):369-378.
Treatment of Osteoporotic Vertebral Fractures
In Reply We appreciate the comments of Hugon-Rodin et al and Ji and Chen and respond to the issues they raised. Hugon-Rodin et al raised the question of whether the relationship between β-blocker use and breast cancer risk varied when results were stratified according to type of β-blocker. As reported in our article,1 overall we found no relationship between current use or long-term current use (for ≥10 years) of β-blockers and risk of invasive ductal breast cancer (odds ratio [OR], 0.9 [95% CI, 0.7-1.2], and OR, 1.1 [95% CI, 0.7-1.8], respectively). No appreciable variations in risk jamainternalmedicine.com
To the Editor McCullough et al1 reported that apparent mortality reductions following vertebroplasty and kyphoplasty likely result from selection bias. These findings are important to counter hasty conclusions from several recent population-based studies and reviews. Yet these new results are hardly surprising, given the a priori lack of evidence to assume a causal association between vertebral fractures and mortality, let alone mortality risk modifiable by targeting the spine. Reduced pulmonary function following vertebral fracture would be a plausible mechanistic explanation, but only small, short-term improvements in vital capacity following vertebral augmentation have been demJAMA Internal Medicine April 2014 Volume 174, Number 4
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Ndsu Library Periodicals User on 05/25/2015
641
gram (eg, PubMed, diagnostic support, Google). The key to harnessing any software program’s potential is to have it detect, extract, and interpret the relevant variables from the electronic medical record (and other inputs) without interrupting physician workflow. Societies and organizations that shift from the business of generating guidelines to the business of delivering guidelines’ most relevant content at the right place and the right time, and in the most brain- and workflow-friendly way, will have the greatest potential to bring best practices to the bedside. I share Dr Ross’ optimism that well-designed software will have an increasing role in improving our diagnostic and therapeutic performance and therefore should garner increased attention and academic credit. Gurpreet Dhaliwal, MD Author Affiliations: Department of Medicine, University of California, San Francisco; Medical Service, San Francisco Veterans Affairs Medical Center, San Francisco, California. Corresponding Author: Gurpreet Dhaliwal, MD, Department of Medicine, University of California, San Francisco, San Francisco VA Medical Center, 4150 Clement St (111), San Francisco, CA 94131 ([email protected]).
tween antihypertensive medications and breast cancer risk. Moreover, long-term hypertension exposure could be associated with increased cancer risk as it is associated with cellular senescence, telomere shortening, and inhibition of apoptosis.4 However, in the study of Li et al,1 the authors did not separate the independent effects of the condition of hypertension itself (varying levels of severity) and treatment in the form of antihypertensive medications on the risk of breast cancer. Furthermore, the doseresponse relationship of antihypertensive medications exposure on subgroups of patients has yet not been explored in their study.1 The carcinogenic potential of antihypertensive medications has been debated for nearly 40 years.5 However, despite the apparent widespread use of antihypertensive drugs, the current data are limited. Many publications were not subjected to the usual stringency of phase 1 to 3 clinical trials, and most were not prospective or randomized. Do antihypertensive medications influence breast cancer risk? Prospective randomized clinical trials may provide the only way to overcome the selection and ascertainment bias and answer this question more accurately. Yi Ji, MD, PhD Siyuan Chen, MD, PhD
Conflict of Interest Disclosures: None reported. 1. Bond WF, Schwartz LM, Weaver KR, Levick D, Giuliano M, Graber ML. Differential diagnosis generators: an evaluation of currently available computer programs. J Gen Intern Med. 2012;27(2):213-219.
Author Affiliations: Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China (Ji); Intensive Care Unit, West China Hospital of Sichuan University, Chengdu, China (Chen).
2. Meyer AN, Payne VL, Meeks DW, Rao R, Singh H. Physicians’ diagnostic accuracy, confidence, and resource requests: a vignette study. JAMA Intern Med. 2013;173(21):1952-1958.
Corresponding Author: Yi Ji, MD, PhD, Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, 37 Guo-Xue-Xiang, Chengdu 610041, China ([email protected]).
3. Cook DA, Sorensen KJ, Wilkinson JM, Berger RA. Barriers and decisions when answering clinical questions at the point of care: a grounded theory study. JAMA Intern Med. 2013;173(21):1962-1969.
Conflict of Interest Disclosures: None reported.
Antihypertensive Medications and Breast Cancer Risk
2. Bangalore S, Kumar S, Kjeldsen SE, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol. 2011;12(1):65-82.
To the Editor We read with great interest the article published in JAMA Internal Medicine titled “Use of Antihypertensive Medications and Breast Cancer Risk Among Women Aged 55 to 74 Years” by Li et al.1 The study provided further evidence that long-term current use of calcium channel blockers is associated with an increased risk of breast cancer. Moreover, the data revealed that a reduction in breast cancer risk was associated with long-term use of angiotensin-converting enzyme inhibitors. We appreciate the authors’ extraordinary contribution, which provides us with a basis for further investigation of the effects of antihypertensive medications on breast cancer risk. Nonetheless, there are several major points that need further discussion with respect to this article. It has been well documented that host factors (eg, alcohol or tobacco use), confounding with other pharmacologic exposures (eg, aspirin), and comorbid medical conditions (eg, system inflammation or heart disease) are associated with cancer risk.2,3 In the study by Li et al,1 the authors used polytomous logistic regression to calculate odds ratios and their associated 95% confidence intervals to compare patients with breast cancer with controls. The models are adjusted for age, reference year, county, race/ethnicity, and recency of alcohol use (Tables 2, 3, and 4). However, many other important factors were not included in the analysis (eg, history of heart disease). This brings up the possibility that the current study is not likely to accurately establish the association be640
1. Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-1637.
3. Fung TT, Hu FB, Hankinson SE, Willett WC, Holmes MD. Low-carbohydrate diets, dietary approaches to stop hypertension-style diets, and the risk of postmenopausal breast cancer. Am J Epidemiol. 2011;174(6):652-660. 4. Hamet P, Richard L, Dam TV, et al. Apoptosis in target organs of hypertension. Hypertension. 1995;26(4):642-648. 5. Boston Collaborative Drug Surveillance Program. Reserpine and breast cancer. Lancet. 1974;2(7882):669-671.
To the Editor In their article, Li and colleagues1 assess the association between antihypertensive medication use and increased breast cancer risk in women aged 55 to 74 years. They conclude that only continued use of calcium channel blockers for 10 years or more was significantly associated with a higher risk of breast cancer. However, we query the lack of significant results in their study concerning β-blocker use and breast cancer risk. The potential effect of β-blocker use on the risk of cancer is an important issue, and we believe that the results deserve to be reported stratified by β-adrenergic receptor (AR) antagonist subtype. Published data indicate that β2-AR signaling plays the most prominent role in breast tumor regulation and that the relative effects of β1-selective and β1/β2-nonselective antagonists are different.2 In vitro, in vivo, and preclinical models show that propranolol (β 2 -AR) can specifically inhibit stress-
JAMA Internal Medicine April 2014 Volume 174, Number 4
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Ndsu Library Periodicals User on 05/25/2015
jamainternalmedicine.com
Letters
induced tumor growth and metastatic spread through antiangiogenic and immunostimulatory mechanisms. Accumulating clinical evidence suggests that β-AR antagonist, and propranolol in particular, may increase survival and decrease recurrence in patients with breast cancer.3 Barron et al2 have studied the associations between use of β2-AR (propranolol) or β1-selective antagonists (atenolol) and risk of breast cancer. They show that propranolol is associated with significantly less advanced disease at diagnosis and lowers breast cancer-specific mortality. Furthermore, Pasquier et al3 strongly suggest that propranolol with chemotherapy may improve the outcome of women with breast cancer. In contrast, a recent study found no protective effect of propranolol (which represented 16% of the β-blockers prescribed) and increased recurrence rates associated with metoprolol.4 Propranolol is also a new and emerging treatment for melanoma, multiple myeloma, pancreatic cancer, head and neck squamous cell carcinoma cell lines, or severe infantile haemangioma.5 It would thus be interesting to evaluate the risk of breast cancer according to the subtype of β-blockers and, in particular, nonselective β-blockers. Would it be possible for the authors of this article to provide breast cancer risk data according to the type of β-blockers? Justine Hugon-Rodin, MD Anne Gompel, MD, PhD Geneviève Plu-Bureau, MD, PhD Author Affiliations: Department of Gynecology and Endocrinology, Hôpital Universitaire Paris Centre, Paris-Descartes University, Paris, France (Hugon-Rodin, Gompel, Plu-Bureau). Corresponding Author: Geneviève Plu-Bureau, MD, Department of Gynecology and Endocrinology, Hôpital Universitaire Paris Centre, Paris-Descartes University, 53 Ave de l’Observatoire, Paris 75014, France ([email protected]). Conflict of Interest Disclosures: None reported. 1. Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-1637. 2. Barron TI, Sharp L, Visvanathan K. Beta-adrenergic blocking drugs in breast cancer: a perspective review. Ther Adv Med Oncol. 2012;4(3):113-125. 3. Pasquier E, Ciccolini J, Carre M, et al. Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment. Oncotarget. 2011;2(10):797-809.
were seen when we analyzed risks according to current use of β1selective blockers vs nonselective β-blockers. Specifically, current users of β1-selective blockers of any duration and for 10 years or more had ORs of 0.9 (95% CI, 0.7-1.2) and 1.2 (95% CI, 0.7-1.9), respectively, and current users of nonselective β-blockers of any duration and for 10 years or more had ORs of 0.8 (95% CI, 0.4-1.6) and 0.8 (95% CI, 0.3-2.4), respectively. However, 90% of control women who were current β-blocker users were users of a β1selective blocker (the other 10% were current users of nonselective β-blockers), limiting our power to detect differences in risk between β1-selective blockers vs nonselective β-blockers. Ji and Chen asked about the influence other potential confounders may have had on our risk estimates, specifically heart disease and duration of hypertension history. Adjustment for heart disease did not appreciably influence the magnitude or direction of any of the risk estimates reported in Table 2 of our article. Specifically, in Table 2, the risk estimate associated with current use of calcium channel blockers for 10 years or more (OR, 2.4 [95% CI, 1.2-4.9]) did not change after additional adjustment for history of heart disease (OR, 2.4 [95% CI, 1.2-5.0]). With respect to duration of hypertension history, we defined this as years between age at initial hypertension diagnosis and reference age. This variable is highly correlated with duration of antihypertensive use, and thus we only assessed its potential to confound current antihypertensive use risk estimates. None of our current use risk estimates reported in Table 2 were statistically significant, and additional adjustment for duration of hypertension history did not appreciably change the magnitude or direction of any of these estimates. We did not collect information on hypertension severity (how well hypertension was controlled), and our ascertainment of only self-reported dose information limited our ability to evaluate dose-response relationships. Christopher I. Li, MD, PhD Mei-Tzu C. Tang, PhD Kathleen E. Malone, PhD Author Affiliations: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington (Li, Tang, Malone). Corresponding Author: Christopher I. Li, MD, PhD, Translational Research Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-C308, Seattle, WA 98109-1024 ([email protected]). Conflict of Interest Disclosures: None reported.
4. Sørensen GV, Ganz PA, Cole SW, et al. Use of β-blockers, angiotensinconverting enzyme inhibitors, angiotensin II receptor blockers, and risk of breast cancer recurrence: a Danish nationwide prospective cohort study. J Clin Oncol. 2013;31(18):2265-2272.
1. Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-1637.
5. Monami M, Filippi L, Ungar A, et al. Further data on beta-blockers and cancer risk: observational study and meta-analysis of randomized clinical trials. Curr Med Res Opin. 2013;29(4):369-378.
Treatment of Osteoporotic Vertebral Fractures
In Reply We appreciate the comments of Hugon-Rodin et al and Ji and Chen and respond to the issues they raised. Hugon-Rodin et al raised the question of whether the relationship between β-blocker use and breast cancer risk varied when results were stratified according to type of β-blocker. As reported in our article,1 overall we found no relationship between current use or long-term current use (for ≥10 years) of β-blockers and risk of invasive ductal breast cancer (odds ratio [OR], 0.9 [95% CI, 0.7-1.2], and OR, 1.1 [95% CI, 0.7-1.8], respectively). No appreciable variations in risk jamainternalmedicine.com
To the Editor McCullough et al1 reported that apparent mortality reductions following vertebroplasty and kyphoplasty likely result from selection bias. These findings are important to counter hasty conclusions from several recent population-based studies and reviews. Yet these new results are hardly surprising, given the a priori lack of evidence to assume a causal association between vertebral fractures and mortality, let alone mortality risk modifiable by targeting the spine. Reduced pulmonary function following vertebral fracture would be a plausible mechanistic explanation, but only small, short-term improvements in vital capacity following vertebral augmentation have been demJAMA Internal Medicine April 2014 Volume 174, Number 4
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Ndsu Library Periodicals User on 05/25/2015
641
