Letters
Figure 2. Dispensing Rates of Opioids Other Than Codeine During the First 6 Months of the Postpartum Period Before and After 2 Public Health Advisories, British Columbia, Canada, 2002-2011 1.8 Tramadol
Postpartum Women With ≥1 Prescription Dispensation, %
1.6 1.4 1.2 1.0 0.8
Hydromorphone
0.6 0.4
Oxycodone
0.2 Morphine
0 2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
Year of Giving Birth
Error bars indicate 95% confidence intervals.
uncertain. Important study limitations include not capturing drugs dispensed in hospitals. We could not ascertain if the women were actually breastfeeding at the time of codeine dispensation. In addition, we used data on drugs dispensed, which is not the same as drugs used. However, there is no reason to believe that the proportion of filled prescriptions that are not taken would systematically differ over time. Kate Smolina, PhD Deirdre Weymann, MA Steve Morgan, PhD Colin Ross, PhD Bruce Carleton, PharmD Author Affiliations: Centre for Health Services and Policy Research, School of Population and Public Health, University of British Columbia, Vancouver, Canada (Smolina, Weymann, Morgan); Department of Pediatrics, University of British Columbia, Vancouver, Canada (Ross, Carleton). Corresponding Author: Kate Smolina, PhD, Centre for Health Services and Policy Research, School of Population and Public Health, University of British Columbia, 215-2206 E Mall, Vancouver, BC V6T 1Z3, Canada ([email protected]). Author Contributions: Dr Smolina had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Smolina, Morgan, Ross, Carleton. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Smolina, Weymann. Critical revision of the manuscript for important intellectual content: Morgan, Ross, Carleton. Statistical analysis: Smolina, Weymann, Morgan. Obtained funding: Smolina, Morgan. Administrative, technical, or material support: Weymann, Morgan. Study supervision: Morgan, Carleton. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Funding/Support: This study was supported by Canadian Institutes for Health Research (CIHR) grant DC0190GP. Dr Smolina is funded in part by a CIHR Banting postdoctoral fellowship. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of 1862
the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 1. Sistonen J, Sajantila A, Lao O, Corander J, Barbujani G, Fuselli S. CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenet Genomics. 2007; 17(2):93-101. 2. Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2006;368(9536):704. 3. US Food and Drug Administration. Public health advisory: use of codeine by some breastfeeding mothers may lead to life-threatening side effects in nursing babies. http://www.fda.gov/Drugs/DrugSafety /PostmarketDrugSafetyInformationforPatientsandProviders /ucm054717.htm. Accessed January 28, 2015. 4. Health Canada. Use of codeine products by nursing mothers. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc /2008/13255a-eng.php. Accessed January 28, 2015. 5. British Columbia Ministry of Health; Population Data BC. Discharge Abstracts Database (hospital separations), Medical Services Plan Payment (MSP) Information File (physician billings), Consolidation File (MSP registration and premium billing), PharmaNet (prescriptions database); Perinatal Services BC: perinatal services births and stillbirths; British Columbia Vital Statistics Agency: vital statistics deaths. https://www.popdata.bc.ca/data. Accessed April 1, 2015. 6. Hamilton JD. Time Series Analysis. Princeton, NJ: Princeton University Press; 1994.
COMMENT & RESPONSE
Chlorhexidine Bathing and Infections in Critically Ill Patients To the Editor Dr Noto and colleagues1 reported results of a trial of daily bathing with chlorhexidine gluconate cloths compared with nonantimicrobial cloths in critically ill patients. They found that chlorhexidine did not reduce the incidence of health care–associated infections and concluded that the findings did not support daily bathing of critically ill patients with chlorhexidine. Some issues need further clarification because several aspects may have influenced the effectiveness of the primary intervention of chlorhexidine bathing in this pragmatic study. No data were available on adherence, so the dose of the intervention is not clear. In the accompanying Editorial, an alternative horizontal infection prevention strategy (improved hand hygiene) was recommended in settings of low rates of infections.2 However, both chlorhexidine bathing and hand hygiene have been shown to be dose-dependent interventions, relying on high adherence to be successful.3 In addition, data were not available on the numbers of infections present on admission to the intensive care unit (ICU) or on the antibiotics that were commenced immediately on admission. Differences between study groups or ICUs may have affected environmental bacterial pressure and the success of the intervention. Furthermore, 235 patients in the cardiovascular ICU were bathed with nonantimicrobial cloths when they were supposed to be bathed with chlorhexidine cloths. Two of the 5 ICUs used chlorhexidine bathing prior to the study start, potentially disrupting environmental contamination and colonization pressure. Only once in this study did an ICU start using nonantimicrobial bathing without using chlorhexidine before admission to the trauma ICU.
JAMA May 12, 2015 Volume 313, Number 18 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
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Letters
Although the study reported some reductions in catheter-associated urinary tract infection and Clostridium difficile infections and reported an increase in ventilatorassociated pneumonia, it is important to know whether oral chlorhexidine or other interventions were used as part of ventilator-associated pneumonia prevention strategies. Moreover, chlorhexidine is part of the central line– associated bloodstream infection prevention strategy. Thus, other prevention strategies applied are relevant because the incidence of new infections was low and may differ from other regions and countries. Based on this pragmatic single-center study with some potential confounding aspects of the intervention and outcome measures, it is unclear whether chlorhexidine bathing is useful in reducing health care–associated infections. Arthur R. H. van Zanten, MD, PhD Author Affiliation: Department of Intensive Care, Gelderse Vallei Hospital, Ede, the Netherlands. Corresponding Author: Arthur R. H. van Zanten, MD, PhD, Medical Manager Care Division, Department of Intensive Care, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP Ede, the Netherlands ([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. Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care–associated infections: a randomized clinical trial. JAMA. 2015;313(4):369378. 2. Pittet D, Angus DC. Daily chlorhexidine bathing for critically ill patients: a note of caution. JAMA. 2015;313(4):365-366. 3. Derde LP, Cooper BS, Goossens H, et al; MOSAR WP3 Study Team. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis. 2014;14(1):31-39.
To the Editor The study by Dr Noto and colleagues,1 a singlecenter, multiple crossover, cluster randomized clinical trial involving 9340 patients admitted to 5 ICUs at a tertiary care medical center compared daily bathing with chlorhexidine against washing with nonantimicrobial cloths. Chlorhexidine bathing did not reduce the incidence of health care– associated infections. It is not surprising to find a low health care-related infection rate of 2.86 per 1000 patient-days during the chlorhexidine period and 2.90 per 1000 patient-days during the control bathing period in their ICU patients when the median length of stay was only 2.56 days in the chlorhexidine group and 2.39 days in the control group, and the mean duration of hospital stay was 5 days in both groups. The length of stay in the study by Noto and colleagues1 contrasts with the study by Climo et al2 in which the mean ICU stay for medical and surgical ICUs ranged from 5.1 days to 6.4 days and was 18.8 days in a bone marrow transplantation ICU. In that study, a 23% reduction in the acquisition of multidrugresistant organisms was observed along with a 28% lower rate of hospital-acquired bloodstream infections with the use of chlorhexidine-impregnated washcloths. Multiple studies have found that the acquisition of multidrug-resistant organisms has a significant association with
the length of stay in the ICU for vancomycin-resistant Enterococcus3 and methicillin-resistant Staphylococcus aureus,4 and antibiotic treatments are a major determinant of the ICU prevalence of these pathogens. In addition, a nonrandomized study5 reported a sustained reduction in acquisition of methicillin-resistant S aureus in trauma patients during 4 weeks using chlorhexidine baths. The negative study by Noto and colleagues1 is useful to suggest the type of ICU in which chlorhexidine baths may not be useful, namely, those in which patients have a short length of stay, low background rates of health c are– associated infections, and low prevalence of multidrugresistant organisms. However, these conditions are not universal and adherence to basic infection control measures is not uniform. Chlorhexidine bathing is not the ideal infection control intervention; however, it deserves further study to define the ICU settings in which it can make a difference in patient outcomes. José Luis Soto-Hernandez, MD Author Affiliation: Department of Infectious Diseases, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Tlalpan, Mexico. Corresponding Author: José Luis Soto-Hernandez, MD, Department of Infectious Diseases, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Insurgentes Sur 3877, La Fama, Tlalpan CP 14269, Mexico ([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. Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care-associated infections: a randomized clinical trial. JAMA. 2015;313(4):369378. 2. Climo MW, Yokoe DS, Warren DK, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med. 2013;368(6):533-542. 3. Jung E, Byun S, Lee H, Moon SY, Lee H. Vancomycin-resistant Enterococcus colonization in the intensive care unit: clinical outcomes and attributable costs of hospitalization. Am J Infect Control. 2014;42(10):1062-1066. 4. Marshall C, Harrington G, Wolfe R, Fairley CK, Wesselingh S, Spelman D. Acquisition of methicillin-resistant Staphylococcus aureus in a large intensive care unit. Infect Control Hosp Epidemiol. 2003;24(5):322-326. 5. Evans HL, Dellit TH, Chan J, Nathens AB, Maier RV, Cuschieri J. Effect of chlorhexidine whole-body bathing on hospital-acquired infections among trauma patients. Arch Surg. 2010;145(3):240-246.
In Reply Dr van Zanten asks about other infection prevention strategies and adherence in our pragmatic, clusterrandomized, crossover trial testing the effectiveness of chlorhexidine bathing on health care–associated infection rates. The intervention was layered on routine care, which included numerous infection control practices such as hand washing, chlorhexidine oral solution for intubated patients, and chlorhexidine skin cleansing prior to central venous catheter insertion. We did not have ready electronic access to adherence data for these practices, an inherent limitation of pragmatic effectiveness trials. Nevertheless, we have no reason to suspect a biased adherence to any infection control practice, including chlorhexidine bathing, during the study. In addition, we acknowledge that we do not know the effect of chlorhexidine bathing on infection rates in the
jama.com
(Reprinted) JAMA May 12, 2015 Volume 313, Number 18
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fudan University User on 05/17/2015
1863
Letters
absence of oral or precatheter insertion chlorhexidine use, as mentioned by van Zanten, or in ICUs with high infection rates and long lengths of stay, as questioned by Dr SotoHernandez. However, a key advantage of the study design is that antibiotic use, community-acquired infections, and innumerable other unmeasured covariates are expected to be evenly distributed between groups as a result of randomization, crossover, and large sample size. In addition, the multiple crossover design serves to minimize seasonal effects. The supposition by van Zanten that prior exposure of an ICU to chlorhexidine bathing may have environmental consequences that extend beyond the bathed patient and thereby altered the effect of the chlorhexidine bathing intervention is interesting but is not supported by our findings. Regarding prior exposure to chlorhexidine, van Zanten is incorrect; 2 of the 5 participating ICUs were naive to chlorhexidine bathing at the outset of the study and were randomized to begin the trial in the control bathing group (neurological and cardiovascular). Therefore, these units were not exposed to chlorhexidine bathing until after the first crossover event, yet chlorhexidine bathing provided no detectable reduction in health care–associated infections in any ICU. In addition, although rates of catheter-associated urinary tract infection and C difficile infection were reduced and ventilator-associated pneumonia increased, these differences were not statistically significantly different between groups. Although it is unfortunate that a protocol violation occurred during 1 month in the cardiovascular ICU, resulting in the use of control bathing in patients randomized to chlorhexidine bathing, sensitivity analyses dealing with this violation failed to demonstrate any difference in the result. Soto-Hernandez cites a number of studies of bacterial acquisition. Chlorhexidine bathing likely does reduce skin colonization with multidrug-resistant organisms and might reduce blood cultures positive for skin commensal organisms, 1 but the benefit of these effects to patients remains uncertain. Even though new colonization with methicillin-resistant S aureus or vancomycin-resistant Enterococcus is included as a surrogate outcome in studies of many infection prevention strategies (including chlorhexidine bathing), colonization is not a disease. For this reason, assessment of colonization is not a component of routine patient care at our institution and was not included as an outcome in this study. Michael J. Noto, MD, PhD Todd W. Rice, MD, MSc Arthur P. Wheeler, MD Author Affiliations: Department of Medicine, Vanderbilt University, Nashville, Tennessee. Corresponding Author: Michael J. Noto, MD, PhD, Vanderbilt University Medical Center, Pulmonary and Critical Care Medicine, 1161 21st Ave S, Nashville, TN 37232 ([email protected]).
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Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Climo MW, Yokoe DS, Warren DK, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med. 2013;368(6):533-542.
Use of Wearable Monitoring Devices to Change Health Behavior To the Editor Dr Patel and colleagues,1 in their Viewpoint on the role of wearable devices, drew attention to the dangers of an uncritical adoption of the use of wearable technology without first focusing on the behavioral interventions that these devices can facilitate. The premise that interventions incorporating monitoring are effective in changing behavior is well established.2 Wearable devices have the potential to increase the opportunities for monitoring if they are low-cost and unobtrusive and collect data accurately. However, we would like to comment on the ways in which Patel and colleagues propose implementing these approaches to promote health behavior change. External monitoring can lead to passive behavior with respect to health behavior change, and the use of wearables could increase this problem. Extending continuous monitoring, as is required for high-risk individuals, to a community setting is rarely required for clinical purposes outside the hospital. Our group has been exploring the use of smartphones and tablets wirelessly linked to physiological measurement devices such as pulse oximeters to support patients in self-managing their conditions. Patients actively use the software on their device to acquire physiological data and interpret it in the context of their condition. Qualitative work has identified the way in which such active (as opposed to passive) self-monitoring helps patients feel more confident about managing their condition, and greater than 80% adherence to daily use of the device was achieved without the use of financial incentives.3 The authors propose “interventions using wearable devices that leverage concepts from behavioral economics.”1 Linking the use of wearable technology to behavioral interventions developed using the concepts of economics unnecessarily limits the scope of theoretical approaches used to inform intervention development. Interventions based on behavioral economic theory can be difficult to operationalize without using insights from other health psychology theories. The expectation that behavior can be predicted in a rational manner is also widely critiqued and difficult to reconcile with the findings that behavior is often better explained by the use of heuristic processes.4 Clinical trials using rigorous designs are needed to evaluate the effect of behavioral interventions using wearable devices before wide-scale implementation of approaches based on interesting but unproven theories. Andrew Farmer, DM, FRCGP Lionel Tarassenko, FMedSci, MA
JAMA May 12, 2015 Volume 313, Number 18 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
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Figure 2. Dispensing Rates of Opioids Other Than Codeine During the First 6 Months of the Postpartum Period Before and After 2 Public Health Advisories, British Columbia, Canada, 2002-2011 1.8 Tramadol
Postpartum Women With ≥1 Prescription Dispensation, %
1.6 1.4 1.2 1.0 0.8
Hydromorphone
0.6 0.4
Oxycodone
0.2 Morphine
0 2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
Year of Giving Birth
Error bars indicate 95% confidence intervals.
uncertain. Important study limitations include not capturing drugs dispensed in hospitals. We could not ascertain if the women were actually breastfeeding at the time of codeine dispensation. In addition, we used data on drugs dispensed, which is not the same as drugs used. However, there is no reason to believe that the proportion of filled prescriptions that are not taken would systematically differ over time. Kate Smolina, PhD Deirdre Weymann, MA Steve Morgan, PhD Colin Ross, PhD Bruce Carleton, PharmD Author Affiliations: Centre for Health Services and Policy Research, School of Population and Public Health, University of British Columbia, Vancouver, Canada (Smolina, Weymann, Morgan); Department of Pediatrics, University of British Columbia, Vancouver, Canada (Ross, Carleton). Corresponding Author: Kate Smolina, PhD, Centre for Health Services and Policy Research, School of Population and Public Health, University of British Columbia, 215-2206 E Mall, Vancouver, BC V6T 1Z3, Canada ([email protected]). Author Contributions: Dr Smolina had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Smolina, Morgan, Ross, Carleton. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Smolina, Weymann. Critical revision of the manuscript for important intellectual content: Morgan, Ross, Carleton. Statistical analysis: Smolina, Weymann, Morgan. Obtained funding: Smolina, Morgan. Administrative, technical, or material support: Weymann, Morgan. Study supervision: Morgan, Carleton. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Funding/Support: This study was supported by Canadian Institutes for Health Research (CIHR) grant DC0190GP. Dr Smolina is funded in part by a CIHR Banting postdoctoral fellowship. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of 1862
the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 1. Sistonen J, Sajantila A, Lao O, Corander J, Barbujani G, Fuselli S. CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenet Genomics. 2007; 17(2):93-101. 2. Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2006;368(9536):704. 3. US Food and Drug Administration. Public health advisory: use of codeine by some breastfeeding mothers may lead to life-threatening side effects in nursing babies. http://www.fda.gov/Drugs/DrugSafety /PostmarketDrugSafetyInformationforPatientsandProviders /ucm054717.htm. Accessed January 28, 2015. 4. Health Canada. Use of codeine products by nursing mothers. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc /2008/13255a-eng.php. Accessed January 28, 2015. 5. British Columbia Ministry of Health; Population Data BC. Discharge Abstracts Database (hospital separations), Medical Services Plan Payment (MSP) Information File (physician billings), Consolidation File (MSP registration and premium billing), PharmaNet (prescriptions database); Perinatal Services BC: perinatal services births and stillbirths; British Columbia Vital Statistics Agency: vital statistics deaths. https://www.popdata.bc.ca/data. Accessed April 1, 2015. 6. Hamilton JD. Time Series Analysis. Princeton, NJ: Princeton University Press; 1994.
COMMENT & RESPONSE
Chlorhexidine Bathing and Infections in Critically Ill Patients To the Editor Dr Noto and colleagues1 reported results of a trial of daily bathing with chlorhexidine gluconate cloths compared with nonantimicrobial cloths in critically ill patients. They found that chlorhexidine did not reduce the incidence of health care–associated infections and concluded that the findings did not support daily bathing of critically ill patients with chlorhexidine. Some issues need further clarification because several aspects may have influenced the effectiveness of the primary intervention of chlorhexidine bathing in this pragmatic study. No data were available on adherence, so the dose of the intervention is not clear. In the accompanying Editorial, an alternative horizontal infection prevention strategy (improved hand hygiene) was recommended in settings of low rates of infections.2 However, both chlorhexidine bathing and hand hygiene have been shown to be dose-dependent interventions, relying on high adherence to be successful.3 In addition, data were not available on the numbers of infections present on admission to the intensive care unit (ICU) or on the antibiotics that were commenced immediately on admission. Differences between study groups or ICUs may have affected environmental bacterial pressure and the success of the intervention. Furthermore, 235 patients in the cardiovascular ICU were bathed with nonantimicrobial cloths when they were supposed to be bathed with chlorhexidine cloths. Two of the 5 ICUs used chlorhexidine bathing prior to the study start, potentially disrupting environmental contamination and colonization pressure. Only once in this study did an ICU start using nonantimicrobial bathing without using chlorhexidine before admission to the trauma ICU.
JAMA May 12, 2015 Volume 313, Number 18 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
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Letters
Although the study reported some reductions in catheter-associated urinary tract infection and Clostridium difficile infections and reported an increase in ventilatorassociated pneumonia, it is important to know whether oral chlorhexidine or other interventions were used as part of ventilator-associated pneumonia prevention strategies. Moreover, chlorhexidine is part of the central line– associated bloodstream infection prevention strategy. Thus, other prevention strategies applied are relevant because the incidence of new infections was low and may differ from other regions and countries. Based on this pragmatic single-center study with some potential confounding aspects of the intervention and outcome measures, it is unclear whether chlorhexidine bathing is useful in reducing health care–associated infections. Arthur R. H. van Zanten, MD, PhD Author Affiliation: Department of Intensive Care, Gelderse Vallei Hospital, Ede, the Netherlands. Corresponding Author: Arthur R. H. van Zanten, MD, PhD, Medical Manager Care Division, Department of Intensive Care, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP Ede, the Netherlands ([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. Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care–associated infections: a randomized clinical trial. JAMA. 2015;313(4):369378. 2. Pittet D, Angus DC. Daily chlorhexidine bathing for critically ill patients: a note of caution. JAMA. 2015;313(4):365-366. 3. Derde LP, Cooper BS, Goossens H, et al; MOSAR WP3 Study Team. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis. 2014;14(1):31-39.
To the Editor The study by Dr Noto and colleagues,1 a singlecenter, multiple crossover, cluster randomized clinical trial involving 9340 patients admitted to 5 ICUs at a tertiary care medical center compared daily bathing with chlorhexidine against washing with nonantimicrobial cloths. Chlorhexidine bathing did not reduce the incidence of health care– associated infections. It is not surprising to find a low health care-related infection rate of 2.86 per 1000 patient-days during the chlorhexidine period and 2.90 per 1000 patient-days during the control bathing period in their ICU patients when the median length of stay was only 2.56 days in the chlorhexidine group and 2.39 days in the control group, and the mean duration of hospital stay was 5 days in both groups. The length of stay in the study by Noto and colleagues1 contrasts with the study by Climo et al2 in which the mean ICU stay for medical and surgical ICUs ranged from 5.1 days to 6.4 days and was 18.8 days in a bone marrow transplantation ICU. In that study, a 23% reduction in the acquisition of multidrugresistant organisms was observed along with a 28% lower rate of hospital-acquired bloodstream infections with the use of chlorhexidine-impregnated washcloths. Multiple studies have found that the acquisition of multidrug-resistant organisms has a significant association with
the length of stay in the ICU for vancomycin-resistant Enterococcus3 and methicillin-resistant Staphylococcus aureus,4 and antibiotic treatments are a major determinant of the ICU prevalence of these pathogens. In addition, a nonrandomized study5 reported a sustained reduction in acquisition of methicillin-resistant S aureus in trauma patients during 4 weeks using chlorhexidine baths. The negative study by Noto and colleagues1 is useful to suggest the type of ICU in which chlorhexidine baths may not be useful, namely, those in which patients have a short length of stay, low background rates of health c are– associated infections, and low prevalence of multidrugresistant organisms. However, these conditions are not universal and adherence to basic infection control measures is not uniform. Chlorhexidine bathing is not the ideal infection control intervention; however, it deserves further study to define the ICU settings in which it can make a difference in patient outcomes. José Luis Soto-Hernandez, MD Author Affiliation: Department of Infectious Diseases, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Tlalpan, Mexico. Corresponding Author: José Luis Soto-Hernandez, MD, Department of Infectious Diseases, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Insurgentes Sur 3877, La Fama, Tlalpan CP 14269, Mexico ([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. Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care-associated infections: a randomized clinical trial. JAMA. 2015;313(4):369378. 2. Climo MW, Yokoe DS, Warren DK, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med. 2013;368(6):533-542. 3. Jung E, Byun S, Lee H, Moon SY, Lee H. Vancomycin-resistant Enterococcus colonization in the intensive care unit: clinical outcomes and attributable costs of hospitalization. Am J Infect Control. 2014;42(10):1062-1066. 4. Marshall C, Harrington G, Wolfe R, Fairley CK, Wesselingh S, Spelman D. Acquisition of methicillin-resistant Staphylococcus aureus in a large intensive care unit. Infect Control Hosp Epidemiol. 2003;24(5):322-326. 5. Evans HL, Dellit TH, Chan J, Nathens AB, Maier RV, Cuschieri J. Effect of chlorhexidine whole-body bathing on hospital-acquired infections among trauma patients. Arch Surg. 2010;145(3):240-246.
In Reply Dr van Zanten asks about other infection prevention strategies and adherence in our pragmatic, clusterrandomized, crossover trial testing the effectiveness of chlorhexidine bathing on health care–associated infection rates. The intervention was layered on routine care, which included numerous infection control practices such as hand washing, chlorhexidine oral solution for intubated patients, and chlorhexidine skin cleansing prior to central venous catheter insertion. We did not have ready electronic access to adherence data for these practices, an inherent limitation of pragmatic effectiveness trials. Nevertheless, we have no reason to suspect a biased adherence to any infection control practice, including chlorhexidine bathing, during the study. In addition, we acknowledge that we do not know the effect of chlorhexidine bathing on infection rates in the
jama.com
(Reprinted) JAMA May 12, 2015 Volume 313, Number 18
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fudan University User on 05/17/2015
1863
Letters
absence of oral or precatheter insertion chlorhexidine use, as mentioned by van Zanten, or in ICUs with high infection rates and long lengths of stay, as questioned by Dr SotoHernandez. However, a key advantage of the study design is that antibiotic use, community-acquired infections, and innumerable other unmeasured covariates are expected to be evenly distributed between groups as a result of randomization, crossover, and large sample size. In addition, the multiple crossover design serves to minimize seasonal effects. The supposition by van Zanten that prior exposure of an ICU to chlorhexidine bathing may have environmental consequences that extend beyond the bathed patient and thereby altered the effect of the chlorhexidine bathing intervention is interesting but is not supported by our findings. Regarding prior exposure to chlorhexidine, van Zanten is incorrect; 2 of the 5 participating ICUs were naive to chlorhexidine bathing at the outset of the study and were randomized to begin the trial in the control bathing group (neurological and cardiovascular). Therefore, these units were not exposed to chlorhexidine bathing until after the first crossover event, yet chlorhexidine bathing provided no detectable reduction in health care–associated infections in any ICU. In addition, although rates of catheter-associated urinary tract infection and C difficile infection were reduced and ventilator-associated pneumonia increased, these differences were not statistically significantly different between groups. Although it is unfortunate that a protocol violation occurred during 1 month in the cardiovascular ICU, resulting in the use of control bathing in patients randomized to chlorhexidine bathing, sensitivity analyses dealing with this violation failed to demonstrate any difference in the result. Soto-Hernandez cites a number of studies of bacterial acquisition. Chlorhexidine bathing likely does reduce skin colonization with multidrug-resistant organisms and might reduce blood cultures positive for skin commensal organisms, 1 but the benefit of these effects to patients remains uncertain. Even though new colonization with methicillin-resistant S aureus or vancomycin-resistant Enterococcus is included as a surrogate outcome in studies of many infection prevention strategies (including chlorhexidine bathing), colonization is not a disease. For this reason, assessment of colonization is not a component of routine patient care at our institution and was not included as an outcome in this study. Michael J. Noto, MD, PhD Todd W. Rice, MD, MSc Arthur P. Wheeler, MD Author Affiliations: Department of Medicine, Vanderbilt University, Nashville, Tennessee. Corresponding Author: Michael J. Noto, MD, PhD, Vanderbilt University Medical Center, Pulmonary and Critical Care Medicine, 1161 21st Ave S, Nashville, TN 37232 ([email protected]).
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Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Climo MW, Yokoe DS, Warren DK, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med. 2013;368(6):533-542.
Use of Wearable Monitoring Devices to Change Health Behavior To the Editor Dr Patel and colleagues,1 in their Viewpoint on the role of wearable devices, drew attention to the dangers of an uncritical adoption of the use of wearable technology without first focusing on the behavioral interventions that these devices can facilitate. The premise that interventions incorporating monitoring are effective in changing behavior is well established.2 Wearable devices have the potential to increase the opportunities for monitoring if they are low-cost and unobtrusive and collect data accurately. However, we would like to comment on the ways in which Patel and colleagues propose implementing these approaches to promote health behavior change. External monitoring can lead to passive behavior with respect to health behavior change, and the use of wearables could increase this problem. Extending continuous monitoring, as is required for high-risk individuals, to a community setting is rarely required for clinical purposes outside the hospital. Our group has been exploring the use of smartphones and tablets wirelessly linked to physiological measurement devices such as pulse oximeters to support patients in self-managing their conditions. Patients actively use the software on their device to acquire physiological data and interpret it in the context of their condition. Qualitative work has identified the way in which such active (as opposed to passive) self-monitoring helps patients feel more confident about managing their condition, and greater than 80% adherence to daily use of the device was achieved without the use of financial incentives.3 The authors propose “interventions using wearable devices that leverage concepts from behavioral economics.”1 Linking the use of wearable technology to behavioral interventions developed using the concepts of economics unnecessarily limits the scope of theoretical approaches used to inform intervention development. Interventions based on behavioral economic theory can be difficult to operationalize without using insights from other health psychology theories. The expectation that behavior can be predicted in a rational manner is also widely critiqued and difficult to reconcile with the findings that behavior is often better explained by the use of heuristic processes.4 Clinical trials using rigorous designs are needed to evaluate the effect of behavioral interventions using wearable devices before wide-scale implementation of approaches based on interesting but unproven theories. Andrew Farmer, DM, FRCGP Lionel Tarassenko, FMedSci, MA
JAMA May 12, 2015 Volume 313, Number 18 (Reprinted)
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