1688
Letters to the Editor
and a trend toward decreased cost associated with weekend ERCP. The aim of the study was focused on the length of stay and hospital costs. Previous studies have compared mortality after weekend vs. weekday admission showing evidence of a weekend effect for 7-day patient mortality. Previous studies have also shown an acute risk pattern to be consistent with a weekend effect. In the present study, this could have been obscured by the small sample size. In addition, this might have been better appreciated if the acuity of the problem would have been analyzed. It would have been interesting to see a comparison between indications such as stone decompression or elevated liver function tests (chronic conditions) compared with acute cholangitis (acute condition). In the presented study, the two most common diagnoses were choledocolithiasis and elevated liver function tests in post-transplant patients (35% and 25% of the cases, respectively), both accounting for 60% of the cases, which would have been classified as nonacute problems. With regard to Table 1 (baseline characteristics), within the “Procedure was emergent” group, this showed a P value less than 0.05. This suggests that the two variables (weekday and weekend) are significantly different to begin with, and this disparity possibly could have affected the results analysis. Patient baseline risk is another factor that could have been taken into consideration. Perez Concha et al. (2) concluded that patients admitted over the weekend had a lower baseline risk because they were younger and had less comorbidity; the explanation was that these patients are more likely to be employed and postpone seeking medical care. Finally, the presented study was conducted in a single tertiary academic center; results might not be applicable for smaller hospitals with a lower complexity of cases, low volume of patients, small number of endoscopists performing ERCPs, reduced number of staff and ancillary services, as well as private institutions where endoscopists and staff have different incentives and procedures have different costs. CONFLICT OF INTEREST The authors declare no conflict of interest. The American Journal of GASTROENTEROLOGY
nature publishing group
REFERENCES 1. Neehar D. Parikh, Rachel Issaka, Brittany Lapin et al. Inpatient weekend ERCP is associated with a reduction in patient length of stay. Am J Gastroenterol 2014;109:465–70. 2. Concha OP, Gallego B, Lapin B et al. Do variations in Hospital Mortality patterns after weekend admission reflect reduced quality of care or different patient cohorts? A population based study. BMJ Qaul Saf 2014;23:215–22. 1
Department of Gastroenterology, Beaumont Hospital, Royal Oak, Michigan, USA. Correspondence: Ross A. Sage, MD, Department of Gastroenterology, Beaumont Hospital, 3601W. Thirteen Mile Road, Royal Oak, Michigan 48073, USA. E-mail: [email protected]
Response to Sage and Mogrovejo Neehar D. Parikh, MD, MS1 and Rajesh Keswani, MD2 doi:10.1038/ajg.2014.257
To the Editor: We thank Dr Sage and Dr Mogrovejo for their thoughtful comments regarding our manuscript and the opportunity to clarify many of the points made in their comments (1). They correctly note that the focus of this study was to determine the effect on length of stay and costs when performing nonemergent procedures on weekends rather than a full analysis of the safety and outcomes of weekend procedures, which might require a larger sample size. However, the similarly low complication rates for both weekday and weekend procedures does suggest that performing weekend ERCPs with an experienced team is safe, in addition to being cost-effective. As expected, there is a significant difference in emergent procedures between the weekend and weekday cohorts, but this variable was included in our multivariate and propensity score analysis, and a significant difference remained between groups. To their next point regarding taking baseline risk of patients into account, we did this by taking several factors into account in our analysis, including ASA score, patient age, and indication for the procedure. We did not collect data to calcu-
late a formal comorbidity index. However, when we removed the post-liver transplant patients—who often have a high amount of comorbidity (Supplementary Table 2 online)—the subanalysis showed that significant differences remained between the weekend and weekday cohorts (1,2). With regard to their final point regarding the external validity of these findings, we fully acknowledge in our discussion that these findings may not be applicable to all healthcare settings, and they may not be logistically possible in many low resource areas. This study was conducted at a high ERCP volume academic center, with weekend procedures performed by one of three experienced on-call therapeutic endoscopists in conjunction with an experienced ERCP nurse and anesthesiologist. We contend that when appropriate resources are present to conduct weekend ERCPs hospital length of stay and costs will improve (3). We improved external validity through our subanalysis, but acknowledge that repeating the study in other healthcare settings would enhance the impact of our findings. In the 2001 Institute of Medicine report, “Crossing the Quality Chasm,” the following principles of achieving quality care were emphasized: safety, effectiveness, patientcenteredness, timeliness, efficiency, and equitability (4). Our study shows that performance of weekend ERCPs can improve the timeliness, efficiency, and, ultimately, patient-centeredness of inpatient care. We thank the authors for their thoughtful comments and appreciate the opportunity to clarify many of the points that have been made. CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES 1. Parikh ND, Issaka R, Lapin B et al. Inpatient weekend ERCP is associated with a reduction in patient length of stay. Am J Gastroenterol 2014;109:465–70. 2. Jepsen P, Vilstrup H, Lash TL. Development and validation of a comorbidity scoring system for patients with cirrhosis. Gastroenterology 2014;146:147–56. 3. Polverejan E, Gardiner JC, Bradley CJ et al. Estimating mean hospital cost as a function of length of stay and patient characteristics. Health Econ 2003;12:935–47.
VOLUME 109 | OCTOBER 2014 www.amjgastro.com
Letters to the Editor
nature publishing group
4. Committee On Quality Of Health Care In A, Medicine I. Crossing the Quality Chasm: A New Health System for the 21st Century National Academies Press; 2001.
1
Division of Gastroenterology, University of Michigan, Ann Arbor Michigan, USA; 2Division of Gastroenterology, Northwestern University, Chicago, Illinois, USA. Correspondence: Neehar D. Parikh, MD, MS, Division of Gastroenterology, University of Michigan, 3912 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, Michigan 48104, USA. E-mail: [email protected]
Immortal Time Bias: A Likely Alternate Explanation for the Purported Benefits of DXA Screening in Ulcerative Colitis Laura E. Targownik, MD, MSHS1 doi:10.1038/ajg.2014.234
To the Editor: We have read with interest your recent article in the April 2014 issue of the American College of Gastroenterology entitled “Adherence and Efficacy of Screening for Low Bone Mineral Density Among Ulcerative Colitis Patients Treated With Corticosteroids” (1). In this study, Khan et al. (1) aimed to evaluate the role of dual-energy X-ray absorptiometry (DXA) screening for preventing the occurrence of fracture in persons who have received corticosteroids for the treatment of ulcerative colitis. The authors report, somewhat surprisingly, that merely undergoing a DXA is associated with a 50% reduction in the risk for subsequent fracture, independent of the results or any specific intervention based on the DXA findings. Unfortunately, it is likely that the purported benefits of this manuscript are the result of immortal time bias (2,3). Immortal time bias occurs when person-time is accrued among members of a treated or screened cohort during which time the adverse event of interest cannot occur. © 2014 by the American College of Gastroenterology
Furthermore, if the adverse events were to occur in this time period, it would be counted against the untreated or unscreened group. Therefore, it is important for researchers to be aware of immortal time bias when performing time-to-event analyses, as this may give the erroneous appearance of benefit, particularly in studies involving drug therapies or screening tests. In this study, the issue of concern is how the person-time accumulated between the date of the initial prescription of corticosteroids (the condition for cohort entry) and the date of the DXA (for the DXA cohort) is “immortal”, in the sense that every person who receives a DXA is obliged to be alive and fracture free for this period. If this person-time is counted in the denominator of the DXA-exposed group, it falsely deflates the incidence rate of events in the DXA-based group. In this study, as the average time between corticosteroid prescription and DXA is just under 3 years, and the average total follow-up time is around 6 years, the incidence rate is probably underestimated by 50% (an amount roughly equivalent to the stated benefits). It would be greatly appreciated if you could let us know whether and how you accounted for immortal time bias, and, if not, would you be willing to rerun this analysis taking this unaccounted persontime into your calculations. This is most commonly performed by treating the intervention (DXA) as a time-dependent covariate (2). CONFLICT OF INTEREST The author declares no conflict of interest.
REFERENCES 1. Khan N, Abbas AM, Almukhtar RM et al. Adherence and efficacy of screening for low bone mineral density among ulcerative colitis patients treated with corticosteroids. Am J Gastroenterol 2014;109:572–8. 2. Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol 2008;167:492–9. 3. Rothman KJ, Suissa S.. Exclusion of immortal person-time. Pharmacoepidemiol Drug Saf 2008;17:1036. 1
Department of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada. Correspondence: Laura E. Targownik, MD, MSHS, Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin, Otago 9054, New Zealand. E-mail: [email protected]
Polypectomy to Eradicate Cap Polyposis With Protein-Losing Enteropathy Yoshiaki Arimura, MD, PhD1, Hiroyuki Isshiki, MD1, Daisuke Hirayama, MD1, Kei Onodera, MD1, Kayo Murakami, MD1, Kentaro Yamashita, MD, PhD1 and Yasuhisa Shinomura, MD, PhD1 doi:10.1038/ajg.2014.227
To the Editor: Cap polyposis is a rare disease characterized by mucoid, bloody diarrhea, and polyps covered by a cap of fibrinopurulent mucous. Neither optimal treatment nor the etiology has been established. Polyp removal appears to provide only temporary relief (1), although cure is possible in patients with solitary lesions (2). We herein describe a patient with extensive cap polyposis whose disorganized tight junctions led to the manifestation of protein-losing enteropathy. The patient’s condition was successfully eradicated by polypectomy. A 43-year-old man was referred to our university hospital because of intractable bloody diarrhea and hypoproteinemia. Upon admission, he was seen to have been experiencing 12 bowel movements a day with straining, and exhibited moderate pitting edema extending up to both knees. Blood tests revealed a total protein level of 5.1 g/dl, an albumin level of 2.2 g/dl, and severe anemia with a hemoglobin concentration of 8.7 g/dl. Approximately 500 polyps involving the entire colon, excluding the cecum and ascending colon (Figure 1a), were removed by seven polypectomy procedures (Figure 1b). The total protein, albumin, and hemoglobin levels recovered to the reference ranges, and the diarrhea disappeared. No signs of polyp recurrence were present 1 year after the first visit (6 months after the last polypectomy). The two novel findings in this case are that polypectomy with curative intent can be safe and minimally invasive and that the polyps in patients with cap polyposis can be “leaky.” The American Journal of GASTROENTEROLOGY
1689
Letters to the Editor
and a trend toward decreased cost associated with weekend ERCP. The aim of the study was focused on the length of stay and hospital costs. Previous studies have compared mortality after weekend vs. weekday admission showing evidence of a weekend effect for 7-day patient mortality. Previous studies have also shown an acute risk pattern to be consistent with a weekend effect. In the present study, this could have been obscured by the small sample size. In addition, this might have been better appreciated if the acuity of the problem would have been analyzed. It would have been interesting to see a comparison between indications such as stone decompression or elevated liver function tests (chronic conditions) compared with acute cholangitis (acute condition). In the presented study, the two most common diagnoses were choledocolithiasis and elevated liver function tests in post-transplant patients (35% and 25% of the cases, respectively), both accounting for 60% of the cases, which would have been classified as nonacute problems. With regard to Table 1 (baseline characteristics), within the “Procedure was emergent” group, this showed a P value less than 0.05. This suggests that the two variables (weekday and weekend) are significantly different to begin with, and this disparity possibly could have affected the results analysis. Patient baseline risk is another factor that could have been taken into consideration. Perez Concha et al. (2) concluded that patients admitted over the weekend had a lower baseline risk because they were younger and had less comorbidity; the explanation was that these patients are more likely to be employed and postpone seeking medical care. Finally, the presented study was conducted in a single tertiary academic center; results might not be applicable for smaller hospitals with a lower complexity of cases, low volume of patients, small number of endoscopists performing ERCPs, reduced number of staff and ancillary services, as well as private institutions where endoscopists and staff have different incentives and procedures have different costs. CONFLICT OF INTEREST The authors declare no conflict of interest. The American Journal of GASTROENTEROLOGY
nature publishing group
REFERENCES 1. Neehar D. Parikh, Rachel Issaka, Brittany Lapin et al. Inpatient weekend ERCP is associated with a reduction in patient length of stay. Am J Gastroenterol 2014;109:465–70. 2. Concha OP, Gallego B, Lapin B et al. Do variations in Hospital Mortality patterns after weekend admission reflect reduced quality of care or different patient cohorts? A population based study. BMJ Qaul Saf 2014;23:215–22. 1
Department of Gastroenterology, Beaumont Hospital, Royal Oak, Michigan, USA. Correspondence: Ross A. Sage, MD, Department of Gastroenterology, Beaumont Hospital, 3601W. Thirteen Mile Road, Royal Oak, Michigan 48073, USA. E-mail: [email protected]
Response to Sage and Mogrovejo Neehar D. Parikh, MD, MS1 and Rajesh Keswani, MD2 doi:10.1038/ajg.2014.257
To the Editor: We thank Dr Sage and Dr Mogrovejo for their thoughtful comments regarding our manuscript and the opportunity to clarify many of the points made in their comments (1). They correctly note that the focus of this study was to determine the effect on length of stay and costs when performing nonemergent procedures on weekends rather than a full analysis of the safety and outcomes of weekend procedures, which might require a larger sample size. However, the similarly low complication rates for both weekday and weekend procedures does suggest that performing weekend ERCPs with an experienced team is safe, in addition to being cost-effective. As expected, there is a significant difference in emergent procedures between the weekend and weekday cohorts, but this variable was included in our multivariate and propensity score analysis, and a significant difference remained between groups. To their next point regarding taking baseline risk of patients into account, we did this by taking several factors into account in our analysis, including ASA score, patient age, and indication for the procedure. We did not collect data to calcu-
late a formal comorbidity index. However, when we removed the post-liver transplant patients—who often have a high amount of comorbidity (Supplementary Table 2 online)—the subanalysis showed that significant differences remained between the weekend and weekday cohorts (1,2). With regard to their final point regarding the external validity of these findings, we fully acknowledge in our discussion that these findings may not be applicable to all healthcare settings, and they may not be logistically possible in many low resource areas. This study was conducted at a high ERCP volume academic center, with weekend procedures performed by one of three experienced on-call therapeutic endoscopists in conjunction with an experienced ERCP nurse and anesthesiologist. We contend that when appropriate resources are present to conduct weekend ERCPs hospital length of stay and costs will improve (3). We improved external validity through our subanalysis, but acknowledge that repeating the study in other healthcare settings would enhance the impact of our findings. In the 2001 Institute of Medicine report, “Crossing the Quality Chasm,” the following principles of achieving quality care were emphasized: safety, effectiveness, patientcenteredness, timeliness, efficiency, and equitability (4). Our study shows that performance of weekend ERCPs can improve the timeliness, efficiency, and, ultimately, patient-centeredness of inpatient care. We thank the authors for their thoughtful comments and appreciate the opportunity to clarify many of the points that have been made. CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES 1. Parikh ND, Issaka R, Lapin B et al. Inpatient weekend ERCP is associated with a reduction in patient length of stay. Am J Gastroenterol 2014;109:465–70. 2. Jepsen P, Vilstrup H, Lash TL. Development and validation of a comorbidity scoring system for patients with cirrhosis. Gastroenterology 2014;146:147–56. 3. Polverejan E, Gardiner JC, Bradley CJ et al. Estimating mean hospital cost as a function of length of stay and patient characteristics. Health Econ 2003;12:935–47.
VOLUME 109 | OCTOBER 2014 www.amjgastro.com
Letters to the Editor
nature publishing group
4. Committee On Quality Of Health Care In A, Medicine I. Crossing the Quality Chasm: A New Health System for the 21st Century National Academies Press; 2001.
1
Division of Gastroenterology, University of Michigan, Ann Arbor Michigan, USA; 2Division of Gastroenterology, Northwestern University, Chicago, Illinois, USA. Correspondence: Neehar D. Parikh, MD, MS, Division of Gastroenterology, University of Michigan, 3912 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, Michigan 48104, USA. E-mail: [email protected]
Immortal Time Bias: A Likely Alternate Explanation for the Purported Benefits of DXA Screening in Ulcerative Colitis Laura E. Targownik, MD, MSHS1 doi:10.1038/ajg.2014.234
To the Editor: We have read with interest your recent article in the April 2014 issue of the American College of Gastroenterology entitled “Adherence and Efficacy of Screening for Low Bone Mineral Density Among Ulcerative Colitis Patients Treated With Corticosteroids” (1). In this study, Khan et al. (1) aimed to evaluate the role of dual-energy X-ray absorptiometry (DXA) screening for preventing the occurrence of fracture in persons who have received corticosteroids for the treatment of ulcerative colitis. The authors report, somewhat surprisingly, that merely undergoing a DXA is associated with a 50% reduction in the risk for subsequent fracture, independent of the results or any specific intervention based on the DXA findings. Unfortunately, it is likely that the purported benefits of this manuscript are the result of immortal time bias (2,3). Immortal time bias occurs when person-time is accrued among members of a treated or screened cohort during which time the adverse event of interest cannot occur. © 2014 by the American College of Gastroenterology
Furthermore, if the adverse events were to occur in this time period, it would be counted against the untreated or unscreened group. Therefore, it is important for researchers to be aware of immortal time bias when performing time-to-event analyses, as this may give the erroneous appearance of benefit, particularly in studies involving drug therapies or screening tests. In this study, the issue of concern is how the person-time accumulated between the date of the initial prescription of corticosteroids (the condition for cohort entry) and the date of the DXA (for the DXA cohort) is “immortal”, in the sense that every person who receives a DXA is obliged to be alive and fracture free for this period. If this person-time is counted in the denominator of the DXA-exposed group, it falsely deflates the incidence rate of events in the DXA-based group. In this study, as the average time between corticosteroid prescription and DXA is just under 3 years, and the average total follow-up time is around 6 years, the incidence rate is probably underestimated by 50% (an amount roughly equivalent to the stated benefits). It would be greatly appreciated if you could let us know whether and how you accounted for immortal time bias, and, if not, would you be willing to rerun this analysis taking this unaccounted persontime into your calculations. This is most commonly performed by treating the intervention (DXA) as a time-dependent covariate (2). CONFLICT OF INTEREST The author declares no conflict of interest.
REFERENCES 1. Khan N, Abbas AM, Almukhtar RM et al. Adherence and efficacy of screening for low bone mineral density among ulcerative colitis patients treated with corticosteroids. Am J Gastroenterol 2014;109:572–8. 2. Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol 2008;167:492–9. 3. Rothman KJ, Suissa S.. Exclusion of immortal person-time. Pharmacoepidemiol Drug Saf 2008;17:1036. 1
Department of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada. Correspondence: Laura E. Targownik, MD, MSHS, Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin, Otago 9054, New Zealand. E-mail: [email protected]
Polypectomy to Eradicate Cap Polyposis With Protein-Losing Enteropathy Yoshiaki Arimura, MD, PhD1, Hiroyuki Isshiki, MD1, Daisuke Hirayama, MD1, Kei Onodera, MD1, Kayo Murakami, MD1, Kentaro Yamashita, MD, PhD1 and Yasuhisa Shinomura, MD, PhD1 doi:10.1038/ajg.2014.227
To the Editor: Cap polyposis is a rare disease characterized by mucoid, bloody diarrhea, and polyps covered by a cap of fibrinopurulent mucous. Neither optimal treatment nor the etiology has been established. Polyp removal appears to provide only temporary relief (1), although cure is possible in patients with solitary lesions (2). We herein describe a patient with extensive cap polyposis whose disorganized tight junctions led to the manifestation of protein-losing enteropathy. The patient’s condition was successfully eradicated by polypectomy. A 43-year-old man was referred to our university hospital because of intractable bloody diarrhea and hypoproteinemia. Upon admission, he was seen to have been experiencing 12 bowel movements a day with straining, and exhibited moderate pitting edema extending up to both knees. Blood tests revealed a total protein level of 5.1 g/dl, an albumin level of 2.2 g/dl, and severe anemia with a hemoglobin concentration of 8.7 g/dl. Approximately 500 polyps involving the entire colon, excluding the cecum and ascending colon (Figure 1a), were removed by seven polypectomy procedures (Figure 1b). The total protein, albumin, and hemoglobin levels recovered to the reference ranges, and the diarrhea disappeared. No signs of polyp recurrence were present 1 year after the first visit (6 months after the last polypectomy). The two novel findings in this case are that polypectomy with curative intent can be safe and minimally invasive and that the polyps in patients with cap polyposis can be “leaky.” The American Journal of GASTROENTEROLOGY
1689
