ORIGINAL ARTICLE: Clinical Endoscopy
Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bowel preparation: development and validation of a prediction score Vincent K. Dik, MD,1 Leon M.G. Moons, MD, PhD,1 Melek Hüyük, BSc,1 Peter van der Schaar, MD, PhD,2 Wouter H. de Vos tot Nederveen Cappel, MD, PhD,3 Pieter C.J. ter Borg, MD, PhD,4 Maarten A.C. Meijssen, MD, PhD,3 Rob J.T.H. Ouwendijk, MD, PhD,4 Doris M. Le Fèvre,5 Merijn Stouten,6 Onno van der Galiën,5 Theo J. Hiemstra,5 Jan F. Monkelbaan, MD,1 Martijn G.H. van Oijen, PhD,1 Peter D. Siersema, MD, PhD,1 for the Colonoscopy Quality Initiative Utrecht, The Netherlands
Background: Adequate bowel preparation is important for optimal colonoscopy. It is important to identify patients at risk for inadequate bowel preparation because this allows taking precautions in this specific group. Objective: To develop a prediction score to identify patients at risk for inadequate bowel preparation who may benefit from an intensified bowel cleansing regimen. Design: Patient and colonoscopy data were prospectively collected, whereas clinical data were retrospectively collected for a total of 1996 colonoscopies in participants who received split-dose bowel preparation. Multivariate logistic regression analyses were conducted in a random two-thirds of the cohort to develop a prediction model. Validation and evaluation of the discriminative power of the prediction model were performed within the remaining one-third of the cohort. Setting: Four centers, including one academic and three medium-to-large size nonacademic centers. Patients: Consecutive colonoscopies in November and December 2012. Mean age was 57.3 15.9 years, 45.8% were male and indications for colonoscopy were screening and/or surveillance (27%), abdominal symptoms and/ or blood loss and/or anemia (60%), inflammatory bowel disease (9%), and others (4%). Interventions: Colonoscopy. Main Outcome Measurements: Inadequate bowel preparation defined as Boston Bowel Preparation Scale score !6. Results: A total of 1331 colonoscopies were included in the development cohort, of which 172 (12.9%) had an inadequate bowel preparation. Independent factors included in the prediction model were American Society of Anesthesiologists Physical Status Classification System score R3, use of tricyclic antidepressants, use of opioids, diabetes, chronic constipation, history of abdominal and/or pelvic surgery, history of inadequate bowel preparation, and current hospitalization. The discriminative ability of the scale was good, with an area under the curve of 0.77 in the validation cohort. Limitations: Study design partially retrospective, no data on patient compliance. Conclusion: We developed a validated, easy-to-use prediction scale that can be used to identify subjects with an increased risk of inadequate bowel preparation with good accuracy. (Gastrointest Endosc 2015;81:665-72.)
Abbreviations: ASA, American Society of Anesthesiologists Physical Status Classification System; AUC, area under the curve; BBPS, Boston Bowel Preparation Scale; BMI, body mass index; NPV, negative predictive value; PG, polyethylene glycol; PPV, positive predictive value. DISCLOSURE: All authors disclosed no financial relationships relevant to this article. Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy
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0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.09.066 Received May 10, 2014. Accepted September 29, 2014. Current affiliations: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht (1), Department of (footnotes continued on last page of article)
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Colonoscopy is currently the predominant method for detecting mucosal abnormalities in the colorectum. Adequate bowel preparation is essential for the efficacy of colonoscopy, because inadequate bowel preparation is associated with incomplete colonoscopy, lower adenoma detection rates, increased procedure times, and need to repeat the procedure.1-5 Despite its importance, recent studies still report inadequate bowel preparation in 10% to 30% of colonoscopies, even with split-dose bowel preparation.4-9 The addition of laxatives such as bisacodyl or sennosides to standard bowel cleansing regimens can improve the quality of bowel preparation.10,11 Furthermore, some data suggest that it is possible to achieve higher cleansing rates with intensified regimens in patients with previous inadequate bowel preparation.12 Identification of patients at an increased risk for inadequate bowel preparation may therefore enable physicians to intensify the bowel preparation regimen in order to prevent unnecessary repeat endoscopies and the risk of missing neoplastic lesions. Risk factors that have been found to negatively affect quality of bowel preparation through inhibition of bowel motility include chronic constipation, liver cirrhosis, diabetes, previous intra-abdominal or pelvic surgery, use of multiple medications, use of opioids or tricyclic antidepressants, and factors related to immobilization such as older age, physical condition, obesity, neurologic disease, and hospitalization.1,7,8,13-17 An increasing number of these baseline risk factors has been found to be associated with a higher risk of inadequate bowel preparation.13 Hassan et al8 developed a prediction model to identify patients at increased risk for inadequate bowel preparation. It was found that this model had fair accuracy (area under the curve [AUC] 0.63). However, this study also included participants who were noncompliant with the bowel preparation regimen. Moreover, only 12% of participants took split-dose bowel preparation, which is nowadays recommended as optimal bowel preparation by the European Society of Gastrointestinal Endoscopy.18 The aim of the present study was to develop a validated, easy-to-use, prediction score to identify patients at risk for inadequate bowel preparation who may benefit from an intensified bowel cleansing regimen.
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citrate was used as standard bowel preparation, with sodium phosphate used in a selected group of young participants without comorbidities, and 4 L PG in case of hospitalization. Patient-related and procedure-related factors were prospectively collected for quality auditing purposes. Data on comorbidities and medication use were collected from the hospital’s electronic medical charts.
Study variables The primary outcome of this study was inadequate bowel preparation, defined as a Boston Bowel Preparation Scale (BBPS) score !6.19,20 The BBPS score was assigned by the endoscopist directly after the colonoscopy. Factors possibly associated with the quality of bowel preparation that were collected for this study were based on the available literature1,7,8,13-17 and included age, body mass index (BMI), the American Society of Anesthesiologists Physical Status Classification System (ASA) score, number of nontopical medications, tricyclic antidepressant use, opioid use, diabetes, liver cirrhosis, chronic constipation, history of neurologic disease (stroke, spina bifida, dementia, paraplegia, or Parkinson disease), history of intra-abdominal and/or pelvic surgery, current hospitalization, previous colonoscopies, and history of inadequate bowel preparation. Male sex was not included in the prediction score because its association with inadequate bowel preparation has previously been found to be related to noncompliance with the bowel preparation regimen.21 Other procedural factors collected included indication for colonoscopy (screening/ surveillance, abdominal symptoms, blood loss/anemia, inflammatory bowel disease, or other), cecal intubation and cause of cecal intubation failure, procedure time (morning or afternoon), inpatient bowel preparation, and whether the bowel preparation was used.
Statistical analyses
Centers participating in this study were 3 medium-tolarge size, nonacademic and 1 academic center located in 3 different regions in The Netherlands. For this observational cohort study, we enrolled consecutive colonoscopies that were performed from November 1 to December 31, 2012. Bowel preparation regimens that were applied in the 4 centers included 4 L polyethylene glycol (PG) in 2 centers and 2 L PG plus ascorbic acid in another center. In a fourth center, sodium picosulfate plus magnesium
Standard descriptive statistics were used to assess the distribution of study variables. A two-thirds random sample of the total cohort was used for the development cohort to identify risk factors for inadequate bowel preparation and to develop a prediction score. Randomization was done by using computer-defined randomization. Data of the remaining one third of the cohort were used for the validation of the prediction score. Differences between colonoscopies with adequate and inadequate bowel preparation in the development cohort were tested with the Pearson chi-square test. Study variables that were statistically significantly associated with inadequate bowel preparation were included in a multivariate binary logistic regression analysis in which a selection procedure was performed based on a backward stepwise elimination by using likelihood ratio statistics. The regression coefficients of the remaining predictive factors were used to assign integer points for the prediction score. The discriminative power of the prediction score was assessed by calculating the
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METHODS Study population and data collection
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Figure 1. Study flow chart. BBPS, Boston Bowel Preparation Scale.20
AUC of the receiver operating characteristic curves (ROCs) in both the development and validation cohorts. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of different cut-off points were determined in the validation cohort. All statistical analyses were conducted with IBM SPSS Statistics 20.0 (IBM Corp, Armonk, NY). Two-sided P values ! .05 were considered statistically significant. This study was approved by the institutional review board before the start of the study.
RESULTS After the exclusion of colonoscopies with unknown bowel preparation scores (n Z 29), cases with absence of clinical data (n Z 98), incomplete colonoscopies caused by other than inadequate bowel preparation (n Z 76), patients who did not use the bowel preparation (n Z 8), and patients who were hospitalized for inpatient bowel preparation because of previous inadequate bowel preparation (n Z 74), a total of 1996 colonoscopies remained for the analyses (Fig. 1). Indications for colonoscopy were screening and/or surveillance (n Z 542, 27%), abdominal symptoms and/or blood loss and/or anemia (n Z 1194, 60%), inflammatory bowel disease (n Z 177, 9%), and others (n Z 83, 4%). All patients used a split-dose bowel preparation according to the standard protocols of the participating centers, with 4 L PG (n Z 922, 46%), 2 L PG plus ascorbic acid (n Z 798, 40%), sodium picosulfate plus magnesium citrate (n Z 236, 12%), or sodium phosphate (n Z 40, 2%). Mean ( standard deviation) BBPS scores were 7.3 1.8 in the development cohort and 7.4 1.9 in the validation cohort (P Z .25). Inadequate bowel preparation was found in 172 cases (12.9%) in the development cohort and in 77 cases (11.6%) in the validation cohort (P Z .39). Mean age (P Z .38) and male-female distribution (P Z .27) were similar in the development (57.5 15.9 years, 44.9% male) and validation cohorts (56.8 16.0 years, 47.5% male). In addition, there were no statistically significant differences between the development cohort and the www.giejournal.org
validation cohort with respect to clinical and procedural characteristics (data not shown).
Univariate and multivariate analyses Results of univariate and multivariate analyses in the development cohort are shown in Table 1. Factors that were univariate and associated with inadequate bowel preparation were increasing ASA score, increasing number of medications, use of tricyclic antidepressants, use of opioids, a history of diabetes, chronic constipation, neurologic disease, intra-abdominal and/or pelvic surgery and inadequate bowel preparation, and current hospitalization. After multivariate logistic regression analysis with backward stepwise elimination, ASA scores R3, tricyclic antidepressant use, opioid use, a history of diabetes, chronic constipation, intra-abdominal and/or pelvic surgery, history of inadequate bowel preparation, and current hospitalization remained independently associated with inadequate bowel preparation and were included for the development of the prediction score. Male sex (univariate odds ratio [OR] 1.48; 95% confidence interval [CI], 1.08-2.05) and screening and/or surveillance colonoscopy versus other indications (univariate OR 0.67; 95% CI, 0.46-0.99) were associated with inadequate bowel preparation but not included in the prediction model.
Prediction score for inadequate bowel preparation We assigned points for each predictive factor based on the regression coefficients as displayed in Table 2. The total prediction score may range between 0 and 12, and higher risk scores are associated with an increasing risk of inadequate bowel preparation (Fig. 2). The ROC curves of the development and validation cohorts are shown in Figure 3. The prediction score had an AUC of 0.72 (95% CI, 0.68-0.76) in the development cohort and 0.77 (95% CI, 0.71-0.83) in the validation cohort. In the validation cohort, a prediction score of R2 was found in 26% of the participants and resulted in a 66% sensitivity, 79% specificity, 29% PPV, and 95% NPV. A prediction score of R3 Volume 81, No. 3 : 2015 GASTROINTESTINAL ENDOSCOPY 667
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TABLE 1. Distribution and multivariate binary logistic regression analyses for patient, clinical, and procedural factors in association with inadequate bowel preparation in the development cohort Adequate bowel preparation (n [ 1159)
Inadequate bowel preparation (n [ 172)
P value*
!50
337 (29.1)
42 (24.4)
.50
50-59
244 (21.0)
34 (19.8)
60-69
302 (26.1)
49 (28.5)
R70
276 (23.8)
47 (27.3)
506 (43.7)
92 (53.5)
653 (56.3)
80 (46.5)
!25
198 (17.1)
26 (15.1)
25-29
181 (15.6)
25 (14.5)
R30
110 (9.5)
21 (12.2)
Missing
670 (57.8)
100 (58.1)
1
735 (63.4)
73 (42.4)
2
365 (31.5)
69 (40.1)
1.3 (0.9-2.0)
59 (5.1)
30 (17.5)
2.5 (1.3-4.6)
0-3
736 (63.5)
77 (44.8)
4-6
240 (20.7)
42 (24.4)
1.2 (0.8-1.8)
7-9
106 (9.1)
24 (14.0)
0.8 (0.4-1.5)
R10
77 (6.7)
29 (16.9)
1.0 (0.5-1.8)
Tricyclic antidepressants
15 (1.3)
11 (6.4)
! .001
5.3 (2.3-12.5)
Opioids
51 (4.4)
23 (13.4)
! .001
1.9 (1.0-3.6)
114 (9.8)
39 (22.7)
! .001
2.1 (1.3-3.4)
4 (0.3)
2 (1.2)
.14
120 (10.4)
39 (22.7)
! .001
2.7 (1.7-4.3)
31 (2.7)
13 (7.6)
! .01
1.8 (0.8-4.0)
399 (34.4)
84 (48.8)
! .001
1.8 (1.3-2.6)
Current hospitalization, no. (%)
66 (5.7)
27 (15.7)
! .001
1.8 (1.0-3.1)
Previous colonoscopy, no. (%)
408 (35.2)
58 (33.7)
.70
81 (7.0)
27 (15.7)
! .001
Risk factor
Adjusted OR (95% CI)
Age, no. (%), y
Sex, no. (%) Male Female
.02
2
BMI (kg/m ), no. (%) .66
ASA score, no. (%)
R3
! .001
ref.
No. of medications, no. (%) ! .001
ref.
Medication use, no. (%)
Comorbidities, no. (%) Diabetes Liver cirrhosis Chronic constipation Neurologic disease History of intra-abdominal and/or pelvic surgery, no. (%)
History of inadequate bowel preparation, no. (%)
1.8 (1.1-3.0)
(continued on next page)
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TABLE 1. Continued Adequate bowel preparation (n [ 1159)
Inadequate bowel preparation (n [ 172)
P value*
Abdominal symptoms/blood loss/anemia
673 (58.1)
114 (66.3)
.04
Screening/surveillance
327 (28.2)
36 (20.9)
Inflammatory bowel disease
105 (9.1)
19 (11.1)
Other
54 (4.6)
3 (1.7)
Morning
595 (51.3)
79 (45.9)
Afternoon
564 (48.7)
93 (54.1)
Risk factor
Adjusted OR (95% CI)
Indication for colonoscopy, no. (%)
Procedure time, no. (%) .19
OR, Odds ratio; CI, confidence interval; BMI, body mass index; ASA, American Society of Anesthesiologists Physical Status Classification System; ref, reference. *Pearson chi-square.
For an optimal colonoscopy, it is indispensable to achieve an adequate level of bowel preparation. This study shows that the clinical factors including ASA score R3, use of tricyclic antidepressants, use of opioids, diabetes, chronic constipation, abdominal and/or pelvic surgery, hospitalization, and a history of inadequate bowel preparation are independent risk factors for inadequate
bowel preparation. Based on these risk factors, we were able to design a validated and easy-to-use prediction score that allows identifying patients at risk for inadequate bowel preparation. To our knowledge, the present study is the first that describes a prediction model with this level of discrimination. Moreover, we developed this prediction score in a well-defined and representative population undergoing colonoscopy. Several previous studies have reported independent risk factors for inadequate bowel preparation. A distinction can be made between factors associated with poor bowel cleansing through a biologic effect, that is by inhibiting bowel motility, and factors associated with noncompliance to the bowel preparation regimen such as health awareness, educational level, illiteracy, marital status, appointment waiting time, indication for colonoscopy, and male sex.14,16,17,22 Because we intended to develop a prediction model for the identification of participants who may benefit from an intensified bowel preparation regimen, we did not include factors associated with noncompliance in the model. Factors included in our final prediction score have all been reported previously.1,7,8,13-17 However, some of these risk factors, such as increasing age, taking multiple medications, overweight, and liver cirrhosis were not independently associated with inadequate bowel preparation in our study. In the case of liver cirrhosis, this is probably related to a lower number of participants with this condition in our study population. BMI information was missing for more than half of the patients and is likely to be not statistically significant because of insufficient sample size. ASA score was found to be an independent risk factor for inadequate bowel preparation, which, to our knowledge, has not been reported previously. The ASA score reflects the clinical condition of a patient and serves as a surrogate marker for patient age, physical condition, obesity,
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TABLE 2. Independent predictive factors for inadequate bowel preparation and derivation of a prediction score Regression coefficient
Score
ASA score R3
0.993
2
Tricyclic antidepressant use
1.653
3
Opioid use
0.535
1
Diabetes
0.748
1
Chronic constipation
0.935
2
History of intra-abdominal/pelvic surgery
0.490
1
Current hospitalization
0.617
1
History of inadequate bowel preparation
0.673
1
Predictive factor
Total score
12
was found in 14% of participants and resulted in a 43% sensitivity, 90% specificity, 34% PPV, and 93% NPV.
DISCUSSION
Prediction score for inadequate bowel preparation
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Figure 2. Frequencies of patients with inadequate bowel preparation for different prediction scores.
Figure 3. Receiver operating characteristic curves of the prediction model in the development cohort and validation cohort. AUC, area under the curve.
medication use, and comorbiditiesdall factors associated with poor bowel preparation. Although it is difficult to directly compare results between different studies, we were able to develop a prediction model with a better discriminative power than a previous model reported by Hassan et al.8 An important factor that may have contributed to this discrepancy is the case mix of the study populations. This is reflected by the remarkable difference in inadequate bowel preparation rates of 32.9% reported by Hassan et al and only 12.5% in our study. The difference may have resulted from routine use of split-dose bowel preparation in our
population versus use of split-dose preparation by only 12.3% of participants in the study by Hassan et al. Furthermore, we excluded participants who did not comply with the bowel preparation regimen or were admitted to the hospital for inpatient bowel preparation. Most important, however, is the differences in risk factors that were included in both prediction models. Apart from diabetes and previous colorectal surgeries, none of the clinical factors included in our model were included by Hassan et al.8 On the other hand, Hassan et al included noncompliance with the bowel preparation instructions, factors associated with noncompliance, and procedural
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factors such as split-dose preparation and time between preparation and colonoscopy to predict inadequate bowel preparation. The strengths of our study include the large study population from 4 different centers in The Netherlands and the prospectively collected data on BBPS scores, demographic characteristics, ASA scores, and procedural variables. Furthermore, to improve the generalizability and applicability of our prediction scale, we included only risk factors that can be modified by using an intensified bowel cleansing regimen, and we excluded factors that relate to noncompliance. Finally, we excluded all patients who underwent inpatient bowel preparation because in those cases the treating physician already anticipated an increased risk of poor bowel cleansing. Nonetheless, there are some limitations. First, data on BMI, medication use, and comorbidities were retrospectively collected from electronic medical charts and were incomplete in 98 cases (4.3%), as were data on BBPS scores in 29 cases (1.3%). The potentially important factor BMI was not registered in more than half of the participants and could therefore not be included in our prediction model. Second, only 12.5% of the total study population had an inadequate bowel preparation, which is on the lower end of the range reported in the medical literature, with inadequate bowel preparation rates varying between 10% and 44% in participants using split-dose bowel preparation.4-9 Patients in our cohort may have been more compliant with the bowel preparation instructions compared with populations from previous studies. This is supported by the fact that in 3 of the 4 participating centers, patients were actively informed about the importance of bowel preparation quality during precolonoscopy screening visits. Furthermore, we found that only 8 patients did not take any bowel preparation at all. On the other hand, endoscopists may have systematically rated the quality of the bowel preparation too high in patients who actually had a poorer bowel preparation, leading to an underestimation of the association between predictive factors and the study outcome. Although we did not test this in the present study, we believe this is unlikely because the inter-rater and intra-rater reliability is reported to be high for the BBPS.19,23 Third, although we know of 8 patients who did not use the bowel preparation at all, we do not have data on how many patients were only partially compliant with the dietary instructions and prescribed bowel preparation. Fourth, we did not exclude repeat colonoscopies, meaning that in cases where a patient underwent 2 colonoscopies in the study period, he or she was included twice. The reason that we did not exclude these repeat colonoscopies was that we a priori hypothesized that a history of inadequate bowel preparation is a risk factor for future bowel preparation. Finally, although we randomly divided the study population into a development cohort and validation cohort, we did not validate our findings in a new cohort. Nonetheless,
we validated our prediction model in a separate cohort, and this showed that our scores are likely to be reproducible. Moreover, we included 4 centers from different regions in the country, which also contributes to the generalizability of the results. Our findings have several important implications for clinical practice. First, we confirmed that various clinical risk factors are associated with inadequate bowel preparation. Second, our prediction scale is based only on clinical factors that interfere with bowel motility and is able to identify patients at risk for inadequate bowel preparation with sufficient accuracy. This means that it is possible to identify high-risk patients who could benefit from an intensified bowel preparation regimen. Such an approach requires a prediction model with good sensitivity to identify high-risk patients but with sufficient specificity to prevent patients from undergoing unnecessary interventions to improve bowel cleansing. When we used a cut-off point of R2 to define an increased risk, 66% of participants with poor bowel preparation were identified in our cohort. However, 21% of patients with adequate bowel preparation were wrongly classified as participants with an increased risk. A cut-off point of R3 would remarkably improve the specificity, resulting in only 10% of low-risk participants mistakenly being classified as high-risk patients, but this lowers the sensitivity to 43%. A cut-off value of R2 therefore gives the most optimal sensitivity, but depending on the intensiveness of intervention that is prescribed to patients to improve the quality of bowel cleansing in the high-risk group, a cut-off of R3 may be more suitable if unnecessary measures should be as low as possible. Nonetheless, by applying this prediction score, the quality of colonoscopy may well be improved through better visualization and preventing unnecessary repeat colonoscopies. In conclusion, in this study some important independent clinical risk factors for inadequate bowel preparation were identified, and a validated, easy-to-use prediction score with good discriminative power was developed. By applying this prediction score, a considerable number of subjects at risk for poor bowel preparation who are potentially eligible for intensified bowel preparation can be identified, with only a small subgroup of subjects being wrongly classified as having an increased risk of poor bowel preparation.
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ACKNOWLEDGMENTS Collaborators of the Colonoscopy Quality Initiative: Leon M.G. Moons,1 MD, PhD, Peter van der Schaar,2 MD, PhD, Wouter H. de Vos tot Nederveen Cappel, MD, PhD,3 Pieter C.J. ter Borg,4 MD, PhD, Thjon J. Tang7 Frank ter Borg8 Maarten A.C. Meijssen, MD, PhD,3 Rob J.T.H. Ouwendijk, MD, PhD,4 Doris M. Le Fèvre,5 Merijn Stouten,6 Onno van der Galiën,5 Theo J. Hiemstra,5 Ernst J. Kuipers, MD, PhD,9 Peter D. Siersema, MD, PhD1
Prediction score for inadequate bowel preparation
REFERENCES 1. Froehlich F, Wietlisbach V, Gonvers JJ, et al. Impact of colonic cleansing on quality and diagnostic yield of colonoscopy: the European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study. Gastrointest Endosc 2005;61:378-84. 2. Harewood GC, Sharma VK, de Garmo P. Impact of colonoscopy preparation quality on detection of suspected colonic neoplasia. Gastrointest Endosc 2003;58:76-9. 3. Hendry PO, Jenkins JT, Diament RH. The impact of poor bowel preparation on colonoscopy: a prospective single centre study of 10,571 colonoscopies. Colorectal Dis 2007;9:745-8. 4. Lebwohl B, Kastrinos F, Glick M, et al. The impact of suboptimal bowel preparation on adenoma miss rates and the factors associated with early repeat colonoscopy. Gastrointest Endosc 2011;73: 1207-14. 5. Sherer EA, Imler TD, Imperiale TF. The effect of colonoscopy preparation quality on adenoma detection rates. Gastrointest Endosc 2012; 75:545-53. 6. Calderwood AH, Schroy PC III, Lieberman DA, et al. Boston Bowel Preparation Scale scores provide a standardized definition of adequate for describing bowel cleanliness. Gastrointest Endosc 2014;80:269-76. 7. Fayad NF, Kahi CJ, Abd El-Jawad KH, et al. Association between bodymass index and quality of split bowel preparation. Clin Gastroenterol Hepatol 2013;11:1478-85. 8. Hassan C, Fuccio L, Bruno M, et al. A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy. Clin Gastroenterol Hepatol 2012;10:501-6. 9. Valiante F, Bellumat A, De Bona M, et al. Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy. World J Gastroenterol 2013;19: 5493-9. 10. Hookey LC, Vanner SJ. Pico-salax plus two-day bisacodyl is superior to pico-salax alone or oral sodium phosphate for colon cleansing before colonoscopy. Am J Gastroenterol 2009;104:703-9. 11. Vradelis S, Kalaitzakis E, Sharifi Y, et al. Addition of senna improves quality of colonoscopy preparation with magnesium citrate. World J Gastroenterol 2009;15:1759-63. 12. Ibanez M, Parra-Blanco A, Zaballa P, et al. Usefulness of an intensive bowel cleansing strategy for repeat colonoscopy after preparation failure. Dis Colon Rectum 2011;54:1578-84. 13. Borg BB, Gupta NK, Zuckerman GR, et al. Impact of obesity on bowel preparation for colonoscopy. Clin Gastroenterol Hepatol 2009;7:670-5.
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Dik et al 14. Chan WK, Saravanan A, Manikam J, et al. Appointment waiting times and education level influence the quality of bowel preparation in adult patients undergoing colonoscopy. BMC Gastroenterol 2011;11:86. 15. Chung YW, Han DS, Park KH, et al. Patient factors predictive of inadequate bowel preparation using polyethylene glycol: a prospective study in Korea. J Clin Gastroenterol 2009;43:448-52. 16. Lebwohl B, Wang TC, Neugut AI. Socioeconomic and other predictors of colonoscopy preparation quality. Dig Dis Sci 2010;55:2014-20. 17. Ness RM, Manam R, Hoen H, et al. Predictors of inadequate bowel preparation for colonoscopy. Am J Gastroenterol 2001;96: 1797-802. 18. Hassan C, Bretthauer M, Kaminski MF, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2013;45:142-50. 19. Calderwood AH, Jacobson BC. Comprehensive validation of the Boston Bowel Preparation Scale. Gastrointest Endosc 2010;72:686-92. 20. Lai EJ, Calderwood AH, Doros G, et al. The Boston Bowel Preparation Scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc 2009;69(3 Pt 2):620-5. 21. Romero RV, Mahadeva S. Factors influencing quality of bowel preparation for colonoscopy. World J Gastrointest Endosc 2013;5:39-46. 22. Menees SB, Kim HM, Wren P, et al. Patient compliance and suboptimal bowel preparation with split-dose bowel regimen in average-risk screening colonoscopy. Gastrointest Endosc 2014;79:811-20; e3. 23. Gao Y, Lin JS, Zhang HD, et al. Pilot validation of the Boston Bowel Preparation Scale in China. Dig Endosc 2013;25:167-73.
Gastroenterology and Hepatology, Antonius Hospital, Nieuwegein (2), Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle (3), Department of Gastroenterology and Hepatology, Ikazia Hospital, Rotterdam (4), Achmea Health Care, Leiden (5), Gupta Strategists, Ophemert (6), Department of Gastroenterology and Hepatology, IJsselland Hospital, Capelle aan den IJssel (7), Department of Gastroenterology and Hepatology, Deventer Hospital, Deventer (8), Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands (9). Reprint requests: Vincent K. Dik, MD, Department of Gastroenterology and Hepatology (F02.618), University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. If you would like to chat with an author of this article, you may contact Dr Dik at [email protected].
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Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bowel preparation: development and validation of a prediction score Vincent K. Dik, MD,1 Leon M.G. Moons, MD, PhD,1 Melek Hüyük, BSc,1 Peter van der Schaar, MD, PhD,2 Wouter H. de Vos tot Nederveen Cappel, MD, PhD,3 Pieter C.J. ter Borg, MD, PhD,4 Maarten A.C. Meijssen, MD, PhD,3 Rob J.T.H. Ouwendijk, MD, PhD,4 Doris M. Le Fèvre,5 Merijn Stouten,6 Onno van der Galiën,5 Theo J. Hiemstra,5 Jan F. Monkelbaan, MD,1 Martijn G.H. van Oijen, PhD,1 Peter D. Siersema, MD, PhD,1 for the Colonoscopy Quality Initiative Utrecht, The Netherlands
Background: Adequate bowel preparation is important for optimal colonoscopy. It is important to identify patients at risk for inadequate bowel preparation because this allows taking precautions in this specific group. Objective: To develop a prediction score to identify patients at risk for inadequate bowel preparation who may benefit from an intensified bowel cleansing regimen. Design: Patient and colonoscopy data were prospectively collected, whereas clinical data were retrospectively collected for a total of 1996 colonoscopies in participants who received split-dose bowel preparation. Multivariate logistic regression analyses were conducted in a random two-thirds of the cohort to develop a prediction model. Validation and evaluation of the discriminative power of the prediction model were performed within the remaining one-third of the cohort. Setting: Four centers, including one academic and three medium-to-large size nonacademic centers. Patients: Consecutive colonoscopies in November and December 2012. Mean age was 57.3 15.9 years, 45.8% were male and indications for colonoscopy were screening and/or surveillance (27%), abdominal symptoms and/ or blood loss and/or anemia (60%), inflammatory bowel disease (9%), and others (4%). Interventions: Colonoscopy. Main Outcome Measurements: Inadequate bowel preparation defined as Boston Bowel Preparation Scale score !6. Results: A total of 1331 colonoscopies were included in the development cohort, of which 172 (12.9%) had an inadequate bowel preparation. Independent factors included in the prediction model were American Society of Anesthesiologists Physical Status Classification System score R3, use of tricyclic antidepressants, use of opioids, diabetes, chronic constipation, history of abdominal and/or pelvic surgery, history of inadequate bowel preparation, and current hospitalization. The discriminative ability of the scale was good, with an area under the curve of 0.77 in the validation cohort. Limitations: Study design partially retrospective, no data on patient compliance. Conclusion: We developed a validated, easy-to-use prediction scale that can be used to identify subjects with an increased risk of inadequate bowel preparation with good accuracy. (Gastrointest Endosc 2015;81:665-72.)
Abbreviations: ASA, American Society of Anesthesiologists Physical Status Classification System; AUC, area under the curve; BBPS, Boston Bowel Preparation Scale; BMI, body mass index; NPV, negative predictive value; PG, polyethylene glycol; PPV, positive predictive value. DISCLOSURE: All authors disclosed no financial relationships relevant to this article. Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy
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0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.09.066 Received May 10, 2014. Accepted September 29, 2014. Current affiliations: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht (1), Department of (footnotes continued on last page of article)
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Prediction score for inadequate bowel preparation
Colonoscopy is currently the predominant method for detecting mucosal abnormalities in the colorectum. Adequate bowel preparation is essential for the efficacy of colonoscopy, because inadequate bowel preparation is associated with incomplete colonoscopy, lower adenoma detection rates, increased procedure times, and need to repeat the procedure.1-5 Despite its importance, recent studies still report inadequate bowel preparation in 10% to 30% of colonoscopies, even with split-dose bowel preparation.4-9 The addition of laxatives such as bisacodyl or sennosides to standard bowel cleansing regimens can improve the quality of bowel preparation.10,11 Furthermore, some data suggest that it is possible to achieve higher cleansing rates with intensified regimens in patients with previous inadequate bowel preparation.12 Identification of patients at an increased risk for inadequate bowel preparation may therefore enable physicians to intensify the bowel preparation regimen in order to prevent unnecessary repeat endoscopies and the risk of missing neoplastic lesions. Risk factors that have been found to negatively affect quality of bowel preparation through inhibition of bowel motility include chronic constipation, liver cirrhosis, diabetes, previous intra-abdominal or pelvic surgery, use of multiple medications, use of opioids or tricyclic antidepressants, and factors related to immobilization such as older age, physical condition, obesity, neurologic disease, and hospitalization.1,7,8,13-17 An increasing number of these baseline risk factors has been found to be associated with a higher risk of inadequate bowel preparation.13 Hassan et al8 developed a prediction model to identify patients at increased risk for inadequate bowel preparation. It was found that this model had fair accuracy (area under the curve [AUC] 0.63). However, this study also included participants who were noncompliant with the bowel preparation regimen. Moreover, only 12% of participants took split-dose bowel preparation, which is nowadays recommended as optimal bowel preparation by the European Society of Gastrointestinal Endoscopy.18 The aim of the present study was to develop a validated, easy-to-use, prediction score to identify patients at risk for inadequate bowel preparation who may benefit from an intensified bowel cleansing regimen.
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citrate was used as standard bowel preparation, with sodium phosphate used in a selected group of young participants without comorbidities, and 4 L PG in case of hospitalization. Patient-related and procedure-related factors were prospectively collected for quality auditing purposes. Data on comorbidities and medication use were collected from the hospital’s electronic medical charts.
Study variables The primary outcome of this study was inadequate bowel preparation, defined as a Boston Bowel Preparation Scale (BBPS) score !6.19,20 The BBPS score was assigned by the endoscopist directly after the colonoscopy. Factors possibly associated with the quality of bowel preparation that were collected for this study were based on the available literature1,7,8,13-17 and included age, body mass index (BMI), the American Society of Anesthesiologists Physical Status Classification System (ASA) score, number of nontopical medications, tricyclic antidepressant use, opioid use, diabetes, liver cirrhosis, chronic constipation, history of neurologic disease (stroke, spina bifida, dementia, paraplegia, or Parkinson disease), history of intra-abdominal and/or pelvic surgery, current hospitalization, previous colonoscopies, and history of inadequate bowel preparation. Male sex was not included in the prediction score because its association with inadequate bowel preparation has previously been found to be related to noncompliance with the bowel preparation regimen.21 Other procedural factors collected included indication for colonoscopy (screening/ surveillance, abdominal symptoms, blood loss/anemia, inflammatory bowel disease, or other), cecal intubation and cause of cecal intubation failure, procedure time (morning or afternoon), inpatient bowel preparation, and whether the bowel preparation was used.
Statistical analyses
Centers participating in this study were 3 medium-tolarge size, nonacademic and 1 academic center located in 3 different regions in The Netherlands. For this observational cohort study, we enrolled consecutive colonoscopies that were performed from November 1 to December 31, 2012. Bowel preparation regimens that were applied in the 4 centers included 4 L polyethylene glycol (PG) in 2 centers and 2 L PG plus ascorbic acid in another center. In a fourth center, sodium picosulfate plus magnesium
Standard descriptive statistics were used to assess the distribution of study variables. A two-thirds random sample of the total cohort was used for the development cohort to identify risk factors for inadequate bowel preparation and to develop a prediction score. Randomization was done by using computer-defined randomization. Data of the remaining one third of the cohort were used for the validation of the prediction score. Differences between colonoscopies with adequate and inadequate bowel preparation in the development cohort were tested with the Pearson chi-square test. Study variables that were statistically significantly associated with inadequate bowel preparation were included in a multivariate binary logistic regression analysis in which a selection procedure was performed based on a backward stepwise elimination by using likelihood ratio statistics. The regression coefficients of the remaining predictive factors were used to assign integer points for the prediction score. The discriminative power of the prediction score was assessed by calculating the
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METHODS Study population and data collection
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Prediction score for inadequate bowel preparation
Figure 1. Study flow chart. BBPS, Boston Bowel Preparation Scale.20
AUC of the receiver operating characteristic curves (ROCs) in both the development and validation cohorts. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of different cut-off points were determined in the validation cohort. All statistical analyses were conducted with IBM SPSS Statistics 20.0 (IBM Corp, Armonk, NY). Two-sided P values ! .05 were considered statistically significant. This study was approved by the institutional review board before the start of the study.
RESULTS After the exclusion of colonoscopies with unknown bowel preparation scores (n Z 29), cases with absence of clinical data (n Z 98), incomplete colonoscopies caused by other than inadequate bowel preparation (n Z 76), patients who did not use the bowel preparation (n Z 8), and patients who were hospitalized for inpatient bowel preparation because of previous inadequate bowel preparation (n Z 74), a total of 1996 colonoscopies remained for the analyses (Fig. 1). Indications for colonoscopy were screening and/or surveillance (n Z 542, 27%), abdominal symptoms and/or blood loss and/or anemia (n Z 1194, 60%), inflammatory bowel disease (n Z 177, 9%), and others (n Z 83, 4%). All patients used a split-dose bowel preparation according to the standard protocols of the participating centers, with 4 L PG (n Z 922, 46%), 2 L PG plus ascorbic acid (n Z 798, 40%), sodium picosulfate plus magnesium citrate (n Z 236, 12%), or sodium phosphate (n Z 40, 2%). Mean ( standard deviation) BBPS scores were 7.3 1.8 in the development cohort and 7.4 1.9 in the validation cohort (P Z .25). Inadequate bowel preparation was found in 172 cases (12.9%) in the development cohort and in 77 cases (11.6%) in the validation cohort (P Z .39). Mean age (P Z .38) and male-female distribution (P Z .27) were similar in the development (57.5 15.9 years, 44.9% male) and validation cohorts (56.8 16.0 years, 47.5% male). In addition, there were no statistically significant differences between the development cohort and the www.giejournal.org
validation cohort with respect to clinical and procedural characteristics (data not shown).
Univariate and multivariate analyses Results of univariate and multivariate analyses in the development cohort are shown in Table 1. Factors that were univariate and associated with inadequate bowel preparation were increasing ASA score, increasing number of medications, use of tricyclic antidepressants, use of opioids, a history of diabetes, chronic constipation, neurologic disease, intra-abdominal and/or pelvic surgery and inadequate bowel preparation, and current hospitalization. After multivariate logistic regression analysis with backward stepwise elimination, ASA scores R3, tricyclic antidepressant use, opioid use, a history of diabetes, chronic constipation, intra-abdominal and/or pelvic surgery, history of inadequate bowel preparation, and current hospitalization remained independently associated with inadequate bowel preparation and were included for the development of the prediction score. Male sex (univariate odds ratio [OR] 1.48; 95% confidence interval [CI], 1.08-2.05) and screening and/or surveillance colonoscopy versus other indications (univariate OR 0.67; 95% CI, 0.46-0.99) were associated with inadequate bowel preparation but not included in the prediction model.
Prediction score for inadequate bowel preparation We assigned points for each predictive factor based on the regression coefficients as displayed in Table 2. The total prediction score may range between 0 and 12, and higher risk scores are associated with an increasing risk of inadequate bowel preparation (Fig. 2). The ROC curves of the development and validation cohorts are shown in Figure 3. The prediction score had an AUC of 0.72 (95% CI, 0.68-0.76) in the development cohort and 0.77 (95% CI, 0.71-0.83) in the validation cohort. In the validation cohort, a prediction score of R2 was found in 26% of the participants and resulted in a 66% sensitivity, 79% specificity, 29% PPV, and 95% NPV. A prediction score of R3 Volume 81, No. 3 : 2015 GASTROINTESTINAL ENDOSCOPY 667
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TABLE 1. Distribution and multivariate binary logistic regression analyses for patient, clinical, and procedural factors in association with inadequate bowel preparation in the development cohort Adequate bowel preparation (n [ 1159)
Inadequate bowel preparation (n [ 172)
P value*
!50
337 (29.1)
42 (24.4)
.50
50-59
244 (21.0)
34 (19.8)
60-69
302 (26.1)
49 (28.5)
R70
276 (23.8)
47 (27.3)
506 (43.7)
92 (53.5)
653 (56.3)
80 (46.5)
!25
198 (17.1)
26 (15.1)
25-29
181 (15.6)
25 (14.5)
R30
110 (9.5)
21 (12.2)
Missing
670 (57.8)
100 (58.1)
1
735 (63.4)
73 (42.4)
2
365 (31.5)
69 (40.1)
1.3 (0.9-2.0)
59 (5.1)
30 (17.5)
2.5 (1.3-4.6)
0-3
736 (63.5)
77 (44.8)
4-6
240 (20.7)
42 (24.4)
1.2 (0.8-1.8)
7-9
106 (9.1)
24 (14.0)
0.8 (0.4-1.5)
R10
77 (6.7)
29 (16.9)
1.0 (0.5-1.8)
Tricyclic antidepressants
15 (1.3)
11 (6.4)
! .001
5.3 (2.3-12.5)
Opioids
51 (4.4)
23 (13.4)
! .001
1.9 (1.0-3.6)
114 (9.8)
39 (22.7)
! .001
2.1 (1.3-3.4)
4 (0.3)
2 (1.2)
.14
120 (10.4)
39 (22.7)
! .001
2.7 (1.7-4.3)
31 (2.7)
13 (7.6)
! .01
1.8 (0.8-4.0)
399 (34.4)
84 (48.8)
! .001
1.8 (1.3-2.6)
Current hospitalization, no. (%)
66 (5.7)
27 (15.7)
! .001
1.8 (1.0-3.1)
Previous colonoscopy, no. (%)
408 (35.2)
58 (33.7)
.70
81 (7.0)
27 (15.7)
! .001
Risk factor
Adjusted OR (95% CI)
Age, no. (%), y
Sex, no. (%) Male Female
.02
2
BMI (kg/m ), no. (%) .66
ASA score, no. (%)
R3
! .001
ref.
No. of medications, no. (%) ! .001
ref.
Medication use, no. (%)
Comorbidities, no. (%) Diabetes Liver cirrhosis Chronic constipation Neurologic disease History of intra-abdominal and/or pelvic surgery, no. (%)
History of inadequate bowel preparation, no. (%)
1.8 (1.1-3.0)
(continued on next page)
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TABLE 1. Continued Adequate bowel preparation (n [ 1159)
Inadequate bowel preparation (n [ 172)
P value*
Abdominal symptoms/blood loss/anemia
673 (58.1)
114 (66.3)
.04
Screening/surveillance
327 (28.2)
36 (20.9)
Inflammatory bowel disease
105 (9.1)
19 (11.1)
Other
54 (4.6)
3 (1.7)
Morning
595 (51.3)
79 (45.9)
Afternoon
564 (48.7)
93 (54.1)
Risk factor
Adjusted OR (95% CI)
Indication for colonoscopy, no. (%)
Procedure time, no. (%) .19
OR, Odds ratio; CI, confidence interval; BMI, body mass index; ASA, American Society of Anesthesiologists Physical Status Classification System; ref, reference. *Pearson chi-square.
For an optimal colonoscopy, it is indispensable to achieve an adequate level of bowel preparation. This study shows that the clinical factors including ASA score R3, use of tricyclic antidepressants, use of opioids, diabetes, chronic constipation, abdominal and/or pelvic surgery, hospitalization, and a history of inadequate bowel preparation are independent risk factors for inadequate
bowel preparation. Based on these risk factors, we were able to design a validated and easy-to-use prediction score that allows identifying patients at risk for inadequate bowel preparation. To our knowledge, the present study is the first that describes a prediction model with this level of discrimination. Moreover, we developed this prediction score in a well-defined and representative population undergoing colonoscopy. Several previous studies have reported independent risk factors for inadequate bowel preparation. A distinction can be made between factors associated with poor bowel cleansing through a biologic effect, that is by inhibiting bowel motility, and factors associated with noncompliance to the bowel preparation regimen such as health awareness, educational level, illiteracy, marital status, appointment waiting time, indication for colonoscopy, and male sex.14,16,17,22 Because we intended to develop a prediction model for the identification of participants who may benefit from an intensified bowel preparation regimen, we did not include factors associated with noncompliance in the model. Factors included in our final prediction score have all been reported previously.1,7,8,13-17 However, some of these risk factors, such as increasing age, taking multiple medications, overweight, and liver cirrhosis were not independently associated with inadequate bowel preparation in our study. In the case of liver cirrhosis, this is probably related to a lower number of participants with this condition in our study population. BMI information was missing for more than half of the patients and is likely to be not statistically significant because of insufficient sample size. ASA score was found to be an independent risk factor for inadequate bowel preparation, which, to our knowledge, has not been reported previously. The ASA score reflects the clinical condition of a patient and serves as a surrogate marker for patient age, physical condition, obesity,
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TABLE 2. Independent predictive factors for inadequate bowel preparation and derivation of a prediction score Regression coefficient
Score
ASA score R3
0.993
2
Tricyclic antidepressant use
1.653
3
Opioid use
0.535
1
Diabetes
0.748
1
Chronic constipation
0.935
2
History of intra-abdominal/pelvic surgery
0.490
1
Current hospitalization
0.617
1
History of inadequate bowel preparation
0.673
1
Predictive factor
Total score
12
was found in 14% of participants and resulted in a 43% sensitivity, 90% specificity, 34% PPV, and 93% NPV.
DISCUSSION
Prediction score for inadequate bowel preparation
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Figure 2. Frequencies of patients with inadequate bowel preparation for different prediction scores.
Figure 3. Receiver operating characteristic curves of the prediction model in the development cohort and validation cohort. AUC, area under the curve.
medication use, and comorbiditiesdall factors associated with poor bowel preparation. Although it is difficult to directly compare results between different studies, we were able to develop a prediction model with a better discriminative power than a previous model reported by Hassan et al.8 An important factor that may have contributed to this discrepancy is the case mix of the study populations. This is reflected by the remarkable difference in inadequate bowel preparation rates of 32.9% reported by Hassan et al and only 12.5% in our study. The difference may have resulted from routine use of split-dose bowel preparation in our
population versus use of split-dose preparation by only 12.3% of participants in the study by Hassan et al. Furthermore, we excluded participants who did not comply with the bowel preparation regimen or were admitted to the hospital for inpatient bowel preparation. Most important, however, is the differences in risk factors that were included in both prediction models. Apart from diabetes and previous colorectal surgeries, none of the clinical factors included in our model were included by Hassan et al.8 On the other hand, Hassan et al included noncompliance with the bowel preparation instructions, factors associated with noncompliance, and procedural
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Prediction score for inadequate bowel preparation
factors such as split-dose preparation and time between preparation and colonoscopy to predict inadequate bowel preparation. The strengths of our study include the large study population from 4 different centers in The Netherlands and the prospectively collected data on BBPS scores, demographic characteristics, ASA scores, and procedural variables. Furthermore, to improve the generalizability and applicability of our prediction scale, we included only risk factors that can be modified by using an intensified bowel cleansing regimen, and we excluded factors that relate to noncompliance. Finally, we excluded all patients who underwent inpatient bowel preparation because in those cases the treating physician already anticipated an increased risk of poor bowel cleansing. Nonetheless, there are some limitations. First, data on BMI, medication use, and comorbidities were retrospectively collected from electronic medical charts and were incomplete in 98 cases (4.3%), as were data on BBPS scores in 29 cases (1.3%). The potentially important factor BMI was not registered in more than half of the participants and could therefore not be included in our prediction model. Second, only 12.5% of the total study population had an inadequate bowel preparation, which is on the lower end of the range reported in the medical literature, with inadequate bowel preparation rates varying between 10% and 44% in participants using split-dose bowel preparation.4-9 Patients in our cohort may have been more compliant with the bowel preparation instructions compared with populations from previous studies. This is supported by the fact that in 3 of the 4 participating centers, patients were actively informed about the importance of bowel preparation quality during precolonoscopy screening visits. Furthermore, we found that only 8 patients did not take any bowel preparation at all. On the other hand, endoscopists may have systematically rated the quality of the bowel preparation too high in patients who actually had a poorer bowel preparation, leading to an underestimation of the association between predictive factors and the study outcome. Although we did not test this in the present study, we believe this is unlikely because the inter-rater and intra-rater reliability is reported to be high for the BBPS.19,23 Third, although we know of 8 patients who did not use the bowel preparation at all, we do not have data on how many patients were only partially compliant with the dietary instructions and prescribed bowel preparation. Fourth, we did not exclude repeat colonoscopies, meaning that in cases where a patient underwent 2 colonoscopies in the study period, he or she was included twice. The reason that we did not exclude these repeat colonoscopies was that we a priori hypothesized that a history of inadequate bowel preparation is a risk factor for future bowel preparation. Finally, although we randomly divided the study population into a development cohort and validation cohort, we did not validate our findings in a new cohort. Nonetheless,
we validated our prediction model in a separate cohort, and this showed that our scores are likely to be reproducible. Moreover, we included 4 centers from different regions in the country, which also contributes to the generalizability of the results. Our findings have several important implications for clinical practice. First, we confirmed that various clinical risk factors are associated with inadequate bowel preparation. Second, our prediction scale is based only on clinical factors that interfere with bowel motility and is able to identify patients at risk for inadequate bowel preparation with sufficient accuracy. This means that it is possible to identify high-risk patients who could benefit from an intensified bowel preparation regimen. Such an approach requires a prediction model with good sensitivity to identify high-risk patients but with sufficient specificity to prevent patients from undergoing unnecessary interventions to improve bowel cleansing. When we used a cut-off point of R2 to define an increased risk, 66% of participants with poor bowel preparation were identified in our cohort. However, 21% of patients with adequate bowel preparation were wrongly classified as participants with an increased risk. A cut-off point of R3 would remarkably improve the specificity, resulting in only 10% of low-risk participants mistakenly being classified as high-risk patients, but this lowers the sensitivity to 43%. A cut-off value of R2 therefore gives the most optimal sensitivity, but depending on the intensiveness of intervention that is prescribed to patients to improve the quality of bowel cleansing in the high-risk group, a cut-off of R3 may be more suitable if unnecessary measures should be as low as possible. Nonetheless, by applying this prediction score, the quality of colonoscopy may well be improved through better visualization and preventing unnecessary repeat colonoscopies. In conclusion, in this study some important independent clinical risk factors for inadequate bowel preparation were identified, and a validated, easy-to-use prediction score with good discriminative power was developed. By applying this prediction score, a considerable number of subjects at risk for poor bowel preparation who are potentially eligible for intensified bowel preparation can be identified, with only a small subgroup of subjects being wrongly classified as having an increased risk of poor bowel preparation.
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ACKNOWLEDGMENTS Collaborators of the Colonoscopy Quality Initiative: Leon M.G. Moons,1 MD, PhD, Peter van der Schaar,2 MD, PhD, Wouter H. de Vos tot Nederveen Cappel, MD, PhD,3 Pieter C.J. ter Borg,4 MD, PhD, Thjon J. Tang7 Frank ter Borg8 Maarten A.C. Meijssen, MD, PhD,3 Rob J.T.H. Ouwendijk, MD, PhD,4 Doris M. Le Fèvre,5 Merijn Stouten,6 Onno van der Galiën,5 Theo J. Hiemstra,5 Ernst J. Kuipers, MD, PhD,9 Peter D. Siersema, MD, PhD1
Prediction score for inadequate bowel preparation
REFERENCES 1. Froehlich F, Wietlisbach V, Gonvers JJ, et al. Impact of colonic cleansing on quality and diagnostic yield of colonoscopy: the European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study. Gastrointest Endosc 2005;61:378-84. 2. Harewood GC, Sharma VK, de Garmo P. Impact of colonoscopy preparation quality on detection of suspected colonic neoplasia. Gastrointest Endosc 2003;58:76-9. 3. Hendry PO, Jenkins JT, Diament RH. The impact of poor bowel preparation on colonoscopy: a prospective single centre study of 10,571 colonoscopies. Colorectal Dis 2007;9:745-8. 4. Lebwohl B, Kastrinos F, Glick M, et al. The impact of suboptimal bowel preparation on adenoma miss rates and the factors associated with early repeat colonoscopy. Gastrointest Endosc 2011;73: 1207-14. 5. Sherer EA, Imler TD, Imperiale TF. The effect of colonoscopy preparation quality on adenoma detection rates. Gastrointest Endosc 2012; 75:545-53. 6. Calderwood AH, Schroy PC III, Lieberman DA, et al. Boston Bowel Preparation Scale scores provide a standardized definition of adequate for describing bowel cleanliness. Gastrointest Endosc 2014;80:269-76. 7. Fayad NF, Kahi CJ, Abd El-Jawad KH, et al. Association between bodymass index and quality of split bowel preparation. Clin Gastroenterol Hepatol 2013;11:1478-85. 8. Hassan C, Fuccio L, Bruno M, et al. A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy. Clin Gastroenterol Hepatol 2012;10:501-6. 9. Valiante F, Bellumat A, De Bona M, et al. Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy. World J Gastroenterol 2013;19: 5493-9. 10. Hookey LC, Vanner SJ. Pico-salax plus two-day bisacodyl is superior to pico-salax alone or oral sodium phosphate for colon cleansing before colonoscopy. Am J Gastroenterol 2009;104:703-9. 11. Vradelis S, Kalaitzakis E, Sharifi Y, et al. Addition of senna improves quality of colonoscopy preparation with magnesium citrate. World J Gastroenterol 2009;15:1759-63. 12. Ibanez M, Parra-Blanco A, Zaballa P, et al. Usefulness of an intensive bowel cleansing strategy for repeat colonoscopy after preparation failure. Dis Colon Rectum 2011;54:1578-84. 13. Borg BB, Gupta NK, Zuckerman GR, et al. Impact of obesity on bowel preparation for colonoscopy. Clin Gastroenterol Hepatol 2009;7:670-5.
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Dik et al 14. Chan WK, Saravanan A, Manikam J, et al. Appointment waiting times and education level influence the quality of bowel preparation in adult patients undergoing colonoscopy. BMC Gastroenterol 2011;11:86. 15. Chung YW, Han DS, Park KH, et al. Patient factors predictive of inadequate bowel preparation using polyethylene glycol: a prospective study in Korea. J Clin Gastroenterol 2009;43:448-52. 16. Lebwohl B, Wang TC, Neugut AI. Socioeconomic and other predictors of colonoscopy preparation quality. Dig Dis Sci 2010;55:2014-20. 17. Ness RM, Manam R, Hoen H, et al. Predictors of inadequate bowel preparation for colonoscopy. Am J Gastroenterol 2001;96: 1797-802. 18. Hassan C, Bretthauer M, Kaminski MF, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2013;45:142-50. 19. Calderwood AH, Jacobson BC. Comprehensive validation of the Boston Bowel Preparation Scale. Gastrointest Endosc 2010;72:686-92. 20. Lai EJ, Calderwood AH, Doros G, et al. The Boston Bowel Preparation Scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc 2009;69(3 Pt 2):620-5. 21. Romero RV, Mahadeva S. Factors influencing quality of bowel preparation for colonoscopy. World J Gastrointest Endosc 2013;5:39-46. 22. Menees SB, Kim HM, Wren P, et al. Patient compliance and suboptimal bowel preparation with split-dose bowel regimen in average-risk screening colonoscopy. Gastrointest Endosc 2014;79:811-20; e3. 23. Gao Y, Lin JS, Zhang HD, et al. Pilot validation of the Boston Bowel Preparation Scale in China. Dig Endosc 2013;25:167-73.
Gastroenterology and Hepatology, Antonius Hospital, Nieuwegein (2), Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle (3), Department of Gastroenterology and Hepatology, Ikazia Hospital, Rotterdam (4), Achmea Health Care, Leiden (5), Gupta Strategists, Ophemert (6), Department of Gastroenterology and Hepatology, IJsselland Hospital, Capelle aan den IJssel (7), Department of Gastroenterology and Hepatology, Deventer Hospital, Deventer (8), Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands (9). Reprint requests: Vincent K. Dik, MD, Department of Gastroenterology and Hepatology (F02.618), University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. If you would like to chat with an author of this article, you may contact Dr Dik at [email protected].
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