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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgement
  9. References
  10. Supporting Information

Background

Diagnostic imaging plays a pivotal role in the diagnosis and management of inflammatory bowel disease (IBD); however, increasing use has led to concerns about the malignant potential of ionising radiation. Several studies have demonstrated that diagnostic imaging can result in exposure to potentially harmful levels of ionising radiation in IBD patients.

Aim

To determine the pooled prevalence of increased exposure and pooled odds ratio of risk factors associated with exposure to potentially harmful levels of diagnostic medical radiation.

Methods

We searched Medline, EMBASE, CINHAL and reference lists of identified articles, without language restrictions in October 2011.

Results

Six studies with 1704 participants provided data on the proportion of patients receiving potentially harmful levels of radiation defined as ≥50 milli-sieverts (mSv)-equivalent to 5 CT abdomen scans. The pooled prevalence was 8.8% (95% CI 4.4–16.8) for IBD patients and 11.1% (95% CI 5.7–20.5%) and 2% (95% CI 0.8–4.9%) for Crohn's disease and ulcerative colitis patients respectively. Five studies involving 2627 participants provided data for risk factors. IBD-related surgery and corticosteroid use were significant with pooled adjusted odds ratio of 5.4 (95% CI 2.6–11.2) and 2.4 (95% CI 1.7–3.4) respectively.

Conclusions

About 1 in 10 patients may be exposed to potentially harmful levels of diagnostic medical radiation. Corticosteroid use and IBD related surgery increased this risk. Strategies to reduce radiation exposure while assessing disease activity need to be considered.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgement
  9. References
  10. Supporting Information

Inflammatory bowel disease (IBD) that includes both Crohn's disease (CD) and ulcerative colitis (UC) is a lifelong idiopathic disorder characterised by gastrointestinal inflammation and extra-intestinal manifestations which may be present in up to 40% of patients.[1] IBD has a significant disease burden with an estimated 1.4 million and 2.2 million patients affected in United States and Europe respectively.[2] Diagnostic imaging plays a vital role in the diagnosis and management of IBD. Repeated examinations are often required, especially in CD to determine disease extent and severity, assess for complications, monitor response to therapy, for perioperative evaluation and also to evaluate extra-intestinal manifestations of IBD. Patients with IBD are already at risk of colorectal and small intestinal cancers[3-5] from longstanding disease, and immunosuppressive therapy has been linked to an increased risk of lymphoma and other malignancies.[6, 7] There is therefore both clinical and public health concern about young IBD patients being exposed to potentially harmful levels of ionising radiation arising from diagnostic medical radiation (DMR), which may increase the risk of cancer still further in this group. This assumes greater importance, given the increased risk of radiation-induced malignancy in patients exposed at a younger age.[8]

The effects of radiation may be classified as either deterministic effects that are predictable and become worse with increasing exposure or stochastic effects that do not exhibit thresholds and their occurrence is variable.[9, 10] Studies from atomic bomb survivors and nuclear industry workers have demonstrated that acute or protracted exposure to ionising radiation increases the risk of malignancy.[11-15] Radiation from as little as 50 milli-sieverts (mSv) from DMR has been implicated in the development of certain solid tumours particularly of the colon and urogenital tract.[11] Worldwide estimates suggest that up to 2% of malignancies could be attributed to DMR.[16] There are 5500 deaths due to radiation-induced cancer in the US each year[16, 17] and the US National Research Council estimates that one patient will develop a radiation-induced cancer in their lifetime out of every 1000 patients undergoing a 10 mSv CT abdominal scan.[18]

While clinicians generally acknowledge the potential risks of DMR exposure, the actual exposure in IBD patients in clinical practice either remains unknown or is poorly documented. Published studies have demonstrated heterogeneity in predictors associated with excessive radiation exposure. CT scans and fluoroscopy are probably the diagnostic interventions most likely to increase radiation exposure in IBD patients. CT usage in IBD patient has increased by 400 and 840% over a 15-year- and 5-year period respectively.[19, 20] Magnetic resonance imaging (MRI) and ultrasound are alternatives for disease assessment with no radiation exposure, and their use has been advocated in newly published BSG[21] and ECCO[22] guidelines. The aim of the present study was to perform a meta-analysis of published studies assessing DMR exposure in IBD patients to determine the pooled prevalence of increased exposure and pooled odds ratio of risk factors associated with exposure to potentially harmful levels of ionising radiation from diagnostic imaging.

Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgement
  9. References
  10. Supporting Information

We followed a prespecified and peer-reviewed protocol; PRISMA statement, a 27-item checklist deemed essential for reporting of systematic reviews and meta-analyses of randomised controlled trials and observational studies.[23]

Search strategy

With assistance from an experienced librarian, we searched multiple electronic databases including PubMed (1965 to October 2011), OVID (1965 to October 2011), the Cochrane library, EMBASE (1974 to October 2011) and Cumulative index to nursing and allied health (CINAHL, 1982 to October 2011). The search terms entered into PubMed were (inflammatory bowel disease) and (radiation exposure) and (imaging). No limits or language restrictions were applied. Grey literature was excluded including abstracts. Identified articles were hand searched for other potentially relevant references.

Study selection

Studies were eligible for inclusion if they reported on the prevalence or risk factors for high diagnostic medical radiation exposure in IBD (UC or CD) patients. Two reviewers (SC and VS) independently screened titles and abstracts identified by the preliminary searches to identity potentially eligible studies. Both reviewers independently assessed the full text articles of potentially relevant studies for inclusion in the pooled analysis on the basis of the above inclusion criteria. Data from included studies were independently extracted by two investigators (SC and VS) using predefined criteria and a standardised profoma and entered into an Excel 2010 (Microsoft Corp., Redmond, WA, USA) spread sheet. Information was collected on characteristics of the study and outcomes. Agreement between the investigators was greater than 95%, and differences between the datasets were resolved by discussion.

Statistical analysis

We performed a meta-analysis of the following outcomes: pooled proportion of IBD patients exposed to potentially harmful doses of radiation (defined as ≥50 mSv) and pooled analysis of risk factors associated with high radiation exposure. The pooled estimate with 95% confidence intervals (CI) of IBD patients exposed to ≥50 mSv of radiation was calculated using the log odds scale. Odds ratios for each risk factor associated with high radiation were either extracted from the study or calculated from the data provided. As randomisation and blinding is not possible in observational studies, and baseline differences between the groups can confound the results, we used the authors odds ratios with adjustment for potential confounding factors. A fixed effects model was used unless there was significant heterogeneity, in which case the DerSimonian-Laird random effects model was used.[24] Comprehensive Meta Analysis version 2.2 (Biostat, Englewood, NJ, USA) statistical package was used for the data analysis.

Heterogeneity and sensitivity analysis

We used the Cochran's Q to test heterogeneity among pooled estimates.[25] Statistical heterogeneity was also measured by the I2 statistic that quantifies the proportion of inconsistency in individual studies which cannot be explained by chance.[26] Values of I2 equal to 25%, 50% and 75% represent low, moderate and high heterogeneity respectively. Finally, to exclude an excessive influence of any one study, we evaluated whether exclusion of each study substantially affected the magnitude or statistical significance of the summary odds ratio. To test for publication bias, we used a test for asymmetry of the funnel plot proposed by Egger et al.[27] This test detects funnel plot asymmetry by determining whether the intercept deviates significantly from zero in a regression of the normalised effect estimate (estimate divided by the standard error), again precision (reciprocal of the standard error of the estimate) weighted by the reciprocal of the variance of the estimate. The quality of the primary studies assessing the risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS).[28]

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgement
  9. References
  10. Supporting Information

Characteristics of selected studies

Our PubMed search retrieved 49 potentially relevant articles. Figure 1 outlines the fate of the selected articles. A total of eight studies[13, 19, 20, 29-33] involving 3512 participants with a diagnosis of IBD were included in the systematic review. All studies selected were retrospective observational studies published in the English language. No additional articles were retrieved from the other search strategies. Table 1 lists all the included studies and their characteristics. All included studies were deemed good quality as assessed using NOS tool. Six (Kroeker et al., Desmond et al., Fuchs et al., Levi et al., Newnham et al., Sauer et al.)[13, 19, 29-31, 33] of eight studies provided data on proportion of patients exposed to excessive radiation defined as ≥50 mSv. All six studies were from single tertiary centres; however, most of the patients were referred from general practice in one study (Newnham et al.).[31] Two population-based studies (Peloquin et al., Palmer et al.)[20, 32] were excluded because one assessed moderate radiation exposure defined by at least one CT examination or three fluoroscopic procedures during the 2-year observation period, and the other reported exposure by annual mean effective dose and median cumulative effective dose. Attempts were made to include these population studies[20, 32] in the analysis by contacting researchers asking if they measured the data required. Only one group[20] responded confirming that the data required were not available.

image

Figure 1. Flow chart of articles selected from PubMed search.

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Table 1. Study characteristics
StudyYearCountrynDesignPopulation

Outcome

≥50 mSv

Predictors of excessive radiation exposure
  1. NR, not reported; NA, not assessed; FH, family history; CD, Crohn's disease; UC, ulcerative colitis; CED, cumulative effective dose.

Newnham et al.[31]2007Australia

99

(62 CD, 37 UC)

Retrospective study from single tertiary centre, IBD patients recruited consecutively from clinicAdult cohort (16–84 years)

11/99 (11%)

9 CD, 2 UC

Median CED 10 mSv

Assessed: age, gender, disease, disease duration, previous surgery, immunomodulator use, referral source

Significant: none

Desmond et al.[19]2008Ireland354 CDRetrospective study from single tertiary centre, patients identified from IBD database and recruited if were reviewed during July 1992–June 2007

Adult & paediatric cohort

(8.6–78.3 years)

15 year survey period

Mean F/U

6.7 years

84/354 (24%)

Mean CED 36.1 mSv

Assessed: age, gender, smoking, FH, disease distribution, disease behaviour, medication, surgical history

Significant: age < 17 at diagnosis, upper GI tract disease, penetrating disease, infliximab usage, requirement for IV steroids, multiple surgeries

Peloquin et al.[20]2008US

215

(103 CD, 112 UC)

Retrospective study with population based inception cohort diagnosed between 1990 and 2001 from Olmsted County

Adult & paediatric cohort

(2.2–91.4 years)

11-year survey period

Mean F/U:

8.9 years CD

9 years UC

NR

CD: median CED 26.6 mSv

UC: median CED 10.5 mSv

NA
Levi et al.[30]2009Israel

324

(199 CD, 125 UC)

Retrospective study from single tertiary centre, IBD patients recruited from database diagnosed January 1999–December 2006

Adult & Paediatric cohort

≤17 years (18)

>18 years (306)

Mean F/U

5.5 years CD

5.0 years UC

23/324 (7.1%)

CD: mean CED 21.1 mSv

UC: mean CED 15.1 mSv

Assessed: age, surgery, diagnosis, medical therapy, disease duration, gender

Significant: CD, surgery, prednisolone use, disease duration, first year of disease, age

Palmer et al.[32]2009US

1593

(965 CD, 628 UC)

Retrospective study, population based cohort recruited from insurance claims database

Paediatric cohort

(2–18 years)

NR

34% CD and 23% UC patients exposed to moderate radiation defined as at least one CT or three fluoroscopic procedures over 2 years

Assessed: age, gender, region, hospitalisation, surgery, Emergency Depart. (ED) encounter, medication

Significant: hospitalisation, surgery, ED encounter, use of steroids

Kroekar et al.[13]2011Canada

553

(371 CD, 182, UC)

Retrospective study from single tertiary centre, IBD patients diagnosed between 2003 and 2008 recruited from database

Adult & paediatric cohort

(15–84 years)

Mean F/U: 13.8 years CD, 9.4 years UC

28/553 (5%)

(27 CD, 1 UC)

CD: mean CED

14.3 mSv

UC: mean CED

5.9 mSv

Assessed: age, age at diagnosis, gender, disease distribution, previous surgery

Significant: previous surgery

Fuchs et al.[29]2011US

257

(171 CD, 86 UC)

Retrospective study from single tertiary centre, IBD patients reviewed January- May 2008 were recruited

Paediatric cohort

(<18 years)

Mean F/U

5.3 years CD

5.4 years UC

15/257 (5.8%)

(14 CD, 1 UC)

CD: mean CED 20.5 mSv

UC: mean CED 11.7 mSv

Assessed in CD cohort: gender, disease behaviour, previous surgery, disease duration, elevated platelet count at diagnosis

Significant: previous surgery, elevated platelet count at diagnosis

Sauer et al.[33]2011US

117

(86 CD, 31 UC)

Retrospective study from single tertiary centre, patients diagnosed between 2002 and 2008 were recruited

Paediatric cohort

(2–18 years)

Mean F/U:

3.5 years CD

3.3 years UC

6/117

(5%)

(6 CD)

CD: median CED

15.6 mSv

UC: median CED

7.2 mSv

NA

Proportion of patients receiving high dose radiation (≥ 50 mSv)

All inflammatory bowel disease patients

Six studies (Kroeker et al., Desmond et al., Fuchs et al., Levi et al., Newnham et al., Sauer et al.) with 1704 number of patients with IBD provided data on exposure to high cumulative dose (≥50 mSv) of radiation. The pooled estimated proportion of patients receiving high dose radiation was 8.4% (95% CI 4.1–16.2%) (Figure 2). A random effects model was chosen, as the heterogeneity between the studies was high (Cochrans Q = 87, = 0.000 and I2 = 94%). There was no evidence of publication bias as determined using Egger's regression asymmetry test (= 0.15, intercept = −6.7 and 95% CI: −17.2 to 3.7).

image

Figure 2. Forest plot showing event rate defined as proportion of patients exposed to a CED of ≥50 mSv of radiation in IBD patients.

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Crohn's disease patients

Five studies (Kroeker et al., Desmond et al., Fuchs et al., Newnham et al., Sauer et al.) with 1044 number of patients with CD provided data on exposure to high cumulative dose (≥50 mSv) of radiation. The pooled estimated proportion of patients receiving high dose radiation was 11.1% (95% CI 5.7% to 20.5%) (Figure 3). A random effects model was chosen as the heterogeneity between the studies was high (Cochrans Q = 47, = 0.001 and I2 = 91%). There was no evidence of publication bias as determined using Egger's regression asymmetry test (= 0.1, intercept = −5 and 95% CI: −14.6 to 5.6).

image

Figure 3. Forest plot showing event rate defined as proportion exposed to CED ≥50 mSv of radiation in Crohn's disease patients.

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Ulcerative colitis patients

Four studies (Kroeker et al., Newnham et al., Fuchs et al., Sauer et al.) with 336 numbers of patients with UC provided data on exposure to high cumulative dose (≥50 mSv) of radiation. The pooled estimated proportion of patients receiving high dose radiation was 2% (95% CI 0.8% to 4.9%) (Figure 4). A fixed effects model was chosen as the heterogeneity between the studies was low (Cochrans Q = 3.9, = 0.27 and I2 = 23%). There was no evidence of publication bias as determined using Egger's regression asymmetry test (= 0.36, intercept = −2.8 and 95% CI: −12.9 to 7.3).

image

Figure 4. Forest plot showing event rate defined as CED exposure ≥50 mSv radiation in ulcerative colitis patients.

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Risk factors for high radiation exposure

Five studies (Kroeker et al., Desmond et al., Fuchs et al., Levi et al., Palmer et al.) involving 2627 number of patients provided data on risk factors for high dose radiation exposure. Table 2 lists the studies and the risk factors studied. There was a variation in the definition of high dose exposure and the risk factors analysed among the studies. Pooled analysis of the odds ratio was only done when >2 studies provided data on the same risk factor. Pooled analysis was therefore possible on four risk factors: prior IBD-related abdominal surgery, use of oral steroids, gender and use of immunomodulator medication (Figure 5). The pooled adjusted OR for previous IBD-related surgery and corticosteroid use was 5.4 (95% CI 2.6–11.2) and 2.4 (95% CI 1.7–3.4) respectively. There was no evidence of publication bias as determined using Egger's regression asymmetry test (= 0.36, intercept = −2.8 and 95% CI: −12.9 to 7.3) (data in Table S1).

image

Figure 5. Forest plot showing odds ratio of risk factors of high radiation exposure grouped according to exposure.

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Table 2. Pooled adjusted odds ratio of risk factors for high radiation exposure
Risk factorNo. of studiesPooled adjusted odds ratioLower limitUpper limitCochran's Qdf(Q)P-valueI-squared
Surgery55.392.5911.2011.0240.02663.69
Corticosteroids42.411.703.420.7730.8570.00
Male gender50.930.581.5011.1940.02464.26
Immunomodulator41.040.571.9111.7830.00874.54

The average time to reach total CED ≥ 50 mSv was not reported in all the studies. Desmond et al. reported the mean time to total CED > 75 mSv was 6.2 years. Disease duration was not found to be a significant risk factor associated with CED ≥ 50 mSv in multivariate analysis performed by Newnham et al. and Fuchs et al. suggesting all patients would be deemed at risk. Levi et al. found that first year of diagnosis was significantly associated with CED > 50 mSv in a binary regression model comparing first year of diagnosis with more than 1 year, but the confidence interval was wide and this was not significant in a linear model.

We attempted to gauge CT usage within the studies, but a summary statistic was not possible due to differences in reporting. CT usage was either reported as percentage of all imaging or the percentage of patients who had at least one CT scan. Kroeker et al. reported that 26% of all abdominal imaging was from CT abdomen and/or pelvis and Desmond et al. reported that 16.2% of all imaging was attributed to CT scans, but did not specify what proportion were abdomino-pelvic imaging. Levi et al. reported that 43% of patients had at least one CT abdomen scan, and Sauer et al. reported that 75% of CD patients had at least one CT abdomen and/or pelvis scan, and this figure was 42% in UC patients. All studies were comparable in reporting that CT contributed most to total radiation exposure.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgement
  9. References
  10. Supporting Information

Principal findings

About 1 in 10 IBD patients are at risk of exposure to high DMR. This is mostly due to the higher risk of exposure in CD (~11%) than UC (~2%). Predictors of increased radiation exposure were IBD-related surgery and use of corticosteroids with pooled adjusted odds ratio of 5.4 (95% CI: 2.6–11.2) and 2.4 (95% CI: 1.7–3.4) respectively. In the majority of instances, the need for corticosteroids and surgery are surrogate markers of disease activity. It therefore appears that patients with active disease who are more likely to receive corticosteroids and need surgery undergo diagnostic imaging to guide further management that add to their DMR exposure. All studies included in the review demonstrated that CT contributed most to total effective dose. In the United States, CT has almost replaced small bowel follow-through (SBFT) as the primary diagnostic modality to image the abdomen in CD.[20] In contrast, a recent UK survey has revealed the most frequently requested and performed imaging to assess small bowel is SBFT, and CT is performed most commonly for assessment of IBD-related complications.[34] Interestingly, immunomodulator use as a risk factor was not associated with excessive radiation exposure (pooled OR 1.04, 95% CI 0.57–1.9). One study showed an inverse association between immunomodulator use and DMR exposure.[32] Immunomodulator use could be construed as a surrogate marker of better disease control reducing the need for investigations to assess disease activity.

Clinical Implications

Knowledge of exposure to ionising radiation from tests is poor amongst clinicians.[35-37] In routine clinical practice, cumulative exposure to radiation is often not recorded. IBD healthcare professionals and radiology staff do not have procedures in place to communicate and to filter or flag up those exposed or at risk of exposure to potentially harmful levels of radiation. Our findings from this review highlighting that about 1 in 10 IBD patients are at risk of exposure to potentially harmful ionising radiation. This warrants strategies to minimise their risk of exposure to DMR. The findings are all the more concerning, because the majority of patients in these studies were young adults or children in whom there is an increased risk of radiation-induced malignancy.[8] Concerns arise when CT scans are requested and performed without any clinical rationale when an alternative modality could be used that has an equal diagnostic yield and is radiation free or when CT scans are repeated unnecessarily. It has been estimated that in the US, these scenarios account for up to a third of all CT scans.[12]

Recent advances in CT technology allow significant reductions in radiation dose compared with current techniques. The radiation dose emitted from CT can be reduced either by lowering the X-ray tube current (mA) or tube potential (KV) without sacrificing diagnostic performance.[38] Kroeker et al.[13] found that 35% of CT scans in IBD patients were performed in the emergency department raising questions about the need for MRI and alternatives out of hours or at least at short notice to have any clinical impact on radiation exposure.

A recent prospective study demonstrated that MR and CT enterography are equally accurate in the assessment of disease activity and complications in ileo-colonic CD.[39] A meta-analysis comparing ultrasonography, MRI and CT for the diagnosis of IBD showed high sensitivity and specificity with no statistical difference between modalities.[40] However, in addition to limited availability and higher costs compared with other modalities, the use of MRI is often restricted by lengthy acquisition time and patient intolerance.[41] In many centres, specialities outside gastroenterology are prioritised for MRI access (e.g. orthopaedics, neurology and rheumatology).[42] With increasing awareness of radiation exposure due to CT imaging and improving availability of MRI facilities, it is likely that MR enterography will emerge as a diagnostic tool in the routine assessment of patients with CD. We believe small bowel ultrasound should be considered as an alternative or complementary technique that has proven diagnostic accuracy.[43-46] There are endoscopic modalities available to assess the small bowel such as capsule endoscopy and single or double balloon or spiral enteroscopy; however, these techniques are not widely available and certainly not considered first line. Perhaps their role and use may evolve over time that could potentially impact on DMR exposure when assessing the small bowel; however, they are invasive and not without their own risks.

Study limitations

As with any meta-analysis there are possible limitations in combining results from separate studies. Selection bias could have affected DMR exposure; however, in all studies, patients were recruited either from a database or included prospectively to minimise this risk. Furthermore, the results from this meta-analysis should be interpreted with caution as participants were drawn from tertiary centres making the findings more relevant to those with a more complex and more severe disease course, and thus cannot necessarily be extrapolated to the primary or secondary care setting. All studies used the published standardised tables for calculating the CED making results comparable. However, the estimated radiation dose may have been greater or less than true exposure in all the studies. It is also likely that tests done at other centres may not have been captured, underestimating the total CED. The search was restricted to published articles only; however, there were no language restrictions in the search strategy. There are limitations with the current data, as long-term studies are required to extinction to assess if those who received potentially harmful doses actually develop cancer. The majority of included studies were retrospective and subject to bias. However, the retrospective nature of the studies could be construed as an advantage, as this reflects actual clinical practice and exposure to DMR would therefore be less likely to have been altered by any changes in the investigators clinical approach. Not all studies[13, 20] included non-GI imaging in calculating exposure, and this could have led to underestimation of the total effective dose of radiation received. A majority of the non-GI imaging would have been plain radiographs, and the radiation exposure from these investigations is negligible compared with CT or fluoroscopy. The total effective dose from a chest X-ray or a dual energy X-ray absorptiometry (DEXA) scan, for example, is around 0.02 mSv and 0.002 mSv, respectively, in comparison to 10 mSv and 7.2 mSv from abdominal CT and barium enema respectively.

Conclusions

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgement
  9. References
  10. Supporting Information

Exposure to DMR in patients with IBD is high. One in 10 patients with IBD have exposures of ≥50 mSv. This is more for patients with CD than UC. Exposure to corticosteroids and IBD-related surgery are risk factors associated with potentially harmful doses of radiation. Alternative strategies for disease assessment in patients with active disease and evaluation of post-operative complications are required. Utilisation of MRI and ultrasound that have been shown to be non-invasive, accurate and reliable with no radiation exposure should be increased in line with recent guidelines.[21, 22] Clinicians should document the cumulative radiation exposure in patients with IBD and ensure use of alternatives. Availability of low dose CT profiles, MRI scans and ultrasound need to be increased, especially in emergency settings, to have any clinically meaningful impact.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgement
  9. References
  10. Supporting Information

Supporting Information

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgement
  9. References
  10. Supporting Information
FilenameFormatSizeDescription
apt4975-sup-0001-TableS1.docWord document28KTable S1. Publication bias for risk factors associated with high radiation exposure (Eggers regression intercept).

Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.