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The Association Between Barium Examination and Subsequent Appendicitis

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The incidence and association between appendicitis and barium examination (BE) remain unclear. Such potential risk may be omitted. We conducted a longitudinal, nationwide, population-based cohort study to investigate the association between BE and appendicitis risk.

Methods

From the Taiwan National Health Insurance Research Database, a total of 24,885 patients who underwent BE between January 1, 2000 and December 31, 2010 were enrolled in a BE cohort; an additional 98,384 subjects without BE exposure were selected as a non-BE cohort, matched by age, sex, and index date. The cumulative incidences of subsequent appendicitis in the BE and non-BE cohorts were assessed using the Kaplan-Meier curves and log-rank test. Cox proportional hazards regression analyses were employed to calculate the appendicitis risk between the groups.

Results

The cumulative incidence of appendicitis was higher in the BE cohort than in the non-BE cohort (P = .001). The overall incidence rates of appendicitis for the BE and non-BE cohorts were 1.19 and 0.80 per 1000 person-years, respectively. After adjustment for sex, age, and comorbidities, the risk of appendicitis was higher in the BE cohort (adjusted hazard ratio = 1.46, 95% confidence interval = 1.23-1.73) compared with the non-BE cohort, especially in the first 2 months (adjusted hazard ratio = 9.72, 95% confidence interval = 4.65-20.3).

Conclusions

BE was associated with an increased, time-dependent appendicitis risk. Clinicians should be aware of this potential risk to avoid delayed diagnoses.

 

Barium sulfate is widely used and considered safe in gastrointestinal (GI) imaging studies. The clinical indications for its use include suspicion of GI tract tumor, unexplained abdominal pain, stricture or obstruction of GI tract, bowel habit change, chronic constipation or diarrhea, and so on. However, some rare complications involving its use, such as appendicitis, have been reported. Since Gubler and Kukral1 reported the first case of barium-related appendicitis in 1954, only case reports of subsequent appendicitis after upper GI series and barium enema studies have been documented, and the clinical courses varied widely from hours to years.234567891011The risk and etiology of barium-related appendicitis remain unknown and debatable.9

To ascertain the correlation between barium examination (BE) and appendicitis, a study made up of a relatively large number of BE patients with a high follow-up rate was necessary. We designed a longitudinal, nationwide, population-based cohort study, using data from the Taiwan National Health Insurance Research Database (NHIRD) to determine the subsequent risk of appendicitis in BE patients, and compared the risk with that of a matched non-BE population. We also examined the differences in the appendicitis risk among different entities of BE. There were other examinations reported with subsequent appendicitis, such as colonoscopy.12 This study preliminarily focused on the relationship between BE and appendicitis.

Methods

Data Source

Since 1995, the National Health Insurance (NHI) program has provided universal health care coverage to 99% of the population of 23.75 million in Taiwan.13 The NHIRD consists of comprehensive medical claims data from the Taiwan NHI program. To protect privacy, individual and hospital identifiers were scrambled and encrypted. Data for this study were obtained from a representative NHIRD dataset with one million people, which has been validated by numerous studies.141516 Disease identification was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). This retrospective cohort study was approved by the Institutional Review Board of China Medical University Hospital (CMUH104-REC2-115).

Identification and Definition of Study Cohorts

We identified patients who underwent BE (including upper GI series, small bowel series, single- and double-contrast barium enemas) between January 1, 2000 and December 31, 2010 from the NHIRD as the BE cohort. Those who underwent multiple BEs within 60 days were defined as the “repeated BE subgroup” in the BE cohort. The first date of BE was set as the patient’s index date. Patients with a history of appendicitis and other appendiceal diseases (ICD-9-CM codes 540-543) prior to their index date were not enrolled. The ICD-9-CM codes used in this paper for disease definitions and conditions are listed in the Appendix (Supplementary Table 1, available online). To control potential confounders of severe underlying illness, patients with the following comorbidities were excluded: human immunodeficiency virus disease, disorders involving the immune mechanism, end-stage renal disease, inflammatory bowel disease (including Crohn disease and ulcerative colitis), and GI tract malignancy.161718 To avoid surveillance bias and the interaction of other GI examinations, patients who underwent abdominal computed tomography, colonoscopy, or GI imaging studies using water-soluble contrast within 1 year from the index date were also excluded. After applying the same exclusion criteria, randomly selected subjects without BE exposure were propensity score-matched to each patient of the BE cohort on sex, age, and comorbidities of diabetes and intestinal infectious diseases (indicating proven intestinal infections of specific pathogens like cholera, salmonella, shigella, amoeba, protozoa, viruses) as the non-BE cohort. The year and month of index dates were also matched to avoid confounding effects from seasonal variation or endemic outbreak of appendicitis.1419 Figure 1 shows the flow of patients enrolled in this study.

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-Hao-Ming Li, MD, Lee-Ren Yeh, MD, Ying-Kai Huang, MD, Cheng-Li Lin, MSc, Chia-Hung Kao, MD

This article originally appeared in the January 2017 issue of The American Journal of Medicine.

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