Our results suggest that chronic constipation is associated with several concurrent conditions of variable risk and prevalence and serve to eliminate the paucity of current literature on this topic, as highlighted by Talley et al
. While a causal relationship may already exist for some of these concurrent conditions, for others, such association may provide the impetus for further research.
We note that generally the ORs were higher in the constipation cohort compared to those in the GERD cohort, although several ORs were significant in the latter as well and this may relate to increased screening and recognition prompted by the medical care received for the index condition (constipation or GERD). We found that hemorrhoids were the most prevalent concurrent condition in patients who were diagnosed with constipation and this prevalence increased by about 5% after the latter were diagnosed. Delco and Sonnenberg, in their retrospective case-control study of 96,314 veterans found that constipation was a significant co-morbidity of hemorrhoids (OR 1.48 [95% CI 1.43–1.54]) 
; their results are very similar to ours (OR 1.24 [95% CI 1.20–1.30]). Brook et al
., in a study of 1,215 subjects with constipation and 29,160 propensity score-matched controls, reported the prevalence of hemorrhoids to be 15.2% in the constipation group as compared to 1.5% in the control group (OR 11.8, p<0.001). 
Our study's duration was 1 year, starting 3 months before the diagnosis of constipation and in a study design very similar to ours, Mitra et al
., compared 48,585 subjects with 97,170 controls 
and found the odds ratio of the association between hemorrhoids and constipation to be 4.2; this much stronger association compared to our results is likely secondary to detection bias in their study.
Ano–rectal complications such as fissures, fistulas or ulcers were rare (prevalence less than 1% each) in patients with constipation but were significantly associated with it. Brook et al
., reported 5.8% prevalence of ‘ano–rectal conditions’ 
; this likely includes a combined prevalence of the ano–rectal concurrent conditions that we reported separately and thus probably reflects similar prevalence. Mitra reported significant association of constipation and anal fissures (OR 5.0) and rectal ulcers (OR 4.8) without specifying their prevalence. 
Ano–rectal hemorrhage had a relatively high prevalence in both the constipation as well as the control groups in our study, likely reflecting the similarly high prevalence of hemorrhoids and/or diverticular disease in general. Even then, the risk of ano–rectal hemorrhage was 36% higher in patients with constipation.
Diverticular disease has been proposed to be secondary to small stool volume, longer transit time as well as abnormal colonic motility and thus has been felt to be associated with constipation. 
Indeed, in our previous study 
, we reported -in the same group of patients as the current study- an odds ratio of 2.8 for this association. However, in the current study, when we accounted for possible detection bias, this association was rendered non–significant (OR 1.04 [95% CI 1.00–1.08]). Chronic constipation may be related to rectal neurological dysfunction 
and lead to fecal impaction. Mitra demonstrated a 6.6–fold increased odds of fecal impaction in constipated patients, 
which is similar to what we found (OR 5.6); however, the adjusted odds ratio was less, 3.2, and still significantly high. Hirschsprung's disease is a known cause of chronic constipation in adults; 
such cases are believed to be either less severe or zonal forms of colonic aganglionosis. In our study, even though it was very rare in patients with constipation (0.04%), it was the concurrent condition with the strongest association (OR 4.4 [95% CI 2.5–7.9]).
A small study involving 55 elderly patients with fecal impaction revealed impaired ano–rectal sensation in the subjects as compared to controls, preventing conscious contraction of the external anal sphincter when the internal sphincter was relaxed, thereby causing fecal incontinence. 
This was subsequently confirmed in a much larger study of 16,331 nursing home residents with fecal incontinence and it was shown that chronic constipation increased the odds of fecal incontinence by 30–40% (2–year cross-sectional survey). 
However, both of these studies were done in selected populations, with resulting strong possibility of selection bias. A population–based study using the Rome ll criteria for diagnosis and involving an age–stratified random sample of 507 women in Olmstead county concluded that constipation did not increase the odds of fecal incontinence (OR 1.1 [95% CI 0.8–1.5]). 
The result from our population–based study concurs with that of this last study (OR 1.16 [95% CI 0.99–1.35]). It also follows from our results that, since constipation is associated with increased odds of fecal impaction but not fecal incontinence, constipation is not a confounder of the association between fecal impaction and incontinence. We found increased odds (63% higher) of rectal prolapse in patients with chronic constipation, consistent with prior studies 
and likely resulting from long–term straining.. 
Volvulus, similarly, was significantly associated with constipation in our study (36% higher odds), although not to the extent reported by Mitra (OR 10.3). 
Constipation has been linked with colon cancer in previous studies. A case–control study of 424 incident cases from Seattle found that constipation present for 10 years before the index date (2 years before diagnosis of colon cancer) resulted in an adjusted relative risk of 2.0 (95% CI 1.2–3.6) for colon cancer; the risk associated with the use of commercial laxatives was nullified after adjustment for constipation. 
In a population–based case–control study of 643 cases from North Carolina, the adjusted odds ratio of colon cancer and constipation was 2.36 (95% CI 1.41–3.93). 
The Miyagi cohort study of 41,670 individuals from Japan noted the multivariate relative risk of colon cancer in those with constipation to be 1.35 (95% CI 0.99–1.84). 
These studies support our finding that the odds of colon cancer in constipated patients were higher than those without (OR 1.16 [95% CI 1.05–1.30]).
There are several strengths of our study. It involves a very large sample size, is population–based and, importantly, controls for detection bias (described in Methods
section). In addition, usage of the Medi–Cal population for conducting this study has several advantages of its own: the drop-out rate (loss of eligibility) is significantly less than private payer plans; patients do not drop-out when they qualify for Medicare (since Medi–Cal pays for Medicare deductibles); there is a high representation of minority populations; and records from Medicare are obtained on all patients who have dual-eligibility and merged within the Medi–Cal datasets. Several limitations also apply to our study and its results. Given a different study population and design, our results may not be comparable to those reported in previous studies. We cannot establish causality based only on the strength of the associations that we observed. As is true for research conducted using an administrative database, the identification of cases and controls as well as the associated concurrent conditions are dependent on the accuracy of the claims submitted for them. However, this may not be a significant problem in our study as an audit of Medi-Cal claims found that 96.4% were medically necessary, billed appropriately and were in concordance with the data in the claims files. 
Furthermore, as our study sample was derived from a Medicaid population, it represents data from people who are typically sicker and less affluent, thus potentially limiting the generalizability of our findings to the Medicaid population only. It is possible that diet, lifestyle-changes or treatment for CC might affect the association of the comorbidities with CC. Finally, we cannot rule out the possibility of detection bias persisting in our study; however, this is unlikely to affect the adjusted odds–ratio, thus our results are likely to remain valid.
In summary, we have reported the prevalence and strength of association of various concurrent conditions of constipation. Our findings would hopefully help direct future research in patients with chronic constipation and eventually improve patient care.