Patricia P. Kammer

The Epidemiology of Community-Acquired Clostridium difficile Infection: A Population-Based Study

OBJECTIVES:Clostridium difficile infection (CDI) is a common hospital-acquired infection with increasing incidence, severity, recurrence, and associated morbidity and mortality. There are emerging data on the occurrence of CDI in nonhospitalized patients. However, there is a relative lack of community-based CDI studies, as most of the existing studies are hospital based, potentially influencing the results by referral or hospitalization bias by missing cases of community-acquired CDI.METHODS:To better understand the epidemiology of community-acquired C. difficile infection, a population-based study was conducted in Olmsted County, Minnesota, using the resources of the Rochester Epidemiology Project. Data regarding severity, treatment response, and outcomes were compared in community-acquired vs. hospital-acquired cohorts, and changes in these parameters, as well as in incidence, were assessed over the study period.RESULTS:Community-acquired CDI cases accounted for 41% of 385 definite CDI cases. The incidence of both community-acquired and hospital-acquired CDI increased significantly over the study period. Compared with those with hospital-acquired infection, patients with community-acquired infection were younger (median age 50 years compared with 72 years), more likely to be female (76% vs. 60%), had lower comorbidity scores, and were less likely to have severe infection (20% vs. 31%) or have been exposed to antibiotics (78% vs. 94%). There were no differences in the rates of complicated or recurrent infection in patients with community-acquired compared with hospital-acquired infection.CONCLUSIONS:In this population-based cohort, a significant proportion of cases of CDI occurred in the community. These patients were younger and had less severe infection than those with hospital-acquired infection. Thus, reports of CDI in hospitalized patients likely underestimate the burden of disease and overestimate severity.

The Epidemiology of Microscopic Colitis: A Population-Based Study in Olmsted County, Minnesota

Objective: Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population. Design and setting: In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies). Main outcome measures: Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence. Results: We identified 130 incident cases for an overall rate of 8.6 cases per 100 000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100 000 early in the study to 19.6 per 100 000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100 000 for collagenous colitis and 5.5 per 100 000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100 000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis). Conclusions: The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.

Symptomatic overlap between irritable bowel syndrome and microscopic colitis

Background Microscopic colitis is diagnosed on the basis of histologic criteria, and irritable bowel syndrome (IBS) is diagnosed by symptom‐based criteria. There has been little investigation into the symptomatic overlap between these conditions. Our aim was to assess the prevalence of symptoms of irritable bowel syndrome in a population‐based cohort of patients with microscopic colitis. Methods The Rochester Epidemiology Project (REP), a medical records linkage system providing all health care data for the defined population of Olmsted County, Minnesota, was used to identify all county residents with a diagnosis of microscopic colitis between 1985 and 2001. The medical records of these individuals were reviewed to ascertain symptoms consistent with Rome, Rome II, and Manning criteria for irritable bowel syndrome. Results One hundred thirty‐one cases of microscopic colitis were identified. Median age at diagnosis was 68 years (range, 24–95); 71% were women. Sixty‐nine (53%) and 73 (56%) met Rome and Rome II criteria for irritable bowel syndrome, respectively. Fifty‐four (41%) had three or more Manning criteria. Forty‐three (33%) had previously been diagnosed with irritable bowel syndrome. Conclusions In this population‐based cohort of histologically confirmed microscopic colitis, approximately one‐half met symptom‐based criteria for the diagnosis of irritable bowel syndrome. The clinical symptom‐based criteria for irritable bowel syndrome are not specific enough to rule out the diagnosis of microscopic colitis. Therefore, patients with suspected diarrhea‐predominant irritable bowel syndrome should undergo biopsies of the colon to investigate for possible microscopic colitis if symptoms are not well controlled by antidiarrheal therapy. (Inflamm Bowel Dis 2006)

The Epidemiology of Clostridium difficile Infection in Children: A Population-Based Study

BACKGROUND The incidence of Clostridium difficile infection (CDI) is increasing, even in populations previously thought to be at low risk, including children. Most incidence studies have included only hospitalized patients and are thus potentially influenced by referral or hospitalization biases. METHODS We performed a population-based study of CDI in pediatric residents (aged 0-18 years) of Olmsted County, Minnesota, from 1991 through 2009 to assess the incidence, severity, treatment response, and outcomes of CDI. RESULTS We identified 92 patients with CDI, with a median age of 2.3 years (range, 1 month-17.6 years). The majority of cases (75%) were community-acquired. The overall age- and sex-adjusted CDI incidence was 13.8 per 100 000 persons, which increased 12.5-fold, from 2.6 (1991-1997) to 32.6 per 100 000 (2004-2009), over the study period (P < .0001). The incidence of community-acquired CDI was 10.3 per 100 000 persons and increased 10.5-fold, from 2.2 (1991-1997) to 23.4 per 100 000 (2004-2009) (P < .0001). Severe, severe-complicated, and recurrent CDI occurred in 9%, 3%, and 20% of patients, respectively. The initial treatment in 82% of patients was metronidazole, and 18% experienced treatment failure. In contrast, the initial treatment in 8% of patients was vancomycin and none of them failed therapy. CONCLUSIONS In this population-based cohort, CDI incidence in children increased significantly from 1991 through 2009. Given that the majority of cases were community-acquired, estimates of the incidence of CDI that include only hospitalized children may significantly underestimate the burden of disease in children.

Gastric mechanosensory and lower esophageal sphincter function in rumination syndrome

Our hypothesis was that rumination syndrome is associated with gastric sensory and motor dysfunction. We studied gastric and somatic sensitivity, reflex relaxation of the lower esophageal sphincter (LES), and gastric compliance and accommodation postprandially and postglucagon. A barostatically controlled gastric bag and esophageal manometry were used to compare gastric sensorimotor functions and LES relaxation to gastric distension in 12 patients with rumination syndrome and 12 controls. During bag distensions, patients had greater nausea, bloating, and aggregate score, but not pain, compared with controls ( P < 0.05). At 4 and 8 mmHg gastric distension, LES tone reduction was greater in patients than in controls ( P < 0.05). Gastric compliance, accommodation to a standard meal, and response to glucagon were not different in patients and controls; however, 6 of 12 patients had no gastric accommodation; the latter patients had significantly greater pain perception during distension ( P < 0.05) but normal somatic sensitivity compared with healthy controls. Rumination syndrome is characterized by higher gastric sensitivity and LES relaxation during gastric distension. A subgroup of patients also had absent postprandial accommodation.

“Outcomes in community–acquired clostridium difficile infection”

Community‐acquired Clostridium difficile infection (CA‐CDI) is an increasingly appreciated condition. It is being described in populations lacking traditional predisposing factors that have been previously considered at low‐risk for this infection. As most studies of CDI are hospital‐based, outcomes in these patients are not well known.

The Epidemiology of Microscopic Colitis in Olmsted County From 2002 to 2010: A Population-Based Study

BACKGROUND & AIMS The increasing incidence of microscopic colitis has been partly attributed to detection bias. We aimed to ascertain recent incidence trends and the overall prevalence of microscopic colitis in a population-based study. METHODS Using data from the Rochester Epidemiology Project, we identified residents of Olmsted County, Minnesota, who were diagnosed with collagenous colitis or lymphocytic colitis from January 1, 2002, through December 31, 2010, based on biopsy results and the presence of diarrhea (N = 182; mean age at diagnosis, 65.8 years; 76.4% women). Poisson regression analyses were performed to evaluate associations between incidence and age, sex, and calendar period. RESULTS The age- and sex-adjusted incidence of microscopic colitis was 21.0 cases per 100,000 person-years (95% confidence interval [CI], 18.0-24.1 cases per 100,000 person-years). The incidence of lymphocytic colitis was 12.0 per 100,000 person-years (95% CI, 9.6-14.3 per 100,000 person-years) and collagenous colitis was 9.1 per 100,000 person-years (95% CI, 7.0-11.1 per 100,000 person-years). The incidence of microscopic colitis and its subtypes remained stable over the study period (P = .63). Increasing age (P < .001) and female sex (P < .001) were associated with increasing incidence. On December 31, 2010, the prevalence of microscopic colitis was 219 cases per 100,000 persons (90.4 per 100,000 persons for collagenous colitis and 128.6 per 100,000 persons for lymphocytic colitis). CONCLUSION The incidence of microscopic colitis in Olmsted County residents has stabilized and remains associated with female sex and increasing age.

Gastric Acid Suppression and Outcomes in Clostridium difficile Infection: A Population-Based Study

OBJECTIVE To evaluate the association of gastric acid suppression medications, including proton pump inhibitors and histamine type 2 blockers, with outcomes in patients with Clostridium difficile infection (CDI) in a population-based cohort. PATIENTS AND METHODS To understand the association between acid suppression and outcomes in patients with CDI, we conducted a population-based study in Olmsted County, Minnesota, from January 1, 1991, through December 31, 2005. We compared demographic data and outcomes, including severe, severe-complicated, and recurrent CDI and treatment failure, in a cohort of patients with CDI who were treated with acid suppression medications with these outcomes in a cohort with CDI that was not exposed to acid-suppressing agents. RESULTS Of 385 patients with CDI, 36.4% were undergoing acid suppression (23.4% with proton pump inhibitors, 13.5% with histamine type 2 blockers, and 0.5% with both). On univariate analysis, patients taking acid suppression medications were significantly older (69 vs 56 years; P<.001) and more likely to have severe (34.2% vs 23.6%; P=.03) or severe-complicated (4.4% vs 2.6% CDI; P=.006) infection than patients not undergoing acid suppression. On multivariable analyses, after adjustment for age and comorbid conditions, acid suppression medication use was not associated with severe or severe-complicated CDI. In addition, no association between acid suppression and treatment failure or CDI recurrence was found. CONCLUSION In this population-based study, after adjustment for age and comorbid conditions, patients with CDI who underwent acid suppression were not more likely to experience severe or severe-complicated CDI, treatment failure, or recurrent infection.

Observer variability in the histologic diagnosis of microscopic colitis

Background: Microscopic colitis is diagnosed based on histologic criteria. There has been no investigation of the reproducibility of the histologic diagnosis of microscopic colitis. Our aim was to evaluate interobserver and intraobserver variation in this diagnosis. Methods: Colonic biopsies from 90 subjects (20 lymphocytic colitis, 20 collagenous colitis, 20 inflammatory bowel disease, and 30 normal) were blindly and independently reviewed by 4 gastrointestinal pathologists. The biopsies were classified by each pathologist into 1 of 6 diagnostic categories: lymphocytic colitis, collagenous colitis, active chronic colitis, focal active colitis, normal, or other. The slides were then relabeled and blindly reinterpreted 3 months later. The degree of agreement was determined using kappa statistics (&lgr;). Results: Interobserver agreement with the 6 diagnostic categories was 69% (&kgr; = 0.76, 95% CI 0.69, 0.83) and 70% (&kgr; = 0.71, 95% CI 0.61, 0.79) for the first and second observations, respectively. Interobserver agreement with final diagnostic categories of microscopic colitis versus nonmicroscopic colitis was 91% (&kgr; = 0.90, 95% CI 0.82, 0.96) and 88% (&kgr; = 0.83, 95% CI 0.73, 0.92), respectively. Mean intraobserver agreement with the 6 diagnostic categories was 83% (&kgr; = 0.77). Mean intraobserver agreement with the final diagnostic categories of microscopic colitis versus nonmicroscopic colitis was 95% (&kgr; = 0.89). Conclusions: Both interobserver and intraobserver agreement were good in distinguishing among the 6 diagnostic categories, and excellent in distinguishing between microscopic colitis and nonmicroscopic colitis diagnoses. The histologic criteria for microscopic colitis provide for consistent and reproducible interindividual and intraindividual diagnoses in the evaluation of colonic biopsies.

CYP2C19 pharmacogenetics in the clinical use of proton-pump inhibitors for gastro-oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms

Background:  The rate of metabolic inactivation of proton‐pump inhibitors is determined by polymorphisms of CYP2C19. It is not known if CYP2C19 variant alleles affect responses to proton‐pump inhibitor therapy in gastro‐oesophageal reflux disease (GERD).