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Abstract
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.
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.
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.
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 objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
Toxins A and B are the primary virulence factors of Clostridium difficile. Since 2002, an epidemic of C difficile-associated disease with increased morbidity and mortality has been present in Quebec province, Canada. We characterised the dominant strain of this epidemic to determine whether it produces higher amounts of toxins A and B than those produced by non-epidemic strains. We obtained isolates from 124 patients from Centre Hospitalier Universitaire de Sherbrooke in Quebec. Additional isolates from the USA, Canada, and the UK were included to increase the genetic diversity of the toxinotypes tested. Isolate characterisation included toxinotyping, pulsed-field gel electrophoresis (PFGE), PCR ribotyping, detection of a binary toxin gene, and detection of deletions in a putative negative regulator for toxins A and B (tcdC). By use of an enzyme-linked immunoassay, we measured the in-vitro production of toxins A and B by epidemic strain and non-dominant strain isolates. The epidemic strain was characterised as toxinotype III, North American PFGE type 1, and PCR-ribotype 027 (NAP1/027). This strain carried the binary toxin gene cdtB and an 18-bp deletion in tcdC. We isolated this strain from 72 patients with C difficile-associated disease (58 [67%] of 86 with health-care-associated disease; 14 [37%] of 38 with community-acquired disease). Peak median (IQR) toxin A and toxin B concentrations produced in vitro by NAP1/027 were 16 and 23 times higher, respectively, than those measured in isolates representing 12 different PFGE types, known as toxinotype 0 (toxin A, median 848 microg/L [IQR 504-1022] vs 54 microg/L [23-203]; toxin B, 180 microg/L [137-210] vs 8 microg/L [5-25]; p<0.0001 for both toxins). The severity of C difficile-associated disease caused by NAP1/027 could result from hyperproduction of toxins A and B. Dissemination of this strain in North America and Europe could lead to important changes in the epidemiology of C difficile-associated disease.
The Rochester Epidemiology Project (REP) is a unique research infrastructure in which the medical records of virtually all persons residing in Olmsted County, Minnesota, for over 40 years have been linked and archived. In the present article, the authors describe how the REP links medical records from multiple health care institutions to specific individuals and how residency is confirmed over time. Additionally, the authors provide evidence for the validity of the REP Census enumeration. Between 1966 and 2008, 1,145,856 medical records were linked to 486,564 individuals in the REP. The REP Census was found to be valid when compared with a list of residents obtained from random digit dialing, a list of residents of nursing homes and senior citizen complexes, a commercial list of residents, and a manual review of records. In addition, the REP Census counts were comparable to those of 4 decennial US censuses (e.g., it included 104.1% of 1970 and 102.7% of 2000 census counts). The duration for which each person was captured in the system varied greatly by age and calendar year; however, the duration was typically substantial. Comprehensive medical records linkage systems like the REP can be used to maintain a continuously updated census and to provide an optimal sampling framework for epidemiologic studies.
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