human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Many laboratories use enzyme immunoassays ( EIAs ) for the diagnosis of Clostridium difficile infection ( CDI ) . More recently , polymerase chain reaction (PCR)-based diagnosis has been described as a sensitive test . Real-time PCR for the detection of C. difficile toxin A and B genes was evaluated . A prospect i ve evaluation was performed on stool sample s from 150 hospitalized adult patients and 141 healthy volunteers .  PCR was compared to toxigenic culture ( TC ) , direct cytotoxicity test ( CTT ) , ImmunoCard ® Toxin A and B ( Meridian Bioscience ) , and enzyme-linked immunosorbent assay ( ELISA ) ( Vidas ) . The results were correlated with clinical data using a st and ardized question naire . The diagnostic yield of the PCR was further evaluated after implementation . Using toxigenic culture as the gold st and ard , the sensitivity and specificity of PCR were 100 and 99.2 % , respectively . Patients were categorized as follows : TC/PCR-positive ( n = 17 ) and negative TC ( n = 133 ) . The differences in these groups were more frequent use of antibiotics and leukocytosis ( p < 0.05 ) . The diagnostic yield of PCR  was evaluated during a period of 6 months and showed an increase of positive patients by 50 % . PCR for the detection of toxigenic C. difficile has a high sensitivity and can rule out CDI , but can not differentiate CDI from asymptomatic carriage . Clinicians should be aware of this in order to prevent inappropriate treatment and delay of other diagnostics BACKGROUND The incidence and severity of Clostridium difficile infections are increasing , and there is a need to optimize the prevention of complicated disease . OBJECTIVE To identify modifiable processes of care associated with an altered risk of C difficile complications . METHODS A retrospective cohort study ( with prospect i ve case ascertainment ) of all C difficile infections during 2007⁄2008 at a tertiary care hospital was conducted . RESULTS Severe complications were frequent ( occurring in 97 of 365 [ 27 % ] C difficile episodes ) , with rapid onset ( median three days postdiagnosis ) . On multivariable analysis , nonmodifiable predictors of complications included repeat infection ( OR 2.67 ) , confusion ( OR 2.01 ) , hypotension ( OR 0.97 per increased mmHg ) and elevated white blood cell count ( OR 1.04 per 109 cells⁄L ) . Protection from complications was associated with initial use of vancomycin ( OR 0.24 ) ; harm was associated with ongoing use of exacerbating antibiotics ( OR 3.02 ) . CONCLUSION C difficile infections often occur early in the disease course and are associated with high complication rates . Clinical factors that predicted a higher risk of complications included confusion , hypotension and leukocytosis . The most effective ways to improve outcomes for patients with C difficile colitis are consideration of vancomycin as first-line treatment for moderate to severe cases , and the avoidance of unnecessary antibiotics We performed a Monte Carlo study to evaluate the effect of the number of events per variable ( EPV ) analyzed in logistic regression analysis . The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality ; the number of events per predictive variable was ( 252/7 =) 36 for the full sample . For the simulations , at values of EPV = 2 , 5 , 10 , 15 , 20 , and 25 , we r and omly generated 500 sample s of the 673 patients , chosen with replacement , according to a logistic model derived from the full sample . Simulation results for the regression coefficients for each variable in each group of 500 sample s were compared for bias , precision , and significance testing against the results of the model fitted to the original sample . For EPV values of 10 or greater , no major problems occurred . For EPV values less than 10 , however , the regression coefficients were biased in both positive and negative directions ; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients ; the 90 % confidence limits about the estimated values did not have proper coverage ; the Wald statistic was conservative under the null hypothesis ; and paradoxical associations ( significance in the wrong direction ) were increased . Although other factors ( such as the total number of events , or sample size ) may influence the validity of the logistic model , our findings indicate that low EPV can lead to major problems BACKGROUND New therapies are needed to manage the increasing incidence , severity , and high rate of recurrence of Clostridium difficile infection . METHODS We performed a r and omized , double-blind , placebo-controlled study of two neutralizing , fully human monoclonal antibodies against C. difficile toxins A ( CDA1 ) and B ( CDB1 ) . The antibodies were administered together as a single infusion , each at a dose of 10 mg per kilogram of body weight , in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin .  The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo . RESULTS Among the 200 patients who were enrolled ( 101 in the antibody group and 99 in the placebo group ) , the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies ( 7 % vs. 25 % ; 95 % confidence interval , 7 to 29 ; P<0.001 ) . The recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8 % for the antibody group and 32 % for the placebo group ( P=0.06 ) ; among patients with more than one previous episode of C. difficile infection , recurrence rates were 7 % and 38 % , respectively ( P=0.006 ) . The mean duration of the initial hospitalization for in patients did not differ significantly between the antibody and placebo groups ( 9.5 and 9.4 days , respectively ) . At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group ( P=0.09 ) . CONCLUSIONS The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection . ( Clinical Trials.gov number , NCT00350298 . OBJECTIVE toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis . This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course . DESIGN prospect i ve cohort study . SETTING university teaching hospital . SUBJECTS all patients with symptomatic C. difficile infection during 4 months of an outbreak ( January-April 1995 ) ; n=73 ; median age 74 years ( range 17 - 91 ) . MEASUREMENTS incidence of C. difficile-associated disease ( CDAD ) ; severity of disease ; percentage of patients in each category of severity ; risk factors for severe disease/prolonged symptoms ( univariate and multivariable analyses ) . RESULTS the incidence of CDAD was 0.93 % . Of the cases identified , 18 ( 24.7 % ) had mild , self-limiting disease ; 26 ( 35.6 % ) had moderately severe disease ; 23 ( 31.5 % ) had prolonged symptoms and six ( 8.2 % ) had a complicated course . Although CDAD was more common in older patients ( P < 0.001 ) , increasing age was not a risk factor for severity . Significant risk factors for severe CDAD included low Barthel and abbreviated mental test scores ( P < 0.01 , P < 0.001 respectively ) and recent endoscopy ( P=0.03 ) . Logistic regression analysis revealed the following independent predictors of severe CDAD : endoscopy [ odds ratios ( OR ) 4.0 , P=0.03 ] and cognitive impairment ( OR 11.0 , P < 0.01 ) . A trend towards significance was noted for nasogastric tube insertion ( OR 3.1 , P=0.08 ) . Complications of infection included dehydration , malnutrition and faecal incontinence ( which was statistically significantly associated with more severe disease ; P < 0.01 ) . CONCLUSION risk factors for severity of CDAD include functional disability , cognitive impairment , and recent endoscopy . Anticipation of severe CDAD may limit morbidity and mortality BACKGROUND Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality . Patients generally have a response to oral vancomycin or metronidazole ; however , the rate of recurrence is high . This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection . METHODS Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry . We r and omly assigned patients to receive fidaxomicin ( 200 mg twice daily ) or vancomycin ( 125 mg four times daily ) orally for 10 days . The primary end point was clinical cure ( resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy ) . The secondary end points were recurrence of C. difficile infection ( diarrhea and a positive result on a stool toxin test within 4 weeks after treatment ) and global cure ( i.e. , cure with no recurrence ) . RESULTS A total of 629 patients were enrolled , of whom 548 ( 87.1 % ) could be evaluated for the per- protocol analysis . The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis ( 88.2 % with fidaxomicin and 85.8 % with vancomycin ) and the per- protocol analysis ( 92.1 % and 89.8 % , respectively ) . Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection , in both the modified intention-to-treat analysis ( 15.4 % vs. 25.3 % , P=0.005 ) and the per- protocol analysis ( 13.3 % vs. 24.0 % , P=0.004 ) . The lower rate of recurrence was seen in patients with non – North American Pulsed Field type 1 strains . The adverse-event profile was similar for the two therapies . CONCLUSIONS The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin . Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non – North American Pulsed Field type 1 strains . ( Funded by Optimer Pharmaceuticals ; Clinical Trials.gov number , NCT00314951 . BACKGROUND Neutrophil recruitment coordinated by intestinal interleukin (IL)-8 secretion is a key component in the pathogenesis of Clostridium difficile infection ( CDI ) . We hypothesized that a common single-nucleotide polymorphism ( SNP ) in the -251 region of the IL-8 gene promoter may be predictive of recurrent CDI . METHODS This was a prospect i ve cohort study of hospitalized adult patients with CDI who were admitted to a large , university-affiliated medical center from 2007 through 2008 . Patients were monitored for 3 months after diagnosis of CDI and assessed for recurrent CDI ( defined as a return of diarrhea that required treatment after initial symptom resolution ) . DNA was isolated from blood sample s , and genetic sequencing was performed using polymerase chain reaction and pyrosequencing . The association between IL-8 genotype and recurrent CDI was assessed using univariate and multivariate statistics . RESULTS Ninety-six patients with a mean ( ± st and ard deviation ) age of 61 ± 16 years ( 54 % of whom were female and 63 % of whom were white ) were identified .  The overall incidence of recurrent CDI was 24 % . IL-8 allele frequency was similar to previously reported findings ( for A/A , 27 % ; for A/T , 53 % ; and for T/T , 20 % ) . The incidence of recurrent CDI was 38 % in patients with the A/A allele and 19 % in all other patients ( relative risk , 2.1 ; 95 % confidence interval , 1.04 - 4.13 ) ( P = .043 ) . CONCLUSIONS This study indicates that a common SNP in the IL-8 gene promoter is an independent predictor of recurrent CDI . Our results could offer risk stratification for patients at high risk for recurrent CDI BACKGROUND Most Clostridium difficile infection ( CDI ) surveillance programs neither specify the diagnostic method to be used nor stratify rates accordingly . We assessed the difference in  healthcare-associated CDI ( HA-CDI ) incidence and complication rates obtained by 2 vali date d diagnostic methods . METHODS This was a prospect i ve cohort study of patients for whom a C. difficile test was ordered between 1 August 2010 and 31 July 2011 . All specimens were tested in parallel by a commercial polymerase chain reaction ( 
    Output:
    
agent
Older age , use of antibiotics after diagnosis , use of proton pump inhibitors , and strain type were the most frequent risk factors for recurrence .
Older age , leucocytosis , renal failure and co-morbidities were frequent risk factors for complicated CDI .
When considered alone , mortality was associated with age , co-morbidities , hypo-albuminemia , leucocytosis , acute renal failure , and infection with ribotype 027 .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Many laboratories use enzyme immunoassays ( EIAs ) for the diagnosis of Clostridium difficile infection ( CDI ) . More recently , polymerase chain reaction (PCR)-based diagnosis has been described as a sensitive test . Real-time PCR for the detection of C. difficile toxin A and B genes was evaluated . A prospect i ve evaluation was performed on stool sample s from 150 hospitalized adult patients and 141 healthy volunteers .  PCR was compared to toxigenic culture ( TC ) , direct cytotoxicity test ( CTT ) , ImmunoCard ® Toxin A and B ( Meridian Bioscience ) , and enzyme-linked immunosorbent assay ( ELISA ) ( Vidas ) . The results were correlated with clinical data using a st and ardized question naire . The diagnostic yield of the PCR was further evaluated after implementation . Using toxigenic culture as the gold st and ard , the sensitivity and specificity of PCR were 100 and 99.2 % , respectively . Patients were categorized as follows : TC/PCR-positive ( n = 17 ) and negative TC ( n = 133 ) . The differences in these groups were more frequent use of antibiotics and leukocytosis ( p < 0.05 ) . The diagnostic yield of PCR  was evaluated during a period of 6 months and showed an increase of positive patients by 50 % . PCR for the detection of toxigenic C. difficile has a high sensitivity and can rule out CDI , but can not differentiate CDI from asymptomatic carriage . Clinicians should be aware of this in order to prevent inappropriate treatment and delay of other diagnostics BACKGROUND The incidence and severity of Clostridium difficile infections are increasing , and there is a need to optimize the prevention of complicated disease . OBJECTIVE To identify modifiable processes of care associated with an altered risk of C difficile complications . METHODS A retrospective cohort study ( with prospect i ve case ascertainment ) of all C difficile infections during 2007⁄2008 at a tertiary care hospital was conducted . RESULTS Severe complications were frequent ( occurring in 97 of 365 [ 27 % ] C difficile episodes ) , with rapid onset ( median three days postdiagnosis ) . On multivariable analysis , nonmodifiable predictors of complications included repeat infection ( OR 2.67 ) , confusion ( OR 2.01 ) , hypotension ( OR 0.97 per increased mmHg ) and elevated white blood cell count ( OR 1.04 per 109 cells⁄L ) . Protection from complications was associated with initial use of vancomycin ( OR 0.24 ) ; harm was associated with ongoing use of exacerbating antibiotics ( OR 3.02 ) . CONCLUSION C difficile infections often occur early in the disease course and are associated with high complication rates . Clinical factors that predicted a higher risk of complications included confusion , hypotension and leukocytosis . The most effective ways to improve outcomes for patients with C difficile colitis are consideration of vancomycin as first-line treatment for moderate to severe cases , and the avoidance of unnecessary antibiotics We performed a Monte Carlo study to evaluate the effect of the number of events per variable ( EPV ) analyzed in logistic regression analysis . The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality ; the number of events per predictive variable was ( 252/7 =) 36 for the full sample . For the simulations , at values of EPV = 2 , 5 , 10 , 15 , 20 , and 25 , we r and omly generated 500 sample s of the 673 patients , chosen with replacement , according to a logistic model derived from the full sample . Simulation results for the regression coefficients for each variable in each group of 500 sample s were compared for bias , precision , and significance testing against the results of the model fitted to the original sample . For EPV values of 10 or greater , no major problems occurred . For EPV values less than 10 , however , the regression coefficients were biased in both positive and negative directions ; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients ; the 90 % confidence limits about the estimated values did not have proper coverage ; the Wald statistic was conservative under the null hypothesis ; and paradoxical associations ( significance in the wrong direction ) were increased . Although other factors ( such as the total number of events , or sample size ) may influence the validity of the logistic model , our findings indicate that low EPV can lead to major problems BACKGROUND New therapies are needed to manage the increasing incidence , severity , and high rate of recurrence of Clostridium difficile infection . METHODS We performed a r and omized , double-blind , placebo-controlled study of two neutralizing , fully human monoclonal antibodies against C. difficile toxins A ( CDA1 ) and B ( CDB1 ) . The antibodies were administered together as a single infusion , each at a dose of 10 mg per kilogram of body weight , in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin .  The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo . RESULTS Among the 200 patients who were enrolled ( 101 in the antibody group and 99 in the placebo group ) , the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies ( 7 % vs. 25 % ; 95 % confidence interval , 7 to 29 ; P<0.001 ) . The recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8 % for the antibody group and 32 % for the placebo group ( P=0.06 ) ; among patients with more than one previous episode of C. difficile infection , recurrence rates were 7 % and 38 % , respectively ( P=0.006 ) . The mean duration of the initial hospitalization for in patients did not differ significantly between the antibody and placebo groups ( 9.5 and 9.4 days , respectively ) . At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group ( P=0.09 ) . CONCLUSIONS The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection . ( Clinical Trials.gov number , NCT00350298 . OBJECTIVE toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis . This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course . DESIGN prospect i ve cohort study . SETTING university teaching hospital . SUBJECTS all patients with symptomatic C. difficile infection during 4 months of an outbreak ( January-April 1995 ) ; n=73 ; median age 74 years ( range 17 - 91 ) . MEASUREMENTS incidence of C. difficile-associated disease ( CDAD ) ; severity of disease ; percentage of patients in each category of severity ; risk factors for severe disease/prolonged symptoms ( univariate and multivariable analyses ) . RESULTS the incidence of CDAD was 0.93 % . Of the cases identified , 18 ( 24.7 % ) had mild , self-limiting disease ; 26 ( 35.6 % ) had moderately severe disease ; 23 ( 31.5 % ) had prolonged symptoms and six ( 8.2 % ) had a complicated course . Although CDAD was more common in older patients ( P < 0.001 ) , increasing age was not a risk factor for severity . Significant risk factors for severe CDAD included low Barthel and abbreviated mental test scores ( P < 0.01 , P < 0.001 respectively ) and recent endoscopy ( P=0.03 ) . Logistic regression analysis revealed the following independent predictors of severe CDAD : endoscopy [ odds ratios ( OR ) 4.0 , P=0.03 ] and cognitive impairment ( OR 11.0 , P < 0.01 ) . A trend towards significance was noted for nasogastric tube insertion ( OR 3.1 , P=0.08 ) . Complications of infection included dehydration , malnutrition and faecal incontinence ( which was statistically significantly associated with more severe disease ; P < 0.01 ) . CONCLUSION risk factors for severity of CDAD include functional disability , cognitive impairment , and recent endoscopy . Anticipation of severe CDAD may limit morbidity and mortality BACKGROUND Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality . Patients generally have a response to oral vancomycin or metronidazole ; however , the rate of recurrence is high . This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection . METHODS Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry . We r and omly assigned patients to receive fidaxomicin ( 200 mg twice daily ) or vancomycin ( 125 mg four times daily ) orally for 10 days . The primary end point was clinical cure ( resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy ) . The secondary end points were recurrence of C. difficile infection ( diarrhea and a positive result on a stool toxin test within 4 weeks after treatment ) and global cure ( i.e. , cure with no recurrence ) . RESULTS A total of 629 patients were enrolled , of whom 548 ( 87.1 % ) could be evaluated for the per- protocol analysis . The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis ( 88.2 % with fidaxomicin and 85.8 % with vancomycin ) and the per- protocol analysis ( 92.1 % and 89.8 % , respectively ) . Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection , in both the modified intention-to-treat analysis ( 15.4 % vs. 25.3 % , P=0.005 ) and the per- protocol analysis ( 13.3 % vs. 24.0 % , P=0.004 ) . The lower rate of recurrence was seen in patients with non – North American Pulsed Field type 1 strains . The adverse-event profile was similar for the two therapies . CONCLUSIONS The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin . Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non – North American Pulsed Field type 1 strains . ( Funded by Optimer Pharmaceuticals ; Clinical Trials.gov number , NCT00314951 . BACKGROUND Neutrophil recruitment coordinated by intestinal interleukin (IL)-8 secretion is a key component in the pathogenesis of Clostridium difficile infection ( CDI ) . We hypothesized that a common single-nucleotide polymorphism ( SNP ) in the -251 region of the IL-8 gene promoter may be predictive of recurrent CDI . METHODS This was a prospect i ve cohort study of hospitalized adult patients with CDI who were admitted to a large , university-affiliated medical center from 2007 through 2008 . Patients were monitored for 3 months after diagnosis of CDI and assessed for recurrent CDI ( defined as a return of diarrhea that required treatment after initial symptom resolution ) . DNA was isolated from blood sample s , and genetic sequencing was performed using polymerase chain reaction and pyrosequencing . The association between IL-8 genotype and recurrent CDI was assessed using univariate and multivariate statistics . RESULTS Ninety-six patients with a mean ( ± st and ard deviation ) age of 61 ± 16 years ( 54 % of whom were female and 63 % of whom were white ) were identified .  The overall incidence of recurrent CDI was 24 % . IL-8 allele frequency was similar to previously reported findings ( for A/A , 27 % ; for A/T , 53 % ; and for T/T , 20 % ) . The incidence of recurrent CDI was 38 % in patients with the A/A allele and 19 % in all other patients ( relative risk , 2.1 ; 95 % confidence interval , 1.04 - 4.13 ) ( P = .043 ) . CONCLUSIONS This study indicates that a common SNP in the IL-8 gene promoter is an independent predictor of recurrent CDI . Our results could offer risk stratification for patients at high risk for recurrent CDI BACKGROUND Most Clostridium difficile infection ( CDI ) surveillance programs neither specify the diagnostic method to be used nor stratify rates accordingly . We assessed the difference in  healthcare-associated CDI ( HA-CDI ) incidence and complication rates obtained by 2 vali date d diagnostic methods . METHODS This was a prospect i ve cohort study of patients for whom a C. difficile test was ordered between 1 August 2010 and 31 July 2011 . All specimens were tested in parallel by a commercial polymerase chain reaction ( 
    Output:
    