Probiotics and prevention of Clostridium difficile infection.

The role of probiotics as adjunctive measures in the prevention of Clostridium difficile infection (CDI) has been controversial. However, a growing body of evidence has suggested that they have a role in primary prevention of CDI. Elements of this controversy are reviewed and the proposed mechanisms of action, the value and cost effectiveness of probiotics are addressed with a focus on three agents, Saccharomyces boulardii, Lactobacillus rhamnosus GG and the combination of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, Lactobacillus rhamnosus CLR2 (Bio-K+).

Dietetics students' perceptions and experiences of interprofessional education.

BACKGROUND: Interprofessional education (IPE) is a process through which students are provided with learning opportunities with other professions aiming to improve client care. The need to include effective IPE in preregistration programmes for health professionals is increasingly being recognised. The overall aim of the present study was to explore the perceptions and experiences of final-year dietetics students of IPE delivered through interactive online learning groups. METHODS: A questionnaire was developed to evaluate the students' satisfaction with the IPE modules, including importance to their clinical placements, and their understanding of the roles of other professions. Six dietetics students took part in a focus group that addressed the impact of participating in the IPE modules. The focus group discussion was recorded, transcribed and subjected to content analysis. RESULTS: Twenty students completed the questionnaire (77% of the cohort). Satisfaction with the IPE modules increased as the programme progressed, with 65%, 90% and 95% of the respondents, respectively, being satisfied with the content, assessment and access of the final module. Participating in the programme enhanced the students' opinions on the value of the roles of other professionals (80%) and enhanced their awareness of interprofessional issues (75%). Four key areas of interest emerged from the focus group analysis: key impressions; understanding the role of the dietitian and other professionals; the advantages and disadvantages of online delivery; and interprofessional working in the work environment. CONCLUSIONS: The most important outcome of participating in IPE was that students' knowledge of other professions was enhanced, which had a positive impact on placements. An effective information technology infrastructure and appropriate scenarios are key requirements for the online delivery of IPE.

Primary prevention of Clostridium difficile infections with a specific probiotic combining Lactobacillus acidophilus, L. casei, and L. rhamnosus strains: assessing the evidence.

Clostridium difficile infection (CDI) has become the leading healthcare-associated infection and cause of outbreaks around the world. Although various innovative treatments have been developed, preventive strategies using multi-faceted infection control programmes have not been successful in reducing CDI rates. The major risk factor for CDI is the disruption of the normally protective gastrointestinal microbiota, typically by antibiotic use. Supplementation with specific probiotics has been effective in preventing various negative outcomes, including antibiotic-associated diarrhoea and CDI. However, a consensus of which probiotic strains might prevent CDI has not been reached and meta-analyses report high degrees of heterogeneity when studies of different probiotic products are pooled together. We searched the literature for probiotics with sufficient evidence to assess clinical efficacy for the prevention of CDI and focused on one specific probiotic formulation comprised of three lactobacilli strains (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, Lactobacillus rhamnosus CLR2, Bio-K+) for its ability to prevent CDI in healthcare settings. A literature search on this probiotic formulation was conducted using electronic databases (PubMed, Google Scholar), abstracts from infectious disease and infection control meetings, and communications from the probiotic company. Supporting evidence was found for its mechanisms of action against CDI and that it has an excellent safety and tolerability profile. Evidence from randomized controlled trials and facility-level interventions that administer Bio-K+ show reduced incidence rates of CDI. This probiotic formulation may have a role in primary prevention of healthcare-associated CDI when administered to patients who receive antibiotics.

Is there a role for modified probiotics as beneficial microbes: a systematic review of the literature.

Our objective was to conduct a systematic review and meta-analysis for the use of modified (heat-killed or sonicated) probiotics for the efficacy and safety to prevent and treat various diseases. Recent clinical research has focused on living strains of probiotics, but use in high-risk patients and potential adverse reactions including bacteremia has focused interest on alternatives to the use of live probiotics. We searched MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Alt Health Watch, Web of Science, Scopus, PubMed, from inception to February 14, 2017 for randomised controlled trials involving modified probiotic strains. The primary outcome was efficacy to prevent or treat disease and the secondary outcome was incidence of adverse events. A total of 40 trials were included (n=3,913): 14 trials (15 arms with modified probiotics and 20 control arms) for the prevention of diseases and 26 trials (29 arms with modified probiotics and 32 control arms) for treatment of various diseases. Modified microbes were compared to either placebo (44%), or the same living probiotic strain (39%) or to only standard therapies (17%). Modified microbes were not significantly more or less effective than the living probiotic in 86% of the preventive trials and 69% of the treatment trials. Modified probiotic strains were significantly more effective in 15% of the treatment trials. Incidence rates of adverse events were similar for modified and living probiotics and other control groups, but many trials did not collect adequate safety data. Although several types of modified probiotics showed significant efficacy over living strains of probiotics, firm conclusions could not be reached due to the limited number of trials using the same type of modified microbe (strain, daily dose and duration) for a specific disease indication. Further research may illuminate other strains of modified probiotics that may have potential as clinical biotherapeutics.

Cholera in Louisiana. Widening spectrum of seafood vehicles.

The largest cholera outbreak in the United States in over a century occurred in Louisiana from August through October 1986. Eighteen persons in 12 family clusters had stool culture or serologic evidence of infection with toxigenic Vibrio cholerae 0-group 1. Thirteen of these persons had severe diarrhea, and 4 required intensive care unit treatment. Although all 18 survived, 1 96-year-old woman with suspected cholera died shortly after hospital admission. A case-control study showed that case-patients were more likely than neighborhood control subjects to have eaten cooked crabs or cooked or raw shrimp during the week before illness. Case-patients who ate crabs were more likely than control subjects who ate crabs to have undercooked and mishandled the crabs after cooking. A third vehicle from the Gulf waters, raw oysters, caused V cholerae 01 infection in two persons residing in Florida and Georgia. All three seafood vehicles came from multiple sources. Stool isolates from the Louisiana case-patients were genetically identical to other North American strains isolated since 1973, but differ from African and Asian isolates. While crabs are the most important vehicle for V cholerae 01 infection in the United States, shrimp and oysters from the Gulf coast can also be vehicles of transmission. A persisting reservoir of V cholerae 01 along the Gulf coast may continue to cause sporadic cases and outbreaks of cholera in Gulf states and in states importing Gulf seafood.

Deciphering meta-analytic results: a mini-review of probiotics for the prevention of paediatric antibiotic-associated diarrhoea and Clostridium difficile infections.

Meta-analyses are used to evaluate pooled effects of a wide variety of investigational agents, but the interpretation of the results into clinical practices may be difficult. This mini-review offers a three-step process to enable healthcare providers to decipher pooled meta-analysis estimates into results that are useful for therapeutic decisions. As an example of how meta-analyses should be interpreted, a recent meta-analysis of probiotics for the prevention of paediatric antibiotic-associated diarrhoea (AAD) and the prevention of Clostridium difficile infections (CDI) will be used. First, the pooled results of this meta-analysis indicates a significant protective efficacy for AAD is found when the 16 different types of probiotics are combined (pooled relative risk (RR) = 0.43, 95% confidence interval (CI)=0.33-0.56) and also a significant reduction of paediatric CDI (pooled RR=0.34, 95%CI=0.16-0.74) was found pooling four different types of probiotics. Secondly, because the efficacy of probiotics is strain-specific, it is necessary to do a sensitivity analysis, restricting the meta-analysis to one specific strain. Two strains, Saccharomyces boulardii lyo and Lactobacillus rhamnosus GG showed significant efficacy for paediatric AAD when pooled (pooled RR for S. boulardii = 0.43, 95%CI=0.21-0.86 and pooled RR for L. rhamnosus GG = 0.44, 95%CI=0.20-0.95). Thirdly, if studies within probiotic types have different results, it is prudent to examine these studies individually to determine the reasons why non-significant differences in efficacy were found. By drilling down through these three analytic layers, physicians will be confident in recommending the correct probiotic strain to their patients.

Weight loss intention, dietary behaviors, and barriers to dietary change in veterans with lower extremity amputations.

BACKGROUND: Obesity is thought to be highly prevalent in persons with lower extremity amputations (LEAs) and can impair physical and social functioning. OBJECTIVE: The aim of this study was to determine the prevalence of weight loss intention, weight loss strategies, dietary patterns, and barriers to making dietary changes, and their associations with body mass index (BMI, kg/m(2)), amputation characteristics, health status, and socioeconomic factors. METHODS: We conducted a cross-sectional study (n = 150) using data from a self-administered questionnaire. RESULTS: 43% of participants were obese and 48% were trying to lose weight; 83% of those trying to lose weight reported trying to "eat differently", but only 7% were following a comprehensive weight loss program involving dietary changes, physical activity, and behavioral counseling. 21% of participants reported ≥ 6 barriers to changing their eating habits (e.g., habit, too little money, stress/depression). Obesity was associated with younger age, lower physical health scores, hypertension, arthritis, and diabetes. Compared to those not trying to lose weight, a greater proportion of those trying to lose weight had a BMI ≥ 35 kg/m(2), age <55 years, higher physical and mental health scores, and more frequent consumption of vegetables, beans, chicken, and fish. CONCLUSIONS: Though over half of overweight and obese individuals with LEA were trying to lose weight, few reported following a comprehensive program to lose weight, which may indicate an unmet need for services for this group. To be effective, these programs will need to address the complex physical and mental health challenges that many of these individuals face.

Measurement of in vivo microsomal epoxide hydrolase activity in white subjects.

An impairment or hereditary defect in microsomal epoxide hydrolase is considered a possible risk factor for drug and chemical toxicity. However, nothing is known about variability of in vivo epoxide hydrolase activity in humans. Our objectives were to develop and test a simple pharmacokinetic approach for measuring microsomal epoxide hydrolase activity in a population. After administration of carbamazepine-10,11-epoxide (100 mg), oral clearance showed a nearly linear relationship to the log (transdihydrodiol/epoxide) urine ratio in the 24- to 36-hour interval (log metabolic ratio). Intrasubject variability was assessed by administering the epoxide twice to 13 subjects (1- to 4-month interval); the log metabolic ratio did not change significantly (mean difference, 11%; paired t test, p = 0.79). In 110 healthy white adults, the log metabolic ratio ranged from 1.28 to 2.05 (mean +/- SD, 1.68 +/- 0.155). Outliers indicating enzyme-deficient phenotypes were not observed, and the frequency distribution was unimodal normal. The log metabolic ratio detected pronounced inhibition of epoxide hydrolase by valpromide (six subjects; median ratio, 0.91) and induction by phenobarbital/phenytoin (six subjects; median ratio, 2.42). We conclude that distribution of microsomal epoxide hydrolase activity in a study group can be measured pharmacokinetically by use of carbamazepine epoxide.

Increased CSF F2-isoprostane concentration in probable AD.

OBJECTIVE: To quantify F2-isoprostane levels in CSF obtained from the lumbar cistern of patients with AD, ALS, and controls. BACKGROUND: Studies of human postmortem tissue and experimental models have suggested a role for oxidative damage in the pathogenesis of several neurodegenerative diseases, especially AD and ALS. F2-isoprostanes are exclusive products of free-radical-mediated peroxidation of arachidonic acid that have been widely used as quantitative biomarkers of lipid peroxidation in vivo in humans. Recently, we showed that F2-isoprostane concentrations are significantly elevated in CSF obtained postmortem from the lateral ventricles of patients with definite AD compared with controls. METHODS: F2-isoprostanes were quantified by gas chromatography/negative ion chemical ionization mass spectrometry. RESULTS: CSF F2-isoprostanes were increased significantly in patients with probable AD, but not in ALS patients, compared with controls. CONCLUSIONS: Increased CSF F2-isoprostanes are not an inevitable consequence of neurodegeneration and suggest that increased brain oxidative damage may occur early in the course of AD.

Gastroenteritis in patients with stool isolates of Vibrio vulnificus.

Vibrio vulnificus, a marine Vibrio associated with severe extraintestinal infections, has not been previously implicated as a cause of infectious diarrhea. Three patients were identified with diarrheal illness from whom this organism was the sole pathogen recovered from cultured stool specimens. All three had eaten raw oysters within one week of becoming ill. These patients were all taking medication that reduces gastric acidity, two were heavy drinkers of alcohol, and one had unrecognized colon cancer; these factors may have predisposed to the development of disease. Clinicians should consider that V. vulnificus may be a cause of gastroenteritis in patients who have consumed raw oysters.

Behaviour of Saccharomyces boulardii in recurrent Clostridium difficile disease patients.

BACKGROUND: Despite recent interest in therapeutic microorganisms taken orally, little is known about the pharmacodynamics of these agents in a target population of patients with disease. The present study reports the stool concentrations of Saccharomyces boulardii in a patient population with Clostridium difficile disease (CDD) and correlates stool concentrations with efficacy. METHODS: Patients with recurrent CDD all received a 10-day standard antibiotic regimen together with 28 days of S. boulardii or placebo. Stool samples were collected from patients at various time points and assayed for S. boulardii. RESULTS: The mean concentration of S. boulardii of patients who recurred was 2.5 x 104 CFU/g compared to 1 x 106 CFU/g in patients that did not recur (P=0.02). Patients with low yeast concentrations in their stools (<104/g) recurred more often (14/15, 93%) compared with patients with higher levels (19/35, 54%, P=0.007). Clearance of S. boulardii was rapid; only 4% had positive stools 3 days after stopping dosing. CONCLUSIONS: After chronic dosing of S. boulardii, patients with low stool concentrations had a higher likelihood of recurrence of CDD. Stool concentrations were also lower during periods of diarrhoea. These results show the importance of characterizing the dynamics of a therapeutic microorganism in patients with disease, as kinetic studies in healthy volunteers may not give a true reflection of the disturbed microecology in the disease state.

Recurrent Clostridium difficile disease: epidemiology and clinical characteristics.

OBJECTIVE: To describe the epidemiology, diagnosis, risk factors, patient impact, and treatment strategies for recurrent Clostridium difficile-associated disease (CDAD). DESIGN: Data were collected as part of a blinded, placebo-controlled clinical trial testing a new combination treatment for recurrent CDAD. Retrospective data regarding prior CDAD episodes were collected from interviews and medical-chart review. Prospective data on the current CDAD episode, risk factors, and recurrence rates were collected during a 2-month follow-up. SETTINGS: National referral study. PARTICIPANTS: Patients with recurrent CDAD. INTERVENTIONS: Treatment with a 10-day course of low-dose (500 mg/d) or high-dose (2 g/d) vancomycin or metronidazole (1 g/d). RESULTS: Recurrent CDAD was found to have a lengthy course involving multiple episodes of diarrhea, abdominal cramping, nausea, and fever. CDAD may recur over several years despite frequent treatment with antibiotics. Recurrence rates were similar regardless of the choice or dose of antibiotic. Recurrent CDAD is not a trivial disease: patients may have multiple episodes (as many as 14), may require hospitalization, and the mean lifetime cost of direct medical care was $10,970 per patient. Fortunately, the disease does not become progressively more severe as the number of episodes increase. Two risk factors predictive for recurrent CDAD were found: increasing age and a decreased quality-of-life score at enrollment. CONCLUSIONS: Recurrent CDAD is a persistent disease that may result in prolonged hospital stays, additional medical costs, and rare serious complications.

Epidemiology of infectious and iatrogenic nosocomial diarrhea in a cohort of general medicine patients.

BACKGROUND: Nosocomial diarrhea is a common problem in hospitals, but the epidemiology, causes, and consequences of infectious and iatrogenic nosocomial diarrhea are rarely documented in follow-up or surveillance studies of nosocomial infections. The objective of this study was to describe the epidemiology of nosocomial diarrhea in a cohort study of hospitalized patients. METHODS: The setting was a general medicine ward with a total of 30 beds in private or semiprivate rooms in a county hospital. A prospective cohort study of all consenting patients in the study ward was performed during an 11-month period. Patients were interviewed and cultures were obtained to check for stool pathogens within 48 hours of admission, and patients were followed up during their stay in the study ward. Data from medical notes, laboratory tests, antibiotic logs, and patient interviews were collected daily. RESULTS: Among the 382 eligible patients, nosocomial diarrhea developed in 126 (32.9%): 37 cases were of infectious origin, 57 were iatrogenic, and 32 were of unknown origin. The most common causes of nosocomial diarrhea were Clostridium difficile and antibiotic therapy. Multivariate analysis revealed four risk factors for infectious nosocomial diarrhea: age, length of stay, number of antibiotics, and nasogastric tube feedings. Multivariate analysis also revealed four risk factors for iatrogenic nosocomial diarrhea: number of antibiotics, current gastrointestinal conditions, current renal conditions, and recent surgery. Comorbidity associated with nosocomial diarrhea included increased risk of acquiring another type of nosocomial infection, increased risk of death, and increased length of stay. CONCLUSIONS: Nosocomial diarrhea was found to be common and associated with an additional burden of comorbidity. Analyses indicated different risk factors, depending on the etiology of nosocomial diarrhea (infectious or iatrogenic). Further studies are recommended to document the epidemiology and cost analysis of nosocomial diarrhea in other hospital populations.

Review of Clostridium difficile-associated diseases.

Clostridium difficile has recently become recognized as an important nosocomial pathogen. This review summarizes what is known about the isolation of the organism, the spectrum of clinical disease, virulence factors, treatments, and methods of prevention. Risk factors for C. difficile disease are also discussed. The most important risk factor is the use of certain antibiotics (ampicillin, cephalosporins, and clindamycin). C. difficile is associated with 96% to 100% of cases of pseudomembraneous colitis, 60% to 75% of antibiotic-associated cases of colitis, and 11% to 33% of antibiotic-associated cases of diarrhea. Other risk factors include gastrointestinal manipulations, advanced age, female sex, inflammatory bowel disease, cancer chemotherapy, and renal disorders. Hospital outbreaks of C. difficile disease are examined. Data from nosocomial outbreaks support transmission of C. difficile by contaminated fomites and hand carriage by hospital personnel.

Erb/Duchenne's palsy: a consequence of fetal macrosomia and method of delivery.

Methods of delivery, maternal and neonatal characteristics were examined to determine their role in the occurrence of Erb/Duchenne's palsy. Data from 210,947 Washington state birth certificates from 1980 through 1982 were examined. The incidence was 50.2 cases of Erb's palsy per 100,000 live births. A case control study design was used to analyze 106 cases and 386 controls by both univariable and multivariable analysis. Birth weight was shown to be a significant risk factor regardless of which method of delivery was used. A high birth weight infant (4001-4500 g) had 2.5 times the risk of incurring an upper brachial plexus injury compared with normal size infants (2501-4000 g). The risk for infants greater than 4500 g increased another tenfold (OR = 21.0). When birth weight was controlled for in the analysis, midforceps (OR = 18.3), vacuum extraction (OR = 17.2), and low forceps (OR = 3.7) remained significantly associated with the Erb's palsy. Delivery by cesarean section was associated with a significant protective effect (OR = 0.5) compared with instrumental vaginal delivery. These data demonstrate a high risk for serious birth injury associated with instrumental midpelvic delivery.

Clinical and laboratory features of an outbreak of Vibrio cholerae O1 infections in the United States.

A point source outbreak of Vibrio cholerae O1 El Tor Inaba infections occurred aboard an oil rig south of Port Arthur, Texas, in September 1981. Sixteen crew members had V. cholerae O1 infections as determined by serology or stool specimens; 15 were symptomatic. The high percentage of symptomatic infections was attributed in part to the ingestion of a large number of V. cholerae O1 organisms by susceptible individuals. Symptoms included diarrheal stools (100%), weakness (60%), abdominal cramps (53%), nausea (40%), and vomiting (27%). Only one of the three patients who sought medical attention was diagnosed by his physician as having cholera. Physicians who treat patients who live near or travel to the Gulf Coast should consider cholera in patients with watery stools. If cholera is suspected, laboratories should use thiosulfate-citrate-bile salts-sucrose (TCBS) agar in addition to routine enteric media for processing stool specimens.

Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting.

OBJECTIVE: The goal of this study was to determine the prevalence of Clostridium difficile diarrhea (CDD) and the risk for CDD associated with different oral antibiotics commonly used in the ambulatory care setting. METHODS: The prevalence of CDD was determined for enrollees in 4 UnitedHealth Group-affiliated health plans between January 1, 1992, and December 31, 1994. Cases were identified based on the presence of an inpatient or outpatient claim with a primary diagnosis of diarrhea, a pharmacy claim for a prescription drug used to treat CDD, or a physician or facility claim for the C. difficile toxin test, and were confirmed using full-text medical records. Within a retrospective cohort design, periods of risk for CDD were defined on the basis of duration of antibiotic therapy. To control for potential selection bias created by heterogeneous rates of C. difficile testing and to limit confounding due to multiple antibiotic exposures, we used a nested case-control design, restricting eligibility to subjects who underwent screening for C. difficile and who had been exposed to only 1 antibiotic risk period with a single antibiotic. RESULTS: The global prevalence of CDD in 358,389 ambulatory care enrollees was 12 per 100,000 person-years. In the nested case-control study, after controlling for other risk factors, 2 antibiotics demonstrated an increased association with CDD: cephalexin (odds ratio [OR] = 7.5, 95% CI = 1.8 to 34.7) and cefixime (OR = 6.4, 95% CI = 1.2 to 39.0). CONCLUSIONS: Although CDD is thought to occur primarily in hospitalized patients, it was found to be present in an ambulatory care population, but at a low frequency. In this population, it appeared to be associated with 2 cephalosporins but not with other types of antibiotics usually linked with nosocomial CDD. Because the frequency of C. difficile testing was shown to be more common with high-risk antibiotics, CDD may be underdiagnosed in the ambulatory care setting.

Evaluation of an intervention program in the control of an urban outbreak of shigellosis.

Community-wide outbreaks of shigellosis are a persistent public health problem. We evaluated the effect of a household-based intervention program on the control of an urban outbreak of S. sonnei gastroenteritis. During the intervention we attempted to contact all households with culture-confirmed S. sonnei and provide education in methods to prevent spread of Shigella. Subsequently we conducted a survey of intervention (n = 43) and nonintervention (n = 33) households. We also conducted a serosurvey of children three to five years of age. The number of new cases of S. sonnei infection declined steadily over several months after the intervention began. Members of the intervention households were more knowledgeable about handwashing (rate ratio [RR] 4.7, 95% confidence interval [CI] = 2.1-10.8) and others methods of S. sonnei transmission and control than members of nonintervention households. However, intervention households had higher attack rates of Shigella-associated diarrhea in susceptible household members (RR 1.4, 95% CI = 1.0-2.0). During the intervention we were able to contact only 25% of households by the eighth day after onset of diarrhea in the index case, when 90% of intrahousehold transmission of Shigella had already occurred. Two months after the outbreak ended, 42% of children in the outbreak community had elevated antibody titers against S. sonnei; an additional 19% had borderline elevated titers. The intervention program improved knowledge but may have occurred too late to prevent intrahousehold transmission of Shigella. Exhaustion of susceptible hosts, rather than the education program, likely accounted for the decline in shigellosis cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial microbes: health or hazard?

Normal microbial flora support the health of the host by diverse mechanisms. When antibiotics, stress, disease or medications disrupt normal microflora, the ability to ward off infection by pathogens is compromised. The use of beneficial microbes (also known as biotherapeutic agents, probiotics, synbiotics) has been shown to be an effective therapeutic agent for some diseases. Various types of diarrhoea (antibiotic-associated diarrhoea, Clostridium difficile disease, traveller's diarrhoea) are most responsive to these beneficial microbes. Serious risks associated with these microbes are largely theoretical at this point, but the risks need to be studied as the use of these beneficial microbes increases in popularity. Beneficial microbes are living organisms used as therapeutic agents to restore the health of the host in times when normal microflora have been disturbed. The efficacy to prevent or treat diarrhoea has been documented in multiple large, placebo-controlled, blinded clinical trials with only a few of these beneficial microbes. Risks of these beneficial microbes are limited, but potential risks have not been extensively studied in large numbers of patients.

Cerebrospinal fluid abeta42, tau, and f2-isoprostane concentrations in patients with Alzheimer disease, other dementias, and in age-matched controls.

OBJECTIVE: To test the hypothesis that quantification of cerebrospinal fluid (CSF) F(2)-isoprostanes (F(2)-IsoPs), in vivo biomarkers of free radical damage, along with CSF Abeta(42) and tau levels improves laboratory diagnostic accuracy for Alzheimer disease (AD). PARTICIPANTS: Patients with probable AD (n = 19), dementias other than AD (n = 8), and age-matched controls (n = 10). MAIN OUTCOME MEASURES: Cerebrospinal fluid concentrations of Abeta(42) and tau were determined by a commercially available test (Athena Diagnostics, Worcester, Mass). Cerebrospinal fluid F(2)-IsoP levels were quantified by gas chromatography/mass spectrometry. RESULTS: Individuals were classified as AD or non-AD by a published method using CSF Abeta(42) and tau levels (95% sensitivity, 50% specificity), by CSF F(2)-IsoP levels greater than 25 pg/mL and Abeta(42) concentrations less than 1125 pg/mL (90% sensitivity, 83% specificity), and by combined analysis using CSF F(2)-IsoP, Abeta(42), and tau levels (84% sensitivity, 89% specificity). CONCLUSION: Cerebrospinal fluid F(2)-IsoP quantification may enhance the accuracy of the laboratory diagnosis of AD.