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.

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+).

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.

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.

Current practice of venous thromboembolism prevention in acute trusts: a qualitative study.

OBJECTIVE: To explore the current practice of venous thromboembolism (VTE) prevention in acute trusts. DESIGN: A qualitative research design was used to explore the perceived current practice of thromboprophylaxis, and knowledge and experience of VTE prevention. Data were collected via interviews with personnel from acute trusts and other relevant organisations and charities. Constant comparison was used to generate themes grounded in the data. SETTING: The UK. PARTICIPANTS: 17 participants, sampled due to their expertise and knowledge in the field of VTE, were interviewed for the study. RESULTS: No one felt directly responsible for VTE risk assessment and treatment in acute trusts. There were concerns whether any action takes place based on the risk assessment. Low levels of VTE knowledge existed throughout the system. CONCLUSIONS: Our study highlights the importance of continuous training to prevent VTE risk assessment being considered a tick box exercise and for clinicians to understand the significance of the procedure to ensure that VTE preventative measures are administered. It is essential that acute trust staff acknowledge that VTE prevention is the responsibility of everyone involved in a patient's care. Concerns remain around prophylaxis treatment, administration and contraindications.

Making the transition from physiotherapy student to interprofessional team member.

OBJECTIVES: To explore final-year physiotherapy students' perceptions and experiences of interprofessional learning in the university and placement setting. STUDY DESIGN: Focus group and mixed qualitative and quantitative questionnaire. SETTING: Coventry University. PARTICIPANTS: Third-year physiotherapy students at Coventry University. METHODS: The final-year physiotherapy cohort was invited to complete a questionnaire containing a mix of closed- and open-ended questions. Eight volunteers from the same cohort took part in a focus group. RESULTS: The questionnaire achieved a response rate of 97% (97/100), and the focus group transcript revealed several themes. The majority of students identified an impact of interprofessional learning on their awareness and understanding of professional roles (74%, 72/97) and issues (71%, 69/97). The students also valued the role of other professionals (63%, 61/97), and recognised the support they could offer (60%, 58/97). These findings were reinforced and developed with respect to interprofessional working in the focus group discussion. Students were aware of increased personal and professional confidence which supported their developing identity as physiotherapists. They also recognised an ability to seek out ways to improve working relationships and to refer patients on to the most appropriate professional. Many students recognised the significance of clinical placements in their interprofessional learning (69%, 67/97), and identified that face-to-face interaction facilitated the social aspect of team working. CONCLUSIONS: Interprofessional learning is effective in improving student physiotherapists' awareness of roles, issues and ability to develop collaborative working relationships, thus potentially leading to improved patient care.

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.

A genome-wide scan in an Amish pedigree with parkinsonism.

The identification of familial Parkinson Disease (PD) genes is yielding important molecular pathogenetic insights. In an effort to identify additional PD genes, we studied an eight generation Amish pedigree with apparent autosomal dominant parkinsonism with incomplete penetrance. Phenotypic variability ranged from idiopathic PD to progressive supranuclear palsy (PSP), with the average age at onset 53 years (range of 39 to 74 years). We identified markers on chromosome 3 and 7 that were significant at a genome-wide level by parametric and nonparametric criteria, lod > 3 and non-parametric P-value < 0.10, respectively. We also identified markers on chromosomes 10 and 22 with lod > 3. These data suggest that parkinsonism in this pedigree is genetically complex, with contributions from several loci.

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE varepsilon4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (alpha-catenin gene). There was a modest (P=0.20) increase in the LOD score for D12S368 (MLOD=1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P<0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n=228) when using alpha-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or alpha-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

A gastropod scavenger serving as paratenic host for larval helminth communities in shore crabs.

The whelk Cominella glandiformis is an important predator-scavenger of New Zealand intertidal ecosystems; a few whelks can quickly eat all the soft tissues of recently dead crabs. In this study, we demonstrate that whelks can also ingest and act as paratenic hosts for at least 4 helminth species that use crabs as intermediate hosts: metacercariae of the trematode Maritrema sp. and of another unidentified trematode, larval acuariid nematodes, and cystacanths of the acanthocephalans Profilicollis spp. Large whelks ingest disproportionately more helminth larvae than small whelks, but the survival of parasites during their short stay in the whelks is not affected by whelk size. The majority of metacercariae and nematodes are passed out in whelk feces within 3 days of ingestion, whereas the few cystacanths found did not leave whelks until after that time; no parasite was left in whelks 5 days postingestion. Survival of all 4 helminth species was generally very high, though it decreased day by day in 2 species. Given that the avian definitive hosts of all 4 helminths also eat whelks, our results indicate that alternative transmission pathways exist and that parasites can take routes through food webs that are too often ignored.

From first to second and back to first intermediate host: the unusual transmission route of Curtuteria australis (Digenea: Echinostomatidae).

The trematode Curtuteria australis uses the whelk Cominella glandiformis as first intermediate host and the cockle Austrovenus stutchburyi as second intermediate host before maturing in shorebirds. The whelk also happen to be an important predator of cockles on intertidal mudflats. In this study we show that whelks can act as temporary paratenic hosts for the trematode. A single whelk feeding on 1 cockle can ingest large numbers of metacercariae, which remain within the whelk for 1-3 days before passing out in feces. The viability of these metacercariae assessed as the percentage capable of successfully excysting under conditions simulating those inside a bird's digestive tract, is lower after passage through a whelk (48%) than before (59%). Still, given that shorebird definitive hosts prey on whelks as well as cockles, survival inside the whelk allows C. australis to complete its life cycle: overall, though, whelk predation is likely to be an important sink for the trematode population. To our knowledge, this is the first report of a trematode using a snail as both first intermediate host and paratenic host, offering an alternative transmission route for the parasite as a result of the unusual trophic relationships of its hosts.

Biotherapeutic agents in the treatment of infectious diarrhea.

Biotherapeutic agents offer unique advantages over traditional treatments for infectious diarrhea, and several have been shown to be effective (Table 4). These therapeutic microbial agents are most effective in types of infectious diseases that are associated with a disruption of the normal intestinal microecology (e.g., AAD, C. difficile disease). The impact of biotherapeutic agents on rotaviral diarrhea is of special clinical importance because this is the most common cause of pediatric diarrhea, and there is no defined treatment. Strong efforts need to be made to limit antibiotic exposure in children. Biotherapeutic agents offer a safe and effective nonantibiotic method of treating this important pathogen, especially after the withdrawal of a rotaviral vaccine from the market by the FDA. However, for many biotherapeutic agents, well-done, placebo-controlled trials still are lacking, and not all types of infectious diarrhea respond to these agents. Continued research in this innovative therapeutic area is warranted.

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.

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.

The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii.

Recurrent Clostridium difficile disease (CDD) is a difficult clinical problem because antibiotic therapy often does not prevent further recurrences. In a previous study, the biotherapeutic agent Saccharomyces boulardii was used in combination with standard antibiotics and was found to be effective in reducing subsequent recurrences of CDD. In an effort to further refine a standard regimen, we tested patients receiving a regimen of a standard antibiotic for 10 days and then added either S. boulardii (1 g/day for 28 days) or placebo. A significant decrease in recurrences was observed only in patients treated with high-dose vancomycin (2 g/day) and S. boulardii (16.7%), compared with those who received high-dose vancomycin and placebo (50%; P=.05). No serious adverse reactions were observed in these patients. Comparison of data from this trial with data from previous studies indicates that recurrent CDD may respond to a short course of high-dose vancomycin or to longer courses of low-dose vancomycin when either is combined with S. boulardii.

Variance in faking across noncognitive measures.

There are discrepant findings in the literature regarding the effects of applicant faking on the validity of noncognitive measures. One explanation for these mixed results may be the failure of some studies to consider individual differences in faking. This study demonstrates that there is considerable variance across individuals in the extent of faking 3 types of noncognitive measures (i.e., personality test, biodata inventory, and integrity test). Participants completed measures honestly and with instructions to fake. Results indicated some measures were more difficult to fake than others. The authors found that integrity, conscientiousness, and neuroticism were related to faking. In addition, individuals faked fairly consistently across the measures. Implications of these results and a model of faking that includes factors that may influence faking behavior are provided.

Multi-state outbreaks of acute gastroenteritis traced to fecal-contaminated oysters harvested in Louisiana.

Norwalk-like viruses (NLVs), or small round structured viruses, are known to cause acute gastroenteritis associated with eating contaminated shellfish. Between 1993 and 1996, three oyster-related gastroenteritis outbreaks attributed to NLV occurred in Louisiana. Intensive trace-back and environmental investigations revealed that the overboard disposal of sewage by oyster harvesters into oyster-bed waters was the most likely source of contamination in at least two of the outbreaks. The small infectious dose of NLV, the large quantity of virus particles in stool, and the ability of oysters to concentrate virus particles suggest that oyster-related outbreaks will continue unless strong control measures are established. Efforts to halt improper sewage disposal in oyster-harvesting waters, including overboard sewage discharge, must be undertaken if future outbreaks are to be prevented.