Evidence Table & Evidence Summary form RSMITH

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NURS 563 Evidence-Based Practice for Quality and Safety

Gonzaga University, School of Nursing and Human Physiology

Evidence Table and Evidence Summary Assignment

This form has 2 parts: evidence table and evidence summary.

Part I of II. Evidence Table

An evidence table will allow you to easily see the types of studies, levels of evidence, results, and how and where the studies compare. Be concise

and clear in entering data from each study.

Directions: Obtain the full text of each of your highest quality and most relevant 8 keeper studies found through your PICOT and Evidence

Searching Strategy assignment. Use the directions in the key for the Evidence Table to extract information for the evidence table from all quantitative

and qualitative studies. Include page numbers from the study for “Authors’ Major Conclusions” and “Specific Statistical Results for Outcomes of

Interest”. Use the specified Hierarchy of Evidence found in Module 1 to identify the type and level of each study.

For each study in the evidence table, the APA citation and the following components should be provided. For some types of studies, certain elements

in the evidence table will not be applicable (NA).

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Evidence Table (ET) Adapted from Fineout-Overholt et al. (2010). Critical appraisal of the evidence: Part 111. AJN, 110(14), 44.

Your Name: Robert Smith Date: 19 FEB 15

Your PICOT question:

P= Hospitalized patients at risk of developing Clostridium difficile colitis

I= Prophylactic probiotic supplement in addition to hospital-based infectious disease guidelines

C= Hospital-based infectious disease guidelines alone

O= Decreased instances of C. difficile associated diarrhea (CDAD) in at-risk populations

T= Up to eight weeks after antibiotic therapy

Study #1 APA Citation

Allen SJ, Wareham K, Wang D, Bradley C, Sewell B, Hutchings H, et al. A high-dose preparation of lactobacilli and

bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people

admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE).

Health Technology Assessment 2013;17(57).

Study Type (specific

type e.g., cohort, RCT,

specific qualitative

study, and etc.).

A multicenter, randomized, double blind, placebo-controlled, parallel arm trial (Wareham et al., 2013, p. vii).

*Evidence Level (I, II, III, IVA, IVB, VA. VB, VI)

This study is evidence level II, “[E]vidence obtained from at least one well-designed Randomized Controlled Trial (RCT)”

(Melnyk & Fineout-Overholt, 2015, p. 92)

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Sample Size

Wareham et al. screened17420 patients, recruiting 2981 for the study; the authors allocated them “sequentially according to

a computer-generated random allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488 (49.9%) to the

placebo arm” (2013, p. vii).

Setting & Sample Characteristics

The study’s setting was “medical, surgical and elderly care inpatient wards in five NHS hospitals in the UK” (2013, p. vii).

Participants were older than 65, “exposed to one or more oral or parenteral antibiotics and were without pre-existing

diarrhoeal disorders, recent CDD or at risk of probiotic adverse effects (Wareham et al., 2013, p. vii).

Intervention or issue

“Vegetarian capsules containing two strains of lactobacilli and two strains of bifidobacteria (a total of 6 × 1010 organisms

per day) were taken daily for 21 days” (Wareham et al., 2013, p. vii).

Comparison

The authors compared the probiotic intervention to an “inert maltodextrin powder in identical capsules” (Wareham et al.,

2013, p. vii).

Length of Follow-up The authors gathered information regarding treatment and gastrointestinal involvement via telephone interview for eight

weeks post-recruitment, and “participants were encouraged to contact a named member of the research staff to report

potential SAEs at any time during follow-up. Review of laboratory data regarding stool assays was continued until 12

weeks after recruitment (Wareham et al., 2013, p. 8).

Type of statistical measure(s) (RR, OR, %, NNT, etc.) or thematic analysis.

The authors determined the mean duration of hospital stays of the experiment and control (placebo) groups (95% CI),

readmission percentages, duration of readmissions (as a percentage), mean number of healthcare contacts per patient, and

mean number of days in care homes per patient (at a 95% CI).

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“Clostridium difficile diarrhoea was uncommon and occurred in 12 (0.8%) participants in the probiotic arm

and 17 (1.2%) participants in the placebo arm (RR 0.71; 95% CI 0.34 to 1.47; p = 0.35; see Table 10).

Based on this effect size and the low prevalence of CDD, the number needed to treat to prevent one case is

295. This would be reduced to 95 for an effect size at the lower limit of the 95% CI (a threefold reduction

in CDD in the probiotic arm). The corresponding number needed to harm (the upper 95% CI) is 267” (Wareham

et al., 2013, p. 26).

Specific Statistical Results for Outcomes of Interest. Or, the major themes from a qualitative study. Cite pages.

“Antibiotic-associated diarrhoea (including CDD) occurred with a similar frequency in the probiotic arm

(159 participants, 10.8%) and placebo arm (153 participants, 10.4%; RR 1.04; 95% CI 0.84 to 1.28;

p = 0.71; Table 10). This included 12 participants with frequent stools that they described as looser than

normal but who were unable to describe stool consistency using the Bristol Stool Form Scale” (Wareham et al.,

2013, p. 26).

Authors’ Major

Conclusions (cite

pages).

“We did not find adequate evidence to suggest that probiotic administration was effective in preventing AAD.

Although there was a trend towards reduced CDD in the probiotic arm, the administration of this probiotic seems

unlikely to benefit older patients exposed to antibiotics. Alternative probiotic preparations may be effective in

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the prevention of AAD. However, future clinical trials should be guided by a better understanding of the

mechanisms underlying AAD and the strain specific effects of probiotics. Furthermore, a probiotic is less likely

to be effective where other measures have reduced CDD rates” (Wareham et al., 2013, p. xvi).

Funding Source and potential conflicts of interest

“This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health

Technology Assessment; Vol. 17, No. 57” (Wareham et al., 2013, p. xvii).

“The project is organised and carried-out by the research teams in Swansea University and NHS Trust and

County Durham and Darlington Foundation Trust. The NHS Research and Development Health Technology Association

are providing funding” (Wareham et al., 2013, p. 68).

“Declared competing interests of authors: Stephen Allen has undertaken research in probiotics supported

by Cultech Ltd, Baglan, Port Talbot, UK; the Children and Young People’s Research Network, Cardiff

University, Wales; the Knowledge Exploitation Fund, Welsh Development Agency and the National

Ankylosing Spondylitis Society, UK. He has also been an invited guest at the Yakult Probiotic Symposium in

2011 and received research funding from Yakult, UK, in 2010 (Wareham et al., 2013, p. 72).

My comments: Study biases and implications for answering PICOT.

The authors’ study was limited to patients over the age of 65 in the UK. While this comprises most of my PICOT

population, patients at risk of developing C. difficile-associated diarrhea, it does not include the whole of that population

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(immune-compromised patients, pediatrics, etc.). Further, this study’s population and setting were based in the in the UK.

While there are some assumed standards for infection control, one may wonder if their hospital-based protocols are

analogous to their United States counterparts. Before abandoning the question to the authors’ conclusions (that there is no

statistically-significant rationale for adopting probiotic therapy to prevent CDAF) more research is needed.


Goldenberg JZ, Ma SSY, Saxton JD, Martzen MR, Vandvik PO, Thorlund K, Guyatt GH, Johnston BC. Probiotics for the

prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database of Systematic

Reviews 2013, Issue 5. Art. No.: CD006095. DOI: 10.1002/14651858.CD006095.pub3.




study, and etc.).

Systematic Review/Meta-Analysis of 23 randomized controlled trials (Goldenberg et al., 2013, p. 5)


Systematic reviews of randomized controlled pairs represent level I evidence (Melnyk & Fineout-Overholt, 2015, p. 92).

Sample Size

This review includes 31 randomized trials with a total of 4492 participants (Goldenberg et al., 2013, p. 2)


Adults and children exposed to antibiotics in inpatient and outpatient settings (Goldenberg et al., 2013, p. 6)

Intervention or issue.

“The interventions of interest compared probiotics (any strain or dose) versus placebo, alternative prophylaxis, or no

treatment for the prevention of C. difficile-associated diarrhea in adults and children receiving antibiotic therapy

(Goldenberg et al., 2013, p. 6).

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Comparison

Patients receiving placebo, alternative treatments, or no treatment specifically preventing C. difficile-associated diarrhea in

adults and children receiving antibiotic therapy (Goldenberg et al., 2013, p. 6).

Length of Follow-up Follow-up varied by study, with times ranging from nine days to three months post treatment. In one study, there was no

stated follow-up (Goldenberg et al., 2013, p. 61).


Goldenberg et al. measured risk ratios to a 95% confidence interval for incidents of CDAD, associated adverse events, and

incidence of Clostridium difficile infection. They measured the mean difference of hospital stays to a 95% confidence

interval (Goldenberg et al., 2013, p. 100-103).

“Using a random-effects model, dichotomous data were presented as a relative risk (RR) along with corresponding

95% confidence intervals (95% CI). The number needed to treat for an additional beneficial outcome (NNTB) or

the number needed to treat for an additional harmful outcome (NNTH) were also calculated for each outcome as

appropriate, as well as the absolute risk expressed as both a percentage and as natural units (Goldenberg et al.,

2013, p. 8).


Clostridium difficile associated diarrhea, as defined by the authors with the presence of cytotoxin and culture or both was 55

per 1000 in the control population and 20 per 1000 in the probiotics population with a RR of 0.36 at a 95% CI (Goldenberg

et al., 2013, p. 8).

Authors’ Major

Conclusions (cite pages)

“Moderate quality evidence supports a large protective effect of probiotics in preventing CDAD (RR 0.36; 95%

CI: 0.26, 0.51), but not in reducing the incidence of Clostridium difficile infection (RR 0.89; 95%CI: 0.64, 1.24).

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Stated in absolute terms, probiotic prophylaxis would prevent 35 CDAD episodes per 1000 patients treated

(Goldenberg et al., 2013, p. 19).


The Canadian Institutes of Health Research (CIHR) Knowledge Translation Branch and the CIHR Institutes of Nutrition,

Metabolism and Diabetes (INMD); and Infection and Immunity (III) and the Ontario Ministry of Health and Long Term

Care funded the IBD/FBD Review Group (Goldenberg et al., 2013, p. 19).

Bastyr University Student Center grants “provided funding for systematic review and meta-analysis training to Joshua

Goldenberg (Goldenberg et al., 2013, p. 149).


In terms of applicability, this systematic review factors favorably, in that it attempts to mitigate heterogeneity by

establishing a priori subgroup analyses on probiotic type and dose, patient population (geriatric versus pediatric), and risk

of bias (Goldenberg et al., 2013, p. 2). This improves the quality of evidence and makes the results more pertinent to the

specific PICOT question.


Johnston, B., Ma, S., Goldenberg, J., Thorlund, K., Vandvik, P., Loeb, M., & Guyatt, G. (2012). Probiotics for the

prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Annals Of Internal

Medicine, 157(12), 878-888.




A systematic review and meta-analysis of twenty trials (Johnston et al., 2012, p 878).

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study, and etc.).


Meta-analyses of randomized control trials are level I evidence (Melnyk & Fineout-Overholt, 2015, p. 92).

Sample Size

This study encompassed twenty trials including 3818 participants (Johnston et al., 2012, p 878).


“The patient or population was adults and children given antibiotics; the settings were inpatients and outpatients; and the

intervention was probiotics” (Johnston et al., 2012, p 884).


Administration of probiotic in conjunction with antibiotic therapy (Johnston et al., 2012, p 881).

Comparison

Administration of a placebo or no additional treatment with antibiotic therapy (Johnston et al., 2012, p 881).

Length of Follow-up In the cited studies, follow-up ranged from seven days to three months after last dose (Johnston et al., 2012, p 881).


Johnston et al. measured relative risk of populations, mean ages of participants, and quality of evidence (Johnston et al.,

2012, p 883-884).


“Twenty trials including 3818 participants met the eligibility criteria. Probiotics reduced the incidence of CDAD

by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I2 = 0%). In a population with a 5% incidence of

antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25

to 38 episodes) per 1000 persons. Of probiotic treated patients, 9.3% experienced adverse events, compared with

12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I2 = 17%)” (Johnston et al., 2012, p 878).

Authors’ Major

Conclusions (cite

pages).

Johnston et al. found “[M]oderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD

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without an increase in clinically important adverse events” 2012, p 878).


“Dr. Johnston was supported in part by a postdoctoral fellowship from the SickKids Foundation. Mr. Goldenberg is

supported by grants BUCSR-Y2-005 and BUCSR-Y2-019 from the Bastyr Center for Student Research” (Johnston et al.,

2012, p 887).

Regarding potential conflicts of interest, Dr. Johnston received grants or had grants pending at the time of publication

(money to institution) from Biocodex. Mr. Goldenberg received grant support from the Bastyr Center for Student Research

and support for travel to meetings for the study or other purposes from the Bastyr Center for Student Research (Johnston et

al., 2012, p 887).


This study was concise and east to read. It included a flow chart detailing the authors study selection and literature review,

as well as rationales for data synthesis and analysis. As with all of the rest of the meta-analyses included thus far in the

assignment, its timeframe post-treatment does not match perfectly with the research (PICOT) question. However, some of

the included studies did consider follow-up visits close to the eight-week mark, and certainly under that. It is also beneficial

that the authors considered unpublished studies, as well as excluded those with missing outcome data (Johnston et al., 2012,

p 879). The study included a variety of types of probiotic prophylaxis in the inpatient setting.

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Pillai A, Nelson RL. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database of

Systematic Reviews 2008, Issue 1. Art. No.: CD004611. DOI: 10.1002/14651858.CD004611.pub2.




study, and etc.).

“A systematic review of randomized controlled trials using probiotics alone or in conjunction with conventional antibiotics

for the treatment of documented C. difficile colitis” (Pillai & Nelson, 2008, p.1).


Systematic reviews of randomized controlled trials are level I evidence (Melnyk & Fineout-Overholt, 2015, p. 92).

Sample Size

This review synthesizes data from for studies. The first has 124 patients. The second 168. The third 21. And the third 15.

Three hundred twenty-eight patients in sum participated (Pillai & Nelson, 2008, p. 4).


Participants were patients with documented CDAD in an inpatient setting, including “patients with symptomatic diarrhea,

those with stool positive C. difficile cytotoxin or positive culture for C. difficile, those with current or recent prior exposure

to antibiotics, and those with absence of other pathogens in stool. Patients under 18 years of age were excluded from this

study” (Pillai & Nelson, 2008, p. 3).


Adding probiotic therapy to conventional precautions to treat recurrent C. difficile-associated diarrhea in adult patients in

inpatient and outpatient settings (Pillai & Nelson, 2008, p. 5).

Comparison

Conventional infection-control measures (Pillai & Nelson, 2008, p. 5).

Length of Follow-up The four cited studies ranged from sixty days post treatment, to an open-ended occurrence or reoccurrence of C. difficile-

associated diarrhea (Pillai & Nelson, 2008, p. 8-10).

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“For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived for each study. When

appropriate, the results of included studies were to be combined for each outcome. For dichotomous outcomes, a pooled RR

and 95% CI were to be calculated using a fixed effects model” (Pillai & Nelson, 2008, p. 4).


Of the four cited studies, one had a statistically significant likelihood of preventing recurrence of CDAD (RR 0.59; 95% CI

0.35 to 0.98) (Pillai & Nelson, 2008, p. 4).

Authors’ Major

Conclusions (cite

pages).

“There is insufficient evidence to recommend probiotic therapy as an adjunct to antibiotic therapy for C. difficile colitis.

There is no evidence to support the use of probiotics alone in the treatment of C. difficile colitis”


The “Canadian Institutes of Health Research (CIHR) Knowledge Translation Branch; the Canadian Agency for Drugs and

Technologies in Health (CADTH); and the CIHR Institutes of Health Services and Policy Research; Musculoskeletal Health

and Arthritis; Gender and Health; Human Development, Child and Youth Health; Nutrition, Metabolism and Diabetes; and

Infection and Immunity provided funding for this review group (Pillai & Nelson, 2008, p. 6).


The authors note that this review has several negative implications, including small sample size and lack of randomness in

applying antibiotics and a high dropout rate (Pillai & Nelson, 2008, p. 6). Although this study focuses primarily on

treatment and not prophylaxis, it does correlate in terms of preventing recurrence of CDAD (Pillai & Nelson, 2008, p. 3).

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Hood K, Nuttall J, Gillespie D, Shepherd V, Wood F, Duncan D, et al. Probiotics for Antibiotic-Associated Diarrhoea

(PAAD): a prospective observational study of antibiotic-associated diarrhoea (including Clostridium difficile-

associated diarrhoea) in care homes. Health Technology Assessment 2014;18(63).




study, and etc.).

Probiotics for Antibiotic-Associated Diarrhoea (PAAD) ”stage 1 was a prospective observational cohort study in care

homes in South Wales with up to 12 months’ follow-up for each resident (Hood et al., 2014, p. vii).


Evidence from well-designed case-control and cohort studies is level IV evidence (Melnyk & Fineout-Overholt, 2015, p.

92).

Sample Size

“Advanced consent was required from at least 607 residents (assuming that 66% would be prescribed at least one course of

antibiotics during the 12-month monitoring period and subsequently randomised). Approximately 1214 residents would be

approached in order to achieve this consent rate (assuming that only 50% will provide consent)” (Hood et al., 2014, p. vii).


Adult residents of eleven care homes in the UK: “Eleven care homes were recruited, but one withdrew before any residents

were recruited. A total of 279 care home residents were recruited to the observational study and 19 withdrew, 16 (84%)

because of moving to a non-participating care home” (Hood et al., 2014, p. viii).


The study included two planned intervention arms. The active arm (intervention) was one dose of VSL#3

Probiotic, administered in “25–50 ml of cold water or any non-fizzy drink or sprinkled onto cold food and consumed

immediately, twice a day for twenty-one days” (Hood et al., 2014, p. 46). The participants were to receive the study

medication “in between the antibiotic therapy and not in conjunction with the antibiotic. The study medication would be

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commenced within 72 hours of the resident being prescribed an antibiotic (Hood et al., 2014, p. 46).

Comparison

The comparison arm was a similar schedule of antibiotic therapy, with a placebo consisting “of freeze-dried powder (4.4 g),

matched for taste, consistency, odour and colour” (Hood et al., 2014, p. 46).

Length of Follow-up The authors planned and eight-week follow-up period (Hood et al., 2014, p. 47).


The authors measured variability in clinical frailty, care home type, antibiotics usage prior to study entry, care home type,

stool monitoring, and ability to provide own consent comparing OR to 95% CI and P-value in univariable and multivariable

characteristics (Hood et al., 2014, p. 47).


The authors’ primary outcomes “were the rate of antibiotic prescribing, incidence of AAD, defined as three or more loose

stools (type 5–7 on the Bristol Stool Chart) in a 24-hour period, and C. difficile carriage confirmed on stool culture.

Of the patients recruited, the authors collected stool samples for 81% of the participants. Participants received an average av

of 2.16 antibiotic prescriptions per year (95% confidence interval 1.90 to 2.46). The incidence of antibiotic-associated

diarrhea was 0.57 episodes per year among participants taking antibiotics (95% CI 0.41 to 0.81) (Hood et al., 2014, p. vii).

Authors’ Major

Conclusions (cite

pages).

Long-term care residents are frequently prescribed antibiotics and often experience diarrhea following antibiotic courses.

The authors acknowledge that they cannot ascribe all episodes of diarrhea to antibiotics, Therefore their study did not seek

to demonstrate causality, merely association, between antibiotic therapy and AAD. Another factor affecting the study

directly was the amount of antibiotic-resistant organisms found in the collected stool samples (Hood et al., 2014, p. xxix).

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The National Institute for Health Research (NIHR) Health Technology Assessment program funded and published this

study (Hood et al., 2014, p. viii).

There was no potential conflict of interest noted among the authors. However, the authors noted a potential conflict of

interest among study stakeholders, particularly physicians recruited to participate the study. They felt that these physicians

may have “conflict of interest if GPs prescribe antibiotics and are paid to enter a resident into the trial (in which case GPs

may be more likely to prescribe an antibiotic” (Hood et al., 2014, p. 42).


The authors considered this study to have relatively low bias related to the high inclusion rates in each care home and nearly

complete follow-up data (Hood et al., 2014, p. 59). They do acknowledge the possibility of sample bias by including only

residents who gave consent, or whose guardians gave consent, thereby only including subjects that wanted to participate in

the research.

As a prospective study, the findings are directly applicable to many aspects of the PICOT question, especially population,

intervention, comparison, and outcome. Unfortunately similar results by another major study “probiotic lactobacilli and

bifidobacteria in AAD and C. difficile diarrhoea in the elderly (PLACIDE)”, which addressed a similar question as the

authors’ PAAD stage 2 but in hospitals caused the authors reconsider proceeding with PAAD stage 2. They felt that latter’s

population and setting were like enough to preclude the second stage (Hood et al., 2014, p. xxvi).

As an interested student, this reinforces the premise that probiotics have some benefit in preventing instances and

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recurrences of CDAD and AAD. Unfortunately, it felt as if the study was incomplete, and that the authors quit their research

prematurely, especially considering the moderate advantage other researchers have found in administering probiotic therapy

in the prevention of CDAD and AAD.


Pattani R, Palda VA, Hwang SW, Shah PS. Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium

difficile infection among hospitalized patients: systematic review and meta-analysis. Open Med 2013;7(2):e56–e67.




study, and etc.).

A systematic review and meta-analysis of randomized controlled trials (Pattani et al., 2013, p. 56).


Systematic reviews of randomized controlled trials are level I evidence (Melnyk & Fineout-Overholt, 2015, p. 92).

Sample Size

This systematic review and meta-analysis included 2875 adult patients in sixteen included trials (Pattani et al., 2013, p. 59,

60).


The authors’ sample included adult inpatients at hospitals in the United States and United Kingdom, “who were receiving

antibiotics and who were randomly assigned to co-administration of probiotics or usual care, with or without the use of

placebo. Studies were included if they reported on AAD or CDI (or both) as outcomes” (Pattani et al., 2013, p. 56).

pg. 17


Administration of probiotics with antibiotics to reduce instances of AAD (antibiotic-associated diarrhea) and CDI (C.

difficile infection) as separate outcomes in adult inpatients (Pattani et al., 2013, p. 57).

Comparison

Administration of antibiotics and usual care, with or without the use of a placebo (Pattani et al., 2013, p. 56).

Length of Follow-up Additional follow-up lengths ranged from no time for cited low-quality studies, to three to seven weeks for high quality

studies (Pattani et all., 2013, p. 60, 62).


The authors calculated relative risk, odds ratios, number needed to treat (Pattani et al., 2013, p. 56).


“Pooled analyses revealed significant reductions in the risks of AAD [antibiotic-associated diarrhea] (RR 0.61, 95%

CI 0.47 to 0.79) and CDI [C. difficile infection] (RR 0.37, 95% CI 0.22 to 0.61) among patients randomly assigned

to co-administration of probiotics. The number needed to treat for benefit was 11 (95% CI 8 to 20) for AAD and 14

(95% CI 9 to 50) for CDI. With subgroup analysis, significant reductions in rates of both AAD and CDI were

retained in the subgroups of good-quality trials, the trials assessing a primarily Lactobacillus-based probiotic

formulation, and the trials for which the follow-up period was less than 4 weeks” (Pattani et al., 2013, p. 56).

Authors’ Major

Conclusions (cite

pages).

The authors’ findings reflect favorably on the benefits of probiotics “in preventing both AAD and CDI in the specific

patient population of adult inpatients requiring antibiotics. On the basis of the current review, probiotics can be

recommended for such patients in the absence of contraindications” (Pattani et all., 2013, p. 65). However, they also

recommend the prevalence of AAD and CDI before developing guidelines including probiotics, and that while these studies

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do not clearly indicate a most effective probiotic, evidence favors Lactobacillus formulations (Pattani et al., 2013, p. 65).


The authors received no external funding for this research and declared no competing interests (Pattani et al., 2013, p. 56).


This study is thorough in its rigor in separating studies by quality by investigating risk of bias, length of study, and

characteristics (Pattani et al., 2013, p. 56). Two independent reviewers evaluated each included study for bias risks using

US Preventive Services Task Force recommendations (Pattani et al., 2013, p. 58). Using these criteria, the authors rated

each included study on a global scale rating each as “good, fair, or poor” (Pattani et al., 2013, p. 58). A third independent

reviewer decided in the case of disagreements on quality between the initial two reviewers (Pattani et al., 2013, p. 58).

This meta-analysis addresses many aspects of the posed research question. Its criteria for population, intervention,

comparison, and outcome correlate closely with the established PICOT. Only timelines vary significantly. Additionally, the

authors’ efforts to categorize included studies qualitatively, and their separation of AAD from CDAD clarify the issue

significantly, demonstrating strong evidence that for their studies’ population “probiotics used concurrently with antibiotics

reduce the risk of AAD and CDI (Pattani et al., 2013, p. 56).


Hickson M, D’Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C, Bulpitt CJ. Use of probiotic Lactobacillus preparation to

prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 2007;

:bmj;bmj.39231.599815.55v1. doi:10.1136/bmj.39231.599815.55

pg. 19




study, and etc.).

This study is a randomized, double blind, placebo-controlled trial (Hickson et al., 2007, p. 1).



(Melnyk & Fineout-Overholt, 2015, p. 92)

Sample Size

Participants were 135 hospital patients (Hickson et al., 2007, p. 1).


Participants had a mean age 74, and were taking antibiotics. Exclusion criteria included “diarrhoea on admission, bowel

pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression,

bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis” (Hickson et al., 2007,

p. 1). The authors also excluded patients that regularly consumed the experimental or control beverage (Hickson et al.,

2007, p. 3).


Each member of the experiment group consumed of a 100 g (97 ml) drink containing L. casei, L bulgaricus, and S.

thermophilus twice daily during a course of antibiotics and for one week after the course finished (Hickson et al., 2007, p.

1).

Comparison

The placebo group received “a longlife sterile milkshake” (Hickson et al., 2007, p. 1).

Length of Follow-up Patients continued with their study drink (experimental or placebo) for one week following their course of antibiotic

therapy. The authors set a final follow-up date for four weeks after finishing the drink regimen. They contacted participants

by telephone weekly during that time. If any participant had an episode of diarrhea, the researchers collected stool samples

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to determine the presence of C. difficile toxin (Hickson et al., 2007, p. 2).


The authors calculated odds ratios at a 95% confidence level. They also calculate p-values, absolute risk reduction, and

number needed to treat (Hickson et al., 2007, p. 5).


The primary outcome measured the occurrence of antibiotic-associated diarrhea. The secondary outcome was the presence

of C. difficile toxin and diarrhea. 7/57 (12%) of the probiotic group developed diarrhea associated with antibiotic use

compared with 19/56 (34%) in the placebo group (P=0.007) (Hickson et al., 2007, p. 5).

Logistical regression controlling all other factors calculated and odds ratio of 0.25 (at a 95% confidence interval 0.07 to

0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhea, and an absolute risk

reduction of 21.6% (6.6% to 36.6%). The number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53

(17%) in the placebo group had diarrhea caused by C. difficile (P=0.001). The absolute risk reduction was 17% (7% to

27%), and the number needed to treat was 6 (4 to 14) (Hickson et al., 2007, p. 1).

Authors’ Major

Conclusions (cite

pages).

The authors concluded that:

“Consumption of a probiotic drink containing L. casei, L. bulgaricus, and S. thermophilus can reduce the incidence of

antibiotic associated diarrhoea and C. difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare

costs, and mortality if used routinely in patients aged over 50” (Hickson et al., 2007, p. 1).

Funding Source Health Foundation and Hammersmith Hospital Trustees research committee and Danone Vitapole (Paris, France) provided

pg. 21

funding for this study. Although Healthcare Foundation made initial comments on the design of the study, none of the

funding had any influence, “any role in the data collection, analysis, interpretation of data, writing of the report, or the

decision to submit he paper for publication (Hickson et al., 2007, p. 5).


This study correlates well to the posed research question, comparing hospitalized at-risk adult patients (mean age 74)

receiving prophylactic probiotic therapy in conjunction with antibiotics, and a double blind control group receiving

antibiotic alone. The only aspect of the PICOT that this study did not address is the possible variability in the

implementation of standard and hospital-based infectious disease protocols. However, one may assumed, since the study did

not list different facilities, that all participants were patients at the same hospital. This study also did address cost savings as

a result of implementing probiotic therapy for at-risk patients, which was part of the original interest in this topic.


Wullt M, Hagslatt M, Odenholt I. Lactobacillus plantarum 299v for the Treatment of Recurrent Clostridium difficile-

associated Diarrhoea: A Double-blind, Placebo-controlled Trial. Scand J Infect Dis 2003;35(365-367). DOI:

10.1080/00365540310010985.




study, and etc.).

This study is of an “investigator-initiated, prospective, randomized, placebo-controlled multicentre trial” (Wullt et al., 2003,

p. 365).



(Melnyk & Fineout-Overholt, 2015, p. 92),

Sample Size

The authors initially enrolled 29 patients in the study. Of these, the authors excluded eight patients; five related to violating

pg. 22

study protocols, two left voluntarily, and one was lost in follow-up, leaving 21 patients to evaluate (Wullt et al., 2003, p.

365).


These patients were hospitalized in nine different large hospitals in southern Sweden. Participants were all over eighteen

years of age, gave informed consent, and had a history of positive C. difficile toxin and C. difficile-associated diarrhea

(CDAD) within two months of beginning the study (Wullt et al., 2003, p. 365).


Recurrence of CDAD in patients who received metronidazole in combination with L. plantarum 299v for 38 days (Wullt et

al., 2003, p. 365).

Comparison

Patients who received metronidazole in combination with placebo for 38 days (Wullt et al., 2003, p. 365).

Length of Follow-up The authors assessed for clinical recurrence of symptoms by toxin assay for 41 day, by telephone through day 75 and then

monthly for another three months (Wullt et al., 2003, p. 365).



Authors’ Major

Conclusions (cite

Wullt et al. state:

pg. 23

pages). “Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum

in patients with RCDAD, the results of this study may contribute to the ongoing discussion about the benefits of

probiotics in patients with RCDAD and encourage the performance of larger multicentre studies” (2003, p. 367).


The authors do not declare any external funding or conflict of interest.


The small sample of this study does not authoritatively answer the posited research question. However, it does acknowledge

the importance of further research on the topic, especially double-blind, placebo-controlled studies in the use of probiotics

to prevent recurrence of colonization by C. difficile. Although it focuses more on recurrence than prevention, there is

correlation in causality, the reduction of gut microflora by long-term courses of antibiotics (Wullt et al., 2003, p. 366). The

authors also note that increased use of vancomycin for the treatment of C. difficile associated diarrhea has implications in

the increase of resistant enterococci. This has further consequences in best practices for the treatment of bacterial infections

in general and C. difficile associated diarrhea in particular (Wullt et al., 2003, p. 365).

pg. 24

Your name _____________________________________ Date ____________________

Part II of II. Evidence Summary (4 page limit)

Directions: Use your evidence table, keeper studies, and critical thinking to complete the following five questions. Be concise and analytical. Use

APA format to cite any facts from a study (ies) to support your assertions. Provide an APA reference list.

Your PICOT:

1. Identify two or more best practices that emerged from this body of evidence. Cite the studies that supported these practices.

2. Using the U.S. Preventive Services Task Force (USPTF) grades of evidence USPSTF Grades of Evidence 2012, generate an overall evidence

conclusion statement for a) the grade of evidence and b) Levels of Certainty Regarding Net Benefit.

3. How did the research answer your PICOT? What inclusion criteria were addressed and not addressed?

4. How did specific clinical practice guidelines (e.g. from the National Guideline Clearinghouse) directly or indirectly support or relate to your

findings?

5. Based on your new insights gleaned from this evidence table and evidence summary assignment, explain how you will specifically use the findings

from the evidence summary to improve population health outcomes e.g., safety, effectiveness, efficiency, patient-centeredness, timeliness, or equity

of care.

References (include the 8 keeper studies including all clinical practice guidelines, and other references)

Allen SJ, Wareham K, Wang D, Bradley C, Sewell B, Hutchings H, et al. A high-dose preparation of lactobacilli and bifidobacteria in the prevention

of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind,

placebo-controlled, parallel arm trial (PLACIDE). Health Technology Assessment 2013;17(57).

http://www.uspreventiveservicestaskforce.org/uspstf/grades.htm

pg. 25

Goldenberg JZ, Ma SSY, Saxton JD, Martzen MR, Vandvik PO, Thorlund K, Guyatt GH, Johnston BC. Probiotics for the prevention of Clostridium

difficile-associated diarrhea in adults and children. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD006095. DOI: 10.1

Johnston, B., Ma, S., Goldenberg, J., Thorlund, K., Vandvik, P., Loeb, M., & Guyatt, G. (2012). Probiotics for the prevention of Clostridium

difficile-associated diarrhea: a systematic review and meta-analysis. Annals Of Internal Medicine, 157(12), 878-

888.002/14651858.CD006095.pub3.

Johnston, B., Ma, S., Goldenberg, J., Thorlund, K., Vandvik, P., Loeb, M., & Guyatt, G. (2012). Probiotics for the prevention of Clostridium

difficile-associated diarrhea: a systematic review and meta-analysis. Annals Of Internal Medicine, 157(12), 878-888.

Melnyk, B. M., & Fineout-Overholt, E. E. (2015). Evidence-based practice in nursing and healthcare: A guide to best practice (3rd ed.). Philadelphia:

Wolters Kluwer Health.

Pillai A, Nelson RL. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database of Systematic Reviews 2008,

Issue 1. Art. No.: CD004611. DOI: 10.1002/14651858.CD004611.pub2.

BJM/March 2014, rev May, July, 2014; Oct. 2014 rev Dec. 2014

Documents

Evidence Table & Evidence Summary form RSMITH