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National Collaborating Centre for Methods and Tools

October 2013 · Issue 57

In this issue:

The Fast Track to Evidence-Informed Public Health

a story from Manitoba Health

Dr. Joselito Montalban, a policy analyst for Communicable Disease Control (CDC) at Manitoba Health, continues to try to formulate the “perfect search expression”. He is a clear proponent of using as much research as it takes to arrive at the best possible policy advice, using journals, online resources and contact with experts in the particular areas he is investigating. Joselito does get frustrated though, with the filtering process – dealing with an onslaught of material if search criteria are too broad, or running the risk of missing that one key article by using a narrower search.   
Shortly after starting work at Manitoba Health, Joselito attended a workshop on Evidence-Informed Public Health (EIPH) held by the NCCMT. Since then, he refers to the EIPH “wheel” regularly. The wheel identifies the stages involved in evidence-informed public health: define, search, appraise, synthesize, adapt, implement and evaluate. The workshop explains the process of finding, appraising, distilling and disseminating the best available evidence from research – both quantitative and qualitative – and using that evidence to inform and improve health policy and practice.

When Joselito was tasked with creating a methodology for reviewing a post-exposure prophylaxis (PEP) brochure for HIV, Hepatitis B and Hepatitis C, designed for the general public, he drafted guidelines for reviewing and revising all CDC documents, including those intended for health professionals.

Joselito started his review of the original PEP brochure at the “appraise” step in the EIPH wheel. His proposed next step in reviewing documents was to search for the most recent and appropriate research evidence to ensure that any advice is completely up-to-date. For this, the EIPH wheel points to the 6S Pyramid as a way to find the best research evidence with the least amount of time and effort.

According to Joselito, “The EIPH wheel is like a snap-shot of everything that we do as policy analysts. It can thus serve as a reminder in a neat, handy package of the different facets of our work, thereby allowing us to approach our tasks more systematically.”

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New in Registry of Methods and Tools

New from Public Health+

Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer screening in asymptomatic individuals.

BACKGROUND: Colorectal cancer is the third most frequent cancer in the world. As the sojourn time for this cancer is several years and a good prognosis is associated with early stage diagnosis, screening has been implemented in a number of countries. Both screening with faecal occult blood test and flexible sigmoidoscopy have been shown to reduce mortality from colorectal cancer in randomised controlled trials. The comparative effectiveness of these tests on colorectal cancer mortality has, however, never been evaluated, and controversies exist over which test to choose. OBJECTIVES: To compare the effectiveness of screening for colorectal cancer with flexible sigmoidoscopy to faecal occult blood testing. SEARCH METHODS: We searched MEDLINE and EMBASE (November 16, 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11) and reference lists for eligible studies. SELECTION CRITERIA: Randomised controlled trials comparing screening with flexible sigmoidoscopy or faecal occult blood testing to each other or to no screening. Only studies reporting mortality from colorectal cancer were included. Faecal occult blood testing had to be repeated (annually or biennially). DATA COLLECTION AND ANALYSIS: Data retrieval and assessment of risk of bias were performed independently by two review authors. Standard meta-analyses using a random-effects model were conducted for flexible sigmoidoscopy and faecal occult blood testing (FOBT) separately and we calculated relative risks with 95% confidence intervals (CI). We used a Bayesian approach (a contrast-based network meta-analysis method) for indirect analyses and presented the results as posterior median relative risk with 95% credibility intervals. We assessed the quality of evidence using GRADE. MAIN RESULTS: We identified nine studies comprising 338,467 individuals randomised to screening and 405,919 individuals to the control groups. Five studies compared flexible sigmoidoscopy to no screening and four studies compared repetitive guaiac-based FOBT (annually and biennially) to no screening. We did not consider that study risk of bias reduced our confidence in our results. We did not identify any studies comparing the two screening methods directly. When compared with no screening, colorectal cancer mortality was lower with flexible sigmoidoscopy (relative risk 0.72; 95% CI 0.65 to 0.79, high quality evidence) and FOBT (relative risk 0.86; 95% CI 0.80 to 0.92, high quality evidence). In the analyses based on indirect comparison of the two screening methods, the relative risk of dying from colorectal cancer was 0.85 (95% credibility interval 0.72 to 1.01, low quality evidence) for flexible sigmoidoscopy screening compared to FOBT. No complications occurred after the FOBT test itself, but 0.03% of participants suffered a major complication after follow-up. Among more than 60,000 flexible sigmoidoscopy screening procedures and almost 6000 work-up colonoscopies, a major complication was recorded in 0.08% of participants. Adverse event data should be interpreted with caution as the reporting of adverse effects was incomplete. AUTHORS` CONCLUSIONS: There is high quality evidence that both flexible sigmoidoscopy and faecal occult blood testing reduce colorectal cancer mortality when applied as screening tools. There is low quality indirect evidence that screening with either approach reduces colorectal cancer deaths more than the other. Major complications associated with screening require validation from studies with more complete reporting of harms.

The full text may be available from PubMed

Hyperimmune IV Immunoglobulin Treatment: A Multicenter Double-Blind Randomized Controlled Trial for Patients With Severe 2009 Influenza A(H1N1) Infection.

BACKGROUND: Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking. METHODS: This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-IVIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-IVIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared. RESULTS: Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-IVIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04). CONCLUSIONS: Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality. TRIAL REGISTRY: ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.

The full text may be available from PubMed

Strategies for partner notification for sexually transmitted infections, including HIV.

BACKGROUND: Partner notification (PN) is the process whereby sexual partners of an index patient are informed of their exposure to a sexually transmitted infection (STI) and the need to obtain treatment. For the person (index patient) with a curable STI, PN aims to eradicate infection and prevent re-infection. For sexual partners, PN aims to identify and treat undiagnosed STIs. At the level of sexual networks and populations, the aim of PN is to interrupt chains of STI transmission. For people with viral STI, PN aims to identify undiagnosed infections, which can facilitate access for their sexual partners to treatment and help prevent transmission. OBJECTIVES: To assess the effects of different PN strategies in people with STI, including human immunodeficiency virus (HIV) infection. SEARCH METHODS: We searched electronic databases (the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE) without language restrictions. We scanned reference lists of potential studies and previous reviews and contacted experts in the field. We searched three trial registries. We conducted the most recent search on 31 August 2012. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) or quasi-RCTs comparing two or more PN strategies. Four main PN strategies were included: patient referral, expedited partner therapy, provider referral and contract referral. Patient referral means that the patient notifies their sexual partners, either with (enhanced patient referral) or without (simple patient referral) additional verbal or written support. In expedited partner therapy, the patient delivers medication or a prescription for medication to their partner(s) without the need for a medical examination of the partner. In provider referral, health service personnel notify the partners. In contract referral, the index patient is encouraged to notify partner, with the understanding that the partners will be contacted if they do not visit the health service by a certain date. DATA COLLECTION AND ANALYSIS: We analysed data according to paired partner referral strategies. We organised the comparisons first according to four main PN strategies (1. enhanced patient referral, 2. expedited partner therapy, 3. contract referral, 4. provider referral). We compared each main strategy with simple patient referral and then with each other, if trials were available. For continuous outcome measures, we calculated the mean difference (MD) with 95% confidence intervals (CI). For dichotomous variables, we calculated the risk ratio (RR) with 95% CI. We performed meta-analyses where appropriate. We performed a sensitivity analysis for the primary outcome re-infection rate of the index patient by excluding studies with attrition of greater than 20%. Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. MAIN RESULTS: We included 26 trials (17,578 participants, 9015 women and 8563 men). Five trials were conducted in developing countries. Only two trials were conducted among HIV-positive patients. There was potential for selection bias, owing to the methods of allocation used and of performance bias, owing to the lack of blinding in most included studies. Seven trials had attrition of greater than 20%, increasing the risk of bias.The review found moderate-quality evidence that expedited partner therapy is better than simple patient referral for preventing re-infection of index patients when combining trials of STIs that caused urethritis or cervicitis (6 trials; RR 0.71, 95% CI 0.56 to 0.89, I2 = 39%). When studies with attrition greater than 20% were excluded, the effect of expedited partner therapy was attenuated (2 trials; RR 0.8, 95% CI 0.62 to 1.04, I2 = 0%). In trials restricted to index patients with chlamydia, the effect was attenuated (2 trials; RR 0.90, 95% CI 0.60 to 1.35, I2 = 22%). Expedited partner therapy also increased the number of partners treated per index patient (three trials) when compared with simple patient referral in people with chlamydia or gonorrhoea (MD 0.43, 95% CI 0.28 to 0.58) or trichomonas (MD 0.51, 95% CI 0.35 to 0.67), and people with any STI syndrome (MD 0.5, 95% CI 0.34 to 0.67). Expedited partner therapy was not superior to enhanced patient referral in preventing re-infection (3 trials; RR 0.96, 95% CI 0.60 to 1.53, I2 = 33%, low-quality evidence). Home sampling kits for partners (four trials) did not result in lower rates of re-infection in the index case (measured in one trial), or higher numbers of partners elicited (three trials), notified (two trials) or treated (one trial) when compared with simple patient referral. There was no consistent evidence for the relative effects of provider, contract or other patient referral methods. In one trial among men with non-gonococcal urethritis, more partners were treated with provider referral than with simple patient referral (MD 0.5, 95

The full text may be available from PubMed

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