Knowledge translation is the use of knowledge in health care decision making

Objective

To provide an overview of the science and practice of knowledge translation.

Study Design

Narrative review outlining what knowledge translation is and a framework for its use.

Results

Knowledge translation is defined as the use of knowledge in practice and decision making by the public, patients, health care professionals, managers, and policy makers. Failures to use research evidence to inform decision making are apparent across all these key decision maker groups. There are several proposed theories and frameworks for achieving knowledge translation. A conceptual framework developed by Graham et al., termed the knowledge-to-action cycle, provides an approach that builds on the commonalities found in an assessment of planned action theories.

Conclusions

Review of the evidence base for the science and practice of knowledge translation has identified several gaps including the need to develop valid strategies for assessing the determinants of knowledge use and for evaluating sustainability of knowledge translation interventions.     

Protective and Risk Factors Associated with Adolescent Sexual and Reproductive Health in the English-speaking Caribbean: A Literature Review

Purpose

To identify risk and protective factors associated with adolescent sexual and reproductive health (ASRH) in the English-speaking Caribbean through a structured literature review.

Methods

Peer-reviewed articles published between January 1998 and December 2009 focused on the sexual and reproductive health of adolescents, aged 10-19 years, were included in this review. Articles were organized according to Bronfenbrenner's ecological systems theory. Research gaps were also identified.

Results

A total of 30 studies assessed ASRH. At the individual level, gender, psychosocial well-being, and mental health were key factors associated with ASRH. Within the microsystem, the quality of the parent-adolescent relationship, the presence of violence, substance abuse or mental health problems in the family, and peer relationships were important determinants of ASRH. Within the macrosystem, cultural attitudes had an effect on youth's sexual behavior and generally, safer sex practices appear to be increasing. Within the chronosystem, a history of physical and sexual abuse was associated with several ASRH outcomes.

Conclusion

A research agenda that incorporates a multisystem approach and advocates for the inclusion of socially marginalized youth is needed to fully understand and adequately address ASRH in the Caribbean.     

McMaster Premium LiteratUre Service (PLUS) performed well for identifying new studies for updated Cochrane reviews

Objective

We compared the performance of McMaster Premium LiteratUre Service (PLUS) and Clinical Queries (CQs) to that of the Cochrane Controlled Trials Register, MEDLINE, and EMBASE for locating studies added during an update of reviews.

Study Design and Setting

A sample of new studies in updated Cochrane systematic reviews was used as a reference standard. Searches were performed for each study in each database. Where a new study was not indexed in PLUS, we examined the effect on the review of excluding the study.

Results

Ninety-eight updated Cochrane reviews were identified. For the 87 reviews with a usable meta-analysis, PLUS contained all new studies for 13 reviews. No statistically significant difference between PLUS and non-PLUS new studies was found when ratio of odds ratios (RORs) were pooled across 39 reviews (ROR_⊕/?: 0.99; 95% confidence interval: 0.87-1.14). Thirty-five updated reviews had no new studies indexed in PLUS, but conclusions were seldom altered by addition of new studies.

Conclusions

PLUS included less than a quarter of the new studies in Cochrane updates, but most reviews appeared unaffected by the omission of these studies. Reviewers should consider adopting PLUS and CQ filters to improve the efficiency of keeping their reviews up to date.     

Adding low-dose estrogen to the hormone-free interval: impact on bleeding patterns in users of a 91-day extended regimen oral contraceptive

Background

A cross-study analysis of contraceptive clinical trials for two different 91-day oral contraceptive (OC) regimens was performed to examine the impact on bleeding patterns when supplementing the 7-day hormone-free interval with 10 mcg ethinyl estradiol (EE) daily.

Study Design

Two separate 1-year Phase 3 clinical programs were conducted using similar study designs. The percentages of subjects reporting bleeding and spotting using electronic diaries for each 91-day cycle were compared.

Results

Scheduled bleeding with the EE regimen was less than that reported with the regimen utilizing placebo during Days 85-91, with significant differences noted for all four 91-day cycles. Unscheduled bleeding decreased more quickly with the 91-day regimen containing low-dose EE in place of placebo, with significant differences noted during the third cycle.

Conclusions

This cross-study comparison suggests that the administration of low-dose estrogen in place of placebo in a 91-day extended regimen OC improves the bleeding profile.     

Testing a tool for the classification of study designs in systematic reviews of interventions and exposures showed moderate reliability and low accuracy

Objectives

To develop and test a study design classification tool.

Study Design

We contacted relevant organizations and individuals to identify tools used to classify study designs and ranked these using predefined criteria. The highest ranked tool was a design algorithm developed, but no longer advocated, by the Cochrane Non-Randomized Studies Methods Group; this was modified to include additional study designs and decision points. We developed a reference classification for 30 studies; 6 testers applied the tool to these studies. Interrater reliability (Fleiss’ κ) and accuracy against the reference classification were assessed. The tool was further revised and retested.

Results

Initial reliability was fair among the testers (κ = 0.26) and the reference standard raters κ = 0.33). Testing after revisions showed improved reliability (κ = 0.45, moderate agreement) with improved, but still low, accuracy. The most common disagreements were whether the study design was experimental (5 of 15 studies), and whether there was a comparison of any kind (4 of 15 studies). Agreement was higher among testers who had completed graduate level training versus those who had not.

Conclusion

The moderate reliability and low accuracy may be because of lack of clarity and comprehensiveness of the tool, inadequate reporting of the studies, and variability in tester characteristics. The results may not be generalizable to all published studies, as the test studies were selected because they had posed challenges for previous reviewers with respect to their design classification. Application of such a tool should be accompanied by training, pilot testing, and context-specific decision rules.     

Inclusion of methodological filters in searches for diagnostic test accuracy studies misses relevant studies

Objective

To compare the performance of MEDLINE searches using index test(s) and target condition (subject searches) with the same searches combined with methodological filters for test accuracy studies.

Study Design and Setting

We derived a reference set of 506 test accuracy studies indexed on MEDLINE from seven systematic reviews that conducted extensive searches. We compared the performance of “subject” with “filtered” searches (same searches combined with each of 22 filters). Outcome measures were number of reference set records missed, sensitivity, number needed to read (NNR), and precision (Number of reference set studies identified for every 100 records screened).

Results

Subject searches missed 47 of the 506 reference studies; filtered searches missed an additional 21 to 241 studies. Sensitivity was 91% for subject searches and ranged from 43% to 87% for filtered searches. The NNR was 56 (precision 2%) for subject searches and ranged from 7 to 51 (precision 2-15%) for filtered searches.

Conclusions

Filtered searches miss additional studies compared with searches based on index test and target condition. None of the existing filters provided reductions in the NNR for acceptable sensitivity; currently available methodological filters should not be used to identify studies for inclusion in test accuracy reviews.     

Sensitive Clinical Queries retrieved relevant systematic reviews as well as primary studies: an analytic survey

Objective

To determine how well the previously validated broad and narrow Clinical Queries for treatment, diagnosis, prognosis, and etiology studies, retrieve not only primary studies but also relevant systematic reviews.

Study Design and Setting

Using the Clinical Hedges Database housed at McMaster University, we tested the retrieval performance of the Clinical Queries.

Results

For most purpose categories (therapy, diagnosis, prognosis, and etiology) and most databases (MEDLINE, EMBASE, CINAHL, and PsycINFO), the sensitive (broad) Clinical Queries search terms had sensitivities higher than 90% for retrieving relevant systematic reviews as well as primary studies. When testing specific (narrow) Clinical Queries, in 8 of 12 cases, specificity was 94% or higher, but sensitivity dropped below 50%. For all purpose categories and all databases, performance was improved when combining the sensitive or specific Clinical Queries with our existing sensitive or specific systematic review search filter using the Boolean OR; sensitivities ranged from 90.7% to 99.7% and specificities ranged from 92.4% to 98.0% with sensitivities higher than 50%.

Conclusion

The sensitive Clinical Queries for therapy, diagnosis, prognosis, and etiology perform well in retrieving not only primary studies but also systematic reviews. Search performance can be improved by combining the Clinical Queries with our sensitive or specific systematic review filter.     

Graphical modeling can be used to illustrate associations between variables describing functioning in head and neck cancer patients

Objective

To examine the associations between variables of functioning measured by the International Classification of Functioning, Disability and Health (ICF) in head and neck cancer (HNC) patients by means of graphical modeling.

Study Design and Setting

Graphical modeling was used on a data set of a cross-sectional multicentric study of 145 patients with HNC. Functioning was qualified using the extended ICF checklist. Multiple imputation was used to handle missing data. The least absolute shrinkage and selection operator for generalized linear models was used to identify conditional associations between the ICF categories. Bootstrap aggregating was used to enhance the accuracy and validity of model selection.

Results

The resulting graph shows largely meaningful associations between the ICF categories. One central point could be visualized consisting of a circular path of d330 Speaking, d350 Conversation, b510 Ingestion functions, s320 Structure of mouth, and b310 Voice functions. Another important structure in the graph were the bow-shaped associations beginning with d335 Producing nonverbal messages to b130 Energy and drive functions.

Conclusion

Graphical modeling can be used to describe associations between different areas of functioning in HNC patients. They found associations can be the basis for improved rehabilitation and gives a deeper understanding of functioning in HNC patients.     

Researching routine immunization-do we know what we don't know?

Background

The Expanded Programme on Immunization (EPI), launched in 1974, has developed and implemented a range of strategies and practices over the last three decades to ensure that children and adults receive the vaccines they need to help protect them against vaccine-preventable diseases. Many of these strategies have been implemented, resulting in immunization coverage exceeding 80% among children one year of age in many countries. Yet millions of infants remain under-immunized or unimmunized, particularly in poorer countries. In November 2009, a panel of external experts met at the United States Centers for Disease Control and Prevention (CDC) to review and identify areas of research required to strengthen routine service delivery in developing countries.

Methods

Research opportunities were identified utilizing presentations emphasizing existing research, gaps in knowledge and key questions. Panel members prioritized the topics, as did other meeting participants.

Findings

Several hundred research topics covering a wide range were identified by the panel members and participants. However there were relatively few topics for which there was a consensus that immediate investment in research is warranted. The panel identified 28 topics as priorities. 18 topics were identified as priorities by at least 50% of non-panel participants; of these, five were also identified as priorities by the panel. Research needs included identifying the best ways to increase coverage with existing vaccines and introduce new vaccines, integrate other services with immunizations, and finance immunization programmes.

Interpretation

There is an enormous range of research that could be undertaken to support routine immunization. However, implementation of strategic plans, rather than additional research will have the greatest impact on raising immunization coverage and preventing disease, disability, and death from vaccine-preventable diseases. The panel emphasized the importance of tying operational research to programmatic needs, with a focus on efforts to scale up proven best practices in each country, facilitating the full implementation of immunization strategies.     

Development of a framework for effective community engagement in Ontario, Canada

Objectives

This study aims to: (1) conceptualize effective community engagement (CE) within the Local Health Integration Networks (LHIN) of Ontario, Canada, (2) develop an effective CE framework and (3) compare the CE framework to public engagement (PE) frameworks and assess their relevance to the LHIN context.

Methods

We implemented “concept mapping,” a participatory, mixed-methods approach, with LHIN staff. The method includes three components: (1) “Brainstorming” where participants generated statements describing effective CE; (2) “Sorting and Rating” where participants grouped statements and rated their relative importance to generate a “cluster map” and (3) “Mapping” where participants reviewed and named the clusters to yield the effective CE framework.

Results

Staff generated a list of 64 statements. Participants reviewed the cluster map to generate six categories for the framework: (1) collaboration, (2) accessibility, (3) accountability, (4) education, (5) principles and (6) organizational capacity.

Conclusions

The effective CE framework overlaps with PE frameworks with two caveats. First, applications of PE evaluation frameworks to the LHINs may yield incomplete results given that partnerships with service providers and organizations are integral to CE strategies. Second, “organizational capacity,” largely not captured within existing frameworks, must be integrated as a feature given that emerging research identifies its importance to the successful implementation of engagement strategies.     

PubMed had a higher sensitivity than Ovid-MEDLINE in the search for systematic reviews

Objective

To compare the performance of Ovid-MEDLINE vs. PubMed for identifying randomized controlled trials of methotrexate (MTX) in patients with rheumatoid arthritis (RA).

Study Design and Setting

We created search strategies for Ovid-MEDLINE and PubMed for a systematic review of MTX in RA. Their performance was evaluated using sensitivity, precision, and number needed to read (NNR).

Results

Comparing searches in Ovid-MEDLINE vs. PubMed, PubMed retrieved more citations overall than Ovid-MEDLINE; however, of the 20 citations that met eligibility criteria for the review, Ovid-MEDLINE retrieved 17 and PubMed 18. The sensitivity was 85% for Ovid-MEDLINE vs. 90% for PubMed, whereas the precision and NNR were comparable (precision: 0.881% for Ovid-MEDLINE vs. 0.884% for PubMed and NNR: 114 for Ovid-MEDLINE vs. 113 for PubMed).

Conclusion

In systematic reviews of RA, PubMed has higher sensitivity than Ovid-MEDLINE with comparable precision and NNR. This study highlights the importance of well-designed database-specific search strategies.     

Statistical methods can be improved within Cochrane pregnancy and childbirth reviews

Objectives

To assess statistical methods within systematic reviews of the Cochrane Pregnancy and Childbirth Group (CPCG).

Study Design and Setting

We extracted details about statistical methods within 75 reviews containing at least 10 studies.

Results

The median number of forest plots per review was 52 (min = 5; max = 409). Seven of the 75 reviews assessed publication bias or explained why not. Forty-four of the 75 reviews performed random-effects meta-analyses; just 1 of these justified the approach clinically and none interpreted its pooled result correctly. Of 31 reviews not using random-effects, 26 assumed a fixed-effect given potentially moderate or large heterogeneity (I² > 25%). In their Methods section, 25 (33%) of the 75 reviews said I² was used to decide between fixed-effect and random-effects; however, in 12 of these (48%) reviews, this was not carried out in their Results section. Of 72 reviews with moderate or large heterogeneity, 47 (65%) did not explore the causes of heterogeneity or justify why not.

Conclusion

Within CPCG reviews, publication bias is rarely addressed; heterogeneity is often not appropriately considered, and random-effects analyses are incorrectly interpreted. How these shortcomings impact existing review conclusions needs further investigation, but regardless of this, we recomment the Cochrane Collaboration increase “hands-on” statistical support.     

The Influence of Maternal Acculturation on Child Body Mass Index at Age 24 Months

Objective

Obesity rates in preschool-aged children are greatest among Latinos. Studies of the relationship of acculturation to obesity among Latino immigrants have primarily focused on adults and adolescents. We examined the influence of maternal acculturation on child body mass index (BMI) at age 24 and 36 months among predominantly Latino, low-income mother-child pairs enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children.

Design and methods

Maternal characteristics were obtained from interviewer-administered surveys conducted in English or Spanish at 6 to 20 weeks postpartum among 679 participants in a randomized controlled trial of a health promotion intervention in two urban areas in the Northeast. Acculturation measures included: nativity (born in the United States vs foreign born), parents' nativity, years of US residence (<8 years vs ≥8 years), and exclusive use of native language vs nonexclusive use (mixed or English only). Following repeated mailings and telephone calls requesting permission to obtain their child's height and weight from Special Supplemental Nutrition Program for Women, Infants, and Children records, informed consent was obtained from 108 mothers. Multivariable linear regression models of maternal acculturation and child BMI z score at age 24 months and age 36 months were estimated among all mother-child pairs and within immigrant-only mother-child pairs, adjusting for relevant maternal characteristics.

Results

At age 24 months, children of mothers with exclusive use of native language had higher BMI z scores compared to children of mothers with nonexclusive use among 91 mother-child pairs (β=.74, P=0.02) and within 63 immigrant-only mother-child pairs (β=.92, P=0.009).

Conclusions

Exclusive use of native language was associated with greater BMI in children as young as age 24 months. Future research should examine the mechanisms by which mothers' language acculturation may affect proximal determinants of energy balance in preschool children, including breastfeeding practices, dietary intake, and physical activity.     

Breast cancer screening for women ages 50 to 69 years a systematic review of observational evidence

Objective

To systematically review the observational evidence concerning the effect of screening on breast cancer mortality in actual populations of women ages 50-69 years.

Methods

We searched MEDLINE and multiple reference lists for relevant cohort and ecologic studies. At least 2 authors reviewed abstracts and full texts of studies meeting eligibility criteria. We rated each accepted study on standard quality criteria and developed a Summary Evidence Table.

Results

Seventeen studies met eligibility criteria. Five studies found no to small effect of screening (0-12% relative risk reduction [RRR] in breast cancer mortality), 4 found a large effect (greater than 33% RRR), and 8 found a moderate effect (13% to 33% reduction). The authors found concerns about quality in all studies. There was insufficient evidence to determine whether the effectiveness of screening is decreasing over time.

Conclusions

Current observational evidence shows that breast cancer screening in actual populations of women ages 50 to 69 reduces breast cancer mortality; the magnitude of the effect is probably smaller than predicted in the randomized controlled trials. Because the magnitude may change (either increase or decrease) in the future, further ecologic studies are needed. The methodology and infrastructure for these studies should be improved.     

Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study

Background

Chlorothalonil is a broad spectrum, non-systemic fungicide widely used to control diseases affecting over 50 fruit, vegetable, and agricultural crops. Despite its extensive use for over 30 years, little is known about the potential human carcinogenicity associated with the routine application of chlorothalonil. Rodent studies have shown evidence of renal tubular carcinomas and adenomas. We explored cancer incidence with chlorothalonil exposure using data from the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina.

Methods

Licensed private and commercial pesticide applicators were recruited into this study from 1993 to 1997. Detailed information regarding pesticide use was obtained via self-administered questionnaires. Cancer incidence was followed through December 31, 2004. Chlorothalonil exposure was classified by lifetime exposure days and intensity-weighted lifetime exposure days, and then categorized into tertiles. The intensity-weighted lifetime exposure days metric was calculated based on a complex algorithm which includes pesticide application methods among other factors. This may increase or decrease exposure.

Results

Of the 47,625 pesticide applicators included in this analysis, 3657 applicators reported using chlorothalonil with a median of 3.5 application days per year. Chlorothalonil was not associated with overall cancer incidence, nor did we find any association with colon, lung, and prostate cancers—the only cancers for which we had sufficient numbers to explore associations.

Conclusion

We did not find any strong evidence for an association between chlorothalonil and the cancers investigated. Although animal studies have suggested renal cancer may be associated with chlorothalonil, we had insufficient data to evaluate this cancer.     

Study design attributes influenced patients' willingness to participate in clinical research: a randomized vignette-based study

Objective

To identify characteristics of clinical research projects that influence patients' willingness to participate in research.

Study Design and Setting

We surveyed all patients discharged during 1 month from a Swiss public teaching hospital. We described four hypothetical studies and asked patients whether they would agree to participate. We randomly manipulated three study attributes in each vignette, using a factorial design.

Results

All studies were not equally acceptable to the 1,277 respondents. A higher willingness to participate was found when a new drug had no side effects, no additional visit was required, balanced information was given, results were in the public domain, and the project was approved by a research ethics committee. In contrast, destruction of blood samples at the end of the project, use of placebo controls, and random allocation to study arms were associated with a lower likelihood of participation. The origin of funds, financial reward, the need to complete a questionnaire, and clinical vs. economic purpose of the study did not influence willingness to participate.

Conclusion

Patients valued safety, convenience, oversight, and open communication in research. However, they were put off by some aspects that are valued by health care professionals. Educating the public about research methods may improve participation.     

A framework for applying unfamiliar trial designs in studies of rare diseases

Objective

Rare diseases may be difficult to study through conventional research methods, but are amenable to study through certain uncommonly used designs. We sought to explain these designs and to provide a framework to assist researchers in identifying the most appropriate design for a given research question.

Study Design and Setting

We systematically searched for literature describing rare disease research frameworks, trial designs, and trials that applied them. We present the advantages and disadvantages of each approach using these published examples, and a practical framework to help researchers in selecting between design choices.

Results

When research participants are limited, researchers should consider using: 1) a crossover design; 2) n-of-1 trials; or 3) one of the following adaptive designs: a) a response-adaptive randomization design, b) a ranking and selection design, c) an internal pilot design, or d) a sequential design. Bayesian analysis may be applied to conventional designs, or to any of these uncommon designs. Several of these approaches may also be used in combination. The choice between methods should be guided by factors related to the intervention, disease, anticipated recruitment duration and success, and current state of knowledge about the treatment.

Conclusion

These techniques may facilitate research in rare diseases.     

Implanon users are less likely to be satisfied with their contraception after 6 months than IUD users

Background

The study was conducted to perform a direct comparison of the satisfaction of intrauterine device (IUD) users and Implanon users after 6 months.

Study design

Women were recruited to this study in the contraception clinics of Southern Health and Family Planning Victoria. Each woman completed a questionnaire at the time of starting her contraception with either an IUD or Implanon. Women were sent a follow-up questionnaire after 6 months to assess their satisfaction with their chosen method of contraception.

Results

A total of 439 participants were recruited for this non randomized cohort study; 211 choosing an IUD and 228 choosing to use Implanon. The main reason patients in both groups chose their contraceptive method was recommendation by the doctor. Follow-up was achieved in over 84% in both groups. More than 50% of women in both groups reported at least one side effect. The most commonly reported side effect in both groups was abnormal bleeding and this was also the most common reason for having the contraceptive device removed. The IUD users reported a higher rate of satisfaction with their chosen method of contraception, although there was no difference between groups in the removal rate or whether the women would recommend the contraception to others.

Conclusions

IUD users reported a higher level of satisfaction than did Implanon users at 6 months. Side effects in women using IUDs and Implanon are common. The range of likely side effects should be included in counseling women about long-term reversible contraception.     

Reviews assessing the quality or the reporting of randomized controlled trials are increasing over time but raised questions about how quality is assessed

Objective

Many reviews specifically aimed to assess the quality of randomized controlled trials (RCTs). We evaluated the quality of reporting in such reviews.

Study Design and Setting

PubMed and the Cochrane library were searched for all reviews assessing the quality of RCTs between 1987 and 2007, and experts in the field were also contacted.

Results

We found 177 reviews published from 1987 to 2007, 58% of which were published after 2002. Of these, 131 (74%) focused on the quality of RCTs, 44 (25%) on quality of reporting, and 2 (1%) assessed both. The search strategy was well reported (92%). The criteria for assessment were reported in 97% of the reviews but were defined in only 38%. Seventy-four different items and 26 different scales were identified. Allocation sequence generation and concealment were reported in 41% and 40%, respectively, but their adequacy was assessed in 20% and 29%, respectively; scales were used in 40% and Consolidated Standards of Reporting Trials (CONSORT) checklist in 12%.

Conclusion

The number of methodological reviews has dramatically increased in recent years. Despite an improved reporting of the methodology, how quality is assessed still raises important issues. Heterogeneity of criteria used and lack of definition may limit the relevance of these reviews.