Patients who experience gastrointestinal bleeding after myocardial infarction (MI) often have comorbidities that could place them at increased risk of complications if evaluative endoscopy were to be performed. Although esophagogastroduodenoscopy is considered to be generally safe in high-risk individuals, some post-MI patients may be more susceptible to a variety of cardiopulmonary complications. This cohort study examined cardiopulmonary safety in post-MI patients and evaluated specific predictors of complications of post-MI endoscopy.

BACKGROUND:

Patients who experience myocardial infarction (MI) are at risk of gastrointestinal (GI) bleeding complications. Endoscopic evaluation may lead to cardiopulmonary complications. Guidelines and studies regarding the safety of endoscopy in this population are limited.

OBJECTIVE:

To evaluate the safety of endoscopy in a retrospective cohort of post-MI patients at a Canadian tertiary centre.

METHODS:

Using hospital diagnostic/procedure codes, the charts of patients meeting the inclusion criteria of having ST elevation MI or non-ST elevation MI, and GI bleeding detected at endoscopy were reviewed. The information retrieved included demographics, medical history, medications, endoscopy details and cardiopulmonary/GI events.

RESULTS:

A total of 121 patients experienced an MI and underwent endoscopy within 30 days. However, only 44 met the inclusion criteria and were reviewed. The mean age of the patients was 75 years, and 55% were female. The mean hemoglobin level was 86 g/L, and 38 of 44 patients required a transfusion. Comorbidities included hypertension (82%), diabetes (46%), heart failure (55%), stroke (21%), lung disease (27%), previous MI (46%), cardiac bypass surgery (30%), history of GI bleed (25%), history of ulcer (18%) and ejection fraction <50% (48%). The median number of days to endoscopy after MI was three. Complications included seven patients with acute coronary syndrome, one with arrhythmia, one with respiratory failure, one with aspiration pneumonia and two with perforation. Age, hemoglobin level or timing of endoscopy did not significantly predict a complication.

CONCLUSIONS:

Patients with GI bleeding after MI often have comorbidities and are on antiplatelet agents. Endoscopy is a valuable tool in the diagnosis and management of bleeding complications, but must be weighed against the potential risk of other complications, which in the present study occurred in more than 25% of procedures.

Background:

International guidelines for the management of nonvariceal upper gastrointestinal bleeding have not been widely adopted in clinical practice. We sought to determine whether a national, multifaceted intervention could improve adherence to guidelines, especially for patients at high risk of nonvariceal upper gastrointestinal bleeding.

Methods:

In this randomized trial, we stratified hospitals by region and size and allocated sites to either the control or experimental group. Health care workers in the experimental group were given published guidelines, generic algorithms, stratification scoring systems and written reminders and attended multidisciplinary guideline education groups and case-based workshops. These interventions were implemented over a 12-month period after randomization, with performance feedback and benchmarking. The primary outcome of adherence rates to key guidelines in endoscopic and pharmacologic management, determined by chart review, was adjusted according to site characteristics and possible within-site dependencies. We also report the rates of adherence to other recommendations.

Results:

Forty-three sites were randomized to the experimental (n = 21) or control (n = 22) groups. In our primary analysis, we compared patients before (experimental group: n = 402 patients; control group: n = 424 patients) and after (experimental group: n = 361 patients; control group: n = 389 patients) intervention. Patient-level analysis revealed no significant difference in adherence rates to the guidelines after the intervention (experimental group: 9.8%; control group: 4.8%; p = 0.99) after adjustment for the rate of adherence before the intervention (experimental group: 13.2%; control group: 7.1%). The adherence rates to other guidelines were similar and decreased over time, varying between 5% and 93%.

Interpretation:

This national knowledge translation–based trial suggests poor adherence to guidelines on nonvariceal upper gastrointestinal bleeding. Adherence was not improved by an educational intervention, which highlights both the complexity and poor predictability of attempting to alter the behaviour of health care providers (Trial registration: ClinicalTrials.gov, no. MCT-88113).

The growth in the use of endoscopy to diagnose and treat many gastointestinal disorders, and its central role in cancer screening programs, has led to a significant increase in the number of procedures performed. This growth, however, has also led to many variations in, among others, the provision of services, the choice of sedative medications and the training of providers. The recognition of the significance of quality in endoscopy has prompted several countries, including Canada, to initiate efforts to adopt nationwide quality improvement programs. The Canadian Association of Gastroenterology formed a committee to review endoscopy and quality with the aim of stimulating improvement. This article focuses specifically on patient safety indicators that were developed at a consensus conference aimed at generating a broad range of recommendations for selected endoscopic procedures, which if adopted, could lead to significant changes in how endoscopy services are provided.

INTRODUCTION:

The importance of quality indicators has become increasingly recognized in gastrointestinal endoscopy. Patient safety requires the identification and monitoring of occurrences associated with harm or the potential for harm. The identification of relevant indicators of safety compromise is, therefore, a critical element that is key to the effective implementation of endoscopy quality improvement programs.

OBJECTIVE:

To identify key indicators of safety compromise in gastrointestinal endoscopy.

METHODS:

The Canadian Association of Gastroenterology Safety and Quality Indicators in Endoscopy Consensus Group was formed to address issues of quality in endoscopy. A subcommittee was formed to identify key safety indicators. A systematic literature review was undertaken, and articles pertinent to safety in endoscopy were identified and reviewed. All complications and measures used to document safety were recorded. From this, a preliminary list of 16 indicators was compiled and presented to the 35-person consensus group during a three-day meeting. A revised list of 20 items was subsequently put to the consensus group for vote for inclusion on the final list of safety indicators. Items were retained only if the consensus group highly agreed on their importance.

RESULTS:

A total of 19 indicators of safety compromise were retained and grouped into the three following categories: medication-related – the need for CPR, use of reversal agents, hypoxia, hypotension, hypertension, sedation doses in patients older than 70 years of age, allergic reactions and laryngospasm/bronchospasm; procedure-related early – perforation, immediate postpolypectomy bleeding, need for hospital admission or transfer to emergency department from the gastroenterology unit, instrument impaction, severe persistent abdominal pain requiring evaluation proven to not be perforation; and procedure-related delayed – death within 30 days of procedure, 14-day unplanned hospitalization, 14-day unplanned contact with a health provider, gastrointestinal bleeding within 14 days of procedure, infection or symptomatic metabolic complications.

CONCLUSIONS:

The 19 indicators of safety compromise in endoscopy, identified by a rigorous, evidence-based consensus process, provide clear outcomes to be recorded by all facilities as part of their continuing quality improvement programs.

Several organizations worldwide have developed procedure-based guidelines and/or position statements regarding various aspects of quality and safety indicators, and credentialing for endoscopy. Although important, they do not specifically address patient needs or provide a framework for their adoption in the context of endoscopy services. The consensus guidelines reported in this article, however, aimed to identify processes and indicators relevant to the provision of high-quality endoscopy services that will support ongoing quality improvement across many jurisdictions, specifically in the areas of ethics, facility standards and policies, quality assurance, training and education, reporting standards and patient perceptions.

BACKGROUND:

Increasing use of gastrointestinal endoscopy, particularly for colorectal cancer screening, and increasing emphasis on health care quality, highlight the need for clearly defined, evidence-based processes to support quality improvement in endoscopy.

OBJECTIVE:

To identify processes and indicators of quality and safety relevant to high-quality endoscopy service delivery.

METHODS:

A multidisciplinary group of 35 voting participants developed recommendation statements and performance indicators. Systematic literature searches generated 50 initial statements that were revised iteratively following a modified Delphi approach using a web-based evaluation and voting tool. Statement development and evidence evaluation followed the AGREE (Appraisal of Guidelines, REsearch and Evaluation) and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidelines. At the consensus conference, participants voted anonymously on all statements using a 6-point scale. Subsequent web-based voting evaluated recommendations for specific, individual quality indicators, safety indicators and mandatory endoscopy reporting fields. Consensus was defined a priori as agreement by 80% of participants.

RESULTS:

Consensus was reached on 23 recommendation statements addressing the following: ethics (statement 1: agreement 100%), facility standards and policies (statements 2 to 9: 90% to 100%), quality assurance (statements 10 to 13: 94% to 100%), training, education, competency and privileges (statements 14 to 19: 97% to 100%), endoscopy reporting standards (statements 20 and 21: 97% to 100%) and patient perceptions (statements 22 and 23: 100%). Additionally, 18 quality indicators (agreement 83% to 100%), 20 safety indicators (agreement 77% to 100%) and 23 recommended endoscopy-reporting elements (agreement 91% to 100%) were identified.

DISCUSSION:

The consensus process identified a clear need for high-quality clinical and outcomes research to support quality improvement in the delivery of endoscopy services.

CONCLUSIONS:

The guidelines support quality improvement in endoscopy by providing explicit recommendations on systematic monitoring, assessment and modification of endoscopy service delivery to yield benefits for all patients affected by the practice of gastrointestinal endoscopy.

Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B. We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells. In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation. Low-dose 5-aza induces a p53 transcriptional signature distinct from that induced with cisplatin in NT2/D1 cells and also uniquely downregulates genes associated with pluripotency including NANOG, SOX2, GDF3 and Myc target genes. Changes in the p53 and pluripotency signatures with 5-aza were to a large extent dependent on high levels of DNMT3B. In contrast to the majority of p53 target genes upregulated by 5-aza that did not show DNA hypomethylation, several other genes induced with 5-aza had corresponding decreases in promoter methylation. These genes include RIN1, SOX15, GPER, and TLR4 and are novel candidate tumors suppressors in TGCTs. Our studies suggest that the hypersensitivity of NT2/D1 cells to low-dose 5-aza is multifactorial and involves the combined activation of p53 targets, repression of pluripotency genes, and activation of genes repressed by DNA methylation. Low-dose 5-aza therapy may be a general strategy to treat those tumors that are sustained by cells with embryonic stem-like properties.

GEO number for the microarray data: GSE42647.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer, and the second leading cause of cancer death among men and women in Canada. Prompted by nationally accepted CRC guidelines, the use of colonoscopy – widely regarded to be the optimal method of CRC screening – has increased dramatically in recent years. However, when evaluating colonoscopy performance and the delivery of high-quality care, it is important to also consider factors relevant to the patients who require colonoscopy services. Understanding the patient perspective on what comprises quality in colonoscopy/endoscopy is essential to tailoring improvements in the standards of practice and quality of care. Accordingly, this study systematically reviewed the literature pertaining to aspects of colonoscopy and endoscopy that may be considered to be important to patients.

BACKGROUND:

Given the limited state of health care resources, increased demand for colorectal cancer (CRC) screening raises concerns about the quality of endoscopy services. Little is known about quality in colonoscopy and endoscopy from the patient perspective.

OBJECTIVE:

To systematically review the literature on quality that is relevant to patients who require colonoscopy or endoscopy services.

METHODS:

A systematic PubMed search was performed on articles that were published between January 2000 and February 2011. Keywords included “colonoscopy” or “sigmoidoscopy” or “endoscopy” AND “quality”; “colonoscopy” or “sigmoidoscopy” or “endoscopy” AND “patient satisfaction” or “willingness to return”. The included articles were qualitative and quantitative English language studies regarding aspects of colonoscopy and/or endoscopy services that were evaluated by patients in which data were collected within one year of the colonoscopy/endoscopy procedure.

RESULTS:

In total, 28 quantitative studies were identified, of which eight (28.6%) met the inclusion criteria (four cross-sectional, three prospective cohort and one single-blinded controlled study). Aspects of quality included comfort, management of pain and anxiety, endoscopy unit staff manner, skills and specialty, procedure and results discussion with the doctor, physical environment, wait times for the appointment and procedure, and discharge. Qualitative studies eliciting the patient perspective on what constituted quality in colonoscopy/endoscopy were not found.

CONCLUSIONS:

Factors related to comfort, staff, communication and the service environment were evaluated from the patient perspective using closed-ended questions that were designed by clinicians and researchers. Future research using qualitative methodology to elicit the patient perspective on quality in colonoscopy and/or endoscopy services is needed.

The repertoire of gastrointestinal (GI) symptoms is finite; however, the etiologies and mechanisms underlying symptom generation and perception are diverse and, in many cases, unknown. This review examines the clinical and experimental evidence exploring the putative relationship between gluten sensitivity (GS) and the generation of GI symptoms. It explores the hypothesis that, in a proportion of patients, GS causes functional bowel disorder (FBD)-like symptoms. We propose a model for investigating and understanding the induction of GI symptoms and dysfunction by gluten in FBD and organic disease. We hypothesize that, even in the absence of fully developed celiac disease, gluten can induce symptoms similar to FBD. We discuss the hypothesis that GS and post-infectious irritable bowel syndrome (IBS) provide two triggers that can explain at least part of the spectrum that constitutes IBS, further advancing an understanding of the role of mucosal responses to luminal factors in FBDs. We propose that the animal model of GS in human leukocyte antigen (HLA)-DQ8 mice allows investigation of mucosal pathophysiological changes that occur before the onset of full-blown inflammation in a GS host. A better understanding of how gluten can cause symptoms in sensitive individuals will illuminate the interaction between host genotype, diet, and intestinal microbiota in generating one of the most common GI conditions.

Background

Continuing developments in genetic testing technology together with research revealing gene-disease associations have brought closer the potential for genetic screening of populations. A major concern, as with any screening programme, is the response of the patient to the findings of screening, whether the outcome is positive or negative. Such concern is heightened for genetic testing, which it is feared may elicit stronger reactions than non-genetic testing.

Methods

This paper draws on thematic analysis of 113 semi-structured interviews with 39 patients being tested for familial hypercholesterolaemia (FH), an inherited predisposition to early-onset heart disease. It examines the impact of disease risk assessments based on both genetic and non-genetic information, or solely non-genetic information.

Results

The impact of diagnostic testing did not seem to vary according to whether or not genetic information was used. More generally, being given a positive or negative diagnosis of FH had minimal discernible impact on people's lives as they maintained the continuity of their beliefs and behaviour.

Conclusions

The results suggest that concerns about the use of genetic testing in this context are unfounded, a conclusion that echoes findings from studies in this and other health contexts.

Background

The behavioural impact of pharmacogenomics is untested. We tested two hypotheses concerning the behavioural impact of informing smokers their oral dose of NRT is tailored to analysis of DNA.

Methods and Findings

We conducted an RCT with smokers in smoking cessation clinics (N = 633). In combination with NRT patch, participants were informed that their doses of oral NRT were based either on their mu-opioid receptor (OPRM1) genotype, or their nicotine dependence questionnaire score (phenotype). The proportion of prescribed NRT consumed in the first 28 days following quitting was not significantly different between groups: (68.5% of prescribed NRT consumed in genotype vs 63.6%, phenotype group, difference  =  5.0%, 95% CI −0.9,10.8, p  =  0.098). Motivation to make another quit attempt among those (n  =  331) not abstinent at six months was not significantly different between groups (p  =  0.23). Abstinence at 28 days was not different between groups (p = 0.67); at six months was greater in genotype than phenotype group (13.7% vs 7.9%, difference  =  5.8%, 95% CI 1.0,10.7, p  =  0.018).

Conclusions

Informing smokers their oral dose of NRT was tailored to genotype not phenotype had a small, statistically non-significant effect on 28-day adherence to NRT. Among those still smoking at six months, there was no evidence that saying NRT was tailored to genotype adversely affected motivation to make another quit attempt. Higher abstinence rate at six months in the genotype arm requires investigation.

Trial registration

Controlled-Trials.com ISRCTN14352545.

Immunoglobulin A tissue transglutaminase is the single most efficient serological test for the diagnosis of celiac disease. It is well known that immunoglobulin A tissue transglutaminase levels correlate with the degree of intestinal damage, and that values can fluctuate in patients over time. Serological testing can be used to identify symptomatic individuals that need a confirmatory biopsy, to screen at-risk populations or to monitor diet compliance in patients previously diagnosed with celiac disease. Thus, interpretation of serological testing requires consideration of the full clinical scenario. Antigliadin tests are no longer recommended for the diagnosis of classical celiac disease. However, our understanding of the pathogenesis and spectrum of gluten sensitivity has improved, and gluten-sensitive irritable bowel syndrome patients are increasingly being recognized. Studies are needed to determine the clinical utility of antigliadin serology in the diagnosis of gluten sensitivity.

Objective

The term ‘functional’ has a distinguished history, embodying a number of physiological concepts, but has increasingly come to mean ‘hysterical’. The DSM-V working group proposes to use ‘functional’ as the official diagnostic term for medically unexplained neurological symptoms (currently known as ‘conversion disorder’). This study aimed to explore the current neurological meanings of the term and to understand its resilience.

Design

Mixed methods were used, first interviewing the neurologists in a large UK region and then surveying all neurologists in the UK on their use of the term.

Results

The interviews revealed four dominant uses—‘not organic’, a physical disability, a brain disorder and a psychiatric problem—as well as considerable ambiguity. Although there was much dissatisfaction with the term, the ambiguity was also seen as useful when engaging with patients. The survey confirmed these findings, with a majority adhering to a strict interpretation of ‘functional’ to mean only ‘not organic’, but a minority employing it to mean different things in different contexts - and endorsing the view that ‘functional’ would one day be a neurological construct again.

Conclusions

‘Functional’ embodies real divisions in neurologists' conceptualisation of unexplained symptoms and, perhaps, between those of patients and neurologists: its diversity of meanings allows it to be a common term while meaning different things to different people, or at different times, and thus conceal some of the conflict in a particularly contentious area. This flexibility may help explain the term's longevity.

BACKGROUND

Point-of-care practice audits allow documentation of procedural outcomes to support quality improvement in endoscopic practice.

OBJECTIVE

To evaluate a colonoscopists’ practice audit tool that provides point-of-care data collection and peer-comparator feedback.

METHODS

A prospective, observational colonoscopy practice audit was conducted in academic and community endoscopy units for unselected patients undergoing colonoscopy. Anonymized colonoscopist, patient and practice data were collected using touchscreen smart-phones with automated data upload for data analysis and review by participants. The main outcome measures were the following colonoscopy quality indicators: colonoscope insertion and withdrawal times, bowel preparation quality, sedation, immediate complications and polypectomy, and biopsy rates.

RESULTS

Over a span of 16 months, 62 endoscopists reported on 1279 colonoscopy procedures. The mean cecal intubation rate was 94.9% (10th centile 84.2%). The mean withdrawal time was 8.8 min and, for nonpolypectomy colonoscopies, 41.9% of colonoscopists reported a mean withdrawal time of less than 6 min. Polypectomy was performed in 37% of colonoscopies. Independent predictors of polypectomy included the following: endoscopy unit type, patient age, interval since previous colonoscopy, bowel preparation quality, stable inflammatory bowel disease, previous colon polyps and withdrawal time. Withdrawal times of less than 6 min were associated with lower polyp removal rates (mean difference −11.3% [95% CI −2.8% to −19.9%]; P=0.01).

DISCUSSION

Cecal intubation rates exceeded 90% and polypectomy rates exceeded 30%, but withdrawal times were frequently shorter than recommended. There are marked practice variations consistent with previous observations.

CONCLUSION

Real-time, point-of-care practice audits with prompt, confidential access to outcome data provide a basis for targeted educational programs to improve quality in colonoscopy practice.

With the advent of several innovative wound care management tools, the choice of products and treatment modalities available to clinicians continues to expand. High costs associated with wound care, especially diabetic foot wounds, make it important for clinician scientists to research alternative therapies and optimally incorporate them into wound care protocols appropriately. This article reviews using sugar as a treatment option in diabetic foot care and provides a guide to its appropriate use in healing foot ulcers. In addition to a clinical case study, the physiological significance and advantages of sugar are discussed.

BACKGROUND:

The cost-effectiveness of initial strategies in managing Canadian patients with uninvestigated upper gastrointestinal symptoms remains controversial.

OBJECTIVE:

To assess the cost-effectiveness of six management approaches to uninvestigated upper gastrointestinal symptoms in the Canadian setting.

METHODS:

The present study analyzed data from four randomized trials assessing homogeneous and complementary populations of Canadian patients with uninvestigated upper gastrointestinal symptoms with comparable outcomes. Symptom-free months, quality-adjusted life-years (QALYs) and direct costs in Canadian dollars of two management approaches based on the Canadian Dyspepsia Working Group (CanDys) Clinical Management Tool, and four additional strategies (two empirical antisecretory agents, and two prompt endoscopy) were examined and compared. Prevalence data, probabilities, utilities and costs were included in a Markov model, while sensitivity analysis used Monte Carlo simulations. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were determined.

RESULTS:

Empirical omeprazole cost $226 per QALY ($49 per symptom-free month) per patient. CanDys omeprazole and endoscopy approaches were more effective than empirical omeprazole, but more costly. Alternatives using H2-receptor antagonists were less effective than those using a proton pump inhibitor. No significant differences were found for most incremental cost-effectiveness ratios. As willingness to pay (WTP) thresholds rose from $226 to $24,000 per QALY, empirical antisecretory approaches were less likely to be the most cost-effective choice, with CanDys omeprazole progressively becoming a more likely option. For WTP values ranging from $24,000 to $70,000 per QALY, the most clinically relevant range, CanDys omeprazole was the most cost-effective strategy (32% to 46% of the time), with prompt endoscopy-proton pump inhibitor favoured at higher WTP values.

CONCLUSIONS:

Although no strategy was the indisputable cost-effective option, CanDys omeprazole may be the strategy of choice over a clinically relevant range of WTP assumptions in the initial management of Canadian patients with uninvestigated dyspepsia.

Background

Conversion disorder is largely managed by neurologists, for whom it presents great challenges to understanding and management. This study aimed to quantify these challenges, examining how neurologists understand conversion disorder, and what they tell their patients.

Methods

A postal survey of all consultant neurologists in the UK registered with the Association of British Neurologists.

Results

349 of 591 practising consultant neurologists completed the survey. They saw conversion disorder commonly. While they endorsed psychological models for conversion, they diagnosed it according to features of the clinical presentation, most importantly inconsistency and abnormal illness behaviour. Most of the respondents saw feigning as entangled with conversion disorder, with a minority seeing one as a variant of the other. They were quite willing to discuss psychological factors as long as the patient was receptive but were generally unwilling to discuss feigning even though they saw it as their responsibility. Those who favoured models in terms of feigning were older, while younger, female neurologists preferred psychological models, believed conversion would one day be understood neurologically and found communicating with their conversion patients easier than it had been in the past.

Discussion

Neurologists accept psychological models for conversion disorder but do not employ them in their diagnosis; they do not see conversion as clearly different from feigning. This may be changing as younger, female neurologists endorse psychological views more clearly and find it easier to discuss with their patients.

Background

Estimates of the risk of developing Crohn's disease (CD) can be made using DNA testing for mutations in the NOD2 (CARD15) gene, family history, and smoking status. Smoking doubles the risk of CD, a risk that is reduced by stopping. CD therefore serves as a timely and novel paradigm within which to assess the utility of predictive genetic testing to motivate behaviour change to reduce the risk of disease. The aim of the study is to describe the impact upon stopping smoking of communicating a risk of developing CD that incorporates DNA analysis. We will test the following main hypothesis:

Smokers who are first degree relatives (FDRs) of CD probands are more likely to make smoking cessation attempts following communication of risk estimates of developing CD that incorporate DNA analysis, compared with an equivalent communication that does not incorporate DNA analysis.

Methods/design

A parallel groups randomised controlled trial in which smokers who are FDRs of probands with CD are randomly allocated in families to undergo one of two types of assessment of risk for developing CD based on either:

i. DNA analysis, family history of CD and smoking status, or

ii. Family history of CD and smoking status

The primary outcome is stopping smoking for 24 hours or longer in the six months following provision of risk information. The secondary outcomes are seven-day smoking abstinence at one week and six month follow-ups. Randomisation of 470 smoking FDRs of CD probands, with 400 followed up (85%), provides 80% power to detect a difference in the primary outcome of 14% between randomised arms, at the 5% significance level.

Discussion

This trial provides one of the strongest tests to date of the impact of communicating DNA-based risk assessment on risk-reducing behaviour change. Specific issues regarding the choice of trial design are discussed.

Trial Registration

ISRCTN: ISRCTN21633644

Background

The behavioural impact of pharmacogenomics is untested; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to this medication. The objective of this trial is to estimate the impact upon adherence to nicotine replacement therapy (NRT) of informing smokers that their oral dose of NRT has been tailored to a DNA analysis. Hypotheses to be tested are as follows:

I Adherence to NRT is greater among smokers informed that their oral dose of NRT is tailored to an analysis of DNA (genotype), compared to one tailored to nicotine dependence questionnaire score (phenotype).

II Amongst smokers who fail to quit at six months, motivation to make another quit attempt is lower when informed that their oral dose of NRT was tailored to genotype rather than phenotype.

Methods/Design

An open label, parallel groups randomised trial in which 630 adult smokers (smoking 10 or more cigarettes daily) using National Health Service (NHS) stop smoking services in primary care are randomly allocated to one of two groups:

i. NRT oral dose tailored by DNA analysis (OPRM1 gene) (genotype), or

ii. NRT oral dose tailored by nicotine dependence questionnaire score (phenotype)

The primary outcome is proportion of prescribed NRT consumed in the first 28 days following an initial quit attempt, with the secondary outcome being motivation to make another quit attempt, amongst smokers not abstinent at six months. Other outcomes include adherence to NRT in the first seven days and biochemically validated smoking abstinence at six months. The primary outcome will be collected on 630 smokers allowing sufficient power to detect a 7.5% difference in mean proportion of NRT consumed using a two-tailed test at the 5% level of significance between groups. The proportion of all NRT consumed in the first four weeks of quitting will be compared between arms using an independent samples t-test and by estimating the 95% confidence interval for observed between-arm difference in mean NRT consumption (Hypothesis I). Motivation to make another quit attempt will be compared between arms in those failing to quit by six months (Hypothesis II).

Discussion

This is the first clinical trial evaluating the behavioural impact on adherence of prescribing medication using genetic rather than phenotypic information. Specific issues regarding the choice of design for trials of interventions of this kind are discussed.

Trial details

Funder: Medical Research Council (MRC)

Grant number: G0500274

ISRCTN: 14352545

Date trial stated: June 2007

Expected end date: December 2009

Expected reporting date: December 2010

Background

Monetary incentives are an effective way of increasing response rates to surveys, though they are generally less effective in physicians, and are more effective when the incentive is paid up-front rather than when made conditional on completion.

Methods

In this study we examine the effectiveness of pre- and post-completion incentives on the response rates of all the neurologists in the UK to a survey about conversion disorder, using a cluster randomised controlled design. A postal survey was sent to all practicing consultant neurologists, in two rounds, including either a book token, the promise of a book token, or nothing at all.

Results

Three hundred and fifty-one of 591 eligible neurologists completed the survey, for a response rate of 59%. While the post-completion incentive exerted no discernible influence on response rates, a pre-completion incentive did, with an odds-ratio of 2.1 (95% confidence interval 1.5 - 3.0).

Conclusions

We conclude that neurologists, in the UK at least, may be influenced to respond to a postal survey by a pre-payment incentive but are unaffected by a promised reward.

Conversion disorder (‘hysteria’) was largely considered to be a neurological problem in the 19th century, but without a neuropathological explanation it was commonly assimilated with malingering. The theories of Janet and Freud transformed hysteria into a psychiatric condition, but as such models decline in popularity and a neurobiology of conversion has yet to be found, today's neurologists once again face a disorder without an accepted model. This article explores how today's neurologists understand conversion through in-depth interviews with 22 neurology consultants. The neurologists endorsed psychological models but did not understand their patients in such terms. Rather, they distinguished conversion from other unexplained conditions clinically by its severity and inconsistency. While many did not see this as clearly distinct from feigning, they did not feel that this was their problem to resolve. They saw themselves as ‘agnostic’ regarding non-neuropathological explanations. However, since neurologists are in some ways more expert in conversion than psychiatrists, their continuing support for the deception model is important, and begs an explanation. One reason for the model's persistence may be that it is employed as a diagnostic device, used to differentiate between those unexplained symptoms that could, in principle, have a medical explanation and those that could not.

This paper explores whether and how the behavioral impact of genotype disclosure can be disentangled from the impact of numerical risk estimates generated by genetic tests. Secondary data analyses are presented from a randomized controlled trial of 162 first-degree relatives of Alzheimer’s disease (AD) patients. Each participant received a lifetime risk estimate of AD. Control group estimates were based on age, gender, family history, and assumed ε4-negative apolipoprotein E (APOE) genotype; intervention group estimates were based upon the first three variables plus true APOE genotype, which was also disclosed. AD-specific self-reported behavior change (diet, exercise, and medication use) was assessed at 12 months. Behavior change was significantly more likely with increasing risk estimates, and also more likely, but not significantly so, in ε4-positive intervention group participants (53% changed behavior) than in control group participants (31%). Intervention group participants receiving ε4-negative genotype feedback (24% changed behavior) and control group participants had similar rates of behavior change and risk estimates, the latter allowing assessment of the independent effects of genotype disclosure. However, collinearity between risk estimates and ε4-positive genotypes, which engender high-risk estimates, prevented assessment of the independent effect of the disclosure of an ε4 genotype. Novel study designs are proposed to determine whether genotype disclosure has an impact upon behavior beyond that of numerical risk estimates.

Background

Many interventions shown to be effective through clinical trials are not readily implemented in clinical practice. Unfortunately, little is known regarding how clinicians construct their perceptions of the effectiveness of medical interventions. This study aims to explore general practitioners' perceptions of the nature of 'effectiveness'.

Methods

The design was qualitative in nature using the repertory grid technique to elicit the constructs underlying the perceived effectiveness of a range of medical interventions. Eight medical interventions were used as stimuli (diclophenac to reduce acute pain, cognitive behaviour therapy to treat depression, weight loss surgery to achieve weight loss, diet and exercise to prevent type 2 diabetes, statins to prevent heart disease, stopping smoking to prevent heart disease, nicotine replacement therapy to stop smoking, and stop smoking groups to stop smoking). The setting involved face-to-face interviews followed by questionnaires in London Primary Care Trusts. Participants included a random sample of 13 general practitioners.

Results

Analysis of the ratings showed that the constructs clustered around two dimensions: low patient effort versus high patient effort (dimension one), and small impact versus large impact (dimension two). Dimension one represented constructs such as 'success requires little motivation', 'not a lifestyle intervention', and 'health-care professional led intervention'. Dimension two represented constructs such as 'weak and/or minimal evidence of effectiveness', 'small treatment effect for users', 'a small proportion of users will benefit' and 'not cost-effective'. Constructs within each dimension were closely related.

Conclusions

General practitioners judged the effectiveness of medical interventions by considering two broad dimensions: the extent to which interventions involve patient effort, and the size of their impact. The latter is informed by trial evidence, but the patient effort required to achieve effectiveness seems to be based on clinical judgement. Some of the failure of evidence-based medicine to be implemented may be more explicable if both dimensions were attended to.

Objective

Neurologists face a dilemma when communicating with their conversion disorder patients – whether to be frank, and risk losing the patient's trust, or to disclose less, in the hope of building a therapeutic relationship. This study reports how neurologists in the UK described dealing with this dilemma in their practice.

Methods

Practicing consultant neurologists from an NHS region were recruited by snowball sampling. Twenty-two of 35 consultants in the region were interviewed in depth, and the interviews qualitatively analysed.

Results

The neurologists were reluctant to disclose conversion disorder as a differential diagnosis until they were certain. They were guided by the receptivity of their patients as to how psychological to make their eventual explanations, but they did not discuss their suspicions about feigning. They described their communications as much easier now than they had seen in training.

Conclusion

Neurologists adapt their disclosure to their patients, which facilitates communication, but imposes some limits on truth-telling. In particular, it may sometimes result in a changed diagnosis.

Practice implications

An optimum strategy for communicating diagnoses will need to balance ethical considerations with demonstrated therapeutic benefit.

BACKGROUND:

The incidence and prevalence rates of childhood Helicobacter pylori infection vary greatly by nation, with infection rates of 8.9% to 72.8% reported in developed and developing countries, respectively. To date, few studies have assessed the prevalence of H pylori in Canadian children, with studies limited to Aboriginal communities and single tertiary care centres from Ontario and Quebec.

OBJECTIVES:

To determine the prevalence of H pylori in consecutive children referred to three Canadian tertiary care academic centres for upper gastrointestinal (GI) endoscopy due to upper GI symptoms, and to determine the sensitivity and specificity of the carbon-13-labelled urea breath test, the rapid urease test and the H pylori stool monoclonal antigen test.

RESULTS:

Two hundred four patients were recruited. The prevalence of H pylori was 7.1%. Of the H pylori-positive patients, 41.7% were male, with a mean age of 10.3 years. Ethnic minorities accounted for 42% of the H pylori-positive patients. Consistent with previous observations, the sensitivity and specificity of the carbon-13-labelled urea breath test were 1.0 and 0.98, respectively. The sensitivity and specificity of the rapid urease test were 1.0 and 0.99, respectively. Stool samples were collected from 34 patients from one centre, with a sensitivity and specificity of 1.0 and 0.68, respectively. No defining symptoms of H pylori infection were evident and no peptic ulcer disease was demonstrated.

CONCLUSION:

H pylori infection rates in Canadian children with upper GI symptoms are low, and are lower than those reported for other developed countries. Further studies are required in Canada to determine the prevalence in the general population and specifically in the populations at risk.

In October 2006, the Chief Medical Officer (CMO) of England asked Professor Sir John Tooke to chair a High Level Group on Clinical Effectiveness in response to the chapter 'Waste not, want not' in the CMOs 2005 annual report 'On the State of the Public Health'. The high level group made recommendations to the CMO to address possible ways forward to improve clinical effectiveness in the UK National Health Service (NHS) and promote clinical engagement to deliver this. The report contained a short section on research needs that emerged from the process of writing the report, but in order to more fully identify the relevant research agenda Professor Sir John Tooke asked Professor Martin Eccles to convene an expert group – the Clinical Effectiveness Research Agenda Group (CERAG) – to define the research agenda. The CERAG's terms of reference were 'to further elaborate the research agenda in relation to pursuing clinically effective practice within the (UK) National Health Service'. This editorial presents the summary of the CERAG report and recommendations.