Using re-randomisation designs to increase the efficiency and applicability of retention studies within trials: a case study.

BACKGROUND: Poor retention in randomised trials can lead to serious consequences to their validity. Studies within trials (SWATs) are used to identify the most effective interventions to increase retention. Many interventions could be applied at any follow-up time point, but SWATs commonly assess interventions at a single time point, which can reduce efficiency. METHODS: The re-randomisation design allows participants to be re-enrolled and re-randomised whenever a new retention opportunity occurs (i.e. a new follow-up time point where the intervention could be applied). The main advantages are as follows: (a) it allows the estimation of an average effect across time points, thus increasing generalisability; (b) it can be more efficient than a parallel arm trial due to increased sample size; and (c) it allows subgroup analyses to estimate effectiveness at different time points. We present a case study where the re-randomisation design is used in a SWAT. RESULTS: In our case study, the host trial is a dental trial with two available follow-up points. The Sticker SWAT tests whether adding the trial logo's sticker to the questionnaire's envelope will result in a higher response rate compared with not adding the sticker. The primary outcome is the response rate to postal questionnaires. The re-randomisation design could double the available sample size compared to a parallel arm trial, resulting in the ability to detect an effect size around 28% smaller. CONCLUSION: The re-randomisation design can increase the efficiency and generalisability of SWATs for trials with multiple follow-up time points.

Triggering palliative care referrals through the identification of poor prognosis in older patients presented to emergency departments in rural Australia.

Background: Without objective screening for risk of death, the palliative care needs of older patients near the end of life may be unrecognised and unmet. Aim: This study aimed to estimate the usefulness of the Criteria for Screening and Triaging to Appropriate aLternative care (CriSTAL) tool in determining older patients' risk of death within 3-months after initial hospital admission. Methods: A prospective cohort study of 235 patients aged 70+ years, who presented to two rural emergency departments in two adjacent Australian states, was utilised. The 'risk of death' of each patient was screened with the CriSTAL prognostic tool. Their 3-month follow-up outcomes were assessed through telephone interviews and a clinical record review. Findings: A CriSTAL cut-off score of more than 7 yielded a sensitivity of 80.7% and specificity of 70.81% for a 3-month risk of death. Palliative care services were only used by 31% of the deceased in their last trimester of life. Conclusion: Prognostic tools provide a viable means of identifying individuals with a poor prognosis. Identification can trigger an earlier referral to palliative care, which will benefit the patient's wellbeing and quality of life.

Photodynamic versus white-light-guided resection of first-diagnosis non-muscle-invasive bladder cancer: PHOTO RCT.

BACKGROUND: Around 7500 people are diagnosed with non-muscle-invasive bladder cancer in the UK annually. Recurrence following transurethral resection of bladder tumour is common, and the intensive monitoring schedule required after initial treatment has associated costs for patients and the NHS. In photodynamic diagnosis, before transurethral resection of bladder tumour, a photosensitiser that is preferentially absorbed by tumour cells is instilled intravesically. Transurethral resection of bladder tumour is then conducted under blue light, causing the photosensitiser to fluoresce. Photodynamic diagnosis-guided transurethral resection of bladder tumour offers better diagnostic accuracy than standard white-light-guided transurethral resection of bladder tumour, potentially reducing the chance of subsequent recurrence. OBJECTIVE: The objective was to assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis-guided transurethral resection of bladder tumour. DESIGN: This was a multicentre, pragmatic, open-label, parallel-group, non-masked, superiority randomised controlled trial. Allocation was by remote web-based service, using a 1 : 1 ratio and a minimisation algorithm balanced by centre and sex. SETTING: The setting was 22 NHS hospitals. PARTICIPANTS: Patients aged ≥ 16 years with a suspected first diagnosis of high-risk non-muscle-invasive bladder cancer, no contraindications to photodynamic diagnosis and written informed consent were eligible. INTERVENTIONS: Photodynamic diagnosis-guided transurethral resection of bladder tumour and standard white-light cystoscopy transurethral resection of bladder tumour. MAIN OUTCOME MEASURES: The primary clinical outcome measure was the time to recurrence from the date of randomisation to the date of pathologically proven first recurrence (or intercurrent bladder cancer death). The primary health economic outcome was the incremental cost per quality-adjusted life-year gained at 3 years. RESULTS: We enrolled 538 participants from 22 UK hospitals between 11 November 2014 and 6 February 2018. Of these, 269 were allocated to photodynamic diagnosis and 269 were allocated to white light. A total of 112 participants were excluded from the analysis because of ineligibility (n = 5), lack of non-muscle-invasive bladder cancer diagnosis following transurethral resection of bladder tumour (n = 89) or early cystectomy (n = 18). In total, 209 photodynamic diagnosis and 217 white-light participants were included in the clinical end-point analysis population. All randomised participants were included in the cost-effectiveness analysis. Over a median follow-up period of 21 months for the photodynamic diagnosis group and 22 months for the white-light group, there were 86 recurrences (3-year recurrence-free survival rate 57.8%, 95% confidence interval 50.7% to 64.2%) in the photodynamic diagnosis group and 84 recurrences (3-year recurrence-free survival rate 61.6%, 95% confidence interval 54.7% to 67.8%) in the white-light group (hazard ratio 0.94, 95% confidence interval 0.69 to 1.28; p = 0.70). Adverse event frequency was low and similar in both groups [12 (5.7%) in the photodynamic diagnosis group vs. 12 (5.5%) in the white-light group]. At 3 years, the total cost was £12,881 for photodynamic diagnosis-guided transurethral resection of bladder tumour and £12,005 for white light. There was no evidence of differences in the use of health services or total cost at 3 years. At 3 years, the quality-adjusted life-years gain was 2.094 in the photodynamic diagnosis transurethral resection of bladder tumour group and 2.087 in the white light group. The probability that photodynamic diagnosis-guided transurethral resection of bladder tumour was cost-effective was never > 30% over the range of society's cost-effectiveness thresholds. LIMITATIONS: Fewer patients than anticipated were correctly diagnosed with intermediate- to high-risk non-muscle-invasive bladder cancer before transurethral resection of bladder tumour and the ratio of intermediate- to high-risk non-muscle-invasive bladder cancer was higher than expected, reducing the number of observed recurrences and the statistical power. CONCLUSIONS: Photodynamic diagnosis-guided transurethral resection of bladder tumour did not reduce recurrences, nor was it likely to be cost-effective compared with white light at 3 years. Photodynamic diagnosis-guided transurethral resection of bladder tumour is not supported in the management of primary intermediate- to high-risk non-muscle-invasive bladder cancer. FUTURE WORK: Further work should include the modelling of appropriate surveillance schedules and exploring predictive and prognostic biomarkers. TRIAL REGISTRATION: This trial is registered as ISRCTN84013636. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 40. See the NIHR Journals Library website for further project information.

Around 7500 people are diagnosed with early-stage bladder cancer in the UK each year. Early bladder cancer is contained within the bladder and has not yet invaded the bladder's muscle wall or spread elsewhere in the body. The cancer will return (recur) in around half of people after initial treatment and they have to attend hospital for regular check-ups, with costs to both them and the NHS. The first step in treating early bladder cancer is surgery to remove the tumour. This surgery is normally performed under white light. Photodynamic diagnosis is a new technique in which a liquid is put into the patient's bladder before surgery and a blue light is used during the operation. This causes the bladder cancer to fluoresce so that it can be seen more easily by the surgeon. The Photodynamic versus white-light-guided resection of first diagnosis non-muscle-invasive bladder cancer ( PHOTO ) trial aimed to find out whether or not using photodynamic diagnosis at initial surgery would reduce how often the cancer recurred and whether or not this could reduce the cost of treating early bladder cancer. A total of 538 people with early bladder cancer who had a medium to high chance of their cancer returning after treatment were enrolled in the PHOTO trial. They were included in one of two treatment groups, at random: 269 had photodynamic surgery and 269 had standard white-light surgery. People in both groups were monitored regularly for any recurrences, with further treatment as appropriate. After 3 years, 4 out of 10 people in each group had a recurrence of their bladder cancer. We found no difference between the treatment groups in the number of people with recurrences. We found no evidence of a benefit to patients, and the total costs of photodynamic surgery were higher than those of standard white light. We therefore recommend that it is no longer used in the treatment of this group of patients.

Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP): a feasibility study.

BACKGROUND: Progression of dental caries can result in irreversible pulpal damage. Partial irreversible pulpitis is the initial stage of this damage, confined to the coronal pulp whilst the radicular pulp shows little or no sign of infection. Preserving the pulp with sustained vitality and developing minimally invasive biologically based therapies are key themes within contemporary clinical practice. However, root canal treatment involving complete removal of the pulp is often the only option (other than extraction) given to patients with irreversible pulpitis, with substantial NHS and patient incurred costs. The European Society of Endodontology's (ESE 2019) recent consensus statement recommends full pulpotomy, where the inflamed coronal pulp is removed with the goal of keeping the radicular pulp vital, as a more minimally invasive technique, potentially avoiding complex root canal treatment. Although this technique may be provided in secondary care, it has not been routinely implemented or evaluated in UK General Dental Practice. METHOD: This feasibility study aims to identify and assess in a primary care setting the training needs of general dental practitioners and clinical fidelity of the full pulpotomy intervention, estimate likely eligible patient pool and develop recruitment materials ahead of the main randomised controlled trial comparing the clinical and cost-effectiveness of full pulpotomy compared to root canal treatment in pre/molar teeth of adults 16 years and older showing signs indicative of irreversible pulpitis. The feasibility study will recruit and train 10 primary care dentists in the full pulpotomy technique. Dentists will recruit and provide full pulpotomy to 40 participants (four per practice) with indications of partial irreversible pulpitis. DISCUSSION: The Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP) study will address the lack of high-quality evidence in the treatment of irreversible pulpitis, to aid dental practitioners, patients and policymakers in their decision-making. The PIP feasibility study will inform the main study on the practicality of providing both training and provision of the full pulpotomy technique in general dental practice. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN17973604 . Registered on 28 January 2021. Protocol version Protocol version: 1; date: 03.02.2021.

A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Recurrence of non­muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection. METHODS: In this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)­guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat. RESULTS: A total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months' median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444). CONCLUSIONS: PDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)

Examining the impact of oral hygiene advice and/or scale and polish on periodontal disease: the IQuaD cluster factorial randomised controlled trial.

Objective To compare the clinical effectiveness and cost benefit of different frequencies of scale and polish (S&P) treatments in combination with different types of oral hygiene advice (OHA).Design Multi-centre, multi-level cluster randomised factorial open trial with blinded outcome evaluation. UK dental practices were cluster randomised to deliver OHA as usual or personalised. In a separate randomisation, patients were allocated to receive S&P 6-monthly, 12-monthly or never.Setting UK primary dental care.Participants Practices providing NHS care and adults who had received regular dental check-ups.Main outcome measures The percent of sites with bleeding on probing, patient confidence in self-care, incremental net benefits (INB) over three years.Results Sixty-three practices and 1,877 adult patients were randomised and 1,327 analysed (clinical outcome). There was no statistically significant or clinically important difference in gingival bleeding between the three S&P groups (for example, six-monthly versus none: difference 0.87% sites, 95% CI: 1.6 to 3.3, p = 0.48) or between personalised or usual OHA groups (difference -2.5% sites, -95%CI: -8.3 to 3.3, p = 0.39), or oral hygiene self-efficacy (cognitive impact) between either group (for example, six-monthly versus none: difference -0.028, 95% CI -0.119 to 0.063, p = 0.543). The general population place a high value on, and are willing to pay for, S&P services. However, from a dental health perspective, none of the interventions were cost-effective.Conclusion Results suggest S&P treatments and delivering brief personalised OHA provide no clinical benefit and are therefore an inefficient approach to improving dental health (38% of sites were bleeding whatever intervention was received). However, the general population value both interventions.

Using systematic data categorisation to quantify the types of data collected in clinical trials: the DataCat project.

BACKGROUND: Data collection consumes a large proportion of clinical trial resources. Each data item requires time and effort for collection, processing and quality control procedures. In general, more data equals a heavier burden for trial staff and participants. It is also likely to increase costs. Knowing the types of data being collected, and in what proportion, will be helpful to ensure that limited trial resources and participant goodwill are used wisely. AIM: The aim of this study is to categorise the types of data collected across a broad range of trials and assess what proportion of collected data each category represents. METHODS: We developed a standard operating procedure to categorise data into primary outcome, secondary outcome and 15 other categories. We categorised all variables collected on trial data collection forms from 18, mainly publicly funded, randomised superiority trials, including trials of an investigational medicinal product and complex interventions. Categorisation was done independently in pairs: one person having in-depth knowledge of the trial, the other independent of the trial. Disagreement was resolved through reference to the trial protocol and discussion, with the project team being consulted if necessary. KEY RESULTS: Primary outcome data accounted for 5.0% (median)/11.2% (mean) of all data items collected. Secondary outcomes accounted for 39.9% (median)/42.5% (mean) of all data items. Non-outcome data such as participant identifiers and demographic data represented 32.4% (median)/36.5% (mean) of all data items collected. CONCLUSION: A small proportion of the data collected in our sample of 18 trials was related to the primary outcome. Secondary outcomes accounted for eight times the volume of data as the primary outcome. A substantial amount of data collection is not related to trial outcomes. Trialists should work to make sure that the data they collect are only those essential to support the health and treatment decisions of those whom the trial is designed to inform.

Verifying participant-reported clinical outcomes: challenges and implications.

BACKGROUND: Researchers often rely on trial participants to self-report clinical outcomes (for example, fractures, re-operations). Little information exists as to the 'accuracy' of participant-reported clinical outcomes, particularly in randomised controlled trials (RCTs). To help address this evidence gap, we report four case studies, nested within different RCTs where participant-reported clinical outcome data were compared with those reported by clinicians or extracted from medical notes. METHODS: Four publicly-funded RCTs with different methods of verifying participant-reported outcomes were identified. In KAT, the participants were asked about hospital admissions for any reason. Where it was thought to be relevant to the trial knee, further information was sought from the lead surgeon at the admitting site to confirm whether or not the admission was relevant to the trial knee. In REFLUX, participants were asked about hospital admissions for any reason. For participants who reported a re-operation, further information was sought from the lead surgeon at the admitting site to confirm this. In RECORD, participants were asked three questions regarding broken bones. Where low-trauma fractures were reported, clinical verification was sought, initially from the research nurse at the site. In CATHETER, participants were asked about urinary tract infections (UTIs), and a prescription of antibiotics was provided for the treatment of UTIs following urethral catheterisation. The GPs of those who reported a UTI were contacted to confirm that an antibiotic prescription had been issued for the suspected UTI. RESULTS: In KAT, 397 of 6882 (6%) participant-reported hospital admissions were confirmed as relevant to the trial knee. In REFLUX, 16 of 19 participants (84%) who appeared to have had a re-operation were confirmed as having had one. In RECORD, 473 of 781 (61%) fractures reported by participants were confirmed as being low-trauma fractures. In CATHETER, 429 of 830 participant-reported UTIs (52%) were confirmed as such by the GPs. CONCLUSIONS: We used different approaches in our verification of participant-reported outcomes in clinical trials, and we believe there is no one optimal solution. Consideration of issues such as what information is sought from participants, the phrasing of questions, whether the medical records are a true 'gold standard' and costs and benefits to the RCT may help determine the appropriate approach.

Three behavior change theory-informed randomized studies within a trial to improve response rates to trial postal questionnaires.

OBJECTIVES: Our aim was to design and evaluate a novel behavior change approach to increase response rates to an annual postal questionnaire in three randomized studies within a trial (SWAT) and replicate the most promising SWAT. STUDY DESIGN AND SETTING: SWAT1 tested a trial logo sticker on questionnaire envelopes vs. no sticker; SWAT2 tested a theoretically informed letter sent with the questionnaire vs. a standard letter; SWAT3 tested a theoretically informed newsletter sent before the questionnaire vs. no newsletter. The SWATs were conducted within a large dental trial (N = 1,877 adults), and SWAT2 replicated in a different trial in a similar setting (N = 2,372). RESULTS: SWAT1 improved response rates by 1.4%, 95% confidence interval (CI) (-7.2%, 10.0%). SWAT2 improved response rates by 7.0%, 95% CI (1.7%, 12.3%). SWAT3 improved response rates by 0.8%, 95% CI (-5.1%, 6.7%). Replication of SWAT2 as the most promising SWAT showed improvement in response rates of 1.0%, 95% CI (-3.2%, 5.3%). Pooled results from SWAT2 showed an overall improvement in response rates of 3.4%, 95% CI (0.1%, 6.7%). CONCLUSION: A theory-based behavioral approach to design interventions to improve trial response rates showed small but meaningful improvements. The approach presented here can be easily implemented and adapted to address other identified barriers to trial retention.

Photodynamic versus white light-guided treatment of non-muscle invasive bladder cancer: a study protocol for a randomised trial of clinical and cost-effectiveness.

INTRODUCTION: Bladder cancer is the most frequently occurring tumour of the urinary system. Ta, T1 tumours and carcinoma in situ (CIS) are grouped as non-muscle invasive bladder cancer (NMIBC), which can be effectively treated by transurethral resection of bladder tumour (TURBT). There are limitations to the visualisation of tumours with conventional TURBT using white light illumination within the bladder. Incomplete resections occur from the failure to identify satellite lesions or the full extent of the tumour leading to recurrence and potential risk of disease progression. To improve complete resection, photodynamic diagnosis (PDD) has been proposed as a method that can enhance tumour detection and guide resection. The objective of the current research is to determine whether PDD-guided TURBT is better than conventional white light surgery and whether it is cost-effective. METHODS AND ANALYSIS: PHOTO is a pragmatic multicentre randomised controlled trial (open parallel group, non-masked and superiority trial) comparing the intervention of PDD-guided TURBT with standard white light resection in newly diagnosed intermediate and high risk NMIBC within the UK National Health Service setting. Clinical effectiveness is measured with time to recurrence. Cost-effectiveness is assessed within trial via the calculation of incremental cost per recurrence avoided and incremental cost per quality-adjusted life per year gained over 3 years and over long term through a modelling exercise over patients' lifetime. ETHICS AND DISSEMINATION: Formal ethics review was undertaken with a favourable opinion, in line with UK regulatory procedures (REC reference number: 14/NE/1062). If reductions in time to recurrence is associated with long-term patient benefits, the cost-effectiveness evaluation will provide further evidence to inform adoption of the technology. Findings will be shared in lay media such as patient and charity forums and will be presented at key meetings and published in academic literature.Trial registration number ISRCTN84013636.

Estimating Site Performance (ESP): can trial managers predict recruitment success at trial sites? An exploratory study.

BACKGROUND: Multicentre randomised trials provide some of the key evidence underpinning healthcare practice around the world. They are also hard work and generally expensive. Some of this work and expense are devoted to sites that fail to recruit as many participants as expected. Methods to identify sites that will recruit to target would be helpful. METHODS: We asked trial managers at the Centre for Healthcare Randomised Trials (CHaRT), University of Aberdeen to predict whether a site would recruit to target. Predictions were made after a site initiation visit and were collected on a form comprising a simple 'Yes/No' prediction and a reason for the prediction. We did not provide guidance as to what trial managers might want to think about when making predictions. After a minimum of eight months of recruitment at each site for which a prediction had been made, all trial mangers in CHaRT were invited to a group discussion where predictions were presented together with sites' actual recruitment performance over that period. Individual trial managers reflected on their predictions and there was a general discussion about predicting site recruitment. The prediction reasons from the forms and the content of the group discussion were used to identify features linked to correct predictions of recruitment failure. RESULTS: Ten trial managers made predictions for 56 site visits recruiting to eight trials. Trial managers' sensitivity was 82% and their specificity was 32%, correctly identifying 65% of sites that would hit their recruitment target and 54% of those that did not. Eight 'red flags' for recruitment failure were identified: previous poor site performance; slow approvals process; strong staff/patient preferences; the site recruitment target; the trial protocol and its implementation at the site; lack of staff engagement; lack of research experience among site staff; and busy site staff. We used these red flags to develop a guided prediction form. CONCLUSIONS: Trial managers' unguided recruitment predictions were not bad but were not good enough for decision-making. We have developed a modified prediction form that includes eight flags to consider before making a prediction. We encourage anyone interested in contributing to its evaluation to contact us.

Improving the Quality of Dentistry (IQuaD): a cluster factorial randomised controlled trial comparing the effectiveness and cost-benefit of oral hygiene advice and/or periodontal instrumentation with routine care for the prevention and management of periodontal disease in dentate adults attending dental primary care.

BACKGROUND: Periodontal disease is preventable but remains the most common oral disease worldwide, with major health and economic implications. Stakeholders lack reliable evidence of the relative clinical effectiveness and cost-effectiveness of different types of oral hygiene advice (OHA) and the optimal frequency of periodontal instrumentation (PI). OBJECTIVES: To test clinical effectiveness and assess the economic value of the following strategies: personalised OHA versus routine OHA, 12-monthly PI (scale and polish) compared with 6-monthly PI, and no PI compared with 6-monthly PI. DESIGN: Multicentre, pragmatic split-plot, randomised open trial with a cluster factorial design and blinded outcome evaluation with 3 years' follow-up and a within-trial cost-benefit analysis. NHS and participant costs were combined with benefits [willingness to pay (WTP)] estimated from a discrete choice experiment (DCE). SETTING: UK dental practices. PARTICIPANTS: Adult dentate NHS patients, regular attenders, with Basic Periodontal Examination (BPE) scores of 0, 1, 2 or 3. INTERVENTION: Practices were randomised to provide routine or personalised OHA. Within each practice, participants were randomised to the following groups: no PI, 12-monthly PI or 6-monthly PI (current practice). MAIN OUTCOME MEASURES: Clinical - gingival inflammation/bleeding on probing at the gingival margin (3 years). Patient - oral hygiene self-efficacy (3 years). Economic - net benefits (mean WTP minus mean costs). RESULTS: A total of 63 dental practices and 1877 participants were recruited. The mean number of teeth and percentage of bleeding sites was 24 and 33%, respectively. Two-thirds of participants had BPE scores of ≤ 2. Under intention-to-treat analysis, there was no evidence of a difference in gingival inflammation/bleeding between the 6-monthly PI group and the no-PI group [difference 0.87%, 95% confidence interval (CI) -1.6% to 3.3%; p = 0.481] or between the 6-monthly PI group and the 12-monthly PI group (difference 0.11%, 95% CI -2.3% to 2.5%; p = 0.929). There was also no evidence of a difference between personalised and routine OHA (difference -2.5%, 95% CI -8.3% to 3.3%; p = 0.393). There was no evidence of a difference in self-efficacy between the 6-monthly PI group and the no-PI group (difference -0.028, 95% CI -0.119 to 0.063; p = 0.543) and no evidence of a clinically important difference between the 6-monthly PI group and the 12-monthly PI group (difference -0.097, 95% CI -0.188 to -0.006; p = 0.037). Compared with standard care, no PI with personalised OHA had the greatest cost savings: NHS perspective -£15 (95% CI -£34 to £4) and participant perspective -£64 (95% CI -£112 to -£16). The DCE shows that the general population value these services greatly. Personalised OHA with 6-monthly PI had the greatest incremental net benefit [£48 (95% CI £22 to £74)]. Sensitivity analyses did not change conclusions. LIMITATIONS: Being a pragmatic trial, we did not deny PIs to the no-PI group; there was clear separation in the mean number of PIs between groups. CONCLUSIONS: There was no additional benefit from scheduling 6-monthly or 12-monthly PIs over not providing this treatment unless desired or recommended, and no difference between OHA delivery for gingival inflammation/bleeding and patient-centred outcomes. However, participants valued, and were willing to pay for, both interventions, with greater financial value placed on PI than on OHA. FUTURE WORK: Assess the clinical effectiveness and cost-effectiveness of providing multifaceted periodontal care packages in primary dental care for those with periodontitis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56465715. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 38. See the NIHR Journals Library website for further project information.

Very long-term outcomes of the Carpentier-Edwards Perimount aortic valve in patients aged 50-65 years.

OBJECTIVES: Aortic valve replacement (AVR) using a bioprosthesis remains controversial for patients aged 50-65 years. This cohort study reports the very long-term outcomes of AVR using Carpentier-Edwards Perimount pericardial bioprosthesis in this age group. METHODS: From 1984 to 2008, 522 Carpentier-Edwards Perimount pericardial aortic bioprostheses were implanted in 516 patients aged 50-65 years (mean age, 60 ± 4 years; 19% female). Multiple valve replacements were excluded fro m our cohort. Baseline demographic, perioperative and follow-up data were recorded prospectively. Mean follow-up was 9 ± 6 years, for a total of 4428 valve-years. Follow-up was complete for 97% of patients included. RESULTS: Operative mortality rate was 2%. One hundred and forty-six late deaths occurred for a linearized rate of 3%/valve-year. Actuarial survival rates averaged 73 ± 2, 59 ± 3 and 35 ± 5% after 10, 15 and 20 years of follow-up, respectively. Mortality rate associated with reoperation was 2%. Actuarial freedom from reoperation rates due to structural valve deterioration (SVD) at 10, 15 and 20 years was respectively of 91 ± 2, 76 ± 3 and 50 ± 6%. Competing risk analysis demonstrated an actual risk of explantation secondary to SVD at 20 years of 30 ± 3%. Expected valve durability was 19 years for this age group. Age was not a significant risk factor for SVD in this middle-aged population. CONCLUSIONS: In patients aged 50-65 years undergoing AVR with the Carpentier-Edwards Perimount bioprosthesis, the expected valve durability was 19 years. Age was not a significant risk factor for SVD within this age group. Patient selection and attention to timing of reintervention may be determinants of long-term outcomes.

Very Long-Term Outcomes of the Carpentier-Edwards Perimount Aortic Valve in Patients Aged 60 or Younger.

BACKGROUND: Aortic valve replacement using a bioprosthesis remains controversial for patients younger than 60 years because of missing data on long-term outcomes in this age group. METHODS: From 1984 to 2008, 383 Carpentier-Edwards Perimount pericardial aortic bioprostheses were implanted in 373 patients 60 years or younger (mean age, 51.0 ± 9.2 years; 19% female). Multiple valve replacements were excluded from our cohort. Baseline clinical, perioperative, and follow-up data were recorded prospectively. The mean follow-up was 8.6 ± 5.9 years, for a total of 3,299 valve-years. Follow-up was complete for 95.3% of patients included. RESULTS: Operative mortality rate was 1.3%. Eighty-five late deaths occurred, for a linearized rate of 2.6%/valve-year. Actuarial survival rates averaged 78.1% ± 2.6%, 65.6% ± 3.5%, and 46.8% ± 6.0% after 10, 15, and 20 years of follow-up, respectively. Mortality rate associated with reoperation was 2.3%. Actuarial freedom from reoperation rates attributable to structural valve deterioration at 10, 15, and 20 years were, respectively, 88.3% ± 2.4%, 70.8% ± 4.1%, and 38.1% ± 5.6%. Competing risk analysis demonstrated an actual risk of explantation secondary to structural valve deterioration at 20 years of 41.6% ± 4.1%. Expected valve durability was 17.6 years for this age group. CONCLUSIONS: In selected patients 60 years or younger undergoing aortic valve replacement with the Carpentier-Edwards Perimount bioprosthesis, the expected valve durability was 17.6 years. Reoperation for structural valve deterioration was associated with a low risk of mortality.

Single port/incision laparoscopic surgery compared with standard three-port laparoscopic surgery for appendicectomy: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: The aim of this study was to compare the effectiveness of single port/incision laparoscopic surgery (SPILS) with standard three-port laparoscopic surgery for appendicectomy in adults. Feasibility data was collected to evaluate generalizability to other single-port techniques such as cholecystectomy. METHODS: This was a single-center, randomized controlled trial. Participants were randomized to receive either SPILS or standard three-port laparoscopic appendicectomy. The primary patient-reported outcomes were body image and cosmesis at 6 weeks. The primary clinical outcome was pain at 1-7 days. Secondary outcomes included duration of operation, conversion rates, complication rates, use of analgesia, hospital re-admission rates, re-operation rates, and time to return to normal activities. RESULTS: Seventy-nine patients were randomized. Sixty-seven completed the day 1-7 diary and 53 completed the 6-week follow-up. SPILS patients answered significantly more favorably to the items in the body image scale [mean (SD) 5.6 (1.0) vs. 7.0 (3.3); -1.4 (95 % CI -2.8 to 1.5; p = 0.03)] and the cosmetic scale [18.9 (4.1) vs. 15.3 (5.8); 3.6 (95 % CI 0.7-6.5; p = 0.016)] compared with patients in the Standard group. The duration of operation was shorter for SPILS, and patients required less morphine in recovery; however, there were no statistically significant differences in other outcomes. CONCLUSIONS: Patient-reported body image and cosmesis outcomes were better, and surgical outcomes were similar following SPILS. However, the SPILS procedure is more technically demanding and may not be achievable or necessary in routine clinical care. Further assessment of the findings is needed through larger multicenter studies.

IQuaD dental trial; improving the quality of dentistry: a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care.

BACKGROUND: Periodontal disease is the most common oral disease affecting adults, and although it is largely preventable it remains the major cause of poor oral health worldwide. Accumulation of microbial dental plaque is the primary aetiological factor for both periodontal disease and caries. Effective self-care (tooth brushing and interdental aids) for plaque control and removal of risk factors such as calculus, which can only be removed by periodontal instrumentation (PI), are considered necessary to prevent and treat periodontal disease thereby maintaining periodontal health. Despite evidence of an association between sustained, good oral hygiene and a low incidence of periodontal disease and caries in adults there is a lack of strong and reliable evidence to inform clinicians of the relative effectiveness (if any) of different types of Oral Hygiene Advice (OHA). The evidence to inform clinicians of the effectiveness and optimal frequency of PI is also mixed. There is therefore an urgent need to assess the relative effectiveness of OHA and PI in a robust, sufficiently powered randomised controlled trial (RCT) in primary dental care. METHODS/DESIGN: This is a 5 year multi-centre, randomised, open trial with blinded outcome evaluation based in dental primary care in Scotland and the North East of England. Practitioners will recruit 1860 adult patients, with periodontal health, gingivitis or moderate periodontitis (Basic Periodontal Examination Score 0-3). Dental practices will be cluster randomised to provide routine OHA or Personalised OHA. To test the effects of PI each individual patient participant will be randomised to one of three groups: no PI, 6 monthly PI (current practice), or 12 monthly PI.Baseline measures and outcome data (during a three year follow-up) will be assessed through clinical examination, patient questionnaires and NHS databases.The primary outcome measures at 3 year follow up are gingival inflammation/bleeding on probing at the gingival margin; oral hygiene self-efficacy and net benefits. DISCUSSION: IQuaD will provide evidence for the most clinically-effective and cost-effective approach to managing periodontal disease in dentate adults in Primary Care. This will support general dental practitioners and patients in treatment decision making. TRIAL REGISTRATION: Protocol ID: ISRCTN56465715.

Defining quality criteria for online continuing medical education modules using modified nominal group technique.

INTRODUCTION: The rapid increase in the use of the Internet for continuing education by physicians suggests the need to define quality criteria for accredited online modules. METHODS: Continuing medical education (CME) directors from Canadian medical schools and academic researchers participated in a consensus process, Modified Nominal Group Technique, to develop agreement on the most important quality criteria to guide module development. Rankings were compared to responses to a survey of a subset of Canadian Medical Association (CMA) members. RESULTS: A list of 17 items was developed, of which 10 were deemed by experts to be important and 7 were considered secondary. A quality module would: be needs-based; presented in a clinical format; utilize evidence-based information; permit interaction with content and experts; facilitate and attempt to document practice change; be accessible for later review; and include a robust course evaluation. There was less agreement among CMA members on criteria ranking, with consensus on ranking reached on only 12 of 17 items. In contrast to experts, members agreed that the need to assess performance change as a result of an educational experience was not important. DISCUSSION: This project identified 10 quality criteria for accredited online CME modules that representatives of Canadian organizations involved in continuing education believe should be taken into account when developing learning products. The lack of practitioner support for documentation of change in clinical behavior may suggest that they favor traditional attendance- or completion-based CME; this finding requires further research.

Is bloodstream infection preventable among premature infants? A tale of two cities.

BACKGROUND: Bloodstream infection (BSI) is a significant cause of morbidity and death encountered in the NICU. The rates of BSIs vary significantly in NICUs across the nation. However, no attempt has been made to correlate this variation with specific infection-control practices and policies. We experienced a significant increase in BSIs in the NICU at the George Washington University Hospital and were seeking additional precautionary measures to reduce BSI rates. Our objective was to review policies and practices associated with lower infection rates nationally and to test their reproducibility in our unit. DESIGN AND METHODS: Data on BSI rates in 16 NICUs were reviewed. The BSI rate at Connecticut Children's Medical Center (CCMC) was the lowest among those reviewed. A team from George Washington University Hospital conducted a site visit to CCMC to examine their practices. Differences in the aseptic precautions used for intravenous line management were noted at CCMC, where a closed medication system is used. This system was applied at George Washington University Hospital starting January 1, 2001. Infection rates among low birth weight infants (<2500 g) at George Washington University Hospital in the period from January 1998 to December 2000 (group 1) were compared with those in the period from January 2001 to December 2003 (group 2). Comparisons between the 2 cohorts were made with Fisher's exact test, the Kruskal-Wallis test, and Student's t test. Multivariate analysis was used to control for differences in birth weight, gestational age, central line days, and ventilator days. Analyses were repeated for the subgroup of very low birth weight infants (<1500 g). RESULTS: A total of 536 inborn low birth weight infants were included in this retrospective study (group 1, N = 169 infants; group 2, N = 367). The incidence of sepsis decreased significantly from group 1 to group 2 (25.4% and 2.2%, respectively). The reduction of sepsis observed in association with the new practice was statistically significant after controlling for birth weight, central line days, and ventilator days in a multiple regression model (regression coefficient: 0.95 +/- 0.29). The odds ratio of reduction in sepsis after implementation of the new practice was 2.6 (95% confidence interval: 1.5-4.5). The central line-related BSI rate decreased from 15.17 infections per 1000 line days to 2.1 infections per 1000 line days. The study included 233 very low birth weight infants, ie, 90 in group 1 and 143 in group 2. The rate of BSIs decreased significantly from group 1 to group 2 (46.7% and 5.6%, respectively). The decrease in sepsis rate remained significant in a multiple regression model (regression coefficient: 1.42 +/- 0.35). The odds ratio of decreased sepsis in relation to the new policy application among the very low birth weight infants was 4.15 (95% confidence interval: 2.1-8.3). CONCLUSION: Applying the closed medication system was associated with reduced BSI rates in our unit. This protocol was easily reproducible in our environment and showed immediate results. Serious attempts to share data can potentially optimize outcomes and standardize policies and practices among NICUs.