A. T. Prevost

Who attends a UK diabetes screening programme? Findings from the ADDITION‐Cambridge study

Diabet. Med. 27, 995–1003 (2010)

Impact of an informed choice invitation on uptake of screening for diabetes in primary care (DICISION): randomised trial.

Objective To compare the effect of an invitation promoting informed choice for screening with a standard invitation on attendance and motivation to engage in preventive action. Design Randomised controlled trial. Setting Four English general practices. Participants 1272 people aged 40-69 years, at risk for diabetes, identified from practice registers using a validated risk score and invited to attend for screening. Intervention Intervention was a previously validated invitation to inform the decision to attend screening, presenting diabetes as a serious potential problem, and providing details of possible costs and benefits of screening and treatment in text and pie charts. This was compared with a brief, standard invitation simply describing diabetes as a serious potential problem. Main outcome measures The primary end point was attendance for screening. The secondary outcome measures were intention to make changes to lifestyle and satisfaction with decisions made among attenders. Results The primary end point was analysed for all 1272 participants. 55.8% (353/633) of those in the informed choice group attended for screening, compared with 57.6% (368/639) in the standard invitation group (mean difference −1.8%, 95% confidence interval −7.3% to 3.6%; P=0.51). Attendance was lower among the more deprived group (most deprived third 47.5% v least deprived third 64.3%; P<0.001). Interaction between deprivation and effect of invitation type on attendance was not significant. Among attenders, intention to change behaviour was strong and unaffected by invitation type. Conclusions Providing information to support choice did not adversely affect attendance for screening for diabetes. Those from more socially deprived groups were, however, less likely to attend, regardless of the type of invitation received. Further attention to invitation content alone is unlikely to achieve equity in uptake of preventive services. Trial registration Current Controlled Trials ISRCTN 73125647.

Cdc7 Kinase Is a Predictor of Survival and a Novel Therapeutic Target in Epithelial Ovarian Carcinoma

Purpose: There is a lack of prognostic and predictive biomarkers in epithelial ovarian carcinoma, and the targeting of oncogenic signaling pathways has had limited impact on patient survival in this highly heterogeneous disease. The origin licensing machinery, which renders chromosomes competent for DNA replication, acts as a convergence point for upstream signaling pathways. We tested the hypothesis that Cdc7 kinase, a core component of the licensing machinery, is predictive of clinical outcome and may constitute a novel therapeutic target in epithelial ovarian carcinoma. Experimental Design: A total of 143 cases of ovarian cancer and 5 cases of normal ovary were analyzed for Cdc7 protein expression dynamics and clinicopathologic features. To assess the therapeutic potential of Cdc7, expression was down-regulated by RNA interference in SKOV-3 and Caov-3 ovarian cancer cells. Results: Increased Cdc7 protein levels were significantly associated with arrested tumor differentiation (P = 0.004), advanced clinical stage (P = 0.01), genomic instability (P < 0.001), and accelerated cell cycle progression. Multivariate analysis shows that Cdc7 predicts disease-free survival independent of patient age, tumor grade and stage (hazard ratio, 2.03; confidence interval, 1.53-2.68; P < 0.001), with the hazard ratio for relapse increasing to 10.90 (confidence interval, 4.07-29.17) for the stages 3 to 4/upper Cdc7 tertile group relative to stages 1 to 2/lower Cdc7 tertile tumors. In SKOV-3 and Caov-3 cells, Cdc7 siRNA knockdown triggered high levels of apoptosis, whereas untransformed cells arrest in G1 phase and remain viable. Conclusions: Our findings show that Cdc7 kinase predicts survival and is a potent anticancer target in epithelial ovarian carcinoma, highlighting its potential as a predictor of susceptibility to small molecule kinase inhibitors currently in development.

An explanatory randomised controlled trial of a nurse-led, consultation-based intervention to support patients with adherence to taking glucose lowering medication for type 2 diabetes

BackgroundFailure to take medication reduces the effectiveness of treatment leading to increased morbidity and mortality. We evaluated the efficacy of a consultation-based intervention to support objectively-assessed adherence to oral glucose lowering medication (OGLM) compared to usual care among people with type 2 diabetes.MethodsThis was a parallel group randomised trial in adult patients with type 2 diabetes and HbA1c≥7.5% (58 mmol/mol), prescribed at least one OGLM. Participants were allocated to a clinic nurse delivered, innovative consultation-based intervention to strengthen patient motivation to take OGLM regularly and support medicine taking through action-plans, or to usual care. The primary outcome was the percentage of days on which the prescribed dose of medication was taken, measured objectively over 12 weeks with an electronic medication-monitoring device (TrackCap, Aardex, Switzerland). The primary analysis was intention-to-treat.Results211 patients were randomised between July 1, 2006 and November 30, 2008 in 13 British general practices (primary care clinics). Primary outcome data were available for 194 participants (91.9%). Mean (sd) percentage of adherent days was 77.4% (26.3) in the intervention group and 69.0% (30.8) in standard care (mean difference between groups 8.4%, 95% confidence interval 0.2% to 16.7%, p = 0.044). There was no significant adverse impact on functional status or treatment satisfaction.ConclusionsThis well-specified, theory based intervention delivered in a single session of 30 min in primary care increased objectively measured medication adherence, with no adverse effect on treatment satisfaction. These findings justify a definitive trial of this approach to improving medication adherence over a longer period of time, with clinical and cost-effectiveness outcomes to inform clinical practice.Trial registrationCurrent Controlled Trials ISRCTN30522359

Effect of adding a diagnostic aid to best practice to manage suspicious pigmented lesions in primary care: randomised controlled trial.

Objectives To assess whether adding a novel computerised diagnostic tool, the MoleMate system (SIAscopy with primary care scoring algorithm), to current best practice results in more appropriate referrals of suspicious pigmented lesions to secondary care, and to assess its impact on clinicians and patients. Design Randomised controlled trial. Setting 15 general practices in eastern England. Participants 1297 adults with pigmented skin lesions not immediately diagnosed as benign. Interventions Patients were assessed by trained primary care clinicians using best practice (clinical history, naked eye examination, seven point checklist) either alone (control group) or with the MoleMate system (intervention group). Main outcome measures Appropriateness of referral, defined as the proportion of referred lesions that were biopsied or monitored. Secondary outcomes related to the clinicians (diagnostic performance, confidence, learning effects) and patients (satisfaction, anxiety). Economic evaluation, diagnostic performance of the seven point checklist, and five year follow-up of melanoma incidence were also secondary outcomes and will be reported later. Results 1297 participants with 1580 lesions were randomised: 643 participants with 788 lesions to the intervention group and 654 participants with 792 lesions to the control group. The appropriateness of referral did not differ significantly between the intervention or control groups: 56.8% (130/229) v 64.5% (111/172); difference −8.1% (95% confidence interval −18.0% to 1.8%). The proportion of benign lesions appropriately managed in primary care did not differ (intervention 99.6% v control 99.2%, P=0.46), neither did the percentage agreement with an expert decision to biopsy or monitor (intervention 98.5% v control 95.7%, P=0.26). The percentage agreement with expert assessment that the lesion was benign was significantly lower with MoleMate (intervention 84.4% v control 90.6%, P<0.001), and a higher proportion of lesions were referred (intervention 29.8% v control 22.4%, P=0.001). Thirty six histologically confirmed melanomas were diagnosed: 18/18 were appropriately referred in the intervention group and 17/18 in the control group. Clinicians in both groups were confident, and there was no evidence of learning effects, and therefore contamination, between groups. Patients in the intervention group ranked their consultations higher for thoroughness and reassuring care, although anxiety scores were similar between the groups. Conclusions We found no evidence that the MoleMate system improved appropriateness of referral. The systematic application of best practice guidelines alone was more accurate than the MoleMate system, and both performed better than reports of current practice. Therefore the systematic application of best practice guidelines (including the seven point checklist) should be the paradigm for management of suspicious skin lesions in primary care. Trial registration Current Controlled Trials ISRCTN79932379.

How much might cardiovascular disease risk be reduced by intensive therapy in people with screen-detected diabetes?

Aims  To assess the cardiovascular disease (CVD) risk of people with screen‐detected Type 2 diabetes and to estimate the risk reduction achievable through early intensive pharmacological intervention.

Adherence to hypoglycaemic medication among people with type 2 diabetes in primary care

AIMS To assess levels and correlates of adherence to hypoglycaemic medication among patients offered organised general practice diabetes care. METHODS 60 patients prescribed oral hypoglycaemic medication were recruited to a two-month prospective study. Prescribed doses taken and days on which the prescribed number of doses was taken were measured by MEMS (Medication Event Monitoring System). RESULTS Overall 99.1% of prescribed doses were taken (median, IQR: 96.8-100%), this was inversely correlated with daily dose frequency (Spearmans rho=0.37, p=0.004). Only 4 patients (6.7%) took less than 90% of prescribed doses. The prescribed dose was taken on 96.4% of days (median, IQR: 89.1-98.2%), this was correlated with age (rho=0.26, p=0.047) and inversely correlated with HbA(1c) levels (rho=-0.29, p=0.02) and daily dose frequency (rho=-0.33, p=0.009). Adherence to metformin was less than to other hypoglycaemic medication (Z=-3.48, p=0.0005). CONCLUSIONS A dispensing practice with a well-run diabetes service can support high rates of adherence to hypoglycaemic medication. Before changing medication, low adherence might be considered as a possible cause of progressive hyperglycaemia, particularly among patients prescribed metformin more than once a day. Selective monitoring with MEMS may have a clinical as well as a research role in such people.

A comparison of technologies used for estimation of body temperature

Body temperature measurement is an important clinical parameter. The performance of a number of non-invasive thermometers was measured by comparing intra- and inter-operator variability (n = 100) and clinical accuracy (n = 61). Variability was elevated in febrile compared to normothermic subjects for axillary and oral electronic contact thermometer measures and a temporal artery thermometer (p < 0.001 for both). Temporal artery thermometry and one mode of an infrared tympanic thermometer demonstrated significant clinical inaccuracy (p < 0.001 for both). Electronic contact thermometer repeatability and reproducibility are highly variable in febrile adults both in the axilla and oral cavity. Infrared thermometry of the skin over the superficial temporal artery is unreliable for measuring core body temperature, particularly in febrile subjects and patients in theatre. The infrared tympanic thermometers tested are acceptable for clinical practice; however, care should be exercised with the different modes of operation offered.

Bladder Cancer Diagnosis and Identification of Clinically Significant Disease by Combined Urinary Detection of Mcm5 and Nuclear Matrix Protein 22

Background Urinary biomarkers for bladder cancer detection are constrained by inadequate sensitivity or specificity. Here we evaluate the diagnostic accuracy of Mcm5, a novel cell cycle biomarker of aberrant growth, alone and in combination with NMP22. Methods 1677 consecutive patients under investigation for urinary tract malignancy were recruited to a prospective blinded observational study. All patients underwent ultrasound, intravenous urography, cystoscopy, urine culture and cytologic analysis. An immunofluorometric assay was used to measure Mcm5 levels in urine cell sediments. NMP22 urinary levels were determined with the FDA-approved NMP22® Test Kit. Results Genito-urinary tract cancers were identified in 210/1564 (13%) patients with an Mcm5 result and in 195/1396 (14%) patients with an NMP22 result. At the assay cut-point where sensitivity and specificity were equal, the Mcm5 test detected primary and recurrent bladder cancers with 69% sensitivity (95% confidence interval = 62–75%) and 93% negative predictive value (95% CI = 92–95%). The area under the receiver operating characteristic curve for Mcm5 was 0.75 (95% CI = 0.71–0.79) and 0.72 (95% CI = 0.67–0.77) for NMP22. Importantly, Mcm5 combined with NMP22 identified 95% (79/83; 95% CI = 88–99%) of potentially life threatening diagnoses (i.e. grade 3 or carcinoma in situ or stage ≥pT1) with high specificity (72%, 95% CI = 69–74%). Conclusions The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways.

Is community treatment best? a randomised trial comparing delivery of cancer treatment in the hospital, home and GP surgery

Background:Care closer to home is being explored as a means of improving patient experience as well as efficiency in terms of cost savings. Evidence that community cancer services improve care quality and/or generate cost savings is currently limited. A randomised study was undertaken to compare delivery of cancer treatment in the hospital with two different community settings.Methods:Ninety-seven patients being offered outpatient-based cancer treatment were randomised to treatment delivered in a hospital day unit, at the patient’s home or in local general practice (GP) surgeries. The primary outcome was patient-perceived benefits, using the emotional function domain of the EORTC quality of life (QOL) QLQC30 questionnaire evaluated after 12 weeks. Secondary outcomes included additional QOL measures, patient satisfaction, safety and health economics.Results:There was no statistically significant QOL difference between treatment in the combined community locations relative to hospital (difference of −7.2, 95% confidence interval: −19·5 to +5·2, P=0.25). There was a significant difference between the two community locations in favour of home (+15·2, 1·3 to 29·1, P=0.033). Hospital anxiety and depression scale scores were consistent with the primary outcome measure. There was no evidence that community treatment compromised patient safety and no significant difference between treatment arms in terms of overall costs or Quality Adjusted Life Year. Seventy-eight percent of patients expressed satisfaction with their treatment whatever their location, whereas 57% of patients preferred future treatment to continue at the hospital, 81% at GP surgeries and 90% at home. Although initial pre-trial interviews revealed concerns among health-care professionals and some patients regarding community treatment, opinions were largely more favourable in post-trial interviews.Interpretation:Patient QOL favours delivering cancer treatment in the home rather than GP surgeries. Nevertheless, both community settings were acceptable to and preferred by patients compared with hospital, were safe, with no detrimental impact on overall health-care costs.