Identification and Characterization of microRNAs Associated With Human ß-Cell Loss in a Mouse Model.

Currently there is no effective approach for monitoring early ß-cell loss during islet graft rejection following human islet transplantation (HIT). Due to ethical and technical constraints, it is difficult to directly study biomarkers of islet destruction in humans. Here, we established a humanized mouse model with induced human ß-cell death using adoptive lymphocyte transfer (ALT). Human islet grafts of ALT-treated mice had perigraft lymphocyte infiltration, fewer insulin+ ß cells, and increased ß-cell apoptosis. Islet-specific miR-375 was used to validate our model, and expression of miR-375 was significantly decreased in the grafts and increased in the circulation of ALT-treated mice before hyperglycemia. A NanoString expression assay was further used to profile 800 human miRNAs in the human islet grafts, and the results were validated using quantitative real-time polymerase chain reaction. We found that miR-4454 and miR-199a-5p were decreased in the human islet grafts following ALT and increased in the circulation prior to hyperglycemia. These data demonstrate that our in vivo model of induced human ß-cell destruction is a robust method for identifying and characterizing circulating biomarkers, and suggest that miR-4454 and miR-199a-5p can serve as novel biomarkers associated with early human ß-cell loss following HIT.

How do patient and hospital features influence outcomes in small-cell lung cancer in England?

BACKGROUND: Our aim was to systematically determine how features of patients and hospitals influence access to chemotherapy and survival for people with small-cell lung cancer in England. METHODS: We linked the National Lung Cancer Audit and Hospital Episode Statistics and used multiple logistic and Cox regression analyses to assess the influence of patient and hospital features on small-cell lung cancer outcomes. RESULTS: There were 7845 patients with histologically proven small-cell lung cancer. Sixty-one percent (4820) of the patients received chemotherapy. Increasing age, worsening performance status, extensive stage and greater comorbidity all reduced the likelihood of receiving chemotherapy. There was wide variation in access to chemotherapy between hospitals in general and patients first seen in centres with a strong interest in clinical trials had a higher odds of receiving chemotherapy (adjusted odds ratio 1.42, 95% confidence interval (CI) 1.06, 1.90). Chemotherapy was associated with a lower mortality rate (adjusted hazard ratio 0.51, 95% CI 0.46, 0.56). CONCLUSION: Patients first seen at a hospital with a keen interest in clinical trials are more likely to receive chemotherapy, and chemotherapy was associated with improved survival.

The importance of ultrasound in staging and gaining a pathological diagnosis in patients with lung cancer--a two year single centre experience.

BACKGROUND: Initial studies on the use of ultrasound in the detection and sampling of supraclavicular lymph nodes in patients with suspected lung cancer show this to be a promising technique, giving both a cytological diagnosis and pathological N3 (pN3) stage. Leicester published its initial experience in 2005 and the aim of this study was to establish if this had been embedded into the diagnostic pathway, and further to examine the use of ultrasound in diagnosing and staging lung cancer by imaging other areas including pleural effusions, chest wall, bone and liver lesions. METHODS: All patients diagnosed with lung cancer, registered on the Leicester lung cancer database over a two year period between January 2007 and December 2008, had their imaging and pathology retrospectively reviewed; 996 primary lung cancer patients were identified (n=996). Of these, 318 patients underwent an ultrasound examination (n=318), consisting of ultrasound of the neck, pleural cavity, and metastatic lesions potentially amenable to ultrasound guided aspiration/biopsy. RESULTS: The overall malignant yield was 45% of patients scanned (95% CI 39.5% to 50.4%) and 81.3% of patients sampled (95% CI 75.5% to 87%). Of the 996 patients, 14.4% (n=143) had a positive ultrasound guided cytological diagnosis (95% CI 12.2% to 16.5%). Of all the pathological diagnoses (n=765), 18.7% were ultrasound guided (95% CI 15.9% to 21.5%). In particular, 32.2% of patients with CT detected neck or mediastinal nodes had a diagnosis and stage achieved by neck ultrasound. CONCLUSION: The use of ultrasound gives a rapid and less invasive method of diagnosing and staging lung cancer and has become embedded into the diagnostic pathway. We advocate its increased use and availability in patients with lung cancer.

A prospective study of conventional transbronchial needle aspiration: performance and cost utility.

BACKGROUND: Conventional transbronchial needle aspiration (TBNA) is a cheap, minimally invasive tool for lung cancer staging and diagnosis. Endobronchial ultrasound-guided TBNA (EBUS-TBNA) is more sensitive but is more expensive and less widely available. We describe a prospective analysis of TBNA diagnostic, staging and cost utility in a centre in the UK. OBJECTIVES: To illustrate the potential diagnostic, staging and cost utility of a low cost conventional TBNA service. METHODS: A prospective analysis of 79 TBNA procedures over a 2-year period was performed looking at performance and cost utility in a 'mixed' cohort with variable pre-test probability of malignancy (year 1) followed by a high probability cohort (year 2). RESULTS: TBNA avoided mediastinoscopy in 25% of the cases overall (37% in high probability vs. 13% in the 'mixed' cohort, p = 0.03). The overall prevalence of malignancy was 84%, sensitivity 79%, negative predictive value 58% and accuracy 85%. Diagnostic utility varied with pre-test probability and nodal station. TBNA down-staged 8% of lung cancer patients to receive surgery and confirmed the pre-treatment stage (inoperability) in 74%. TBNA led to theoretical cost savings of GBP 560 per patient. CONCLUSIONS: TBNA can achieve a high diagnostic sensitivity for cancer in high probability patients and stage the majority appropriately, thereby avoiding unnecessary mediastinoscopies and reducing costs. It may also down-stage a minority to have surgery. TBNA is cheap, routinely available and learnable. As EBUS-TBNA will take time to develop due to its costs, all respiratory centres should perform TBNA at flexible bronchoscopy in suspected lung cancer with accessible mediastinal adenopathy.

Endobronchial ultrasound guided transbronchial needle aspiration.

Staging for non-small cell lung cancer (NSCLC) requires accurate assessment of the mediastinal lymph nodes which determines treatment and outcome. As radiological staging is limited by its specificity and sensitivity, it is necessary to sample the mediastinal nodes. Traditionally, mediastinoscopy has been used for evaluation of the mediastinum especially when radical treatment is contemplated, although conventional transbronchial needle aspiration (TBNA) has also been used in other situations for staging and diagnostic purposes. Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) offers a minimally invasive alternative to mediastinoscopy with additional access to the hilar nodes, a better safety profile, and it removes the costs and hazards of theatre time and general anaesthesia with comparable sensitivity, although the negative predictive value of mediastinoscopy (and sample size) is greater. EBUS-TBNA also obtains larger samples than conventional TBNA, has superior performance and theoretically is safer, allowing real-time sampling under direct vision. It can also have predictive value both in sonographic appearance of the nodes and histological characteristics. EBUS-TBNA is therefore indicated for NSCLC staging, diagnosis of lung cancer when there is no endobronchial lesion, and diagnosis of both benign (especially tuberculosis and sarcoidosis) and malignant mediastinal lesions. The procedure is different than for flexible bronchoscopy, takes longer, and requires more training. EBUS-TBNA is more expensive than conventional TBNA but can save costs by reducing the number of more costly mediastinoscopies. Revenue based tariff systems have been slow to reflect the innovation of techniques such as EBUS-TBNA. In the future, endobronchial ultrasound may have applications in airways disease and pulmonary vascular disease.

Txt2stop: a pilot randomised controlled trial of mobile phone-based smoking cessation support.

AIM: To conduct a pilot randomised controlled trial of mobile phone-based smoking cessation support intervention for the UK population. DESIGN: Randomised controlled trial (txt2stop). SETTING: Community. PARTICIPANTS: 200 participants responding to radio, poster and leaflet-based promotions regarding the trial. MAIN OUTCOME MEASURES: The response rate for the outcome measures planned for the main trial. Participants' qualitative responses to open-ended questions about the intervention content. Secondary outcomes were the outcomes planned for the main trial including the point prevalence of self-reported smoking at 4 weeks and pooled effect estimate for the short-term results for the STOMP and txt2stop trials. RESULTS: The response rate at 4 weeks was 96% and at 6 months was 92%. The results at 4 weeks show a doubling of self-reported quitting relative risk (RR) 2.08 (95% CI 1.11 to 3.89), 26% vs 12%. The pooled effect estimate combining txt2stop and a previous New Zealand trial in the short term is RR 2.18 (95% CI 1.79 to 2.65). CONCLUSIONS: Mobile phone-based smoking cessation is an innovative means of delivering smoking cessation support, which doubles the self-reported quit rate in the short term. It could represent an important, but as yet largely unused, medium to deliver age-appropriate public health measures. The long-term effect of this mobile phone-based smoking cessation support will be established by a large randomised controlled trial currently in recruitment.

Lung cancer outcomes at a UK cancer unit between 1998-2001.

UNLABELLED: There are few data published on lung cancer survival in the UK. Survival rates for lung cancer at a UK Hospital between 1998-2001 are described. METHODS: Analysis of data collected from multidisciplinary team (MDT) meetings, lung cancer registrations and hospital coding. RESULTS: 835 new lung cancers were diagnosed comprising 597 non-small cell lung cancers (NSCLC) (71%), 133 small cell (SCLC) (16%), and 105 clinical diagnoses (13%). Stage at diagnosis; stage I (25%), II (9%), IIIA (8%), IIIB (23%), IV (35%). Surgery was undertaken in 12%, radical radiotherapy (RT) in 4%, palliative RT in 32%, chemotherapy in 8% and best supportive care (BSC) in 36%. The 3-year cumulative survival for NSCLC was: stage I 39%, stage II 30%, stage III 6%, stage IV 0.5%. Only 46% of patients with stage I-IIIA disease received radical treatment. Reasons included poor lung function (32%), unresectable (24%), co-morbidities (17%), performance status (8%), patient choice (8%), unclear (6%), advanced age (5%). CONCLUSIONS: Survival figures are similar to other UK studies but do not compare favourably with US and European data. This may be because a large proportion of patients with early stage disease receive palliative care only.

Diversity and Community Composition of Vertebrates in Desert River Habitats.

Animal species are seldom distributed evenly at either local or larger spatial scales, and instead tend to aggregate in sites that meet their resource requirements and maximise fitness. This tendency is likely to be especially marked in arid regions where species could be expected to concentrate at resource-rich oases. In this study, we first test the hypothesis that productive riparian sites in arid Australia support higher vertebrate diversity than other desert habitats, and then elucidate the habitats selected by different species. We addressed the first aim by examining the diversity and composition of vertebrate assemblages inhabiting the Field River and adjacent sand dunes in the Simpson Desert, western Queensland, over a period of two and a half years. The second aim was addressed by examining species composition in riparian and sand dune habitats in dry and wet years. Vertebrate species richness was estimated to be highest (54 species) in the riverine habitats and lowest on the surrounding dune habitats (45 species). The riverine habitats had different species pools compared to the dune habitats. Several species, including the agamid Gowidon longirostris and tree frog Litoria rubella, inhabited the riverine habitats exclusively, while others such as the skinks Ctenotus ariadnae and C. dux were captured only in the dune habitats. The results suggest that, on a local scale, diversity is higher along riparian corridors and that riparian woodland is important for tree-dependent species. Further, the distribution of some species, such as Mus musculus, may be governed by environmental variables (e.g. soil moisture) associated with riparian corridors that are not available in the surrounding desert environment. We conclude that inland river systems may be often of high conservation value, and that management should be initiated where possible to alleviate threats to their continued functioning.

Non-small cell lung cancer in young adults: presentation and survival in the English National Lung Cancer Audit.

BACKGROUND: Non-small cell lung cancer (NSCLC) in young adults is a rare but devastating illness with significant socioeconomic implications, and studies of this patient subgroup are limited. AIM: This study employed the National Lung Cancer Audit to compare the clinical features and survival of young adults with NSCLC with the older age groups. DESIGN: A retrospective cohort review using a validated national audit dataset. METHODS: Data were analysed for the period between 1 January 2004 and 31 December 2011. Young adults were defined as between 18 and 39 years, and all others were divided into decade age groups, up to the 80 years and above group. We performed logistic and Cox regression analyses to assess clinical outcomes. RESULTS: Of a total of 1 46 422 patients, 651 (0.5%) were young adults, of whom a higher proportion had adenocarcinoma (48%) than in any other age group. Stage distribution of NSCLC was similar across the age groups and 71% of young patients had stage IIIb/IV. Performance status (PS) was 0-1 for 85%. Young adults were more likely to have surgery and chemotherapy compared with the older age groups and had better overall and post-operative survival. The proportion with adenocarcinoma, better PS and that receiving surgery or chemotherapy diminished progressively with advancing decade age groups. CONCLUSION: In our cohort of young adults with NSCLC, the majority had good PS despite the same late-stage disease as older patients. They were more likely to have treatment and survive longer than older patients.

Adrenal steroidogenic actions of cyclic nucleotide derivatives in the rat.

Fifteen 3',5'-cyclic nucleotides and related compounds were studied for ability to mimic the steroidogenic action of ACTH in rats in which secretion of ACTH and corticosterone were suppressed by treatment with betamethasone, or by hypophysectomy. Subcutaneous administration of 8-chloro-cAMP, at doses of 40 mg/kg or greater, elicited the secretion of corticosterone to normal plasma levels in both betamethasone-treated and hypophysectomized animals. Cyclic AMP, dbcAMP, 8-methylthio-cAMP, 8-hydroxy-cAMP and the 6-chloro-8-aminopurine cyclic ribotide analog of cAMP also displayed steroidogenic activity in the betamethasone-treated rat; cGMP, 8-bromo-cGMP and 8-benzylthio-cGMP were inactive. Each of the steroidogenic derivatives of cAMP also displayed ability to activate steroidogenesis in isolated rat adrenal cells. These experiments demonstrate that various derivatives of cAMP mimic the adrenal steroidogenic action of ACTH, in vivo. Structure-activity comparisons support a steroidogenic mechanism involving direct activation by the nucleotides of cAMP-dependent protein kinase of the adrenal cortex.

Mutually independent effects of adrenocorticotropin on luteinizing hormone and testosterone secretion.

In this study, we examined the effect of ACTH on the sensitivity of the testes to gonadotropin and determined the role of the testosterone (T) negative feedback system in mediating the inhibitory effect of ACTH on LH secretion in adult male rats. ACTH infusion for 3 days reduced basal levels of serum T and the T response to GnRH, but did not alter basal levels of serum LH (immunoreactive) or the LH response to GnRH. These effects required the presence of the adrenal glands. Infusion of corticosterone (B) at a dose that increased serum B concentrations 9-fold had an effect similar to that of ACTH on basal serum T levels and the serum T response to GnRH. Basal levels of serum LH and the serum LH response to GnRH were not affected by B administration. These data suggest that ACTH administration reduces the sensitivity of the testes to LH, resulting in a lower basal level of T and a reduced T response to GnRH. This effect was independent of basal serum LH levels or the LH response to GnRH. It appears that B mediates the effect of ACTH on testicular sensitivity to gonadotropin. In another experiment, ACTH administration for 4 days did not alter serum LH values, but reduced serum T levels in sham-castrated male rats. In contrast, ACTH treatment blunted the increase in serum LH after castration by day 2 of treatment, despite the absence of detectable levels of serum T within 6 h after castration. These data suggest that T is not essential for the inhibitory effect of ACTH on LH secretion to occur. They do not support the hypothesis that ACTH enhances the sensitivity of the hypothalamus and/or pituitary to the negative feedback effects of T.

Perinephritis hypertension in Macaca fascicularis (cynomolgus monkey): studies of the renin-angiotensin-aldosterone axis and renal hemodynamic function.

The purpose of the present study was to characterize the etiology of bilateral perinephritis hypertension in the non-human primate. Hypertension was induced in female cynomolgus (Macaca fascicularis) monkeys by wrapping both kidneys under sterile surgical procedures. Mean arterial pressure (MAP), plasma renin activity (PRA), plasma aldosterone concentration (ALDO), para-aminohippurate (PAH) clearance, glomerular filtration rate (GFR), urine volume, and sodium and potassium excretion were measured before and weekly after induction of the hypertension. MAP increased progressively from 108 +/- 1 to 135 +/- 4 mmHg during the first 6 weeks; thereafter, MAP remained at this elevated level, PRA was elevated two- to fivefold for up to 10 weeks after the hypertension and ALDO was elevated during 1 (139%), 4 (60%), 6 (196%), 8 (249%) and 10 (148%) weeks of the hypertension. PAH clearance and GFR were significantly reduced during week 1 of the hypertension, but returned to control values by week 2. Urine volume was increased significantly during the first week of the hypertension, while sodium and potassium excretion were not changed. Captopril (15 mumol/kg, intravenously) normalized the blood pressure regardless of the severity or duration of the disease. Additionally, captopril lowered ALDO and increased PRA. It is concluded that bilateral perinephritis hypertension in the monkey is dependent on increased activity of the renin-angiotensin-aldosterone axis.

Activated ketone based inhibitors of human renin.

Application of the concept of activated ketones to the design of novel and potent transition-state analog inhibitors of the aspartyl protease renin is described. Three different classes of peptidic activated ketones were synthesized: 1,1,1-trifluoromethyl ketones, alpha-keto esters, and alpha-diketones. The corresponding alcohols were also evaluated as renin inhibitors in each series. While the trifluoromethyl alcohol 12 (I50 = 4000 nM) was equipotent to the simple methyl alcohol 7 (I50 = 3200 nM), the structurally similar alpha-hydroxy esters (32 and 30, I50's = 5.3 and 4.7 nM, respectively) and alpha-hydroxy ketones (41 and 42, I50 = 23 and 15 nM, respectively) were 150-300-fold more active. The hydrating capability of the activated ketone functionality was important for intrinsic potency in the case of trifluoromethyl ketones, as illustrated by the significantly better activity of trifluoromethyl ketone 13 (I50 = 250 nM) compared to its alcohol analog 12 (I50 = 4000 nM). It was however unimportant for the alpha-keto ester (20 and 31, I50 = 15 and 4.1 nM, respectively) and alpha-diketone (43 and 44, I50 = 52 and 28 nM, respectively) based inhibitors, since their activity was essentially similar to that of the corresponding alcohols. These results collectively suggest that, whereas the trifluoromethyl ketones derive their renin inhibitory potency primarily from their ability to become hydrated, this is not a critical feature for the activity of alpha-dicarbonyl-based inhibitors. The alpha-keto ester and alpha-diketone based renin inhibitors benefit predominantly from the hydrophobic and/or H-bonding type binding interactions of the neighboring ester or acyl group itself, rather than the ability of this group to deactivate the adjacent ketone group and thereby make it susceptible to hydration.

alpha-Hydroxy phosphinyl-based inhibitors of human renin.

The design and application of alpha-hydroxy phosphonates, a new class of transition state analogs, toward the discovery of novel and potent inhibitors of the aspartyl protease renin is described. Tripeptidic alpha-hydroxy diethyl phosphonate 3, the first example in this series, was found to be a good inhibitor of human renin (IC50 = 29 nM), and preliminary studies led to the choice of alpha-hydroxy dimethyl phosphonate 15 (IC50 = 16 nM) as a base-line compound for further structure-activity relationship study. Corresponding phosphinate (28-30) and phosphine oxide (23 and 24) analogs of 15 were prepared to assess the steric and electronic requirements around the phosphorus center. Evaluation of these analogs suggested that the presence of at least one alkoxy group on phosphorus was a critical requirement for good activity. Inhibitors with leucine at P2 possessed better in vitro activity than the corresponding P2 histidine analogs (15, IC50 = 16 nM vs 37, IC50 = 220 nM; 33, IC50 = 8.5 nM vs 40, IC50 = 41 nM). Compound 34 (IC50 = 31 nM), the P3 aminocaproic analog of 15, showed complete and long-lasting inhibition of plasma renin activity while eliciting a 10-15 mmHg drop in mean arterial pressure when administered intravenously at 1 mumol/kg in conscious, sodium-depleted, cynomolgus monkeys. In summary, the alpha-hydroxy phosphonates represent a promising and structurally novel class of transition state analog inhibitors of human renin.

Bilingual young people's experiences of interpreting in primary care: a qualitative study.

BACKGROUND: Young people are often used as interpreters for family members in the primary healthcare setting. AIM: To explore bilingual young people's accounts of interpreting for family or friends in primary care settings. DESIGN OF STUDY: Qualitative study using in-depth interviews. SETTING: Community and youth groups in London. METHODS: Young people aged nine to 18 years old (n = 77) were purposively sampled to include those from established and recently arrived groups and were from Vietnamese, Kurdish, Bangladeshi or Eastern European backgrounds. Participants were interviewed one-to-one or with a friend, and interview transcripts were analysed to identify key themes. RESULTS: Young people were used for interpreting because of deficiencies in services, and also by choice. They identified advantages and disadvantages in their experiences. The majority of healthcare encounters were regarded as unproblematic. Three factors contributed to less successful encounters: healthcare professionals' or patients' communication skills; young people's own language skills, and the nature of the healthcare problem. CONCLUSION: This study identifies ways in which primary care professionals could facilitate better communication in encounters where young people are used as interpreters.

Evaluating and developing contraceptive services: the results of an audit of the North Lambeth Primary Care Commissioning Group.

Primary care groups are expected to meet the primary health care needs of their local population. In the inner-city London borough of Lambeth there are high levels of sexual health needs. The North Lambeth Primary Care Commissioning Group identified the evaluation and further development of contraceptive services, particularly to those under the age of 25, as a priority. An evaluation of current contraceptive service provision from general practice was carried out. The evaluation covered contraceptive service factors identified from the literature as linked to effective, acceptable, accessible and equitable service delivery. Factors linked to the effectiveness of services included service use, information provision, training of staff, provision of the full range of methods and services. Factors linked to the acceptability of services included confidentiality and the choice of the gender of the provider. The strengths and limitations of the data and indicators used are outlined. Areas requiring further evaluation are highlighted. The evaluation indicated scope for service development in all the key areas evaluated, and illustrated examples of good practice. For example, whilst information in practice leaflets and surgery waiting areas about the contraceptive services available was generally limited, one practice provided excellent information. Recommendations for service development were made covering information provision, staff training, and confidential access to services. These are being taken forward by an ongoing project.

Pre-anaesthetic administration of dantrolene sodium to a patient at risk from malignant hyperthermia: case report.

The pre-anaesthetic administration of dantrolene sodium to individuals at risk from malignant hyperthermia has not yet found an accepted place in human anaesthetic practice, although the effectiveness of dantrolene sodium as a prophylactic drug has been clearly shown in animal studies. In the patient described in this report, no conclusion is drawn about the effectiveness of dantrolene sodium, but attention is drawn to a brief episode of vomiting and diarrhoea some two hours after ingestion of the drug. Modification of the dosage scheme may be advisable.

Pharmacology of novel imidazole alcohol inhibitors of primate renin.

SQ 30,774 and SQ 31,844 are representatives of a novel class of renin inhibitors, the imidazole alcohols. These compounds, which contain an imidazole ring as part of their active site binding group are potent in vitro inhibitors of primate renin, but not rat, hog of dog renin. In conscious, sodium-depleted cynomolgus monkeys both compounds produced a dose-related inhibition of plasma renin activity (PRA) at doses ranging between 0.001 and 1.0 mumol/kg, intravenously, and total inhibition was observed after the highest dose. However, a reduction in blood pressure was observed only after an intravenous dose of 10 mumol/kg or when the compounds were administered by infusion. In sodium-replete monkeys, SQ 30,774 inhibited the rise in arterial pressure and PRA following administration of exogenous monkey renin. When the compounds were administered orally at 50 mumol/kg, only SQ 31,844 significantly inhibited PRA (80%). It is concluded that representatives of the imidazole alcohol class of renin inhibitors are potent inhibitors of renin in vitro and inhibit PRA and lower arterial pressure in vivo.

Adaptive e-learning to improve dietary behaviour: a systematic review and cost-effectiveness analysis.

BACKGROUND: UK public health policy strongly advocates dietary change for the improvement of population health and emphasises the importance of individual empowerment to improve health. A new and evolving area in the promotion of dietary behavioural change is 'e-learning', the use of interactive electronic media to facilitate teaching and learning on a range of issues including health. The high level of accessibility, combined with emerging advances in computer processing power, data transmission and data storage, makes interactive e-learning a potentially powerful and cost-effective medium for improving dietary behaviour. OBJECTIVE: This review aims to assess the effectiveness and cost-effectiveness of adaptive e-learning interventions for dietary behaviour change, and also to explore potential psychological mechanisms of action and components of effective interventions. DATA SOURCES: Electronic bibliographic databases (Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, Dissertation Abstracts, EMBASE, Education Resources Information Center, Global Health, Health Economic Evaluations Database, Health Management Information Consortium, MEDLINE, PsycINFO and Web of Science) were searched for the period January 1990 to November 2009. Reference lists of included studies and previous reviews were also screened; authors were contacted and trial registers were searched. REVIEW METHODS: Studies were included if they were randomised controlled trials, involving participants aged ≥ 13 years, which evaluated the effectiveness of interactive software programs for improving dietary behaviour. Primary outcomes were measures of dietary behaviours, including estimated intakes or changes in intake of energy, nutrients, dietary fibre, foods or food groups. Secondary outcome measures were clinical outcomes such as anthropometry or blood biochemistry. Psychological mediators of dietary behaviour change were also investigated. Two review authors independently screened results and extracted data from included studies, with any discrepancies settled by a third author. Where studies reported the same outcome, the results were pooled using a random-effects model, with weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated. Cost-effectiveness was assessed in two ways: through a systematic literature review and by building a de novo decision model to assess the cost-effectiveness of a 'generic' e-learning device compared with dietary advice delivered by a health-care professional. RESULTS: A total of 36,379 titles were initially identified by the electronic searches, of which 43 studies were eligible for inclusion in the review. All e-learning interventions were delivered in high-income countries. The most commonly used behavioural change techniques reported to have been used were goal setting; feedback on performance; information on consequences of behaviour in general; barrier identification/problem solving; prompting self-monitoring of behaviour; and instruction on how to perform the behaviour. There was substantial heterogeneity in the estimates of effect. E-learning interventions were associated with a WMD of +0.24 (95% CI 0.04 to 0.44) servings of fruit and vegetables per day; -0.78 g (95% CI -2.5 g to 0.95 g) total fat consumed per day; -0.24 g (95% CI -1.44 g to 0.96 g) saturated fat intake per day; -1.4% (95% CI -2.5% to -0.3%) of total energy consumed from fat per day; +1.45 g (95% CI -0.02 g to 2.92 g) dietary fibre per day; +4 kcal (95% CI -85 kcal to 93 kcal) daily energy intake; -0.1 kg/m2 (95% CI -0.7 kg/m2 to 0.4 kg/m2) change in body mass index. The base-case results from the E-Learning Economic Evaluation Model suggested that the incremental cost-effectiveness ratio was approximately £102,112 per quality-adjusted life-year (QALY). Expected value of perfect information (EVPI) analysis showed that although the individual-level EVPI was arguably negligible, the population-level value was between £37M and £170M at a willingness to pay of £20,000-30,000 per additional QALY. LIMITATIONS: The limitations of this review include potential reporting bias, incomplete retrieval of completed research studies and data extraction errors. CONCLUSION: The current clinical and economic evidence base suggests that e-learning devices designed to promote dietary behaviour change will not produce clinically significant changes in dietary behaviour and are at least as expensive as other individual behaviour change interventions. FUTURE WORK RECOMMENDATIONS: Despite the relatively high EVPI results from the cost-effectiveness modelling, further clinical trials of individual e-learning interventions should not be undertaken until theoretically informed work that addresses the question of which characteristics of the target population, target behaviour, content and delivery of the intervention are likely to lead to positive results, is completed. FUNDING: The National Institute for Health Research Health Technology Assessment programme.