The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplantation (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were (1) to assess the incidence of severe PGD in an international cohort; (2) to evaluate the performance of the most strongly validated PGD risk tool, the RADIAL score, in a contemporary cohort; and (3) to redefine clinical risk factors for severe PGD in the current era of HT. METHODS: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis, and its calibration was assessed by plotting the percentage of PGD predicted vs that which was observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. RESULTS: A total of 2746 patients have been enrolled in the registry to date, including 2015 (73.4%) from North America, and 731 (26.6%) from Europe; 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (P value for trend by difference sign test = 0.004). The Kaplan-Meier estimate for 1-year survival was 75.7% (95% CI 69.4-80.9%) in patients with severe PGD as compared to 94.4% (95% CI 93.5-95.2%) in those without severe PGD (log-rank P value < 0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD; it had an AUC of 0.53 (95% CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31-4.43), durable left ventricular assist device support (OR 1.77, 95% CI 1.13-2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02-1.41) were associated with an increased risk of severe PGD. CONCLUSIONS: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.

Early medical abortion by telemedicine in the United Kingdom: a costing analysis.

OBJECTIVE: To determine the potential cost savings resulting from the introduction of routine early medical abortion (EMA) at home by telemedicine in the UK. DESIGN: A costing study. SETTING: The UK. POPULATION: Women in 2020 undergoing EMA provided by three independent abortion providers and two National Health Service (NHS) abortion clinics. METHODS: Computation of the costs of each abortion procedure and of managing failed or incomplete abortion and haemorrhage requiring blood transfusion. MAIN OUTCOME MEASURES: Cost savings. RESULTS: Overall estimated cost savings are £15.80 per abortion undertaken by independent abortion providers, representing a saving to the NHS of over £3 million per year. Limited data from NHS services resulted in an estimated average saving of £188.84 per abortion. CONCLUSIONS: Were telemedicine EMA to become routine, an increase in the number of women eligible for medical rather than surgical abortion, and a reduction in adverse events resulting from earlier abortion, could result in significant cost savings. TWEETABLE ABSTRACT: Early medical abortion at home using telemedicine could save the NHS £3 million per year.

Cytotoxic benzylidene hydrazides of terephthalic acid and related compounds.

The present investigation involved the synthesis of a number of novel benzylidene hydrazides as candidate cytotoxic agents. The preparation of these compounds from terephthalic acid and isophthalic acid proceeded satisfactorily. However, the reaction of phthalic acid hydrazide with various aryl aldehydes was unsuccessful in general. Some of the unexpected products were identified. The shapes and also the distances between the centers of the aryl rings designated B and C of three representative compounds 1b, 2b and 3b were determined. The compounds designated 1a-e, 2a-e and 3b were screened against human HCT116 and HT29 colon cancer cells as well as human CRL1790 non-malignant colon cells which revealed the tumor-selective toxicity displayed by these compounds.

Pediatric Mandibular Central Giant Cell Granuloma: Neoadjuvant Immunotherapy to Minimize Surgical Resection.

ABSTRACT: Central giant cell granuloma (CGCG) is a relatively uncommon benign bony lesion accounting for approximately 7% of all non-neoplastic lesions of the jaw. The clinical behavior of CGCG can vary from a slow-growing, painless lesion to fast-growing and locally destructive. When such a lesion involves the mandible, this can be quite debilitating for the patient, inhibiting oral intake and requiring an extensive resection and bone graft reconstruction. The authors present a case of effectively decreasing the surgical morbidity associated with a large and rapidly growing CGCG of the mandible in a pediatric patient. Neoadjuvant immunotherapy with denosumab (human monoclonal antibody) facilitated treatment of the tumor without the need for a large resection which would have otherwise necessitated a vascularized bony mandibular reconstruction. Consideration of neoadjuvant medical management of CGCG as the primary treatment is advocated.

Exploring the Benefits and Value of Public Health Department Internships for Environmental Health Students.

Internships are an essential component of preparing prospective college graduates for entering the practice-based field of environmental health (EH). EH professionals continually encounter events or hazards of high complexity and impact, and many experienced EH professionals are expected to retire within the next several years. Efforts are needed to ensure a supply of highly qualified and prepared graduates is available to sustain and strengthen the EH workforce. The National Environmental Public Health Internship Program (NEPHIP) addresses this need by supporting health department internships for EH students of academic programs accredited by the National Environmental Health Science and Protection Accreditation Council. We conducted an assessment to examine former NEPHIP intern and mentor experiences and perspectives on 1) how well the internships prepared interns for careers in EH and 2) to what extent the internships provided value to the host health department. Overall, the internships appeared to provide EH students with a well-rounded professional and practice-based experience, while health departments benefited from hosting interns with a foundational knowledge and college education in EH. Promoting the value of public health department EH internships could encourage more students and graduates to seek internship or employment opportunities with health departments, ultimately strengthening the EH workforce.

A national UK audit of suprapubic catheter insertion practice and rate of bowel injury with comparison to a systematic review and meta-analysis of available research.

OBJECTIVES: Limited data exist on the risks of complications associated with a suprapubic catheter (SPC) insertion. Bowel injury (BI) is a well-recognized albeit uncommon complication. Guidelines on the insertion of SPC have been developed by the British Association of Urological Surgeons, but there remains little evidence regarding the incidence of this complication. This study uses contemporary UK data to assess the incidence of SPC insertion and the rate of BI and compares to a meta-analysis of available papers. METHODS: National Hospital Episodes Statistics data were searched on all SPC insertions over an 18-month period for operating procedure codes, Code M38.2 (cystostomy and insertion of a suprapubic tube into bladder). Patients age, 30-day readmission rates, 30-day mortality rate, and catheter specific complication rate were collected. To estimate the BI rate, we searched patients who had undergone any laparotomy or bowel operation within 30 days of SPC insertion. Trusts were contacted directly and directed to ascertain whether there was SPC-related BI. PubMed search to identify papers reporting on SPC related BI was performed for meta-analysis RESULTS: 11 473 SPC insertions took place in the UK in this time period. One hundred forty-one cases had laparotomy within 30 days. Responses from 114 of these cases reported one BI related to SPC insertion. Meta-analysis showed an overall BI rate of 11/1490 (0.7%). CONCLUSIONS: This is the largest dataset reported on SPC insertions showing a lower than previously reported rate of BI. We recommend clinicians use a risk of BI of less than 0.25% when counseling low-risk patients.

Submental flap for reconstruction of anterior skull base, orbital, and high facial defects.

PURPOSE: Large anterior skull base, orbital, and high facial defects can present a challenging reconstructive problem. Limited data exists in the literature on the use of a submental flap for reconstructing such defects. We aimed to describe the feasibility, success, and advantages of using variations of the submental flap for reconstruction of anterior skull base, orbital, and high facial defects. MATERIALS & METHODS: Outcomes measured included flap method, flap survival, flap size, reconstructive site complications, donor site complications, and length of hospital stay. RESULTS: Nine patients were identified that underwent submental flap reconstruction of anterior skull base, orbital, or high facial soft tissue defects. There were 5 pedicled, 2 hybridized, and 2 free submental flap reconstructions. Flap survival was 100%. One flap required leech therapy for early post-operative venous congestion. Average flap skin paddle size was 63.7 cm2. Average length of hospital stay was 7.3 days. No complications from the donor site were reported. CONCLUSIONS: Different variations on the submental flap are viable options for reconstruction of high defects in the head and neck. Such flaps have a number of unique qualities that are suitable for reconstruction of anterior skull base, orbital, and high facial defects.

Symptom appraisal, help seeking, and lay consultancy for symptoms of head and neck cancer.

OBJECTIVE: Early diagnosis is important in head and neck cancer (HNC) patients to maximize the effectiveness of the treatments and minimize the debilitation associated with both the cancer and the invasive treatments of advanced disease. Many patients present with advanced disease, and there is little understanding as to why. This study investigated patients' symptom appraisal, help seeking, and lay consultancy up to the time they first went to see a health care professional (HCP). METHODS: We interviewed 83 patients diagnosed with HNC. The study design was cross sectional and consisted of structured telephone interviews and a medical chart review. We gathered information on the participant's personal reactions to their symptoms, characteristics of their social network, and the feedback they received. RESULTS: We found that 18% of the participants thought that their symptoms were urgent enough to warrant further investigation. Participants rarely (6%) attributed their symptoms to cancer. Eighty-nine percent reported that they were unaware of the early warning signs and symptoms of HNC. Fifty-seven percent of the participants disclosed their symptoms to at least one lay consultant before seeking help from an HCP. The lay consultants were usually their spouse (77%), and the most common advice they offered was to see a doctor (76%). Lastly, 81% of the participants report that their spouse influenced their decision to see an HCP. CONCLUSIONS: The results of this study suggest that patients frequently believe that their symptoms were nonurgent and that their lay consultants influence their decision to seek help from an HCP.

Examining the influence of social-environmental variables on self-injurious behaviour in adolescent boys with fragile X syndrome.

BACKGROUND: Individuals with fragile X syndrome (FXS), the most common known inherited form of intellectual disability, are at increased risk for showing specific forms of self-injurious behaviour (SIB) such as hand biting and head hitting, suggesting that biological factors associated with the syndrome confers increased risk for SIB. Few studies, however, have examined the extent to which social-environmental variables can influence the occurrence of these behaviours in this population. METHOD: Twenty-two adolescent boys with FXS, aged 10 to 18 years were systematically exposed to seven environmental conditions in functional analyses of SIB conducted over 2 days at our research centre. RESULTS: Fourteen (63.6%) boys with FXS engaged in SIB during the functional analyses. Ten (45.5%) boys engaged in SIB that was maintained by social-environmental variables, that is, gaining access to attention/tangibles and/or escaping from social interaction, task demands and/or transition demands. For two boys, SIB was undifferentiated across conditions, and for two boys, SIB appeared to be maintained by automatic reinforcement. CONCLUSIONS: Social-environmental variables appeared to maintain SIB in a significant proportion of boys with FXS. Given that pharmacological treatments for SIB have limited efficacy in this population, the potential role of social-environmental factors on SIB should be examined before pharmacological treatments are implemented for these behaviours.

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

The cost of a patient activation intervention for achieving successful outcomes: results from the PAADRN randomized controlled trial.

In a large, pragmatic clinical trial, we calculated the costs of achieving four successful patient-centered outcomes using a tailored patient activation DXA result letter accompanied by a bone health brochure. The cost to achieve one successful outcome (e.g., a 0.5 standard deviation improvement in care satisfaction) ranged from $127.41 to $222.75. INTRODUCTION: Pragmatic randomized controlled trials (RCTs) should focus on patient-centered outcomes and report the costs for achieving those outcomes. We calculated per person incremental intervention costs, the number-needed-to-treat (NNT), and incremental per patient costs (cost per NNT) for four patient-centered outcomes in a direct-to-patient bone healthcare intervention. METHODS: The Patient Activation after DXA Result Notification (PAADRN) pragmatic RCT enrolled 7749 patients presenting for DXA at three health centers between February 2012 and August 2014. Interviews occurred at baseline and 52 weeks post-DXA. Intervention subjects received an individually tailored DXA result letter accompanied by an educational bone health brochure 4 weeks post-DXA, while the usual care subjects did not. Outcomes focused on patients (a) correctly identifying their results, (b) contacting their providers, (c) discussing their results with their providers, and (d) satisfaction with their bone healthcare. NNTs were determined using intention-to-treat linear probability models, per person incremental intervention costs were calculated, and costs per NNT were computed. RESULTS: Mean age was 66.6 years old, 83.8% were women, and 75.3% were non-Hispanic whites. The incremental per patient cost (costs per NNT) to increase the ability of a patient to (a) correctly identify their DXA result was $171.07; (b) contact their provider about their DXA result was $222.75; (c) discuss their DXA result with their provider was $193.55; and (d) achieve a 0.5 SD improvement in satisfaction with their bone healthcare was $127.41. CONCLUSION: An individually tailored DXA result letter accompanied by an educational brochure can improve four patient-centered outcomes at a modest cost. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01507662.

Identifying people at higher risk of melanoma across the U.K.: a primary-care-based electronic survey.

BACKGROUND: Melanoma incidence is rising rapidly worldwide among white populations. Defining higher-risk populations using risk prediction models may help targeted screening and early detection approaches. OBJECTIVES: To assess the feasibility of identifying people at higher risk of melanoma using the Williams self-assessed clinical risk estimation model in U.K. primary care. METHODS: We recruited participants from the waiting rooms of 22 general practices covering a total population of > 240 000 in three U.K. regions: Eastern England, North East Scotland and North Wales. Participants completed an electronic questionnaire using tablet computers. The main outcome was the mean melanoma risk score using the Williams melanoma risk model. RESULTS: Of 9004 people approached, 7742 (86%) completed the electronic questionnaire. The mean melanoma risk score for the 7566 eligible participants was 17·15 ± 8·51, with small regional differences [lower in England compared with Scotland (P = 0·001) and Wales (P < 0·001), mainly due to greater freckling and childhood sunburn among Scottish and Welsh participants]. After weighting to the age and sex distribution, different potential cut-offs would allow between 4% and 20% of the population to be identified as higher risk, and those groups would contain 30% and 60%, respectively of those likely to develop melanoma. CONCLUSIONS: Collecting data on the melanoma risk profile of the general population in U.K. primary care is both feasible and acceptable for patients in a general practice setting, and provides opportunities for new methods of real-time risk assessment and risk stratified cancer interventions.

Investigating the evolving microstructure of lithium metal electrodes in 3D using X-ray computed tomography.

The growth of electrodeposited lithium microstructures on metallic lithium electrodes has prevented their use in rechargeable lithium batteries due to early performance degradation and safety implications. Understanding the evolution of lithium microstructures during battery operation is crucial for the development of an effective and safe rechargeable lithium-metal battery. This study employs both synchrotron and laboratory X-ray computed tomography to investigate the morphological evolution of the surface of metallic lithium electrodes during a single cell discharge and over numerous cycles, respectively. The formation of surface pits and the growth of mossy lithium deposits through the separator layer are characterised in three-dimensions. This has provided insight into the microstructural evolution of lithium-metal electrodes during rechargeable battery operation, and further understanding of the importance of separator architecture in mitigating lithium dendrite growth.

Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity.

Slow spike and wave discharges (0.5-4 Hz) are a feature of many epilepsies. They are linked to pathology of the thalamocortical axis and a thalamic mechanism has been elegantly described. Here we present evidence for a separate generator in local circuits of associational areas of neocortex manifest from a background, sleep-associated delta rhythm in rat. Loss of tonic neuromodulatory excitation, mediated by nicotinic acetylcholine or serotonin (5HT3A) receptors, of 5HT3-immunopositive interneurons caused an increase in amplitude and slowing of the delta rhythm until each period became the "wave" component of the spike and wave discharge. As with the normal delta rhythm, the wave of a spike and wave discharge originated in cortical layer 5. In contrast, the "spike" component of the spike and wave discharge originated from a relative failure of fast inhibition in layers 2/3-switching pyramidal cell action potential outputs from single, sparse spiking during delta rhythms to brief, intense burst spiking, phase-locked to the field spike. The mechanisms underlying this loss of superficial layer fast inhibition, and a concomitant increase in slow inhibition, appeared to be precipitated by a loss of neuropeptide Y (NPY)-mediated local circuit inhibition and a subsequent increase in vasoactive intestinal peptide (VIP)-mediated disinhibition. Blockade of NPY Y1 receptors was sufficient to generate spike and wave discharges, whereas blockade of VIP receptors almost completely abolished this form of epileptiform activity. These data suggest that aberrant, activity-dependent neuropeptide corelease can have catastrophic effects on neocortical dynamics.

Opposing effects of Sca-1(+) cell-based systemic FGF2 gene transfer strategy on lumbar versus caudal vertebrae in the mouse.

Our previous work showed that a Sca-1(+) cell-based FGF2 therapy was capable of promoting robust increases in trabecular bone formation and connectivity on the endosteum of long bones. Past work reported that administration of FGF2 protein promoted bone formation in red marrow but not in yellow marrow. The issue as to whether the Sca-1(+) cell-based FGF2 therapy is effective in yellow marrow is highly relevant to its clinical potential for osteoporosis, as most red marrows in a person of an advanced age are converted to yellow marrows. Accordingly, this study sought to compare the osteogenic effects of this stem cell-based FGF2 therapy on red marrow-filled lumbar vertebrae with those on yellow marrow-filled caudal vertebrae of young adult W(41)/W(41) mice. The Sca-1(+) cell-based FGF2 therapy drastically increased trabecular bone formation in lumbar vertebrae, but the therapy not only did not promote bone formation but instead caused substantial loss of trabecular bone in caudal vertebrae. The lack of an osteogenic response was not due to insufficient engraftment of FGF2-expressing Sca-1(+) cells or inadequate FGF2 expression in caudal vertebrae. Previous studies have demonstrated that recipient mice of this stem cell-based FGF2 therapy developed secondary hyperparathyroidism and increased bone resorption. Thus, the loss of bone mass in caudal vertebrae might in part be due to an increase in resorption without a corresponding increase in bone formation. In conclusion, the Sca-1(+) cell-based FGF2 therapy is osteogenic in red marrow but not in yellow marrow.

Patient-activation and guideline-concordant pharmacological treatment after bone density testing: the PAADRN randomized controlled trial.

Patients often do not know or understand their bone density test results, and pharmacological treatment rates are low. In a clinical trial of 7749 patients, we used a tailored patient-activation result letter accompanied by a bone health brochure to improve appropriate pharmacological treatment. Treatment rates, however, did not improve. INTRODUCTION: Patients often do not know or understand their dual-energy x-ray absorptiometry (DXA) test results, which may lead to suboptimal care. We tested whether usual care augmented by a tailored patient-activation DXA result letter accompanied by an educational brochure would improve guideline-concordant pharmacological treatment compared to usual care only. METHODS: We conducted a randomized, controlled, double-blinded, pragmatic clinical trial at three health care centers in the USA. We randomized 7749 patients ≥50 years old and presenting for DXA between February 2012 and August 2014. The primary clinical endpoint at 12 and 52 weeks post-DXA was receiving guideline-concordant pharmacological treatment. We also examined four of the steps along the pathway from DXA testing to that clinical endpoint, including (1) receiving and (2) understanding their DXA results and (3) having subsequent contact with their provider and (4) discussing their results and options. RESULTS: Mean age was 66.6 years, 83.8 % were women, and 75.3 % were non-Hispanic whites. Intention-to-treat analyses revealed that guideline-concordant pharmacological treatment was not improved at either 12 weeks (65.1 vs. 64.3 %, p = 0.506) or 52 weeks (65.2 vs. 63.8 %, p = 0.250) post-DXA, even though patients in the intervention group were more likely (all p < 0.001) to recall receiving their DXA results letter at 12 weeks, correctly identify their results at 12 and 52 weeks, have contact with their provider at 52 weeks, and have discussed their results with their provider at 12 and 52 weeks. CONCLUSION: A tailored DXA result letter and educational brochure failed to improve guideline-concordant care in patients who received DXA.

Quantifying Interparticle Forces and Heterogeneity in 3D Granular Materials.

Interparticle forces in granular materials are intimately linked to mechanical properties and are known to self-organize into heterogeneous structures, or force chains, under external load. Despite progress in understanding the statistics and spatial distribution of interparticle forces in recent decades, a systematic method for measuring forces in opaque, three-dimensional (3D), frictional, stiff granular media has yet to emerge. In this Letter, we present results from an experiment that combines 3D x-ray diffraction, x-ray tomography, and a numerical force inference technique to quantify interparticle forces and their heterogeneity in an assembly of quartz grains undergoing a one-dimensional compression cycle. Forces exhibit an exponential decay above the mean and partition into strong and weak networks. We find a surprising inverse relationship between macroscopic load and the heterogeneity of interparticle forces, despite the clear emergence of two force chains that span the system.

Plant nitrogen concentration and isotopic composition in residential lawns across seven US cities.

Human drivers are often proposed to be stronger than biophysical drivers in influencing ecosystem structure and function in highly urbanized areas. In residential land cover, private yards are influenced by individual homeowner preferences and actions while also experiencing large-scale human and biophysical drivers. We studied plant nitrogen (%N) and N stable isotopic composition (δ(15)N) in residential yards and paired native ecosystems in seven cities across the US that span major ecological biomes and climatic regions: Baltimore, Boston, Los Angeles, Miami, Minneapolis-St. Paul, Phoenix, and Salt Lake City. We found that residential lawns in three cities had enriched plant δ(15)N (P < 0.03) and in six cities higher plant N (%) relative to the associated native ecosystems (P < 0.05). Plant δ(15)N was progressively depleted across a gradient of urban density classes in Baltimore and Boston (P < 0.05). Lawn fertilization was associated with depleted plant δ(15)N in Boston and Los Angeles (P < 0.05), and organic fertilizer additions were associated with enriched plant δ(15)N in Los Angeles and Salt Lake City (P < 0.04). Plant δ(15)N was significantly enriched as a function of housing age in Baltimore (r (2) = 0.27, P < 0.02), Boston (r (2) = 0.27, P < 0.01), and Los Angeles (r (2) = 0.34, P < 0.01). These patterns in plant δ(15)N and plant N (%) across these cities suggests that N sources to lawns, as well as greater rates of N cycling combined with subsequent N losses, may be important drivers of plant N dynamics in lawn ecosystems at the national scale.

The bowel cancer awareness campaign 'Be Clear on Cancer': sustained increased pressure on resources and over-accessed by higher social grades with no increase in cancer detected.

AIM: To evaluate the impact of the national 'Be Clear on Cancer' bowel cancer reminder campaign on service and diagnosis at a single UK institution. Secondly, to evaluate the socio-economic background of patients referred before and after the reminder campaign compared with the regional demographic. METHOD: Suspected cancer 2-week wait patients in the 3 months precampaign, postcampaign and after the reminder campaign were included. Demographics, investigations and diagnosis were recorded. The postcode was used to allocate a National Readership Survey social grade. RESULTS: Three hundred and eighty-three referrals were received in the 3 months precampaign, 550 postcampaign and 470 postreminder campaign. There were significant increases in the monthly referral rates following the campaign (P < 0.001 in both the post- and postreminder periods). Significantly more patients from social grades AB and C1C2 than expected from regional demographics were referred precampaign and after the reminder campaign (P < 0.001 in each case). There were no significant differences between the proportions of patients diagnosed with colorectal cancer in the three study periods (P = 0.710). CONCLUSION: The 'Be Clear on Cancer' bowel cancer campaign has had a significant sustained impact on resources. It has failed to increase referrals among lower socio-economic grades, leading to an increase in 'worried well' referrals and no change in numbers, or the stage, of colorectal cancers diagnosed.