A comparison of self-reported risk and protective factors and the death implicit association test in the prediction of future suicide attempts in adolescent emergency department patients.

BACKGROUND: Concerns have been raised about the utility of self-report assessments in predicting future suicide attempts. Clinicians in pediatric emergency departments (EDs) often are required to assess suicidal risk. The Death Implicit Association Test (IAT) is an alternative to self-report assessment of suicidal risk that may have utility in ED settings. METHODS: A total of 1679 adolescents recruited from 13 pediatric emergency rooms in the Pediatric Emergency Care Applied Research Network were assessed using a self-report survey of risk and protective factors for a suicide attempt, and the IAT, and then followed up 3 months later to determine if an attempt had occurred. The accuracy of prediction was compared between self-reports and the IAT using the area under the curve (AUC) with respect to receiver operator characteristics. RESULTS: A few self-report variables, namely, current and past suicide ideation, past suicidal behavior, total negative life events, and school or social connectedness, predicted an attempt at 3 months with an AUC of 0.87 [95% confidence interval (CI), 0.84-0.90] in the entire sample, and AUC = 0.91, (95% CI 0.85-0.95) for those who presented without reported suicidal ideation. The IAT did not add significantly to the predictive power of selected self-report variables. The IAT alone was modestly predictive of 3-month attempts in the overall sample ((AUC = 0.59, 95% CI 0.52-0.65) and was a better predictor in patients who were non-suicidal at baseline (AUC = 0.67, 95% CI 0.55-0.79). CONCLUSIONS: In pediatric EDs, a small set of self-reported items predicted suicide attempts within 3 months more accurately than did the IAT.

Paediatric tibial shaft fractures: an instructional review for the FRCS exam.

This instructional review presents the literature and guidelines relevant to the classification, management and prognosis of paediatric tibial shaft fractures at a level appropriate for the FRCS exit examination in Trauma and Orthopaedic surgery.

Paediatric distal radius fractures: an instructional review for the FRCS examination.

An instructional review of the literature and guidelines relevant for the classification, management and prognosis of paediatric distal radius fractures. Aimed at the knowledge level required for the trauma and orthopaedic FRCS examination.

Risk factors for perioperative blood transfusions after urogenital fistula repair in Uganda: a retrospective cohort study.

OBJECTIVE: To determine the incidence of and risk factors for perioperative blood transfusions after urogenital fistula repairs in Uganda. DESIGN: A retrospective cohort study. SETTING: A community hospital in Masaka, Uganda. POPULATION: Women who underwent fistula repair at the Kitovu Hospital between 2013 and 2019. METHODS: Retrospective review of demographics and clinical perioperative characteristics of patients surgically treated for urogenital fistula. Patient characteristics were compared between those who did and those who did not require a blood transfusion. MAIN OUTCOME MEASURES: Need for perioperative blood transfusion and risk factors. RESULTS: A total of 546 patients treated for urogenital fistulas were included in this study. The median age was 31.1 ± 13.2 years. A vaginal surgical approach was used in the majority of patients (84.6%). Complications occurred in 3.5% of surgical repairs, and the incidence of blood transfusions was 6.2%. In multivariable analyses, for each gram per deciliter (g/dl) increase in preoperative haemoglobin, the odds of blood transfusion decreased by approximately 28% (adjusted OR 0.72, 95% CI 0.59-0.86). Women who had their fistula repaired abdominally were 3.4 times more likely to require transfusions (95% CI 1.40-8.08). CONCLUSIONS: The incidence of blood transfusions among urogenital fistula repairs in our population is twice that of developed nations. An abdominal surgical approach to urogenital fistula is a significant risk factor for perioperative blood transfusions. The timing of the repair may warrant further study. TWEETABLE ABSTRACT: One of the first studies to look at blood transfusion risk factors after fistula repair in a low-resource setting.

First results from five multidisciplinary diagnostic centre (MDC) projects for non-specific but concerning symptoms, possibly indicative of cancer.

BACKGROUND: Patients with non-specific symptoms often experience longer times to diagnosis and poorer clinical outcomes than those with site-specific symptoms. This paper reports initial results from five multidisciplinary diagnostic centre (MDC) projects in England, piloting rapid referral for patients with non-specific symptoms. METHODS: The evaluation covered MDC activity from 1st December 2016 to 31st July 2018, with projects using a common dataset. Logistical regression analyses were conducted, with a diagnosis of any cancer as the dependent variable. Exploratory analysis was conducted on presenting symptoms and diagnoses of cancer, and on comparisons within these groupings. RESULTS: In total, 2961 patients were referred into the MDCs and 241 cancers were diagnosed. The pathway detected cancers across a broad range of tumour sites, including several rare and less common cancers. An association between patient age and cancer was identified (p < 0.001). GP 'clinical suspicion' was identified as a strong predictor of cancer (p = 0.006), with a reduced association with cancer observed in patients with higher numbers of GP consultation before referral (p = 0.008). CONCLUSIONS: The MDC model diagnoses cancer in patients with non-specific symptoms, with a conversion rate of 8%, demonstrating the diagnostic potential of a non-site-specific symptomatic referral pathway.

The impact of mammography screening programmes on incidence of advanced breast cancer in Europe: a literature review.

BACKGROUND: Observational studies have reported conflicting results on the impact of mammography service screening programmes on the advanced breast cancer rate (ABCR), a correlation that was firmly established in randomized controlled trials. We reviewed and summarized studies of the effect of service screening programmes in the European Union on ABCR and discussed their limitations. METHODS: The PubMed database was searched for English language studies published between 01-01-2000 and 01-06-2018. After inspection of titles and abstracts, 220 of the 8644 potentially eligible papers were considered relevant. Their abstracts were reviewed by groups of two authors using predefined criteria. Fifty studies were selected for full paper review, and 22 of these were eligible. A theoretical framework for their review was developed. Review was performed using a ten-point checklist of the methodological caveats in the analysis of studies of ABCR and a standardised assessment form designed to extract quantitative and qualitative information. RESULTS: Most of the evaluable studies support a reduction in ABCR following the introduction of screening. However, all studies were challenged by issues of design and analysis which could at least potentially cause bias, and showed considerable variation in the estimated effect. Problems were observed in duration of follow-up time, availability of reliable reference ABCR, definition of advanced stage, temporal variation in the proportion of unknown-stage cancers, and statistical approach. CONCLUSIONS: We conclude that much of the current controversy on the impact of service screening programmes on ABCR is due to observational data that were gathered and/or analysed with methodological approaches which could not capture stage effects in full. Future research on this important early indicator of screening effectiveness should focus on establishing consensus in the correct methodology.

The variation in chemical composition of barley feed with or without enzyme supplementation influences nutrient digestibility and subsequently affects performance in piglets.

This study investigates the effect of dietary supplementation of a ß-glucanase and ß-xylanase enzyme mix to barley based diets, at two different chemical compositions achieved through different agronomical conditions on growth performance, coefficient of apparent total tract digestibility (CATTD) of nutrients, selected faecal microbial populations and faecal scores in piglets. Sixty-four piglets (11.7 kg (SD 0.96)) housed in pens of two were assigned to one of four dietary treatments (n = 8). The dietary treatments were as follows: (T1) low quality barley diet, (T2) low quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement, (T3) high quality barley diet and (T4) high quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement. Piglets offered the low quality barley-based diet had a higher (p < .05) average daily gain (ADG) (0.73 vs. 0.69 kg, SEM 0.001), gain:feed (G:F) ratio (0.61 vs. 0.58 kg, SEM 0.011) and a higher CATTD (p < .001) of dry matter (DM), organic matter (OM), nitrogen (N), ash, gross energy (GE) and neutral detergent fibre (NDF) compared with piglets offered the high quality barley diet. Piglets offered the high quality barley-based diet had reduced faecal scores compared to piglets offered the low quality barley-based diet (2.44 vs. 2.57, SEM 0.036) (p < .05). There was a higher population of Lactobacillus spp. (11.6 vs. 10.5 log gene copy number/g faeces, SEM 0.177) (p < .001) and total volatile fatty acid (VFA) concentration (185 vs. 165 mmol/g faeces, SEM 5.658) (p < .001) in the faeces of piglets offered the high quality barley-based diet compared to piglets offered the low quality barley-based diet. The inclusion of a ß-glucanase and ß-xylanase enzyme complex had no effect on any variable measured. In conclusion, the higher quality barley-based diet showed beneficial effects on the faecal Lactobacillus spp. population and faecal scores of the piglets; however, the higher level of ß-glucans in the diet decreased nutrient digestibility and subsequently decreased the performance.

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.

BACKGROUND: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. METHODS: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. RESULTS: 247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). CONCLUSIONS: The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction. TRIAL REGISTRATION: ISRCTN 78513845.

Episodic memory in depression: the unique contribution of the anterior caudate and hippocampus.

BACKGROUND: Learning and memory impairments in older adults with depression are linked to hippocampal atrophy. However, other subcortical regions may also be contributing to these deficits. We aimed to examine whether anterior caudate nucleus volume is significantly reduced in older adults with depression compared to controls; whether anterior caudate volume is associated with performance on tasks of episodic learning and memory, and if so, whether this association is independent of the effects of the hippocampus. METHOD: Eighty-four health-seeking participants meeting criteria for lifetime major depressive disorder (mean age = 64.2, s.d. = 9.1 years) and 27 never-depressed control participants (mean age = 63.9, s.d. = 8.0 years) underwent neuropsychological assessment including verbal episodic memory tests [Rey Auditory Verbal Learning Test and Logical Memory (WMS-III)]. Magnetic resonance imaging was conducted, from which subregions of the caudate nucleus were manually demarcated bilaterally and hippocampal volume was calculated using semi-automated methods. RESULTS: Depressed subjects had smaller right anterior caudate (RAC) (t = 2.3, p = 0.026) and poorer memory compared to controls (t = 2.5, p < 0.001). For depressed subjects only, smaller RAC was associated with poorer verbal memory (r = 0.3, p = 0.003) and older age (r = -0.46, p < 0.001). Multivariable regression showed that the RAC and hippocampus volume uniquely accounted for 5% and 3% of the variance in memory, respectively (ß = 0.25, t = 2.16, p = 0.033; ß = 0.19, t = 1.71, p = 0.091). CONCLUSIONS: In older people with depression, the anterior caudate nucleus and the hippocampus play independent roles in mediating memory. While future studies examining this structure should include larger sample sizes and adjust for multiple comparisons, these findings support the critical role of the striatum in depression.

Clopidogrel, prasugrel or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor instead of clopidogrel in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary interventions (PCI). AIM: We sought to describe the trends in uptake of the newer agents and analyse the clinical characteristics and short-term outcomes of patients treated with clopidogrel, prasugrel or ticagrelor. METHODS: We analysed the temporal trends of antiplatelet use since the availability of prasugrel (2009-2013) in patients with ACS from the Melbourne Interventional Group registry. To assess clinical characteristics and outcomes, we included 1850 patients from 2012 to 2013, corresponding to the time all three agents were available. The primary outcome was major adverse cardiovascular events (MACE). The safety end-point was in-hospital bleeding. RESULTS: For the period of 2009-2013, the majority of patients were treated with clopidogrel (72%) compared with prasugrel (14%) or ticagrelor (14%). There was a clear trend towards ticagrelor by the end of 2013. Patients treated with clopidogrel were more likely to present with non-ST-elevation ACS, be older, and have more comorbidities. There was no difference in unadjusted 30-day mortality (0.9 vs 0.5 vs 1.0%, P = 0.76), myocardial infarction (2 vs 1 vs 2%, P = 0.52) or MACE (3 vs 3 vs 4%, P = 0.57) between the three agents. There was no difference in in-hospital bleeding (3 vs 2 vs 2%, P = 0.64). CONCLUSION: Prasugrel and ticagrelor are increasingly used in ACS patients treated with PCI, predominantly in a younger cohort with less comorbidity. Although antiplatelet therapy should still be individualised based on the thrombotic and bleeding risk, our study highlights the safety of the new P2Y12 inhibitors in contemporary Australian practice.

Likely effect of adding flexible sigmoidoscopy to the English NHS Bowel Cancer Screening Programme: impact on colorectal cancer cases and deaths.

BACKGROUND: From 2013, once-only flexible sigmoidoscopy (FS) at age 55 is being phased into the England National Health Service Bowel Cancer Screening Programme (NHSBCSP), augmenting biennial guaiac faecal occult blood testing (gFOBT) at ages 60-74. Here, we project the impact of this change on colorectal cancer (CRC) cases and deaths prevented in England by mid-2030. METHODS: We simulated the life-course of English residents reaching age 55 from 2013 onwards. Model inputs included population numbers, invitation rates and CRC incidence and mortality rates. The impact of gFOBT and FS alone on CRC incidence and mortality were derived from published trials, assuming an uptake of 50% for FS and 57% for gFOBT. For FS plus gFOBT, we assumed the gFOBT effect to be 75% of the gFOBT alone impact. RESULTS: By mid-2030, 8.5 million individuals will have been invited for once-only FS screening. Adding FS to gFOBT screening is estimated to prevent an extra 9627 (-10%) cases and 2207 (-12%) deaths by mid-2030. If FS uptake is 38% or 71%, respectively, an extra 7379 (-8%) or 13 689 (-15%) cases and 1691 (-9%) or 3154 (-17%) deaths will be prevented by mid-2030. CONCLUSIONS: Adding once-only FS at age 55 to the NHSBCSP will prevent ∼10,000 CRC cases and ∼2000 CRC deaths by mid-2030 if FS uptake is 50%. In 2030, one cancer was estimated to be prevented per 150 FS screening episodes, and one death prevented per 900 FS screening episodes. The actual reductions will depend on the FS invitation schedule and uptake rates.

The impact of national cancer awareness campaigns for bowel and lung cancer symptoms on sociodemographic inequalities in immediate key symptom awareness and GP attendances.

BACKGROUND: National campaigns focusing on key symptoms of bowel and lung cancer ran in England in 2012, targeting men and women over the age of 50 years, from lower socioeconomic groups. METHODS: Data from awareness surveys undertaken with samples of the target audience (n=1245/1140 pre-/post-bowel campaign and n=1412/1246 pre-/post-lung campaign) and Read-code data extracted from a selection general practitioner (GP) practices (n=355 for bowel and n=486 for lung) were analysed by population subgroups. RESULTS: Unprompted symptom awareness: There were no significant differences in the magnitude of shift in ABC1 vs C2DE groups for either campaign. For the bowel campaign, there was a significantly greater increase in awareness of blood in stools in the age group 75+ years compared with the 55-74 age group, and of looser stools in men compared with women. Prompted symptom awareness: Endorsement of 'blood in poo' remained stable, overall and across different population subgroups. Men showed a significantly greater increase in endorsement of 'looser poo' as a definite warning sign of bowel cancer than women. There were no significant differences across subgroups in endorsement of a 3-week cough as a definite warning sign of lung cancer. GP attendances: Overall, there were significant increases in attendances for symptoms directly linked to the campaigns, with the largest percentage increase seen in the 50-59 age group. For the bowel campaign, the increase was significantly greater for men and for practices in the most-deprived quintile, whereas for lung the increase was significantly greater for practices in the least-deprived quintile. CONCLUSIONS: The national bowel and lung campaigns reached their target audience and have also influenced younger and more affluent groups. Differences in impact within the target audience were also seen. There would seem to be no unduly concerning widening in inequalities, but further analyses of the equality of impact across population subgroups is warranted.

Orai/CRACM1 and KCa3.1 ion channels interact in the human lung mast cell plasma membrane.

BACKGROUND: Orai/CRACM1 ion channels provide the major Ca(2+) influx pathway for FcεRI-dependent human lung mast cell (HLMC) mediator release. The Ca(2+)-activated K(+) channel KCa3.1 modulates Ca(2+) influx and the secretory response through hyperpolarisation of the plasma membrane. We hypothesised that there is a close functional and spatiotemporal interaction between these Ca(2+)- and K(+)-selective channels. RESULTS: Activation of FcεRI-dependent HLMC KCa3.1 currents was dependent on the presence of extracellular Ca(2+), and attenuated in the presence of the selective Orai blocker GSK-7975A. Currents elicited by the KCa3.1 opener 1-EBIO were also attenuated by GSK-7975A. The Orai1 E106Q dominant-negative mutant ablated 1-EBIO and FcεRI-dependent KCa3.1 currents in HLMCs. Orai1 but not Orai2 was shown to co-immunoprecipitate with KCa3.1 when overexpressed in HEK293 cells, and Orai1 and KCa3.1 were seen to co-localise in the HEK293 plasma membrane using confocal microscopy. CONCLUSION: KCa3.1 activation in HLMCs is highly dependent on Ca(2+) influx through Orai1 channels, mediated via a close spatiotemporal interaction between the two channels.

Functional KCa3.1 channels regulate steroid insensitivity in bronchial smooth muscle cells.

Identifying the factors responsible for relative glucocorticosteroid (GC) resistance present in patients with severe asthma and finding tools to reverse it are of paramount importance. In asthma we see in vivo evidence of GC-resistant pathways in airway smooth muscle (ASM) bundles that can be modeled in vitro by exposing cultured ASM cells to TNF-α/IFN-γ. This action drives GC insensitivity via protein phosphatase 5-dependent impairment of GC receptor phosphorylation. In this study, we investigated whether KCa3.1 ion channels modulate the activity of GC-resistant pathways using our ASM model of GC insensitivity. Immunohistochemical staining of endobronchial biopsies revealed that KCa3.1 channels are localized to the plasma membrane and nucleus of ASM in both healthy controls and asthmatic patients, irrespective of disease severity. Western blot assays and immunofluorescence staining confirmed the nuclear localization of KCa3.1 channels in ASM cells. The functional importance of KCa3.1 channels in the regulation of GC-resistant chemokines induced by TNF-α/IFN-γ was assessed using complementary inhibitory strategies, including KCa3.1 blockers (TRAM-34 and ICA-17043) or KCa3.1-specific small hairpin RNA delivered by adenoviruses. KCa3.1 channel blockade led to a significant reduction of fluticasone-resistant CX3CL1, CCL5, and CCL11 gene and protein expression. KCa3.1 channel blockade also restored fluticasone-induced GC receptor-α phosphorylation at Ser(211) and transactivation properties via the suppression of cytokine-induced protein phosphatase 5 expression. The effect of KCa3.1 blockade was evident in ASM cells from both healthy controls and asthmatic subjects. In summary, KCa3.1 channels contribute to the regulation of GC-resistant inflammatory pathways in ASM cells: blocking KCa3.1 channels may enhance corticosteroid activity in severe asthma.

Prevalence and spatial distribution of bovine brucellosis in San Luis and La Pampa, Argentina.

BACKGROUND: Bovine brucellosis (BB) is a zoonotic disease caused by Brucella abortus. BB is endemic in Argentina, where vaccination with Brucella abortus strain 19 is compulsory for 3-to-8 month-old heifers. The objectives of this study were to quantify the prevalence of BB and to identify factors associated with its occurrence, along with the spatial distribution of the disease, in the provinces of La Pampa and San Luis. A two-stage random sampling design was used to sample 8,965 cows (3,513 in La Pampa and 5,452 in San Luis) from 451 farms (187 in La Pampa and 264 in San Luis). RESULTS: Cow and herd prevalence were 1.8 % (95 % CI: 1.3-2.2; n = 157) and 19.7 % (95 % CI: 17.0-22.4; n = 89), respectively. Both cow-level and herd-level prevalence in La Pampa (2.4 and 26.0 %, respectively) were significantly higher than in San Luis (1.4 and 15.5 %, respectively). There were not differences between the proportions of reactive cattle compared to that obtained in a survey conducted in 2005. However, herd prevalence in La Pampa was significantly (P < 0.05) higher compared to that study. Disease was found to be spatially clustered in west La Pampa. The lower the bovine density and the calf/cow ratio, the higher odds of belonging to the cluster. CONCLUSIONS: The increase of farm prevalence in the last five years suggests that the disease is spreading and that control measures should be applied in the region. The cluster of infected farms was located in the west region of La Pampa. There, farms have lower animal densities and smaller cow/calf indices compared to the rest of the province. Although western La Pampa has more infected herds, within-farm prevalence was not higher, which suggests that the control program has been relatively successful in controlling the disease at the farm level, and/or that low animal density inherently results in low disease prevalence. Our results provide baseline information on the epidemiology of BB and its potential pattern of transmission in Argentina, which will ultimately help to improve BB control programs in the country.

Pre-treatment with dual antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Although dual antiplatelet therapy is the standard of care in non-ST-segment elevation acute coronary syndromes (NSTEACS), it remains unclear when a second antiplatelet agent should be initiated. We sought to assess the safety and efficacy of pre-treatment with clopidogrel in patients with NSTEACS undergoing percutaneous coronary intervention (PCI). METHODS: We analysed baseline clinical and procedural characteristics of 6817 patients with NSTEACS who underwent PCI from the Melbourne Interventional Group registry from 2005 to 2012. Patients were included in the pre-treatment group if clopidogrel was administered prior to cardiac catheterisation. We assessed 30-day mortality, myocardial infarction (MI) and major adverse cardiovascular events. The safety endpoint was in-hospital bleeding. RESULTS: Of the 6817 patients, only 2951 (43%) received pre-treatment with clopidogrel. Patients in the pre-treatment group were more likely to present with unstable angina (70.8% vs 68.2%, P = 0.02) and have a history of MI (35.6% vs 23.6%, P < 0.01) but were less likely to have PCI within 24 h of admission (17.2% vs 25.2%, P < 0.01). There was no difference between the groups in 30-day mortality (0.9% vs 1.4%, P = 0.06), MI (2.0% vs 2.2%, P = 0.52) or major adverse cardiovascular event (3.7% vs 4.2%, P = 0.25). There was no difference in bleeding complications (1.9% vs 1.9%, P = 0.94). CONCLUSIONS: Pre-treatment with dual antiplatelet therapy in NSTEACS is not routine clinical practice in Australia. Pre-treatment appears safe but is not associated with improved short-term clinical outcomes.

Genetic and epigenetic factors influencing chronic kidney disease.

Chronic kidney disease (CKD) has become a serious public health problem because of its associated morbidity, premature mortality, and attendant healthcare costs. The rising number of persons with CKD is linked with the aging population structure and an increased prevalence of diabetes, hypertension, and obesity. There is an inherited risk associated with developing CKD, as evidenced by familial clustering and differing prevalence rates across ethnic groups. Previous studies to determine the inherited risk factors for CKD rarely identified genetic variants that were robustly replicated. However, improvements in genotyping technologies and analytic methods are now helping to identify promising genetic loci aided by international collaboration and multiconsortia efforts. More recently, epigenetic modifications have been proposed to play a role in both the inherited susceptibility to CKD and, importantly, to explain how the environment dynamically interacts with the genome to alter an individual's disease risk. Genome-wide, epigenome-wide, and whole transcriptome studies have been performed, and optimal approaches for integrative analysis are being developed. This review summarizes recent research and the current status of genetic and epigenetic risk factors influencing CKD using population-based information.

Translation of research results to simple estimates of the likely effect of a lung cancer screening programme in the United Kingdom.

BACKGROUND: There is considerable interest in the possibility of provision of lung cancer screening services in many developed countries. There is, however, no consensus on the target population or optimal screening regimen. METHODS: In this paper, we demonstrate the use of published results on lung cancer screening and natural history parameters to estimate the likely effects of annual and biennial screening programmes in different risk populations, in terms of deaths prevented and of human costs, including screening episodes, further investigation rates and overdiagnosis. RESULTS: Annual screening with the UK Lung Screening Study eligibility criteria was estimated to result in 956 lung cancer deaths prevented and 457 overdiagnosed cancers from 330,000 screening episodes. Biennial screening would result in 802 lung cancer deaths prevented and 383 overdiagnosed cancers for 180,000 screening episodes. INTERPRETATION/CONCLUSION: The predictions suggest that the intervention effect could justify the human costs. The evidence base for low-dose CT screening for lung cancer pertains almost entirely to annual screening. The benefit of biennial screening is subject to additional uncertainty but the issue merits further empirical research.

Evaluation of a service intervention to improve awareness and uptake of bowel cancer screening in ethnically-diverse areas.

BACKGROUND: Uptake of bowel cancer screening is lowest in London, in populations of lower socio-economic status, and in particular ethnic or religious groups. METHODS: We report on the evaluation of two interventions to improve uptake in an area including populations of low socio-economic status and considerable ethnic diversity. The interventions were face-to-face health promotion on bowel cancer screening at invitees' general practice and health promotion delivered by telephone only. Nine large general practices in East London were chosen at random to offer face-to-face health promotion, and nine other large practices to offer telephone health promotion, with 24 practices of similar size as comparators. Data at practice level were analysed by Mann-Whitney-Wilcoxon tests and grouped-logistic regression. RESULTS: There were 2034 invitees in the telephone intervention practices, 1852 in the face-to-face intervention practices and 5227 in the comparison practices. Median gFOBt kit uptake in the target population (aged 59-70) was 46.7% in the telephone practices, 43.8% in the face-to-face practices and 39.1% in the comparison practices. Significant improvements in the odds of uptake were observed following telephone intervention in both males (OR=1.39, 95% CI=1.20-1.61, P<0.001) and females (OR=1.49, 95% CI=1.29-1.73, P<0.001), while the face-to-face intervention mainly impacted uptake in males (OR=1.23, 95% CI=1.10-1.36), P<0.001) but did not lead to a significant increase in females (OR=1.12, 95% CI=0.96-1.29, P=0.2). CONCLUSIONS: Personally delivered health promotion improved uptake of bowel cancer screening in areas of low socio-economic status and high ethnic diversity. The intervention by telephone appears to be the most effective method.

Reduction in interval cancer rates following the introduction of two-view mammography in the UK breast screening programme.

BACKGROUND: The introduction of two-view mammography at incident (subsequent) screens in the National Health Service Breast Screening Programme (NHSBSP) has led to an increased number of cancers detected at screen. However, the effect of two-view mammography on interval cancer rates has yet to be assessed. METHODS: Routine screening and interval cancer data were collated from all screening programmes in the United Kingdom for women aged 50-64, screened between 1 April 2003 and 31 March 2005. Interval cancer rates were compared based on whether two-view mammography was in use at the last routine screen. RESULTS: The reduction in interval cancers following screening using two-view mammography compared with one view was 0.68 per 1,000 women screened. Overall, this suggests the introduction of two-view mammography at incident screen was accompanied by a 15-20% reduction in interval cancer rates in the NHSBSP. CONCLUSION: The introduction of two-view mammography at incident screens is associated with a reduction in incidence of interval cancers. This is consistent with previous publications on a contemporaneous increase in screen-detected cancers. The results provide further evidence of the benefit of the use of two-view mammography at incident screens.