The impact of vacuum-assisted excision in the management of indeterminate B3 lesions in the NHS Breast Screening Programme in England.

AIM: To assess the impact of vacuum-assisted excision (VAE) on the management of B3 lesions in the England NHS Breast Screening Programme following an update of national guidance. A secondary aim was to investigate the histological features of malignancies resulting from upgrade of B3 lesions by either VAE or surgery. MATERIALS AND METHODS: The study population was all women recalled for assessment after breast screening who had a wide-bore needle biopsy with a B3 result over the period 01/04/2018 to 31/03/2019. Data were extracted from the National Breast Screening Service (NBSS) computer system at unit level. Women with a B3 result were split into those with and without atypia. The upgrade rates and histological features of malignancies in the different groups were analysed. RESULTS: In total, 2,234,514 women attended for screening between 1/4/218 and 31/3/2019, 84,559 women were referred to assessment, and of those 40,037 women had a core biopsy resulting in 3,355 were B3 lesions (8.38%). Within these, 556 cancers were diagnosed, giving an upgrade rate of 16.57% (556/3,355). The upgrade for B3 lesions with atypia was significantly higher than for B3 lesions without atypia (29.1% versus 13.3%, p<0.001). CONCLUSION: The introduction of the new B3 guidelines has resulted in 73.8% of B3 lesions with atypia and 65.1% of B3 lesions with no atypia having VAE rather than surgery. The data highlights the importance of managing these indeterminate lesions appropriately with an overall upgrade rate of 16.57%.

Non-attendance at diabetes outpatient appointments: a systematic review.

BACKGROUND: Non-attendance at diabetes outpatient appointments is a sizeable problem worldwide and has been associated with suboptimal health outcomes. We aimed to describe the characteristics, health outcomes and reasons given for non-attendance at doctor- or nurse-led diabetes appointments, and interventions to improve attendance. METHODS: PubMed, EMBASE, CINAHL and PsychInfo were searched from database inception to February 2019. Included articles were peer-reviewed, published in English, related to adults or young people with type 1 or type 2 diabetes, and addressed one of the above aspects of non-attendance. Studies were excluded if reporting on other types of diabetes or reviewing attendance at structured education, retinal screening, paediatric, antenatal, podiatry or dietetic clinics. RESULTS: Thirty-four studies of varied designs were identified (15 observational, 1 randomized control trial, 9 qualitative, 5 surveys, 4 service improvements). The definition of non-attendance varied. Younger adults, smokers and those with financial pressures were less likely to attend. Non-attendance was associated with higher HbA1c ; other outcomes were varied but typically worse in non-attenders. Reasons for non-attendance in qualitative studies fell into three categories: balancing the costs and benefits of attendance, coping strategies, and the relationships between the person with diabetes and healthcare professionals. Interventions included appointment management strategies, service improvements, patient navigators and WebCam appointments. CONCLUSIONS: Non-attendance is only partially explained by logistical issues. Qualitative studies suggest complex psychosocial factors are involved. Interventions have progressed from simple appointment reminders in an attempt to address some of the psycho-social determinants, but more work is needed to improve attendance.

Royal College of Psychiatrists Liaison Faculty & Joint British Diabetes Societies (JBDS): guidelines for the management of diabetes in adults and children with psychiatric disorders in inpatient settings.

The Royal College of Psychiatrists Liaison Faculty & Joint British Diabetes Societies (JBDS) for Inpatient Care guidelines for the management of diabetes in adults and children with psychiatric disorders in inpatient settings are available in full at: www.diabetes.org.uk/joint-british-diabetes-society and https://abcd.care/joint-british-diabetes-societies-jbds-inpatient-care-group. This article summarizes the guidelines and recommendations. Commissioners are urged to ensure that the needs of people with diabetes and severe mental illness are specifically addressed in contracts with providers of inpatient care, and to avoid financial or other barriers to cross-organizational working and to ensure that patient-structured education is commissioned to meets the complex needs of people with diabetes and severe mental illness. Acute trusts are asked to develop joint pathways with mental health providers and facilitate multidisciplinary working and to screen for mental ill health in those admitted with acute complications of diabetes whose aetiology is unclear or not medically explained. Mental health trusts should create a diabetes register, screen for diabetes, particularly in those prescribed second-generation antipsychotics and ensure that staff are trained in managing and avoiding hypoglycaemia, and the safe use of insulin. Finally, clinical teams should ensure that all staff can access training in diabetes and mental health to support them to care for people with both diabetes and severe mental illness, develop local pathways for joint working and ensure best practice tariff criteria are met for diabetic ketoacidosis and hypoglycaemia, and for children and young people with diabetes.

Associations of osteoprotegerin with coronary artery calcification among women with systemic lupus erythematosus and healthy controls.

Objective We tested the hypothesis that higher circulating levels of osteoprotegerin (OPG) are related to higher levels of coronary artery calcification (CAC) among women with systemic lupus erythematosus (SLE) compared with healthy controls (HCs). Methods Among 611 women in two age- and race-matched SLE case-control studies, OPG was assayed in stored blood samples (HEARTS: plasma, n cases/controls = 122/124, and SOLVABLE: serum, n cases/controls = 185/180) and CAC was measured by electron beam computed tomography. Results In both studies, SLE patients had higher OPG and CAC levels than HCs. Higher OPG was associated with high CAC (>100 vs.100) among SLE, and with any CAC (>0 vs. 0) among HCs. Multivariable-adjusted OR (95% CI) for OPG tertile 3 vs. 1 was 3.58 (1.19, 10.76), p trend = 0.01 for SLE, and 2.28 (1.06, 4.89), p trend = 0.04 for HCs. Associations were attenuated when age-adjusted, but remained significant for HC women aged ≥ 40 and SLE women aged ≥ 50. ROC analyses identified 4.60 pmol/l as the optimal OPG cutpoint for predicting high CAC (>100) among SLE patients with sensitivity = 0.74 and specificity = 0.61, overall, but 0.92 and 0.52, respectively, for SLE patients aged ≥ 50. Conclusion Our cross-sectional results suggest that higher OPG levels are related to higher CAC levels among women with SLE vs. healthy controls.

Demonstrating PM2.5 and road-side dust pollution by heavy metals along Thika superhighway in Kenya, sub-Saharan Africa.

This study assessed the level of heavy metal in roadside dust and PM2.5 mass concentrations along Thika superhighway in Kenya. Thika superhighway is one of the busiest roads in Kenya, linking Thika town with Nairobi. Triplicate road dust samples collected from 12 locations were analysed for lead (Pb), chromium (Cr), cadmium (Cd), nickel (Ni), zinc (Zn), and copper (Cu) using atomic absorption spectrophotometry (AAS). PM2.5 samples were collected on pre-weighed Teflon filters using a BGI personal sampler and the filters were then reweighed. The ranges of metal concentrations were 39-101 µg/g for Cu, 95-262 µg/g for Zn, 9-28 µg/g for Cd, 14-24 µg/g for Ni, 13-30 µg/g for Cr, and 20-80 µg/g for Pb. The concentrations of heavy metals were generally highly correlated, indicating a common anthropogenic source of the pollutants. The results showed that the majority of the measured heavy metals were above the background concentration, and in particular, Cd, Pb, and Zn levels indicated moderate to high contamination. Though not directly comparable due to different sampling timeframes (8 h in this study and 24 h for guideline values), PM2.5 for all sites exceeds the daily WHO PM2.5 guidelines of 25 µg/m3. This poses a health risk to people using and working close to Thika superhighway, for example, local residents, traffic police, street vendors, and people operating small businesses. PM2.5 levels were higher for sites closer to Nairobi which could be attributed to increased vehicular traffic towards Nairobi from Thika. This study provides some evidence of the air pollution problem arising from vehicular traffic in developing parts of the world and gives an indication of the potential health impacts. It also highlights the need for source apportionment studies to determine contributions of anthropogenic emissions to air pollution, as well as long-term sampling studies that can be used to fully understand spatiotemporal patterns in air pollution within developing regions.

Immunohistochemical Characterization of Sarcomas in Trp53+/- Haploinsufficient Mice.

The use of immunohistochemical (IHC) staining in determining and/or confirming the cellular origin of poorly differentiated sarcomas was evaluated in this study. Sarcomatous neoplasms were evaluated in a research study conducted in 2 strains of p53+/- haploinsufficient mice. The most common neoplasms were undifferentiated sarcomas, followed by osteosarcomas and rhabdomyosarcomas (RMSs). The RMSs were poorly differentiated and appeared similar to the pleomorphic, or adult type, RMS of humans. All sarcomas stained positive by IHC for the mesenchymal cell intermediate filament vimentin. The RMSs were identified by positive IHC staining for myogenin, a transcription factor specific to skeletal muscle. Osteosarcomas were easily identifiable on hematoxylin and eosin-stained slides; no generally accepted IHC stain specific for bone is presently available. Some of the undifferentiated sarcomas contained numerous macrophages that stained positive for F4/80, a macrophage marker; the positive-staining cells were considered to be infiltrating macrophages. One-third of the neoplasms observed in this study were associated with subcutaneous implanted electronic microchips used for animal identification. Based upon histopathologic evaluation and IHC staining, it was not possible to distinguish neoplasms associated with subcutaneous microchips from neoplasms not associated with microchips.

Four-Dimensional Quantum Hall Effect with Ultracold Atoms.

We propose a realistic scheme to detect the 4D quantum Hall effect using ultracold atoms. Based on contemporary technology, motion along a synthetic fourth dimension can be accomplished through controlled transitions between internal states of atoms arranged in a 3D optical lattice. From a semiclassical analysis, we identify the linear and nonlinear quantized current responses of our 4D model, relating these to the topology of the Bloch bands. We then propose experimental protocols, based on current or center-of-mass-drift measurements, to extract the topological second Chern number. Our proposal sets the stage for the exploration of novel topological phases in higher dimensions.

Household carbon monoxide (CO) concentrations in a large African city: An unquantified public health burden?

Carbon monoxide (CO) is a poisonous gas produced by incomplete combustion of carbon-based fuels that is linked to mortality and morbidity. Household air pollution from burning fuels on poorly ventilated stoves can lead to high concentrations of CO in homes. There are few datasets available on household concentrations of CO in urban areas of sub-Saharan African countries. CO was measured every minute over 24 h in a sample of homes in Nairobi, Kenya. Data on household characteristics were gathered by questionnaire. Metrics of exposure were summarised and analysis of temporal changes in concentration was performed. Continuous 24-h data were available from 138 homes. The mean (SD), median (IQR) and maximum 24-h CO concentration was 4.9 (6.4), 2.8 (1.0-6.3) and 44 ppm, respectively. 50% of homes had detectable CO concentrations for 847 min (14h07m) or longer during the 24-h period, and 9% of homes would have activated a CO-alarm operating to European specifications. An association between a metric of total CO exposure and self-reported exposure to vapours >15 h per week was identified, however this were not statistically significant after adjustment for the multiple comparisons performed. Mean concentrations were broadly similar in homes from a more affluent area and an informal settlement. A model of typical exposure suggests that cooking is likely to be responsible for approximately 60% of the CO exposure of Nairobi schoolchildren. Household CO concentrations are substantial in Nairobi, Kenya, despite most homes using gas or liquid fuels. Concentrations tend to be highest during the evening, probably associated with periods of cooking. Household air pollution from cooking is the main source of CO exposure of Nairobi schoolchildren. The public health impacts of long-term CO exposure in cities in sub-Saharan Africa may be considerable and should be studied further.

Hepatitis C in men who have sex with men in London--a community survey.

OBJECTIVES: For the last 10 years there has been an epidemic of hepatitis C virus (HCV) infection in men who have sex with men (MSM) in Europe, North America and Australia. The majority of those infected are also HIV-positive and it is unclear to what extent HIV-negative MSM are also at increased risk of infection with HCV. This study provides the first examination of the association between HIV and hepatitis C serostatus in a sample of MSM recruited in community settings. METHODS: A total of 1121 participants completed a short questionnaire in 2008/2009 giving demographic and behavioural data, and donated a sample of oral fluid that was subsequently tested for antibodies to selected pathogens (HIV, syphilis and HCV). RESULTS: The seroprevalence of hepatitis C antibody was 2.1% [95% confidence interval (CI) 1.4-3.2%]. It was more common in those with HIV infection [7.7% (95% CI 4.2-12.9%) vs. 1.2% (95% CI 0.6-2.1%) in those without HIV infection; P < 0.001], those with a history of syphilis [12.2% (95% CI 4.6-24.8%) vs. 1.7% (95% CI 1.0-2.6%) in those without such a history; P < 0.001] and those who reported casual unprotected anal intercourse in the previous year [4.1% (95% CI 2.0-7.4%) vs. 1.2% (95% CI 0.5-2.2%) in those who did not report such intercourse; P = 0.01]. There was no relationship between hepatitis C antibody (anti-HCV) status and other demographic variables (age, ethnicity, employment status or education). CONCLUSIONS: The seroprevalence of anti-HCV in HIV-negative MSM (1.2%) was higher, but not significantly higher, than that in the general population (0.67%). The prevalence was significantly higher in those infected with HIV or with previous syphilis infection and in those reporting unprotected anal intercourse. Our findings support current British Association for Sexual Health and HIV guidelines recommending the provision of selective HCV testing in MSM according to individual risk profile.

Imaging African trypanosomes.

Trypanosoma brucei are extracellular kinetoplastid parasites transmitted by the blood-sucking tsetse fly. They are responsible for the fatal disease human African trypanosomiasis (HAT), also known as sleeping sickness. In late-stage infection, trypanosomes cross the blood-brain barrier (BBB) and invade the central nervous system (CNS) invariably leading to coma and death if untreated. There is no available vaccine and current late-stage HAT chemotherapy consists of either melarsoprol, which is highly toxic causing up to 8% of deaths, or nifurtimox-eflornithine combination therapy (NECT), which is costly and difficult to administer. There is therefore an urgent need to identify new late-stage HAT drug candidates. Here, we review how current imaging tools, ranging from fluorescent confocal microscopy of live immobilized cells in culture to whole-animal imaging, are providing insight into T. brucei biology, parasite-host interplay, trypanosome CNS invasion and disease progression. We also consider how imaging tools can be used for candidate drug screening purposes that could lead to new chemotherapies.

Managing pediatric psoriasis: update on treatments and challenges-a review.

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory disease with prominent cutaneous features, although the limited number of medications approved for pediatric psoriasis makes treating this population difficult. This review provides an overview of the challenges associated with diagnosing and treating pediatric psoriasis as well as the approved and off-label treatments for children and infants with psoriasis. METHODS: Articles relevant to pediatric psoriasis were identified using a series of PubMed searches. Topics relevant to pediatric psoriasis were explored, including disease characteristics, epidemiology, treatment efficacy and safety, and access to care. Publications previously known to the authors were also included. RESULTS: Clinical features of psoriasis can be challenging to identify clinically, and patients face challenges gaining access to treatment. Most medications that have been approved for adult psoriasis lack data and labeling to support safe and effective use in pediatric patients, and therefore access is limited. A growing number of clinical trials using biologic agents for pediatric psoriasis aim to broaden available treatment options but may also raise unique concerns associated with the use of these medications in children. CONCLUSION: Pediatric psoriasis is underrecognized and often undertreated. Clinicians must balance relative risks and potential benefits when developing a treatment strategy for these patients.

Gene-vitamin D interactions on food sensitization: a prospective birth cohort study.

BACKGROUND: It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine whether cord blood VDD is associated with FS and whether such association can be modified by genetic variants in a prospective birth cohort. METHODS: This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D < 11 ng/ml, and FS as specific IgE ≥ 0.35 kUA/l to any of eight common food allergens in early childhood. We genotyped potentially functional single-nucleotide polymorphisms (SNPs) in 11 genes known to be involved in regulating IgE and 25(OH)D concentrations. Logistic regressions were used to test the effects of VDD on FS individually and jointly with SNPs. RESULTS: Among the 649 children, 44% had VDD and 37% had FS. When examined alone, VDD was not associated with FS. When examined jointly with SNPs, a significant interaction between IL4 gene polymorphism (rs2243250) and VDD (p(interaction) = 0.003, p(FDR) = 0.10) was found: VDD increased the risk of FS among children carrying CC/CT genotypes (OR = 1.79, 95%CI: 1.15-2.77). Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). When all four SNPs were simultaneously considered, a strong gene-VDD interaction was evident (p(interaction) = 9 × 10(-6) ). CONCLUSIONS: Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene-vitamin D interaction on FS.

Impact of personalized cardiovascular disease risk estimates on physical activity-a randomized controlled trial.

AIM: Informing a person of their individual risk of developing a disease in the future may be sufficient to provide the person with the impetus to adopt risk reducing behaviours. The aim of this study was to determine if a personalised 10-year cardiovascular disease (CVD) risk estimate can increase physical activity and other risk reduction behaviours in adults at high risk of CVD. METHODS: Pilot 2 × 2 factorial randomised controlled trial conducted in Oxfordshire, UK including 194 adults at increased CVD risk (10-year CVD risk ≥ 20%) recruited from four general practices. Main outcome measure at one month was physical activity measured by accelerometer. RESULTS: Median (IQR) age was 62.3 (54.9, 66.1) years, 67% were men and 19% had known diabetes. Mean (SD) total accelerometer counts per day was 297 × 10(-3) (110 × 10(-3) ) and activity of moderate or greater intensity was undertaken for 53 (22) minutes per day. In the 185 (95%) participants attending follow-up an increase in physical activity was not seen. There was a non-significant 0.5% (p = 0.56) greater increase in accelerometer counts in those receiving personalised CVD risk estimates. No significant within or between group changes were seen at one month in estimated 10-year CVD risk. A net 7% decrease in mean LDL cholesterol (p = 0.004) was seen in the intervention group despite similar increases in new prescriptions for lipid lowering therapies. CONCLUSION: In adults at increased risk of CVD provision of personalised 10-year CVD risk estimates did not appear to increase physical activity or estimated CVD risk over a one-month period.

Early-generation germplasm introgression from Sorghum macrospermum into sorghum (S. bicolor).

Sorghum has been improved by public and private breeding programs utilizing germplasm mostly from within the species Sorghum bicolor. Recently, hybridization with an Australian species, S. macrospermum (AAB1B1YYZZ), has been demonstrated and the genomic relationship to S. bicolor (AAB1B1) shown to be partially compatible. For this species to be potentially useful to sorghum improvement programs, there must be documented introgression into an S. bicolor background. Fifteen BC1F1 progeny were recovered using the interspecific hybrid as a female and embryo rescue. In these progeny, chromosome numbers ranged from 35 to 70 and all were essentially male-sterile. Repeated backcrossing with S. bicolor pollen produced BC2F1 seed on 3 of the 15 BC1F1 plants. BC2F1 progeny had varying levels of male fertility; selfed seed set ranged from 0% to 95%, with only 2 individuals being completely male-sterile. Using AFLP and SSR markers, genomic introgression of S. macrospermum ranged from 0% to 18.6%. Cytogenetic analysis of 19 individuals revealed that chromosome numbers were 20, except for a single backcross that had 21 chromosomes. Molecular cytogenetic analysis confirmed the presence of recombinant introgression chromosomes as well as alien addition and alien substitution chromosomes within the BC2F1s.

Taking training into your own hands.

The Young Diabetologists' Forum (YDF) is a group designed and run by specialist trainees in endocrinology and diabetes that aims to provide high quality educational events. The YDF recognised that not all trainees in the specialty had equitable access to training opportunities and resolved to try and remedy the situation. This article describes the history and evolution of the YDF into an organisation representing over 400 trainees in endocrinology and diabetes, providing up to seven training events per year and with a budget of over pounds 200,000. As well as offering education and training another key purpose of the YDF is to give trainees from around the country the opportunity to meet up and exchange thoughts and ideas. The overall aim of the organisation is to improve the lives of people with diabetes by helping to ensure that future specialists are fully equipped for their role.

Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10).

AIMS: SUSTAIN 10 compared the efficacy and safety of the anticipated most frequent semaglutide dose (1.0mg) with the current most frequently prescribed liraglutide dose in Europe (1.2mg), reflecting clinical practice. METHODS: In this phase 3b, open-label trial, 577 adults with type 2 diabetes (HbA1c 7.0-11.0%) on 1-3 oral antidiabetic drugs were randomized 1:1 to subcutaneous once-weekly semaglutide 1.0mg or subcutaneous once-daily liraglutide 1.2mg. Primary and confirmatory secondary endpoints were changes in HbA1c and body weight from baseline to week 30, respectively. RESULTS: Mean HbA1c (baseline 8.2%) decreased by 1.7% with semaglutide and 1.0% with liraglutide (estimated treatment difference [ETD] -0.69%; 95% confidence interval [CI] -0.82 to -0.56, P<0.0001). Mean body weight (baseline 96.9kg) decreased by 5.8kg with semaglutide and 1.9kg with liraglutide (ETD -3.83kg; 95% CI -4.57 to -3.09, P<0.0001). The proportions of subjects achieving glycaemic targets of<7.0% and=6.5%, weight loss of=5% and=10%, and a composite endpoint of HbA1c<7.0% without severe or blood glucose-confirmed symptomatic hypoglycaemia and no weight gain were greater with semaglutide vs liraglutide (all P<0.0001). Both treatments had similar safety profiles, except for more frequent gastrointestinal disorders (the most common adverse events [AEs]) and AEs leading to premature treatment discontinuation with semaglutide vs liraglutide (43.9% vs 38.3% and 11.4% vs 6.6%, respectively). CONCLUSION: Semaglutide was superior to liraglutide in reducing HbA1c and body weight. Safety profiles were generally similar, except for higher rates of gastrointestinal AEs with semaglutide vs liraglutide.

Impact of using a non-diabetes-specific risk calculator on eligibility for statin therapy in type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to investigate the impact of using a non-diabetes-specific cardiovascular disease (CVD) risk calculator to determine eligibility for statin therapy according to current UK National Institute for Health and Clinical Excellence (NICE) guidelines for those patients with type 2 diabetes who are at an increased risk of CVD (10 year risk >or=20%). METHODS: The 10 year CVD risks were estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine and the Framingham equation for 4,025 patients enrolled in the Lipids in Diabetes Study who had established type 2 diabetes and LDL-cholesterol <4.1 mmol/l. RESULTS: The mean (SD) age of the patients was 60.7 (8.6) years, blood pressure 141/83 (17/10) mmHg and the total cholesterol:HDL-cholesterol ratio was 3.9 (1.0). The median (interquartile range) diabetes duration was 6 (3-11) years and the HbA(1c) level was 8.0% (7.2-9.0%). The cohort comprised 65% men, 91% whites, 4% Afro-Caribbeans, 5% Asian Indians and 15% current smokers. More patients were classified as being at high risk by the UKPDS Risk Engine (65%) than by the Framingham CVD equation (63%) (p < 0.0001). The Framingham CVD equation classified fewer men and people aged <50 years old as high risk (p < 0.0001). There was no difference between the UKPDS Risk Engine and Framingham classification of women at high risk (p = 0.834). CONCLUSIONS/INTERPRETATION: These results suggest that the use of Framingham-derived rather than UKPDS Risk Engine-derived CVD risk estimates would deny about one in 25 patients statin therapy when applying current NICE guidelines. Thus, under these guidelines the choice of CVD risk calculator is important when assessing CVD risk in patients with type 2 diabetes, particularly for the identification of the relatively small proportion of younger people who require statin therapy.

Memory performance of chemical workers exposed to polybrominated biphenyls.

Twenty-five chemical workers who manufactured polybrominated biphenyls (PBB's) were given objective tests of learning and memory. Although this group had high concentrations of PBB's in adipose tissue, mean scores on all memory tests were normal. The PBB concentration was not correlated with memory performance; the most contaminated workers showed no evidence of memory dysfunction.

HIV opt-out increases HIV testing in low-risk patients.

We audited the effect of introducing HIV opt-out in a genitourinary medicine clinic in central London, UK. We found that opt-out increased the rate at which HIV testing was offered to low-risk patients and that more tests were done.