A prospective audit comparing Optos Widefield imaging to fundus examination for von Hippel-Lindau retinal screening

Background: Von Hippel-Lindau (VHL) disease is an autosomal dominant multisystem disorder caused by germline mutations at chromosome 3p25-26 in the VHLtumour suppressor gene. Retinal manifestations include capillary haemangiomas that develop in up to 80% of gene carriers. Lifelong retinal surveillance involves yearly assessment usually by fundoscopy and often as part of a VHL multidisciplinary clinic. Optos ultra-widefield retinal imaging is now becoming more widely used in virtual retinal screening clinics. We aimed to assess discrepancies in the pickup rate of angioma and angiomatous-associated disease between slit-lamp fundoscopy and Optos ultra-widefield imaging. Methodology: A total of 49 patients had both Optos ultra-widefield retinal imaging and slit-lamp fundoscopy over 16 months in VHL retinal surveillance clinics at the John Radcliffe Hospital, Oxford, UK. Optos images were analysed for image quality and presence of angioma(s) by a Consultant Ophthalmologist who was masked to the fundoscopy findings. The pickup rate was compared between slit-lamp fundoscopy and Optos imaging. Results: In total, data on 94 eyes were collected. Of the total Optos retinal images, 12.8% were positive for angiomas compared to 11.7% from the slit-lamp examination. There was a discrepancy of 1.1% (one value) where the Optos image analysis suggested a possible angioma, which was not identified on slit-lamp examination. Optos imaging identified all angiomas in this cohort. Conclusions: Optos imaging was non-inferior to slit-lamp examination in this sample of 94 eyes. In the current COVID-19 climate, reducing clinician-patient interaction is important. This research supports providing retinal imaging as an acceptable alternative to the yearly slit-lamp fundus examination

Trends and challenges in the use of drugs as forensic evidence:A scientometric approach to map the current literature

The rapid increase in the production and distribution of illicit drugs has led to vast amounts of data being generated through research and other publications, making it difficult to effectively distill and analyze current and emerging trends. The present study used a scientometric approach to identify trends and challenges in the use of drugs as an evidence type in forensic science by examining reference lists available in the INTERPOL IFSMS reports and the citation database Scopus. It has been identified that “new psychoactive substances” is one of the most frequently used keywords by authors, highlighting the swift response by communities to characterize these emerging compounds. However, it was also noted that despite drugs being a global threat, only limited international collaboration was observed between research groups and the majority of the studies are from authors affiliated within the same country. Finally, an argument is made to encourage a more comprehensive approach in aggregating results on drugs for greater transparency and broader distribution of findings

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Online Health Check for Reducing Alcohol Intake among Employees:A Feasibility Study in Six Workplaces across England

BACKGROUND: Most hazardous and harmful drinkers are of working age and do not seek help with their drinking. Occupational health services are uniquely placed to universally screen employees across the range of socioeconomic and ethnic groups. The aim was to explore the feasibility and acceptability of offering electronic screening and brief intervention for alcohol misuse in the context of a health check in six different workplace settings.  METHODS AND FINDINGS: Employees were recruited from six workplaces across England, including three local authorities, one university, one hospital and one petro-chemical company. A total of 1,254 (8%) employees completed the health check and received personalised feedback on their alcohol intake, alongside feedback on smoking, fruit and vegetable consumption and physical activity. Most participants were female (65%) and of 'White British' ethnicity (94%), with a mean age of 43 years (SD 11). Participants were mostly in Intermediate occupations (58%), followed by Higher managerial / professional (39%) and Routine and manual occupations (2%). A quarter of participants (25%) were drinking at hazardous levels (33% male, 21% female), which decreased with age. Sixty-four percent (n=797) of participants completed online follow-up at three months. Most participants were supportive of workplaces offering employees an online health check (95%), their preferred format was online (91%) and many were confident of the confidentiality of their responses (60%). Whilst the feedback reminded most participants of things they already knew (75%), some were reportedly motivated to change their behaviour (13%).  CONCLUSIONS: Online health screening and personalised feedback appears feasible and acceptable, but challenges include low participation rates, potentially attracting 'worried well' employees rather than those at greatest health risk, and less acceptance of the approach among older employees and those from ethnic minority backgrounds and routine or manual occupations

The IASLC Lung Cancer Staging Project: A Renewed Call to Participation

Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes1, with epidemiological association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment

Impact of nonoptimal intakes of saturated, polyunsaturated, and trans fat on global burdens of coronary heart disease

Background: Saturated fat (SFA), ω‐6 (n‐6) polyunsaturated fat (PUFA), and trans fat (TFA) influence risk of coronary heart disease (CHD), but attributable CHD mortalities by country, age, sex, and time are unclear. Methods and Results: National intakes of SFA, n‐6 PUFA, and TFA were estimated using a Bayesian hierarchical model based on country‐specific dietary surveys; food availability data; and, for TFA, industry reports on fats/oils and packaged foods. Etiologic effects of dietary fats on CHD mortality were derived from meta‐analyses of prospective cohorts and CHD mortality rates from the 2010 Global Burden of Diseases study. Absolute and proportional attributable CHD mortality were computed using a comparative risk assessment framework. In 2010, nonoptimal intakes of n‐6 PUFA, SFA, and TFA were estimated to result in 711 800 (95% uncertainty interval [UI] 680 700–745 000), 250 900 (95% UI 236 900–265 800), and 537 200 (95% UI 517 600–557 000) CHD deaths per year worldwide, accounting for 10.3% (95% UI 9.9%–10.6%), 3.6%, (95% UI 3.5%–3.6%) and 7.7% (95% UI 7.6%–7.9%) of global CHD mortality. Tropical oil–consuming countries were estimated to have the highest proportional n‐6 PUFA– and SFA‐attributable CHD mortality, whereas Egypt, Pakistan, and Canada were estimated to have the highest proportional TFA‐attributable CHD mortality. From 1990 to 2010 globally, the estimated proportional CHD mortality decreased by 9% for insufficient n‐6 PUFA and by 21% for higher SFA, whereas it increased by 4% for higher TFA, with the latter driven by increases in low‐ and middle‐income countries. Conclusions: Nonoptimal intakes of n‐6 PUFA, TFA, and SFA each contribute to significant estimated CHD mortality, with important heterogeneity across countries that informs nation‐specific clinical, public health, and policy priorities.peer-reviewe

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication