Model-based evaluation of admission screening strategies for the detection and control of carbapenemase-producing Enterobacterales in the English hospital setting.

BACKGROUND: Globally, detections of carbapenemase-producing Enterobacterales (CPE) colonisations and infections are increasing. The spread of these highly resistant bacteria poses a serious threat to public health. However, understanding of CPE transmission and evidence on effectiveness of control measures is severely lacking. This paper provides evidence to inform effective admission screening protocols, which could be important in controlling nosocomial CPE transmission. METHODS: CPE transmission within an English hospital setting was simulated with a data-driven individual-based mathematical model. This model was used to evaluate the ability of the 2016 England CPE screening recommendations, and of potential alternative protocols, to identify patients with CPE-colonisation on admission (including those colonised during previous stays or from elsewhere). The model included nosocomial transmission from colonised and infected patients, as well as environmental contamination. Model parameters were estimated using primary data where possible, including estimation of transmission using detailed epidemiological data within a Bayesian framework. Separate models were parameterised to represent hospitals in English areas with low and high CPE risk (based on prevalence). RESULTS: The proportion of truly colonised admissions which met the 2016 screening criteria was 43% in low-prevalence and 54% in high-prevalence areas respectively. Selection of CPE carriers for screening was improved in low-prevalence areas by adding readmission as a screening criterion, which doubled how many colonised admissions were selected. A minority of CPE carriers were confirmed as CPE positive during their hospital stay (10 and 14% in low- and high-prevalence areas); switching to a faster screening test pathway with a single-swab test (rather than three swab regimen) increased the overall positive predictive value with negligible reduction in negative predictive value. CONCLUSIONS: Using a novel within-hospital CPE transmission model, this study assesses CPE admission screening protocols, across the range of CPE prevalence observed in England. It identifies protocol changes-adding readmissions to screening criteria and a single-swab test pathway-which could detect similar numbers of CPE carriers (or twice as many in low CPE prevalence areas), but faster, and hence with lower demand on pre-emptive infection-control resources. Study findings can inform interventions to control this emerging threat, although further work is required to understand within-hospital transmission sources.

Changes in antimicrobial resistance in acute otitis media and otitis externa.

OBJECTIVES: Acute otitis media (AOM) and otitis externa (OE) are common ear infections which may warrant antibiotic therapy. For many infections, there is a rise in antimicrobial resistance, which is associated with treatment failure, morbidity, prolonged hospitalisation and mortality. This study aimed to identify longitudinal changes in microbiology and antimicrobial resistance in aural swabs taken from patients with AOM or OE. DESIGN: Retrospective observational analysis. SETTING: Aural samples processed at Manchester Medical Microbiology Partnership Laboratories between January 2008 and December 2018 were analysed to record organism isolated and antimicrobial sensitivity. PARTICIPANTS: Individual aural swabs from 7200 patients. MAIN OUTCOME MEASURES: Changes in the incidence of organisms and antimicrobial resistance between two time periods (2008-2012 and 2013-2018) were compared using the chi-squared test (alpha = 0.05). RESULTS: From 7200 swabs, 2879 (40%) were from children. The most frequently isolated organisms were Staphylococcus aureus (25%), Pseudomonas aeruginosa (24.4%), yeast (9.1%), mixed anaerobes (7.9%) and Haemophilus influenzae (6.1%). In children aged 0-4 years, H. influenzae had particularly high incidence (25%). Overall, the incidence of P. aeruginosa decreased significantly with time (p = 0.05). Isolates displaying resistance to one or more antimicrobial agents increased significantly in number in the second time period for P. aeruginosa (p = 0.04) and H. influenzae (p = 0.03). There was increased resistance to amoxicillin for P. aeruginosa (p = 0.01) and to erythromycin for H. influenzae (p < 0.01). CONCLUSION: Variations in type and frequency of organisms with increasing age likely result from differences in the preponderance of AOM compared to OE in children versus adults. We found increasing antimicrobial resistance for two organisms commonly isolated from AOM and OE infections, suggesting that aspects of current UK treatment practices and national recommendations may need to be revised.

Genomic Epidemiology of Complex, Multispecies, Plasmid-Borne blaKPC Carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014.

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the blaKPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of blaKPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, blaKPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of blaKPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 blaKPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of blaKPC (predominantly blaKPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), blaKPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-blaKPC and blaKPC plasmids and the common presence of multiple replicons within blaKPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control.

Intraoperative interventions for preventing surgical site infection: an overview of Cochrane Reviews.

BACKGROUND: Surgical site infection (SSI) rates vary from 1% to 5% in the month following surgery. Due to the large number of surgical procedures conducted annually, the costs of these SSIs can be considerable in financial and social terms. Many interventions are used with the aim of reducing the risk of SSI in people undergoing surgery. These interventions can be broadly delivered at three stages: preoperatively, intraoperatively and postoperatively. The intraoperative interventions are largely focused on decontamination of skin using soap and antiseptics; the use of barriers to prevent movement of micro-organisms into incisions; and optimising the patient's own bodily functions to promote best recovery. Both decontamination and barrier methods can be aimed at people undergoing surgery and operating staff. Other interventions focused on SSI prevention may be aimed at the surgical environment and include methods of theatre cleansing and approaches to managing theatre traffic. OBJECTIVES: To present an overview of Cochrane Reviews of the effectiveness and safety of interventions, delivered during the intraoperative period, aimed at preventing SSIs in all populations undergoing surgery in an operating theatre. METHODS: Published Cochrane systematic reviews reporting the effectiveness of interventions delivered during the intraoperative period in terms of SSI prevention were eligible for inclusion in this overview. We also identified Cochrane protocols and title registrations for future inclusion into the overview. We searched the Cochrane Library on 01 July 2017. Two review authors independently screened search results and undertook data extraction and 'Risk of bias' and certainty assessment. We used the ROBIS (risk of bias in systematic reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the certainty of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables. MAIN RESULTS: We included 32 Cochrane Reviews in this overview: we judged 30 reviews as being at low risk of bias and two at unclear risk of bias. Thirteen reviews had not been updated in the past three years. Two reviews had no relevant data to extract. We extracted data from 30 reviews with 349 included trials, totaling 73,053 participants. Interventions assessed included gloving, use of disposable face masks, patient oxygenation protocols, use of skin antiseptics for hand washing and patient skin preparation, vaginal preparation, microbial sealants, methods of surgical incision, antibiotic prophylaxis and methods of skin closure. Overall, the GRADE certainty of evidence for outcomes was low or very low. Of the 77 comparisons providing evidence for the outcome of SSI, seven provided high- or moderate-certainty evidence, 39 provided low-certainty evidence and 31 very low-certainty evidence. Of the nine comparisons that provided evidence for the outcome of mortality, five provided low-certainty evidence and four very low-certainty evidence.There is high- or moderate-certainty evidence for the following outcomes for these intraoperative interventions. (1) Prophylactic intravenous antibiotics administered before caesarean incision reduce SSI risk compared with administration after cord clamping (10 trials, 5041 participants; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.44 to 0.81; high-certainty evidence - assessed by review authors). (2) Preoperative antibiotics reduce SSI risk compared with placebo after breast cancer surgery (6 trials, 1708 participants; RR 0.74, 95% CI 0.56 to 0.98; high-certainty evidence - assessed by overview authors). (3) Antibiotic prophylaxis probably reduce SSI risk in caesarean sections compared with no antibiotics (82 relevant trials, 14,407 participants; RR 0.40, 95% CI 0.35 to 0.46; moderate-certainty evidence; downgraded once for risk of bias - assessed by review authors). (4) Antibiotic prophylaxis probably reduces SSI risk for hernia repair compared with placebo or no treatment (17 trials, 7843 participants; RR 0.67, 95% CI 0.54 to 0.84; moderate-certainty evidence; downgraded once for risk of bias - assessed by overview authors); (5) There is currently no clear difference in the risk of SSI between iodine-impregnated adhesive drapes compared with no adhesive drapes (2 trials, 1113 participants; RR 1.03, 95% CI 0.66 to 1.60; moderate-certainty evidence; downgraded once for imprecision - assessed by review authors); (6) There is currently no clear difference in SSI risk between short-term compared with long-term duration antibiotics in colorectal surgery (7 trials; 1484 participants; RR 1.05 95% CI 0.78 to 1.40; moderate-certainty evidence; downgraded once for imprecision - assessed by overview authors). There was only one comparison showing negative effects associated with the intervention: adhesive drapes increase the risk of SSI compared with no drapes (5 trials; 3082 participants; RR 1.23, 95% CI 1.02 to 1.48; high-certainty evidence - rated by review authors). AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on use of intraoperative treatments for the prevention of SSIs from all currently published Cochrane Reviews. There is evidence that some interventions are useful in reducing SSI risk for people undergoing surgery, such as antibiotic prophylaxis for caesarean section and hernia repair, and also the timing of prophylactic intravenous antibiotics administered before caesarean incision. Also, there is evidence that adhesive drapes increase SSI risk. Evidence for the many other treatment choices is largely of low or very low certainty and no quality-of-life or cost-effectiveness data were reported. Future trials should elucidate the relative effects of some treatments. These studies should focus on increasing participant numbers, using robust methodology and being of sufficient duration to adequately assess SSI. Assessment of other outcomes such as mortality might also be investigated as part of non-experimental prospective follow-up of people with SSI of different severity, so the risk of death for different subgroups can be better understood.

Trial-to-trial, uncertainty-based adjustment of decision boundaries in visual categorization.

Categorization is a cornerstone of perception and cognition. Computationally, categorization amounts to applying decision boundaries in the space of stimulus features. We designed a visual categorization task in which optimal performance requires observers to incorporate trial-to-trial knowledge of the level of sensory uncertainty when setting their decision boundaries. We found that humans and monkeys did adjust their decision boundaries from trial to trial as the level of sensory noise varied, with some subjects performing near optimally. We constructed a neural network that implements uncertainty-based, near-optimal adjustment of decision boundaries. Divisive normalization emerges automatically as a key neural operation in this network. Our results offer an integrated computational and mechanistic framework for categorization under uncertainty.

Variability in encoding precision accounts for visual short-term memory limitations.

It is commonly believed that visual short-term memory (VSTM) consists of a fixed number of "slots" in which items can be stored. An alternative theory in which memory resource is a continuous quantity distributed over all items seems to be refuted by the appearance of guessing in human responses. Here, we introduce a model in which resource is not only continuous but also variable across items and trials, causing random fluctuations in encoding precision. We tested this model against previous models using two VSTM paradigms and two feature dimensions. Our model accurately accounts for all aspects of the data, including apparent guessing, and outperforms slot models in formal model comparison. At the neural level, variability in precision might correspond to variability in neural population gain and doubly stochastic stimulus representation. Our results suggest that VSTM resource is continuous and variable rather than discrete and fixed and might explain why subjective experience of VSTM is not all or none.

Implementation of the infection control estimate: A case study on the use of a newly developed digital tool for outbreak management in the acute setting.

Aim: An Infection Control Estimate (ICE) Tool was developed based on a previously published concept of applying military planning techniques to Infection Prevention and Control (IPC) management strategies in the acute healthcare setting. Methods: Initial testing of the outbreak management tool was undertaken in a large acute hospital in the North-West of England during a localised outbreak of COVID-19. The tool, developed using Microsoft Excel, was completed by trained IPC practitioners in real-time to log outbreak details, assign and manage meeting actions and to generate surveillance data. Results: The ICE tool was utilised across five outbreak control meetings to identify and allocate tasks to members of the outbreak control team and to monitor progress. Within the meetings, the tool was used primarily by the trained IPC Specialist Nurses who were guided by and entered data into the relevant sections. Feedback indicated that the tool was easy to use and useful as the sole repository of outbreak information and data. Suggested improvements following the testing period were made and additional functionality was added. Conclusion: Utilisation of the ICE tool has the potential to improve our understanding of the efficacy of currently employed outbreak management interventions and provides a cognitive support and targeted education for teams responsible for the management of outbreaks. It is hoped that by guiding teams through an outbreak with prompts and guidance, as well as facilitating collection and presentation of surveillance data, outbreaks will be resolved sooner and risks to patients will be reduced.

Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis.

BACKGROUND & AIMS: Idiopathic chronic pancreatitis (ICP) is a complex inflammatory disorder associated with multiple genetic and environmental factors. In individuals without cystic fibrosis (CF), variants of CFTR that inhibit bicarbonate conductance but maintain chloride conductance might selectively impair secretion of pancreatic juice, leading to trypsin activation and pancreatitis. We investigated whether sequence variants in the gene encoding the pancreatic secretory trypsin inhibitor SPINK1 further increase the risk of pancreatitis in these patients. METHODS: We screened patients and controls for variants in SPINK1 associated with risk of chronic pancreatitis and in all 27 exons of CFTR. The final study group included 53 patients with sporadic ICP, 27 probands with familial ICP, 150 unrelated controls, 375 additional controls for limited genotyping. CFTR wild-type and p.R75Q were cloned and expressed in HEK293 cells, and relative conductances of HCO(3)(-) and Cl(-) were measured. RESULTS: SPINK1 variants were identified in 36% of subjects and 3% of controls (odds ratio [OR], 18.1). One variant of CFTR not associated with CF, p.R75Q, was found in 16% of subjects and 5.3% of controls (OR, 3.4). Coinheritance of CFTR p.R75Q and SPINK1 variants occurred in 8.75% of patients and 0.38% of controls (OR, 25.1). Patch-clamp recordings of cells that expressed CFTR p.R75Q showed normal chloride currents but significantly reduced bicarbonate currents (P = .0001). CONCLUSIONS: The CFTR variant p.R75Q causes a selective defect in bicarbonate conductance and increases risk of pancreatitis. Coinheritance of p.R75Q or CF causing CFTR variants with SPINK1 variants significantly increases the risk of ICP.

Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated. Results: A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources. Conclusions: While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days. Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. Clinical trial number: NCT04405934.

The Bruce Report and social welfare leadership in the politics of Toronto's "Slums", 1934­1939.

Slum clearance and rebuilding first became a serious political project in Toronto during the 1930s. Following the release of a systematic housing survey known as the Bruce Report (1934), a set of actors distinguished by their planning authority with respect to social agencies, influence over social work education, coordination of social research, and role as spokespersons of religious bodies inaugurated a political struggle over state power. While the campaign failed, it called forth a reaction from established authorities and reconfigured the local political field as it related to low-income housing. This article gives an account of these processes by drawing upon correspondence and minutes of meetings of city officials and the campaign's organizers, newspaper clippings, and published materials.

The use of military planning techniques to manage outbreaks of novel infections in acute inpatient settings: development of an 'infection control estimate' (ICE).

Outbreaks of infection create unique challenges to healthcare leaders and members of infection control teams who lead efforts to manage, control and resolve outbreaks. This is especially true during outbreaks of novel pathogens which may require atypical control methods reflecting the unknowns inherent in such situations. Healthcare providers within the UK have adopted various structures and models of infection prevention and control (IPC) service reflecting the individual needs of different organisations. As such, the roles and responsibilities of IPC practitioners vary between organisations. Variations in models of care combined with challenges created by outbreaks of novel infections may make algorithm based approaches to outbreak management less effective and potentially prone to missing key actions or considerations which may improve outcomes. Here we suggest the application of a widely established military planning technique, developed to aid decision making in combat environments, to the management of outbreaks of novel infection in acute hospital settings. The technique can be applied at all levels within an IPC hierarchy regardless of role or responsibility and may improve the coherency and efficacy of outbreak management efforts made by IPC teams. The technique may also be applied to outbreaks of known infections; however, in order to demonstrate the flexibility of the model, a novel infection has been used to illustrate its potential value in outbreak management when knowledge is limited.

Mental health issues among international touring professionals in the music industry.

Music industry touring professionals are generally assumed to be at elevated risk for mental health issues, highlighted by numerous high-profile suicides in recent years. Few studies have explored the prevalence of depression, suicidality and associated factors within this population. This study aims to gain an empirical understanding of the mental health issues among international touring professionals, with a particular focus on risk for depression and suicidality, and to identify potential protective factors. Data were collected between February-March 2020 as part of the Tour Health Research Initiative's Touring Health and Wellness Survey 2020. Using a multidimensional questionnaire with a sample of 1154 international touring professionals (artists and crew members), participants who completed all psychosocial measures (n = 508) demonstrated elevated levels of suicidality, risk for clinical depression, stress, anxiety and burnout. The median depression score for completers matched the recommended cutoff score of 20, which qualified 254 participants as high risk for clinical depression, while 200 (39.4%) demonstrated high scores for suicidality. In ROC curve analyses, all psychosocial measures were significant predictors of high suicidality, with a combined emotional and social measure yielding the highest classification accuracy (80%). Moderate strength linear relations were observed for all pairs of measures. Positive correlations were found among all risk factors (depression, anxiety, stress, and burnout) and these measures yielded negative correlations with the protective factors (mindfulness and the emotional/social measure). Findings suggest that interventions enhancing mindfulness and emotional/social well-being may serve as valuable treatment components for this population.

Genomic and healthcare dynamics of nosocomial SARS-CoV-2 transmission.

Understanding the effectiveness of infection control methods in reducing and preventing SARS-CoV-2 transmission in healthcare settings is of high importance. We sequenced SARS-CoV-2 genomes for patients and healthcare workers (HCWs) across multiple geographically distinct UK hospitals, obtaining 173 high-quality SARS-CoV-2 genomes. We integrated patient movement and staff location data into the analysis of viral genome data to understand spatial and temporal dynamics of SARS-CoV-2 transmission. We identified eight patient contact clusters (PCC) with significantly increased similarity in genomic variants compared to non-clustered samples. Incorporation of HCW location further increased the number of individuals within PCCs and identified additional links in SARS-CoV-2 transmission pathways. Patients within PCCs carried viruses more genetically identical to HCWs in the same ward location. SARS-CoV-2 genome sequencing integrated with patient and HCW movement data increases identification of outbreak clusters. This dynamic approach can support infection control management strategies within the healthcare setting.

Health Insurance Status of Pregnant Women and the Likelihood of Receipt of Antenatal Screening for HIV in Sub-Saharan Africa.

BACKGROUND: We investigated if initiating preventive care against HIV vertical transmission by antenatal HIV screening is independent of the patients' source of financial reimbursement for the care received in sub-Saharan Africa (SSA). METHODS: Using information from the WHO's Global Health Expenditure Database and the Demographic Health Surveys Database for 27 sub-Saharan countries, we used Spearman's correlation and adjusted survey logistic regression to determine the potential relationship between enrollment in health insurance and the likelihood that expectant mothers would be offered antenatal HIV screening. RESULTS: We found that expectant mothers covered by health insurance were more than twice as likely to be offered antenatal screening for HIV compared to the uninsured. The likelihood differed by the type of insurance plan the expectant mother carried. DISCUSSION: Health insurance is more of a financial tool that this study finds to be necessary to boost the uptake of preventive and therapeutic HIV care in SSA. CONCLUSION: The ensuing disparity in receiving proper care could hinder the goals of 90-90-90 and the forthcoming 95-95-95 plan in SSA.

Routine laboratory surveillance of antimicrobial resistance in community-acquired urinary tract infections adequately informs prescribing policy in England.

OBJECTIVES: To assess whether resistance estimates obtained from sentinel surveillance for antimicrobial resistance (AMR) in community-acquired urinary tract infections (UTIs) differ from routinely collected laboratory community UTI data. METHODS: All patients aged ≥18 years presenting to four sentinel general practices with a suspected UTI, from 13 November 2017 to 12 February 2018, were asked to provide urine specimens for culture and susceptibility. Specimens were processed at the local diagnostic laboratory. Antibiotic susceptibility testing was conducted using automated methods. We calculated the proportion of Escherichia coli isolates that were non-susceptible (according to contemporaneous EUCAST guidelines) to trimethoprim, nitrofurantoin, cefalexin, ciprofloxacin and amoxicillin/clavulanic acid, overall and by age group and sex, and compared this with routine estimates. RESULTS: Sentinel practices submitted 740 eligible specimens. The specimen submission rate had increased by 28 specimens per 1000 population per year (95% CI 21-35). Uropathogens were isolated from 23% (169/740) of specimens; 67% were E. coli (113/169). Non-susceptibility of E. coli to trimethoprim was 28.2% (95% CI 20.2-37.7) on sentinel surveillance (33.4%; 95% CI 29.5-37.6 on routine data) and to nitrofurantoin was 0.9% (95% CI 0-5.7) (1.5%; 95% CI 0.7-3.0 on routine data). CONCLUSIONS: Routine laboratory data resulted in a small overestimation in resistance (although the difference was not statistically significant) and our findings suggest that it provides an adequate estimate of non-susceptibility to key antimicrobials in community-acquired UTIs in England. This study does not support the need for ongoing local sentinel surveillance.

Sexualised drug taking among men who have sex with men: a systematic review.

AIMS:: Sexualised drug taking is increasingly reported on national and international levels. We aim to review existing evidence of the relationship between recreational drug use (RDU) and sexual intercourse among men who have sex with men (MSM). METHODS:: We reviewed published abstracts and full articles identified from Cochrane, MEDLINE and Embase databases from November 2010 to 2017. We included any existing studies investigating RDU in MSM and at least one of the following: high-risk sexual practices, sexually transmitted infections (STIs) or barriers to accessing specialist support. RESULTS:: In total, 112 studies were included. Of them, 38 studies specifically reported the prevalence of chemsex-related drug use. Links with sexualised drug taking and high-risk sexual practices including condomless sex and group sex were reported by several studies. Recreational drug use in the sexual setting appears linked to the acquisition of STIs, including hepatitis C, syphilis and gonorrhoea. Reports of adverse mental health outcomes are increasingly described, with several studies documenting chemsex-related inpatient admission. A paucity of research addressing barriers to those accessing specialist drug support services was identified. CONCLUSION:: This review demonstrates the complex interplay between recreational drug use, high-risk sexual practices and STIs. It identifies the description of adverse mental health outcomes in the chemsex setting, thus highlighting the need for a multidisciplinary approach across specialties in the management of those adversely affected. Finally, it illuminates the need for future research into perceived barriers of those who require access to support services to ensure timely and comprehensive support provision.

Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism.

BACKGROUND: Pancreatic cancer is a deadly disease. Discovery of the mutated genes that cause the inherited form(s) of the disease may shed light on the mechanism(s) of oncogenesis. Previously we isolated a susceptibility locus for familial pancreatic cancer to chromosome location 4q32-34. In this study, our goal was to discover the identity of the familial pancreatic cancer gene on 4q32 and determine the function of that gene. METHODS AND FINDINGS: A customized microarray of the candidate chromosomal region affecting pancreatic cancer susceptibility revealed the greatest expression change in palladin (PALLD), a gene that encodes a component of the cytoskeleton that controls cell shape and motility. A mutation causing a proline (hydrophobic) to serine (hydrophilic) amino acid change (P239S) in a highly conserved region tracked with all affected family members and was absent in the non-affected members. The mutational change is not a known single nucleotide polymorphism. Palladin RNA, measured by quantitative RT-PCR, was overexpressed in the tissues from precancerous dysplasia and pancreatic adenocarcinoma in both familial and sporadic disease. Transfection of wild-type and P239S mutant palladin gene constructs into HeLa cells revealed a clear phenotypic effect: cells expressing P239S palladin exhibited cytoskeletal changes, abnormal actin bundle assembly, and an increased ability to migrate. CONCLUSIONS: These observations suggest that the presence of an abnormal palladin gene in familial pancreatic cancer and the overexpression of palladin protein in sporadic pancreatic cancer cause cytoskeletal changes in pancreatic cancer and may be responsible for or contribute to the tumor's strong invasive and migratory abilities.

Reliability of a Standardized Nasal Anatomic Worksheet and Correlation With Subjective Nasal Airway Obstruction.

IMPORTANCE: Nasal obstruction is a common chief concern; however, a comprehensive standardized worksheet for evaluating nasal obstruction has not been developed. OBJECTIVE: To evaluate the interrater reliability between staff surgeons and otolaryngology residents using a worksheet-based standardized nasal examination and to identify specific examination findings correlated with the Nasal Obstruction Symptom Evaluation quality-of-life score. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study conducted from June to July 2012 involved 50 adults presenting to an otolaryngology clinic at a tertiary care hospital. The patients were examined by 2 board-certified facial plastic surgeons and 2 otolaryngology residents. EXPOSURES: The inferior turbinates, septum, and internal and external nasal valve narrowing and collapse were graded bilaterally from a scale of 0 to 3 with the aid of a standardized nasal anatomy worksheet. The findings were compared between the attending staff, residents, and the entire group. MAIN OUTCOMES AND MEASURES: The Cohen κ coefficient for interrater reliability was calculated for each of the graded metrics. The Nasal Obstruction Symptom Evaluation scores were correlated with anatomic scores. RESULTS: Of the 49 patients included in the final analysis, the mean age was 43.6 years (range, 21-82 years), and 31 were male (66.3%). Among all attending and resident examiners, a moderate to fair, statistically significant interrater reliability coefficient (P < .001) was observed in the following nasal anatomic measurements: left and right Cottle (κ = 0.582 [95% CI, 0.463-0.700] and κ = 0.580 [95% CI, 0.461-0.698], respectively), modified Cottle (κ = 0.491 [95% CI, 0.373-0.609] and κ = 0.560 [95% CI, 0.442-0.679], respectively), dynamic internal nasal valve collapse (κ = 0.204 [95% CI, 0.118-0.290] and κ = 0.232 [95% CI, 0.140-0.323], respectively), and inferior turbinate hypertrophy (κ = 0.252 [95% CI, 0.152-0.352] and κ = 0.235 [95% CI, 0.153-0.317], respectively). The trend of examination interrater reliability was similar for attending staff and the otolaryngology residents. The Nasal Obstruction Symptom Evaluation score correlated with the mean total anatomic worksheet score (Spearman ρ = 0.301; P = .048). CONCLUSIONS AND RELEVANCE: Interrater reliability is high in both residents and attending staff for dynamic nasal airway examinations evaluating the internal and external nasal valves and for turbinate hypertrophy assessment. The total nasal anatomic score using a standardized worksheet correlates to patient-reported nasal-specific quality of life. LEVEL OF EVIDENCE: NA.

The delivered promise of prenatal imaging and a challenge to the utility of sildenafil for severe lymphatic malformations.

We report the case of an infant with severe lymphatic malformation necessitating ex-utero intrapartum treatment (EXIT) procedure and examine recent advances in high resolution ultrasonography and magnetic resonance imaging, which allow for improved prenatal diagnosis of lesions that cause critical airway obstruction in the neonate. Treatments for lymphatic malformations including surgical resection, sclerotherapy, coblation, and sildenafil are discussed. Our patient did not have any reduction in the size of the lymphatic malformation from sildenafil as suggested in another series.