Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

BACKGROUND: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals. AIM: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice. METHODS: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT. FINDINGS: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks. CONCLUSION: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment.

Applying the British Association of Oral and Maxillofacial Surgeons quality outcomes metrics to a UK oncology and reconstructive surgery service - benchmarking the data.

The British Association of Oral and Maxillofacial Surgery is soon to implement the Quality Outcomes in Oral in Maxillofacial Surgery (QOMS) to provide a platform for quality management across the specialty in the UK. The initial oncology and reconstruction audits for QOMS involves data collection on specific procedures and metrics. The aim of this report is to determine their appropriateness using extant audit datasets in our institution that overlap substantially with the QOMS audits. Pre-existing datasets comprising information on patients treated for oral cavity SCC with curative intent were analysed. Data on surgical margins, lymphadenectomy lymph node yield, delay between surgery and adjuvant radiotherapy, duration of hospital stay, and complications including flap failures were analysed. All statistical analyses were performed with SPSS 25. Run charts describing longitudinal data were generated using SPC for Excel version 6. Twenty three patients (3.1%) of 701 resections had a positive surgical margin reported. Seventeen (4.3%) of patients had less than 18 LNs in the ND specimen analysed. Mean time to start date of adjuvant therapy was 62 days. Only 9% of patients commenced adjuvant therapy within 6 weeks. The median duration of stay was 18 days. In 1153 free flaps a failure rate of 4.3% was identified. A total of 1349 complications (CD I-V) were recorded in the 1111 patients undergoing major surgery with free flap reconstruction. The QOMS selected metrics for oncology and reconstruction are clinically relevant, readily measurable, and likely to be actionable by the surgical team.

Postoperative delirium in patients with head and neck oral cancer in the West of Scotland.

Our aims were to determine the prevalence and association of postoperative delirium (POD) in head and neck (H&N) cancer patients undergoing free flap reconstruction at the oral and maxillofacial surgery (OMFS) unit, Queen Elizabeth University Hospital (QEUH) Glasgow, and to assess whether these determinants can be modified to optimise patient care and reduce the occurrence of POD. Delirium remains an important problem in the postoperative care of patients undergoing major H&N surgery, and early detection and management improve overall outcomes. The patient database containing details of the preoperative physical status (including alcohol misuse, chronic comorbidity, and physiological status) of 1006 patients who underwent major H&N surgery with free-flap repair at the QEUH from 2009-2019, was analysed. Factors associated with delirium were studied, identifying univariate associations as well as multivariate models to determine independent risk factors. The incidence of POD was 7.5% (75/1006; 53 male:22 female; mean (SD) age 65.41 (13.16) years). POD was strongly associated with pre-existing medical comorbidities, excess alcohol, smoking, a prolonged surgical operating time (more than 700 minutes), tracheostomy, blood transfusion, and bony free flaps. Those with POD were at an increased risk of postoperative wound and lung complications, and were more likely to require a hospital stay of more than 21 days. Presurgical assessment should identify risk factors to optimise the diagnosis and treatment of POD, and will enhance patient care by reducing further medical and surgical complications, and overall hospital stay.

Nutrition, Immigration and Health Determinants Are Linked to Verbal Fluency among Anglophone Adults in the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVES: Later-life cognitive impairment is an important health issue; however, little is known about the condition among diverse groups such as immigrants. This study aims to examine whether the healthy immigrant effect exists for verbal fluency, an indicator of cognitive functioning, among anglophone middle-aged and older adults in Canada. METHODS: Using from the baseline data of the Canadian Longitudinal Study on Aging (CLSA), multiple linear regression was employed to compare associations among immigrants (recent and long-term) and Canadian-born residents without dementia for two verbal fluency tests, the Controlled Oral Word Association Test (COWAT) and the Animal Fluency (AF) task. Covariates included socioeconomic, physical health, and dietary intake. RESULTS: Of 8,574 anglophone participants (85.7% Canada-born, 74.8% aged 45-65 years, 81.8% married, 81.9% with a post-secondary degree), long-term immigrants (settled in Canada >20 years) performed significantly better than Canadian-born residents for the COWAT (42.8 vs 40.9) but not the AF task (22.4 vs 22.4). Results of the multivariable adjusted regression analyses showed that long-term immigrants performed better than Canadian-born peers in both the COWAT (B=1.57, 95% CI: 0.80-2.34) and the AF test (B=0.57, 95% CI: 0.19-0.95), but this advantage was not observed among recent immigrants. Other factors associated with low verbal fluency performance included being single, socioeconomically disadvantaged, having hypertension, excess body fat, and consuming low amounts of pulses/nuts or fruit/vegetables. CONCLUSIONS: Long-term immigrants had higher verbal fluency test scores than their Canadian-born counterparts. Immigration status, social, health and nutritional factors are important considerations for possible intervention and prevention strategies for cognitive impairment.

Postoperative risk stratification in oral squamous cell carcinoma.

Postoperative prognostic stratification using the Union for International Cancer Control (UICC) TNM 8th edition staging rules (UICC 8) may identify additional groups of patients who could benefit from adjuvant radiotherapy. Currently, selection for such treatment is not based on all known prognostic factors, and their relative importance may vary depending on the overall risk category. The objective of this study therefore was to evaluate these possibilities. We retrospectively studied 644 patients who had surgery with curative intent for oral squamous cell carcinoma (OSCC) between March 2006 and February 2017. The outcomes of interest were disease-specific survival (DSS) and locoregional recurrence (LRR). Patients were re-staged according to the UICC 8 staging rules. Putative clinical and pathological prognostic variables were evaluated and hazard ratios estimated. Regression analysis was done to identify independent prognostic factors, and iterative analyses identified clinically-relevant risk categories with a minimum of residual prognostic variables. The significance of recognised pathological prognostic factors differed according to the overall risk category. An intermediate risk group comprising patients with pN1 disease as well those with pT3 disease solely on the basis of a depth of invasion (DOI) of more than 10 mm, was identified. A trial to evaluate the benefit or otherwise of adjuvant radiotherapy in this group is now required. Individual prognostic risk factors should be considered within the context of the overall risk category in patients with OSCC.

Effect of Liver Disease Etiology on ROTEM Profiles in Patients Undergoing Liver Transplantation.

BACKGROUND: Coagulation abnormalities in liver transplant patients are complex and may be related to the underlying liver disease. We evaluated the effects of disease etiology on whole-blood rotational thromboelastometry (ROTEM; Pentapharm GmbH, Munich, Germany) profile and association with thrombotic complications following liver transplantation. METHODS: Analysis of perioperative data from patients undergoing liver transplantation between January 1, 2012 and December 31, 2016. Patients were grouped based on the biology of their underlying liver disease: hepatocellular carcinoma (HCC), biliary etiology, and non-biliary etiology. The primary outcome was the EXTEM A10 value of the pre-incision ROTEM. Secondary outcomes included associations between EXTEM A10 value and incidence of postoperative thrombotic complications. RESULTS: Three hundred fifty patients met the eligibility criteria: 60 had biliary etiologies, 203 had non-biliary etiologies, and 87 had HCC. EXTEM A10 values were significantly higher in patients with biliary etiologies than those with non-biliary etiologies (mean difference, 13.8; 95% CI: 10.1 to 17.5; P = .001) and those with HCC (mean difference, 10.4; 95% CI: 6.2 to 14.7; P = .001). Patients with non-biliary etiologies had slightly higher values than those with HCC (mean difference, -3.3; 95% CI: -6.6 to -0.1; P = .04). Higher values for biliary etiologies remained after adjusting for liver disease severity, platelet count, and fibrinogen level. There was no significant difference in EXTEM A10 values between patients who suffered thrombotic complications and those who did not (mean difference: 4.3, 95% CI: -1.3 to 9.9, P = .13). CONCLUSION: Patients with biliary diseases demonstrated higher EXTEM A10 values compared to those with non-biliary diseases or HCC. This was not fully explained by differences in disease severity, platelet count, or fibrinogen level. Pre-incision EXTEM A10 values do not predict incidence of postoperative thrombotic complications.

Reliable consultant level data from an Acute Medical Unit: a powerful tool for improvement.

The development of a novel database interrogating the patient management system in the Acute Medical Unit at Forth Valley Royal Hospital, Scotland, has allowed, for the first time, acquisition of reliable individual consultant-level process and outcome data over a 2-year period. These data have a number of uses, including understanding the level of variation between consultant physicians in AMU across key indicators, such as direct discharge percentage (67.5-44.3%), and readmission percentage (4.0-6.8%). Looking at overnight admissions only effectively excluded case mix as a confounder to identify variation in 30-day mortality (0-2.8%). This has allowed benchmarking, and exploring of relationships between volume of work, physician experience, and patient outcomes. For example, no significant relationship was seen between direct discharge percentage and readmission percentage. Furthermore it is extremely useful for individual clinician appraisal and governance. Finally it has practical uses when designing consultant rotas in order to minimise system variation. A key consideration throughout this work has been clear provenance and local clinical ownership of these data, unlike centrally generated data that may not accurately reflect Acute Medical Unit activity.

Is the 8th edition of the Union for International Cancer Control staging of oral cancer good enough?

Depth of invasion is an important predictor of survival. A study by the International Consortium (ICOR) for Outcome Research proposed incorporation of it (together with the greatest surface dimension, or the anatomical criteria, or both) into the T stage. This has been adopted in part by the 8th edition of the Union for International Cancer Control (UICC) TNM 8 classification of malignant tumours for oral squamous cell carcinoma (SCC). Our aim was to verify depth of invasion as an independent prognostic factor, and to validate the staging by comparing it with that specified in the 7th edition (TNM 7) and the T-staging model proposed by the International Consortium. We retrospectively studied 449 patients who had had operations for a previously untreated primary oral cancer between 2006 and 2014 at a single centre, and analysed the independent predictive value of depth of invasion for both disease-specific and overall survival. It was an independent predictor of disease-specific survival as were sex, perineural invasion, and N stage. It was also an independent predictor of overall survival together with sex and N status. Staging in TNM 8 gave a better balance of distribution than that in TNM 7, but did not discriminate between prognosis in patients with T3 and T4 disease. The proposed International Consortium rules for T-staging gave an improved balance in distribution and hazard discrimination. The incorporation of depth of invasion into the T-staging rules for oral SCC improved prognostic accuracy and is likely to influence the selection of patients for adjuvant treatment. Our findings suggest that the TNM 8 staging lacks hazard discrimination in patients with locally-advanced disease because its T4 staging is restricted to anatomical criteria.

Intensification of ice nucleation observed in ocean ship emissions.

Shipping contributes primary and secondary emission products to the atmospheric aerosol burden that have implications for climate, clouds, and air quality from regional to global scales. In this study we exam the potential impact of ship emissions with regards to ice nucleating particles. Particles that nucleate ice are known to directly affect precipitation and cloud microphysical properties. We have collected and analyzed particles for their ice nucleating capacity from a shipping channel outside a large Scandinavia port. We observe that ship plumes amplify the background levels of ice nucleating particles and discuss the larger scale implications. The measured ice nucleating particles suggest that the observed amplification is most likely important in regions with low levels of background particles. The Arctic, which as the sea ice pack declines is opening to transit and natural resource exploration and exploitation at an ever increasing rate, is highlighted as such a region.

Postoperative complications after head and neck operations that require free tissue transfer - prevalent, morbid, and costly.

To understand and reduce the impact of postoperative complications, we studied 568 patients who had had operations over 72 months in our hospital. Multivariate analysis indicated that factors indicative of coexisting conditions (including activated systemic inflammation) and the complexity of the operation are primary determinants of postoperative complications. The enhanced recovery after surgery (ERAS) care pathway did not have an effect on their occurrence or severity. Systematic study of patients' toleration of major head and neck operations is required, as optimal perioperative care pathways remain elusive.

Suppression of colitis by adoptive transfer of helminth antigen-treated dendritic cells requires interleukin-4 receptor-α signaling.

Infection with helminth parasites has been explored as a treatment for autoimmune and inflammatory diseases. As helminth antigens have potent immunomodulation properties capable of inducing regulatory programs in a variety of cell types, transferring cells treated with helminth antigens represents a novel extension to helminth therapy. Previous work determined that transfer of bone marrow-derived dendritic cells (DC) pulsed with a crude extract of the tapeworm Hymenolepis diminuta (HD) can suppress colitis in recipient mice. The present study explored the mechanism of disease suppression and the importance of interleukin (IL)-4 signaling. Transfer of HD-DCs suppressed dinitrobenzene sulfonic acid (DNBS)-induced colitis through activation of recipient IL-4 receptor-α. The transferred HD-DCs required IL-4Rα and the capacity to secrete IL-10 to drive IL-4 and IL-10 production and to suppress colitis in recipient mice. Treatment of DCs with IL-4 evokes an alternatively activated phenotype, but adoptive transfer of these cells did not affect the outcome of colitis. Collectively, these studies demonstrate the complexity between IL-4 and IL-10 in donor cells and recipient, and the requirement for parasite- and host-derived factors in this novel form of cell therapy. Thus IL-4Rα signaling is revealed as a pathway that could be exploited for helminth antigen cell-based therapy.

Attention-deficit/hyperactivity disorder casts a long shadow: findings from a population-based study of adult women with self-reported ADHD.

BACKGROUND: To develop a sociodemographic and health profile of women with self-reported attention deficit/hyperactivity disorder (ADHD) in comparison to women without. METHODS: Chi-square tests and logistic regression analyses were conducted on data from the nationally representative Canadian Community Health Survey-Mental Health (2012) comparing 107 women aged 20 to 39 years (inclusive) with ADHD to 3801 without ADHD. Depression, generalized anxiety disorder and substance abuse were measured using the WHO-CIDI. RESULTS: Women with ADHD had triple the prevalence of insomnia, chronic pain, suicidal ideation, childhood sexual abuse and generalized anxiety disorder and double the prevalence of substance abuse, current smoking, depressive disorders, severe poverty and childhood physical abuse in comparison with women without ADHD (all P < 0.001). Even after adjustments for age, race, education and income, women with ADHD had substantially higher odds of a wide range of problems. CONCLUSION: Our results suggest that women with ADHD are particularly vulnerable to early adversities, health and mental health problems.

The association between adverse childhood experiences (ACEs) and suicide attempts in a population-based study.

OBJECTIVES: To further our understanding of the relationship between Adverse Childhood Experiences (ACEs) and suicidal behaviour, this study investigates the association between three types of ACEs and lifetime suicide attempts, while considering potential gender-specific and mediating effects. METHODS: Data were obtained from the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH), a cross-sectional, population-based survey comprised of respondents aged 18 or older who provided self-reported data on past experiences of suicide attempts, as well as childhood sexual abuse (CSA), childhood physical abuse (CPA) and parental domestic violence (PDV) (n = 22 559). After testing for ACE by gender interactions, we estimated the odds of lifetime suicide attempts for each ACE and then investigated whether depression, anxiety, substance abuse and chronic pain acted as mediators of the relationship. RESULTS: The odds of suicide attempts are significantly higher among those with a history of CPA (OR = 3.29; 99.9% CI 2.33-4.64), CSA (OR = 4.42; 99.9% CI 3.14-6.23) or PDV (OR = 2.52; 99.9% CI 1.69-3.76), when ACEs are mutually adjusted. There is little evidence that gender acts as a moderator; however, depression, anxiety, substance abuse and chronic pain appear to partially mediate the associations. Depression alone accounts for about a quarter of the associations with CSA and CPA. CONCLUSIONS: Mental health factors and chronic pain appear only to partially mediate relationships between ACEs and lifetime suicide attempts. Future research should look at other pathways with the goal of developing multi-level interventions.

Reduced healthcare utilization following successful hepatitis C virus treatment in HIV-co-infected patients with mild liver disease.

New direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection have achieved high cure rates in many patient groups previously considered difficult-to-treat, including those HIV/HCV co-infected. The high price of these medications is likely to limit access to treatment, at least in the short term. Early treatment priority is likely to be given to those with advanced disease, but a more detailed understanding of the potential benefits in treating those with mild disease is needed. We hypothesized that successful HCV treatment within a co-infected population with mild liver disease would lead to a reduction in the use and costs of healthcare services in the 5 years following treatment completion. We performed a retrospective cohort study of HIV/HCV-co-infected patients without evidence of fibrosis/cirrhosis who received a course of HCV therapy between 2004 and 2013. Detailed analysis of healthcare utilization up to 5 years following treatment for each patient using clinical and electronic records was used to estimate healthcare costs. Sixty-three patients were investigated, of whom 48 of 63 (76.2%) achieved sustained virological response 12 weeks following completion of therapy (SVR12). Individuals achieving SVR12 incurred lower health utilization costs (£5,000 per-patient) compared to (£10 775 per-patient) non-SVR patients in the 5 years after treatment. Healthcare utilization rates and costs in the immediate 5 years following treatment were significantly higher in co-infected patients with mild disease that failed to achieve SVR12. These data suggest additional value to achieving cure beyond the prevention of complications of disease.

Induction of general anaesthesia by effect-site target-controlled infusion of propofol: influence of pharmacokinetic model and ke0 value.

We studied the use of a new ke0 value (0.6 min(-1)) for the Marsh pharmacokinetic model for propofol. Speed of induction and side-effects produced were compared with three other target-controlled infusion systems. Eighty patients of ASA physical status 1-2 were studied in four groups in a prospective, randomised study. Median (IQR [range]) induction times were shorter with the Marsh model in effect-site control mode with a ke0 of either 0.6 min(-1) (81 (61-101 [49-302])s, p < 0.01), or 1.2 min(-1) (78 (68-208 [51-325])s, p < 0.05), than with the Marsh model in blood concentration control (132 (90-246 [57-435])). The Schnider model in effect-site control produced induction times that were longer (298 (282-398 [58-513])s) than those observed with the Marsh model in blood control (p < 0.05), or either effect-site control mode (p < 0.001). There were no differences in the magnitude of blood pressure changes or frequency of apnoea between groups.

Is the cluster risk model of parental adversities better than the cumulative risk model as an indicator of childhood physical abuse?: findings from two representative community surveys.

BACKGROUND: Screening strategies for childhood physical abuse (CPA) need to be improved in order to identify those most at risk. This study uses two regionally representative community samples to examine whether a cluster or cumulative model of risk indicators (i.e. parental divorce, parental unemployment, and parental addictions) explains a larger proportion of the variation in CPA. METHODS: Data were drawn from Statistics Canada's National Population Health Survey (1994-1995) and Canadian Community Health Survey 3.1 (2005). Response rates were greater than 80% in both samples. Each survey had approximately 13,000 respondents aged 18 and over who answered questions about the above adverse childhood experiences. RESULTS: A gradient was shown with similar outcomes in each data set. Only 3.4% of adults who experienced none of the three risk indicators reported they had been physically abused during childhood or adolescence. The prevalence of CPA was greater among those who experienced parental divorce alone (8.3%-10.7%), parental unemployment alone (8.9%-9.7%) or parental addictions alone (18.0%-19.5%). When all three risk indicators were present, the prevalence of CPA ranged from 36.0%-41.0% and the age-sex-race adjusted odds were greater than 15 times that of individuals with none of the three risk indicators. The cluster model explained a statistically significantly larger proportion of the variation than the cumulative model although the difference between the two models was modest. For the purposes of parsimony, the cumulative model may be the better alternative. CONCLUSIONS: Adults who were exposed to two or more childhood risk indicators were much more likely to report that they were physically abused during their childhood than those with only one or no risk factors. Medical professionals may use this information on cumulative risk factors to more effectively target screening for potential CPA. Future research should include prospective studies.

Grain boundary melting in ice.

We describe an optical scattering study of grain boundary premelting in water ice. Ubiquitous long ranged attractive polarization forces act to suppress grain boundary melting whereas repulsive forces originating in screened Coulomb interactions and classical colligative effects enhance it. The liquid enhancing effects can be manipulated by adding dopant ions to the system. For all measured grain boundaries this leads to increasing premelted film thickness with increasing electrolyte concentration. Although we understand that the interfacial surface charge densities q(s) and solute concentrations can potentially dominate the film thickness, we cannot directly measure them within a given grain boundary. Therefore, as a framework for interpreting the data we consider two appropriate q(s) dependent limits; one is dominated by the colligative effect and other is dominated by electrostatic interactions.