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Objective: To determine the persistence of human papillomavirus (HPV) infection following treatment of HPV-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC). Methods: A cross-sectional study was undertaken at The Ottawa Hospital (Ottawa, ON, Canada), a tertiary academic hospital and regional cancer center. Adult patients who were diagnosed with HPV + OPSCC between the years of 2014 and 2016 and treated with curative intent, and who were alive and willing to consent were eligible for inclusion. A saliva assay was used to test for the presence of HPV DNA in a random sample of patients. qPCR was used to amplify DNA from saliva samples. Results: Saliva samples were obtained from 69 patients previously treated with HPV + OPSCC. All patients had a minimum of 2 years of follow-up. 5 patients tested positive for HPV: 2 were positive for HPV-16, 2 for HPV-18, and 1 “other” HPV type. No patient in our study cohort had suffered recurrence post-treatment. Conclusions: This study is the first to demonstrate the prevalence of persistent oncogenic HPV DNA in saliva following treatment for HPV + OPSCC. This prevalence appears to be low, despite the fact that persistent HPV infection is a precursor for the development of HPV + OPSCC. This finding raises questions about what factors influence the clearance or persistence of HPV DNA in saliva after treatment for HPV + OPSCC, and may add to our understanding about the longitudinal effects of HPV infection in these cancers.

A retrospective risk-adjusted analysis was completed using data from the National Surgical Quality Improvement Program (NSQIP) to (1) compare the risks of post-operative hematoma for thyroid surgery using conventional cautery compared alternative energy devices (defined as LigaSure and Harmonic Scalpel), and (2) compare operative times for the same. The primary outcome variable was post-operative hematoma occurrence. The secondary outcome variable was operative time. The exposure variable was use of conventional or alternative sources of cautery. All adult patients who underwent a total thyroidectomy, subtotal thyroidectomy or completion thyroidectomy between 2016 and 2018 were included. Multivariable linear and logistic regression analyses were performed to control for potentially confounding variables. A total of 13,330 cases were analyzed; 4342 used conventional cautery, and 8988 used alternative sources. There was a statistically significant decrease in post-operative hematoma risk using alternative sources of cautery compared to conventional cautery (OR 0.75; 95% CI 0.58–0.98) (p = 0.04). Use of alternative sources of cautery added 4.95 min onto operative time (95% CI 2.45–7.45) which was statistically significant (p

In April 2020, close to the start of the first U.K. COVID-19 lockdown, the U.K. government announced the development of a COVID-19 contact tracing app, which was later trialled on the U.K. island, the Isle of Wight, in May/June 2020. United Kingdom surveys found general support for the development of such an app, which seemed strongly influenced by public trust. Institutions developing the app were called upon to fulfil the commitment to public trust by acting with trustworthiness. Such calls presuppose that public trust associated with the app can emerge if the conditions for trustworthiness are met and that public trust is simplistic, i.e., linearly the sum of each member of the publics’ individual – U.K. government trust relationship. Drawing on a synthesis of the trust literature and fifteen interviews with members of the public trialling the app on the Isle of Wight, this paper aims to explore what trust mechanisms and relationships are at play when thinking about public trust in the context of the U.K. COVID-19 app. We argue that public trust is a complex social phenomenon and not linearly correlated with institutional trustworthiness. As such, attention needs to widen from calls for trustworthy infrastructures as a way to build public trust, to a deeper understanding of those doing the trusting; in particular, what or whom do people place their trust in (or not) when considering whether using the app and why. An understanding of this will help when trying to secure public trust during the implementation of necessary public health measures. Supplementary Information The online version contains supplementary material available at 10.1007/s11673-021-10127-x.

In order to combat the COVID-19 pandemic, policymakers around the globe have increasingly invested in digital health technologies to support the 'test, track and trace' approach of containing the spread of the novel coronavirus. These technologies include mobile 'contact tracing' applications (apps), which can trace individuals likely to have come into contact with those who have reported symptoms or tested positive for the virus and request that they self-isolate. This paper takes a critical public health perspective that advocates for 'genuine participation' in public health interventions and emphasises the need to take citizen's knowledge into account during public health decision-making. In doing so, it presents and discusses the findings of a UK interview study that explored public views on the possibility of using a COVID-19 contact-tracing app public health intervention at the time the United Kingdom (UK) Government announced their decision to develop such a technology. Findings illustrated interviewees' range and degree of understandings, misconceptions, and concerns about the possibility of using an app. In particular, concerns about privacy and surveillance predominated. Interviewees associated these concerns much more broadly than health by identifying with pre-existent British national narratives associated with individual liberty and autonomy. In extending and contributing to ongoing sociological research with public health, we argue that understanding and responding to these matters is vital, and that our findings demonstrate the need for a forward-looking, anticipatory strategy for public engagement as part of the responsible innovation of the COVID-19 contact-tracing app in the UK. ispartof: CRITICAL PUBLIC HEALTH vol:32 issue:1 pages:31-43 ispartof: location:England status: published

This study investigates the underlying climate processes behind the largest recorded mangrove dieback event along the Gulf of Carpentaria coast in northern Australia in late 2015. Using satellite-derived fractional canopy cover (FCC), variation of the mangrove canopies during recent decades are studied, including a severe dieback during 2015–2016. The relationship between mangrove FCC and climate conditions is examined with a focus on the possible role of the 2015–2016 El Niño in altering favorable conditions sustaining the mangroves. The mangrove FCC is shown to be coherent with the low-frequency component of sea level height (SLH) variation related to the El Niño Southern Oscillation (ENSO) cycle in the equatorial Pacific. The SLH drop associated with the 2015–2016 El Niño is identified to be the crucial factor leading to the dieback event. A stronger SLH drop occurred during austral autumn and winter, when the SLH anomalies were about 12% stronger than the previous very strong El Niño events. The persistent SLH drop occurred in the dry season of the year when SLH was seasonally at its lowest, so potentially exposed the mangroves to unprecedented hostile conditions. The influence of other key climate factors is also discussed, and a multiple linear regression model is developed to understand the combined role of the important climate variables on the mangrove FCC variation.

Listeria monocytogenes is a Gram-positive, intracellular pathogen responsible for the highly fatal foodborne illness listeriosis. Establishing intracellular infections requires the coordinated expressions of a variety of virulence factors, such as the pore-forming toxin listeriolysin O (LLO), in response to various intra- and extracellular signals. For example, we previously reported that L. monocytogenes differentially modulated LLO production in response to exogenous propionate, a short chain fatty acid either used in salt form as a human food ingredient or produced endogenously by gut microbial fermentation. Therefore, propionate is likely a continuously present signal throughout the L. monocytogenes transmission and infection process. However, little is known about the role of propionate in modulating L. monocytogenes-host interactions. Here we investigated the impact of propionate treatment on L. monocytogenes intracellular infections using cell culture infection models. Propionate treatment was performed separately on L. monocytogenes or host cells before or during infections to better distinguish pathogen-versus-host responses to propionate. Intracellular CFU in RAW264.7 macrophages and plaque diameters in L-fibroblasts were measured as proxy for intracellular infection outcomes. Nitrite levels and cellular morphology were also measured to assess host responses to propionate. We found that propionate pretreatment of anaerobic, but not aerobic, L. monocytogenes significantly enhanced subsequent intracellular infections in both cell types and nitrite production by infected macrophages. Propionate treatment of uninfected macrophages significantly altered cell morphology, seen by longer cells and greater migration, and reduced nitrite concentration in activated macrophages. Treatment of macrophages with propionate prior to or during infections significantly inhibited intracellular growth of L. monocytogenes, including those pre-treated with propionate. These results showcased an opposing effect of propionate on L. monocytogenes intracellular infections and strongly support propionate as an important signaling molecule for both the pathogen and the host cell that can potentially alter the outcome of L. monocytogenes-host interactions.

Abstract Active surveillance (AS) in the management of small, low risk papillary thyroid cancer (PTC) as an alternative option to thyroidectomy, is an area of active research. A national Canadian study is proposed to evaluate the long-term outcomes of patients with small, low risk PTC who choose AS or surgery. This letter describes the proceedings of a national investigator meeting to plan the study. Graphical abstract

Background Salivary detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proposed as an alternative to nasopharyngeal or oropharyngeal swab testing. Our group previously published a study demonstrating that both testing methods identified SARS-CoV-2 using polymerase chain reaction (PCR)-based detection methodology. We therefore conducted a follow-up study using antibody testing to evaluate the accuracy of saliva versus swabs for COVID-19 detection and the durability of antibody response. Methods Venous blood samples were collected from consenting participants and the presence of serum antibodies for SARS-CoV-2 was evaluated on a large, automated immunoassay platform by the Roche anti-SARS-CoV-2 qualitative assay (Roche Diagnostics, Laval Quebec). Individuals with a serum antibody cut-off index (COI) ≥ 1.0 were considered positive. Results In asymptomatic and mildly symptomatic patients with a previously positive standard swab and/or saliva SARS-CoV-2 PCR-test, 42 demonstrated antibodies with 13 patients positive by swab alone, and 8 patients positive by saliva alone. Conclusions Despite their status as ‘current standard’ for COVID-19 testing, these findings highlight limitations of PCR-based tests.

Summary Background Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. Methods The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0–2, and with T1–T2, N0–2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1–2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. Findings 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20–33) for the radiotherapy group and 29 months (23–43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. Interpretation Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. Funding Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.

Alternative energy devices have become a popular alternative to conventional hemostasis in thyroid surgery. These devices have been shown to reduce operative time and thermal nerve injury. As hemostasis is paramount in thyroid surgery, we sought to examine the relative efficacy of 2 alternate energy devices compared to conventional hemostasis in preventing postoperative hematoma following total thyroidectomy.Ovid MEDLINE, EMBASE, PubMed, and Cochrane Central Register of Controlled Trials.A systematic literature search was performed for all relevant English-language studies published between 1946 and July 2018. Two authors independently extracted data and analyzed articles for quality using the National Institute of Health Quality Assessment Scale. Our primary outcome of interest was hematoma requiring reoperation.A total of 348 studies were screened, with 23 meeting the inclusion criteria. We found no significant difference in postoperative hematoma rates using alternate energy devices compared to conventional hemostasis (We found no significant difference in postoperative hematoma rates following total thyroidectomy for any indication with the use of alternate energy devices compared to conventional hemostatic techniques. This suggests that hematoma occurrence does not necessarily need to be considered when choosing between these hemostatic devices. This information may help guide surgeons' decisions regarding choice of hemostatic technique during thyroid surgery.

Introduction The scapula tip free flap has been described for reconstruction of short mandible defects with extensive soft tissue needs. The versatility of this flap has not been extensively described. Methods Retrospective case series of patients who underwent mandibulectomy and reconstruction with the scapula tip free flap from 2005 to 2016. Outcomes include bony union, complications, dental rehabilitation, and donor site morbidity. Results A total of 120 patients were identified. Average harvested bone was 7.7 cm, with 54% undergoing one osteotomy, and 76.7% harvested as a chimeric flap. Radiographically, average inset bone was 6.6 cm. Complete or partial bony union was observed at 74.4% of proximal and 82.6% of distal osteotomies. A 95% of reconstructions met criteria for dental implants. Mean disabilities of the arm, shoulder and hand score was 21.2. Conclusions The scapular tip is an excellent option for reconstruction of segmental mandible defects with the option of osteotomy, excellent bony union rates, low donor site morbidity, and potential for dental rehabilitation.

Purpose/Objective(s) Widespread oral human papillomavirus (HPV) infections have led to a rapid increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC). HPV-related OPSCCs have a better prognosis than conventional alcohol- and smoking-related OPSCCs, suggesting a role for treatment de-escalation. The goal of this phase II randomized trial was to assess survival, oncologic, and toxicity outcomes with two de-escalation approaches: primary reduced-dose radiotherapy (RT) vs. primary transoral surgery plus neck dissection (TOS + ND) with reduced-dose adjuvant therapy. Materials/Methods Weenrolled patients with T1-T2N0-2 (AJCC 8th edition) p16-positive OPSCC. After stratifying by smoking status, we randomized patients (1:1) to either the primary RT arm, which consisted of 60 Gy of RT and concurrent weekly cisplatin chemotherapy in node-positive patients vs. the TOS + ND arm, consisting of surgery and neck dissection, with adjuvant reduced-dose RT depending on pathologic findings. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), quality of life (QOL, using the MDADI and other metrics), and toxicity. The trial was closed to accrual in November 2020 due to excessive toxicity in the TOS + ND arm, consisting of two treatment-related deaths from known complications of TOS (one bleed and one cervical osteomyelitis following post-operative RT). After closure to accrual, all previously enrolled patients remained on follow-up. All analyses were pre-specified and intention-to-treat, unless otherwise specified. Due to these unexpected toxicity findings, the trial is being reported while survival outcomes remain immature, and therefore p-values are not reported for OS and PFS comparisons. Results BetweenFebruary 2018 and November 2020, 61 patients were randomized (n=30 in the RT arm and n=31 in the TOS + ND arm). Median age was 61.9 years, most patients (51%) were never-smokers, and the large majority of patients (n=51; 86%) were male. The arms were well-balanced. Median follow-up was 17 months (IQR: 15-20 months). Two-year estimates of OS were 100% in the RT arm (95% confidence interval [CI]: 100%-100%) and 89.1% (95% CI: 69.6%-96.4%) in the TOS + ND arm. Two-year PFS estimates were 100% in the RT arm (95% CI: 100%-100%) and 83.5% (95% CI: 60.8%-93.7%) in the TOS + ND arm. Grade 2-5 toxicities occurred in 67% of patients in the RT arm and 71% in the TOS + ND arm, with significantly more anorexia and dysgeusia in the RT arm. Mean (±SD) MDADI total scores at 1-year were similar between arms (85.7 ± 15.6 and 84.7 ± 14.5, respectively). One patient in each arm required a percutaneous feeding tube, and none required feeding tubes at 1-year. Conclusion The primary RT approach achieved excellent oncologic outcomes in treatment de-escalation, with a moderate toxicity profile, and should be tested in phase III trials. The primary TOS approach was associated with an upfront risk of treatment-related mortality and suboptimal PFS. (NCT03210103)

Objectives: The aim of this study was to investigate the lived experiences of women living in rural NSW with depression, their beliefs about its causes, their treatment, and ways in which they soug...

The U.S. territory of American Samoa has experienced recent outbreaks of illnesses caused by viruses transmitted by Aedes species mosquitoes, including dengue, chikungunya, and Zika virus. In November 2016, a traveler from the Solomon Islands tested positive for infection with dengue virus type 2 (DENV-2). Additional dengue cases were identified in the subsequent weeks through passive and active surveillance. Suspected dengue cases were tested locally with a dengue rapid diagnostic test (RDT) for DENV nonstructural protein 1 (NS1). Specimens from RDT-positive cases and patients meeting the dengue case definition were tested by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) at Hawaii State Laboratories. During November 2016-October 2018, a total of 3,240 patients were tested for evidence of DENV infection (118 by RDT-NS1 alone, 1,089 by real-time RT-PCR alone, and 2,033 by both methods), 1,081 (33.4%) of whom tested positive for dengue (19.5 per 1,000 population). All 941 real-time RT-PCR-positive specimens were positive for DENV-2. The monthly number of laboratory-confirmed cases peaked at 120 during December 2017. Among laboratory-confirmed dengue cases, 380 (35.2%) patients were hospitalized; one patient, who was transferred to American Samoa for care late in his illness, died. The public health response to this outbreak included disposal of solid waste to remove mosquito breeding sites, indoor residual spraying of pesticides in schools, reinforcement of dengue patient management education, and public education on mosquito avoidance and seeking medical care for symptoms of dengue.

BackgroundThe traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.MethodsThis is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient’s choice. Our primary objective is to determine the rate of ‘failure’ of disease management in respective AS and surgical arms as defined by: i) AS arm – surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.DiscussionThe results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.Registration detailsThis prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery.

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p

Mobile applications are increasingly regarded as important tools for an integrated strategy of infection containment in post-lockdown societies around the globe. This paper discusses a number of questions that should be addressed when assessing the ethical challenges of mobile applications for digital contact-tracing of COVID-19: Which safeguards should be designed in the technology? Who should access data? What is a legitimate role for “Big Tech” companies in the development and implementation of these systems? How should cultural and behavioural issues be accounted for in the design of these apps? Should use of these apps be compulsory? What does transparency and ethical oversight mean in this context? We demonstrate that responses to these questions are complex and contingent and argue that if digital contract-tracing is used, then it should be clear that this is on a trial basis and its use should be subject to independent monitoring and evaluation.

As melanoma is one of the leading cancers in average years of life lost per death from disease, screening and early diagnosis are imperative to decrease morbidity and mortality. Socioeconomic status (SES) has been shown to be associated with melanoma incidence. However, it is unclear if this association holds true in universal healthcare systems where screening, diagnostic, and treatment services are available to all patients. The objective of this systematic review was to evaluate the evidence on the association of SES and melanoma incidence in Canada. A comprehensive search of PubMed and EMBASE yielded 7 studies reporting on melanoma incidence or outcomes with respect to SES in Canada. High SES was associated with increased melanoma incidence across all studies, which encompassed all Canadian provinces, and time periods spanning from 1979 to 2012. Studies also reported an increasing incidence of melanoma over time. There were substantial discrepancies in melanoma incidence across Canadian provinces, after controlling for SES and demographic characteristics. Populations of lower SES and living within certain healthcare regions had increased risks of advanced melanoma at diagnosis. This review highlights the potential for inequities in access to care even within a universal healthcare system. Future research is needed to characterize specific risk factors within different patient groups and within the universal health system context in order to implement targeted strategies to lower melanoma incidence, morbidity, and mortality.

IntroductionFreezing of all good quality embryos and their transfer in subsequent cycles, named the freeze-all strategy (FAS), is widely used for ovarian hyperstimulation syndrome (OHSS) prevention. Indeed, it increases live birth rates among high responders and prevents preterm birth and small for gestational age. Consequently, why shouldn’t we extend it to all?Materials and methodsA retrospective and monocentric study was conducted between January 2008 and January 2018 comparing the cumulative live birth rates (CLBR) between patients having undergone FAS and a control group using fresh embryo transfer (FET) and having at least one frozen embryo available. Analyses were made for the entire cohort (population 1) and for different subgroups according to confounding factors selected by a logistic regression (population 3), and to the BELRAP (Belgian Register for Assisted Procreation) criteria (population 2).Results2216 patients were divided into two groups: Freeze all (FA), 233 patients and control (C), 1983 patients. The CLBR was 50.2% vs 58.1% P=0.021 for population 1 and 53.2% vs 63.3% P=0.023 for population 2, including 124 cases and 1241 controls. The CLBR stayed in favour of the C group: 70.1% vs 55.9% P=0.03 even when confounding variables were excluded (FA and C group respectively 109 and 770 patients). The median time to become pregnant was equally in favour of the C group with a median of 5 days against 61 days.ConclusionsCLBR is significantly lower in the FA group compared to the C group with a longer time to become pregnant. Nevertheless, the CLBR in the FA group remains excellent and superior to that observed in previous studies with similar procedures and population. These results confirm the high efficiency of FAS but underline the necessity to restrict the strategy to selected cases.

Quality metrics are an increasingly important means of improving patient care. Variability in the number of lymph nodes removed during central compartment lymph node dissection (CCLND) at the time of thyroidectomy has not been studied.A retrospective cohort study was performed using American College of Surgeons National Quality Improvement Program (ACS-NSQIP) data.Centers in North America and worldwide contributing data to ACS-NSQIP and performing thyroidectomy on adults in inpatient and outpatient settings were included.Adult patients undergoing thyroidectomy with or without CCLND were included. Outcomes of interest were number of nodes removed during CCLND and risks of postoperative hypocalcemia.In total, 6108 patients met inclusion criteria (1565 with CCLND). The median number of lymph nodes removed during CCLND was 2. There was no statistically significant association between postoperative hypocalcemia and CCNLD, regardless of number of nodes removed. However, we were underpowered to detect this association based on the overall low nodal yield of many CCLNDs performed.In many cases where CCLND is documented as part of thyroidectomy, very few lymph nodes are removed. Our ability to draw conclusions regarding the effect of CCLND on postoperative hypocalcemia is restricted due to the limited nature of many CCLNDs performed.

Background. Xerostomia is a common complication following radiation therapy for head and neck cancer (HNC), for which there is no single, universally accepted therapy. Coconut oil has been anecdotally suggested to provide relief for this complication. This study sought to examine the feasibility and effectiveness of coconut oil as a therapy for radiation-induced xerostomia. Methods. A feasibility study was performed among 30 patients with xerostomia subsequent to radiation for HNC. Coconut oil samples were provided along with a protocol for use over a 2-week period and the option to continue if they found it beneficial. Patients were also instructed to keep diaries to document their patterns of use. The Xerostomia-related Quality of Life Scale (XeQOLS) was administered at baseline and 3-month follow-up. Descriptive methods were used to summarize patterns of coconut oil use and paired t-tests were used to assess changes in XeQOLS scores over time. Results. The mean total duration of coconut oil use during the study period was 16 days (1–71). The average number of uses per day was 3 (1–5), with an average amount per use of 5 mL (1.2–8.5). Twelve patients (41.4%) continued coconut oil use beyond the advised period. There was no statistically significant difference in XeQOLS scores pre- and post-treatment. There were no adverse events during the study period. Conclusions. The use of coconut oil as a treatment strategy for xerostomia post-HNC radiation is feasible, inexpensive, and safe. This study demonstrates that there may be a group of HNC patients that benefit from its use.

BackgroundMaturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders of impaired glucose-stimulated insulin secretion (GSIS). Mechanisms include β-cell KATPchannel dysfunction (e.g.,KCNJ11(MODY13) orABCC8(MODY12) mutations); however, no other β-cell channelopathies have been identified in MODY.MethodsA four-generation family with autosomal dominant non-obese, non-ketotic antibody-negative diabetes, without mutations in known MODY genes, underwent exome sequencing. Whole-cell and single-channel K+currents, Ca2+handling, and GSIS were determined in cells expressing either mutated or wild-type (WT) protein.ResultsWe identified a novel non-synonymous genetic mutation inKCNK16(NM_001135105: c.341T>C, p.Leu114Pro) segregating with MODY.KCNK16is the most abundant and β-cell-restricted K+channel transcript and encodes the two-pore-domain K+channel TALK-1. Whole-cell K+currents in transfected HEK293 cells demonstrated drastic (312-fold increase) gain-of-function with TALK-1 Leu144Pro vs. WT, due to greater single channel activity. Glucose-stimulated cytosolic Ca2+influx was inhibited in mouse islets expressing TALK-1 Leu114Pro (area under the curve [AUC] at 20mM glucose: Leu114Pro 60.1 vs. WT 89.1;P=0.030) and less endoplasmic reticulum calcium storage (cyclopiazonic acid-induced release AUC: Leu114Pro 17.5 vs. WT 46.8;P=0.008). TALK-1 Leu114Pro significantly blunted GSIS compared to TALK-1 WT in both mouse (52% decrease,P=0.039) and human (38% decrease,P=0.019) islets.ConclusionsOur data identify a novel MODY-associated gene,KCNK16; with a gain-of-function mutation limiting Ca2+influx and GSIS. A gain-of-function common polymorphism inKCNK16is associated with type 2 diabetes (T2DM); thus, our findings have therapeutic implications not only forKCNK16-associated MODY but also for T2DM.

Objectives/hypothesis Quality improvement (QI) initiatives emphasize a need for reduction in hospital length of stay (LOS). We sought to determine the impact of surgical site infections (SSIs) on LOS after complex head and neck surgery (HNS). Study design Retrospective cohort analysis. Methods An analysis of the American College of Surgeons National Surgical Quality Improvement Program was undertaken. All adult patients undergoing complex HNS from 2005 to 2016 were included in the analysis. Our main outcomes were SSI incidence and increase in hospital LOS attributable to SSI. Results Of 4,014 patients identified, 16.5% developed SSI. History of smoking, diabetes, preoperative wound infection, contaminated or dirty wound classes, and prolonged operative time were found to significantly predict postoperative SSI. Adjusting for significant pre- and postoperative factors, SSI was associated with significantly increased LOS (hazard ratio = 0.486, 95% confidence interval: 0.419-0.522). Conclusions SSI following complex HNS is associated with significantly increased hospital LOS. This result supports the need for institutional QI strategies that target SSIs after head and neck procedures in an effort to provide the highest quality care at the lowest possible cost. Our analysis identifies risk factors that can allow identification of patients at high risk of SSI and prolonged hospitalization. Level of evidence 2b Laryngoscope, 2020.

Background Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. Methods This is a multicenter phase II study randomizing one hundred and forty patients with T1–2 N0–2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50–60 Gy based on risk factors). Patients will be stratified based on smoking status ( Discussion This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. Trial Registration Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.

Mobile applications are increasingly regarded as important tools for an integrated strategy of post-lockdown policy response around the globe. This paper explores how the use of smartphone applications for digital contact tracing is currently being framed by media, experts and policy-makers and discusses a number of questions raised by the debate on digital surveillance at the time of Covid-19: How can personal data be adequately collected and protected? Who should access data? What is a legitimate role for Big Tech companies in the development and implementation of these systems? How is the cultural and moral context taken into account in the design of these apps? Should use of these apps be compulsory? What does transparency and ethical oversight mean in this context? As we show that responses to these questions are complex and uncertain, we argue that rather than technological fixes to the current emergency these apps should be introduced in society as societal experimental trials whose effectiveness and consequences need to be closely and independently monitored the same level of precaution and safeguards that social experimentation require.

Background We modified and evaluated an advance care planning (ACP) intervention, which had been shown to improve compliance with patient’s end of life (EoL) wishes, in a different patient population. Methods Patients with incurable cancer, and a Family Member (FM), were randomised one-to-one to usual care or usual care plus an ACP intervention, between April 2014 and January 2017. Oncologists and participants were non-blinded. ACP was based on the Respecting Patient Choices model, with an offer to provide individualised ranges for typical, best-case and worst-case scenarios for survival time. Seven facilitators (two oncology nurses, two nurses and three allied health professionals) delivered the intervention within 2 weeks of study enrolment. The primary outcome measure, assessed by interviewing the FM 3 months after patient death, was the FM perception that the patient’s wishes were discussed, and met. Results Six hundred and sixty-five patients from seven Australian metropolitan oncology centres were referred for consideration by their oncologists, 444 (67%) met the study inclusion criteria and were approached by a study researcher. Two hundred and eight patients (47%) and their FM entered the trial as dyads. Fifty-three (46%) dyads in the ACP group and 63 (54%) dyads in the usual-care group had complete primary outcome data (p = 0.16). Seventy-nine patients and 53 FMs attended an ACP discussion. Mean length of discussion was 57 min. FMs from 23 (43%) dyads allocated to ACP and 21 (33%) dyads allocated usual care reported the patient’s EoL wishes were discussed and met (difference 10%, 95% CI: −2 to 8, p = 0.27). There were no differences in EoL care received, patient satisfaction with care; FM satisfaction with care or with death; or FM well being. Rates of palliative care referral were high in both groups (97% vs 96%). Conclusions A formal ACP intervention did not increase the likelihood that EoL care was consistent with patients’ preferences.

Evaluate serum C-reactive protein (CRP) in human papillomavirus (HPV)-positive oropharynx cancer as compared with HPV-negative oropharynx cancer and determine if CRP levels were associated with overall survival and/or recurrence-free survival.Prospective cohort study.Tertiary care academic cancer center between 2007 and 2010.Among patients with oropharynx cancer and confirmed HPV status, plasma CRP levels were measured with a high-sensitivity ELISA kit. Multivariable logistic regression analysis compared 4 categories of CRP (low, moderate, high, very high) between the HPV-positive and HPV-negative groups. Kaplan-Meier methods and Cox regression models were used to determine overall survival and recurrence-free survival by CRP level in both populations.Between 113 HPV-positive and 110 HPV-negative patients, CRP levels were significantly higher in the HPV-positive group, but these levels did not demonstrate a statistically significant dose-response trend. Higher CRP levels were also associated with reduced overall survival ( P = .016) and recurrence-free survival ( P.001) within the HPV-negative group in univariable analysis; in multivariate analysis, the comparisons were not significantly different. Within HPV-positive oropharynx cancer, CRP levels were not significantly associated with overall survival or recurrence-free survival in univariable or multivariable analyses.Circulating CRP was higher in HPV-positive versus HPV-negative oropharynx cancer. Among HPV-negative patients, higher CRP levels were associated with reduced survival.

Objective Controversy exists regarding the surgical management of cutaneous melanoma and the optimal timing of reconstruction. One approach to ensuring an oncologically sound outcome is a two-stage procedure, with reconstruction delayed for negative permanent section margins. Alternatively, a single-stage excision with immediate reconstruction is advantageous because it limits both resource use and patient morbidity from multiple procedures. We sought to examine available published data on the oncologic outcomes associated with immediate versus delayed reconstruction of cutaneous melanoma in the head and neck region. Methods We performed a systematic review using EMBASE, Ovid MEDLINE, and PubMed. We examined all English-language studies reporting oncologic outcomes (positive margins and/or local recurrence rates) of single-stage or delayed reconstruction of cutaneous melanoma in the head and neck region. Our primary outcomes of interest were rates of positive margins requiring re-excision and rates of local recurrence. A total of 1,557 studies were screened by three independent reviewers. Results Nine studies met inclusion criteria for final analysis. Two of the nine studies directly compared immediate versus delayed reconstruction and demonstrated lower rates of positive margins in the immediate reconstruction group (odds ratio 3.7, [95% CI 0. 79-17. 34]). Conclusion There are a paucity of studies directly comparing oncologic outcomes associated with immediate versus delayed reconstruction following excision of head and neck cutaneous melanoma. Based on a limited amount of heterogeneous data, single-stage excision with immediate reconstruction may be an oncologically sound alternative to delayed reconstruction for head and neck cutaneous melanoma. Level of evidence 3a. Laryngoscope, 2566-2572, 2018.

Background: Advance care planning (ACP) is defined in a variety of ways, although it is widely understood as a process undertaken by patients, when they have capacity, to define and communicate their treatment preferences for future care. Few studies have explored the meaning and importance patients place on their ability to participate in directing their medical care. Aim: This study aimed to explore how cancer patients and their family members value autonomy at the end of life (EoL) and understand how this may impact on the way they develop and act on EoL decisions and planning. Methods: Data were collected through in-depth semi-structured interviews with patients and family members of people with cancer. Participants were recruited from metropolitan cancer centres in Sydney, Australia. Interviews were analysed using thematic analysis. Findings: Findings from 11 participant interviews (five patients with cancer and six family members) were organised into four themes: ‘the threat of death and cancer’; ‘patients seek trust and safety at the end of life’; ‘doctors are human and the healthcare system has limitations’; and ‘the role of ACP’. Participants experienced cancer and death as a ‘threat’, to self and others and as something ‘uncontrollable’. ACP was seen to have the potential to enhance EoL care by contributing to decreasing uncertainty, enhancing comfort, helping to achieve ‘the small things’, and in helping the family ‘know what to do’. However, participants were, in general, distrustful of documentation and cognisant of uncertainty around medical outcomes and the legal limitations of their capacity to influence care. Conclusions: These findings suggest that models of ACP which are constructed around patients' ‘rights’ to determine what happens to their bodies may do little to enhance the quality of EoL care, as patients value veracity, trust and comfort at the EoL more than autonomy. Quality EoL care should focus on paying increased attention to the relational and social aspects of care.

Summary Background Research in genetics and infectious diseases (ID) presents novel configurations of ethical, legal, and social issues (ELSIs) related to the intersection of genetics with public health regulations and the control of transmissible diseases. Such research includes work both in pathogen genetics and on the ways that human genetics affect responses to ID. This paper identifies and systematizes the unique issues at this intersection, based on an interdisciplinary expert review. Methodology This paper presents results of a formal issue-spotting exercise among twenty experts in public health, law and genomics, biobanking, genetic epidemiology , ID medicine and public health, philosophy, ethics and ID, ethics and genomics, and law and ID. The focus of the exercise was on the collection, storage, and sharing of genetic information relating to ID. Results The issue-spotting exercise highlighted the following ELSIs: risks in reporting to government authorities, return of individual research results, and resource allocation – each taking on specific configurations based on the balance between public health and individual privacy/protection. Conclusions The public health implications of interactions between genomics and ID frame considerations for equity and justice. In the context of the COVID-19 pandemic, these issues are especially pressing.

Date Presented Accepted for AOTA INSPIRE 2021 but unable to be presented due to online event limitations. There is a need for a modernized quality-of-life (QoL) definition and a greater distinction between global and health-related quality of life (HRQoL) for people with amyotrophic lateral sclerosis (PALS). The available assessments are intended to interpret global quality of life and HRQoL for PALS. OT practitioners will be able to use the research to determine a comprehensive definition of QoL and the appropriate QoL assessment to use for PALS in clinical practice. Primary Author and Speaker: Addie Broom Additional Authors and Speakers: Hannah Prescott, Mallorie Savage, Addie Broom, Emily Crawford, Mackenzie Franklin, Teal Benevides, Stephanie Johnson

The viral-transforming proteins E6 and E7 make human papillomavirus–positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multifunctional CD8+ T-cell responses. Boosting with MG1-E6E7 significantly increased the magnitude of T-cell responses compared with mice treated with a priming vaccine alone (greater than 50 × 106 E7-specific CD8+ T cells per mouse was observed, representing a 39-fold mean increase in boosted animals). MG1-E6E7 vaccination in the HPV+ murine model TC1 clears large tumors in a CD8+-dependent manner and results in durable immunologic memory. MG1-Maraba can acutely alter the tumor microenvironment in vivo and exploit molecular hallmarks of HPV+ cancer, as demonstrated by marked infection of HPV+ patient tumor biopsies and is, therefore, ideally suited as an oncolytic treatment against clinical HPV+ cancer. This approach has the potential to be directly translatable to human clinical oncology to tackle a variety of HPV-associated neoplasms that cause significant morbidity and mortality globally. Cancer Immunol Res; 5(10); 847–59. ©2017 AACR.

The routine implementation of Advance Care Planning (ACP) is now a prominent feature of policy directed at improving end of life care in Australia. However, while complex ACP interventions may modestly reduce medical care at the end of life and enable more people to die at home or outside of acute hospital settings, existing legal, organisational, cultural and conceptual barriers limit the implementation and utility of ACP. We suggest that meaningful improvements in end of life care will not result from the institutionalisation of ACP but from more significant changes to the design and delivery of care.

Background: Non-intestinal-type adenocarcinoma is a malignancy traditionally found in the sinonasal cavity. To our knowledge, this case is the first reported of this rare condition originating in the nasopharynx. Case Presentation: A 67-year-old woman with nasopharyngeal non-intestinal-type adenocarcinoma, with an accompanying parapharyngeal mass received primary radiation treatment for both lesions. Her tumour subsequently persisted, with a concomitant conversion in pathology from a low- to a high-grade malignancy. Results: Non-intestinal-type and intestinal-type adenocarcinomas of the nasopharynx are extremely rare tumours and do not appear in the World Health Organization classification system. We review the pathophysiologic features of these malignancies and propose modifications to the current classification system. Conclusions: Non-intestinal-type adenocarcinoma should be included in the differential diagnosis of nasopharyngeal masses. In our experience, this tumour in this location showed a partial response to primary radiation but later converted from a low- to a high-grade adenocarcinoma.

To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. At enrolment patients recorded their “understanding of how long you may have to live” in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the “median survival of a group of identical patients”. We hypothesized that oncologists’ estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients’ estimates of their own survival. Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists’ estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding “I don’t know”. The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. Oncologists’ estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871

Background Central giant cell granulomas are benign tumours of the mandible, presenting in children and young adults. Divided into non- and aggressive subtypes, the aggressive subtype is relatively rare and can occasionally progress rapidly, resulting in significant morbidity. Case presentation We present a case of an aggressive central giant cell granuloma (CGCG) in a six year-old female. The lesion originated in the right mandibular ramus and progressed rapidly to involve the condyle. Diagnosis was made using a combination of imaging and pathology. A timely en bloc resection of the hemi-mandible was performed with placement of a reconstructive titanium plate and condylar prosthesis. Conclusion Our case demonstrates the importance of considering CGCG in the differential diagnosis of rapidly progressive mandibular lesions in the pediatric population. Prompt diagnosis and management can greatly improve long-term outcomes.

Identify socioeconomic predictors of stage at diagnosis of laryngeal cancer in the United States.Retrospective analysis of theAll centers reporting to the US Centers for Disease Control and Prevention's National Program of Cancer Registries.All cases of laryngeal cancer in adult patients from 2005 to 2013 were reviewed. Ordinal logistic regression models were used to evaluate odd ratios (ORs) for socioeconomic indicators potentially predictive of advancing American Joint Committee on Cancer stage at diagnosis.A total of 72,472 patients were identified and included. Analysis revealed significant correlation between advanced stage at diagnosis and: Medicaid insurance, lack of insurance, female sex, older age, black race, and certain states of residence. The strongest predictor of advanced stage was lack of insurance (OR, 2.212;Multiple socioeconomic factors were predictive of severity of disease at presentation of laryngeal cancer in the United States. This study demonstrated that insurance type was strongly predictive, whereas relative income had surprisingly little influence.

In eukaryotes, a first step towards the nuclear DNA compaction process is the formation of a nucleosome, which is comprised of negatively charged DNA wrapped around a positively charged histone protein octamer. Often, it is assumed that the complexation of the DNA into the nucleosome completely attenuates the DNA charge and hence the electrostatic field generated by the molecule. In contrast, theoretical and computational studies suggest that the nucleosome retains a strong, negative electrostatic field. Despite their fundamental implications for chromatin organization and function, these opposing views of nucleosome electrostatics have not been experimentally tested. Herein, we directly measure nucleosome electrostatics and find that while nucleosome formation reduces the complex charge by half, the nucleosome nevertheless maintains a strong negative electrostatic field. Our studies highlight the importance of considering the polyelectrolyte nature of the nucleosome and its impact on processes ranging from factor binding to DNA compaction.

Using genomic technology to rapidly sequence and analyse pathogens has the potential to deliver a robust, evidence-based approach to the challenge of infectious disease management. The successful implementation of such a response is going to require consideration of the associated ethical, legal and social issues. A genomics-informed response to infectious disease has great potential to improve individual patient treatment as well as public health. This Comment discusses the ethical, legal and social challenges that will need to be overcome if clinical pathogen genomics is to be implemented successfully.