Evaluating paediatric dermatology telephone clinics during COVID-19 from a dual clinician and patient perspective: a prospective study.

BACKGROUND: The landscape of dermatology services, already rapidly evolving into an increasingly digital one, has been irretrievably altered by the COVID-19 (SARS-CoV-2) pandemic. Data are needed to assess how best to deliver virtual dermatology services in specific patient subgroups in an era of ongoing social distancing and beyond. Initial studies of teledermatology in paediatric populations suggest that many of the problems experienced in adult telemedicine are more apparent when treating children and come with additional challenges. AIM: To evaluate the efficacy of a virtual paediatric dermatology telephone clinic in comparison to traditional face-to-face (FTF) clinics, both from the clinician and patient/parental perspective. METHODS: We carried out a prospective service evaluation examining a single centre cohort of paediatric dermatology patients managed during the COVID-19 pandemic via a telephone clinic supported by images. The study period covered June-September 2020. Data on outcomes were collected from clinicians and a qualitative patient/parental telephone survey was undertaken separately. A five-point Likert scale was used to assess both satisfaction and levels of agreement regarding whether a telephone clinic was more convenient than an FTF clinic. RESULTS: Of 116 patients included, 24% were new and 76% were follow-up patients, with a mixture of inflammatory dermatoses (75%) and lesions (25%). From the clinician's perspective, most consultations (91%) were successfully completed over the telephone. However, qualitative patient and parent feedback paradoxically illustrated that although nearly all (98%) respondents had no outstanding concerns, 52% felt highly unsatisfied and only 22% agreed that telephone clinics were more convenient. Most (65%) preferred FTF follow-up in the future. Statistical analysis using χ² test showed that among those with established follow-ups, the preference for future consultation type was independent of specific reasons for follow-up. CONCLUSIONS: Our study demonstrates a clear discrepancy between the practical successes of a virtual service from the clinician's perspective compared with the patient/parental perspective. Parental anxiety appears to be less effectively allayed virtually than with FTF. This raises the question of whether there is a role for virtual paediatric telephone clinics in the postpandemic future, which may be better left to patients/parents to decide on an individual basis.

A paradigm shift in trainee confidence in teledermatology and virtual working during the COVID-19 pandemic: results of a follow-up UK-wide survey.

The entire landscape of dermatology service provision has been transformed by the current SARS-CoV-2 (COVID) pandemic, with virtual working having become the new norm across the UK. A pre-pandemic UK-wide survey of dermatology registrars in training demonstrated a huge shortfall in trainee confidence in their teledermatology skills, with only 15% feeling even slightly confident, while 96% of trainees surveyed felt that more teaching in this area was needed. We carried out a follow-up trainee survey during the COVID-19 pandemic, which showed that the sudden thrust into virtual working had achieved dramatic gains in trainee confidence, propelling the percentage of trainees that now felt slightly confident to 58%. However, the shortfall remains, as does the pressing need to incorporate teledermatology into the trainee teaching timetable.

Single-Stream Recycling Inspires Selective Fish Passage Solutions for the Connectivity Conundrum in Aquatic Ecosystems.

Barrier removal is a recognized solution for reversing river fragmentation, but restoring connectivity can have consequences for both desirable and undesirable species, resulting in a connectivity conundrum. Selectively passing desirable taxa while restricting the dispersal of undesirable taxa (selective connectivity) would solve many aspects of the connectivity conundrum. Selective connectivity is a technical challenge of sorting an assortment of things. Multiattribute sorting systems exist in other fields, although none have yet been devised for freely moving organisms within a river. We describe an approach to selective fish passage that integrates ecology and biology with engineering designs modeled after material recycling processes that mirror the stages of fish passage: approach, entry, passage, and fate. A key feature of this concept is the integration of multiple sorting processes each targeting a specific attribute. Leveraging concepts from other sectors to improve river ecosystem function may yield fast, reliable solutions to the connectivity conundrum.

A UK-wide survey looking at teaching and trainee confidence in teledermatology: a vital gap in a COVID-19-induced era of rapid digital transformation?

Teledermatology has had an explosive impact on the provision of dermatology services in recent times, and even more so with the unprecedented situation created by the COVID-19 pandemic. Although teledermatology is not presently a feature of the Joint Royal Colleges of Physicians Training Board (JRCPTB) curriculum for dermatology training, this is due to change imminently. Specialty trainees need training in this area to be able to confidently and competently meet the demands of the changing face of dermatology services. We surveyed dermatology registrars in training across the UK, prior to the outbreak of COVID-19, to ascertain the teledermatology teaching available and trainee confidence in this area. Our survey found that only 15% of respondents felt slightly confident in their ability to deal with teledermatology referrals and almost all (96%) felt more teaching was needed.

Behavioral responses of fish to a current-based hydrokinetic turbine under mutliple operational conditions.

There is significant international interest in developing current-based marine and hydrokinetic (MHK) technologies to capture the power of tidal energy. However, concerns have been raised regarding the ecological effects of these projects on fish, including the risk of blade collision and behavioral impacts such as the disruption of migratory behavior and food acquisition and displacement from preferred habitats. We conducted mobile hydroacoustic surveys to track fish as they approached a tidal turbine deployed in Cobscook Bay, Maine. There was a significant decline in fish numbers with decreasing distance to the turbine, beginning approximately 140 m from the turbine. Similar declines were not observed at control transects or when the turbine was not spinning. The decline in fish numbers appeared to be the result of horizontal displacement, not vertical, movements to avoid the turbine. Noise rather than visual cues or flow field disturbance seemed to be a likely explanation for the reduced number of fish near the turbine. This finding, combined with near-field blade collision studies indicating a low probability of encounter, suggests that a single turbine poses a low collision risk to pelagic fish and that a single turbine is likely to result in minimal behavioral responses by fish. However, the risk may be different with additional devices, which will become more relevant as commercial-scale MHK arrays come under consideration. Therefore, the risks associated with commercial-scale operations will ultimately have to be evaluated to fully understand the ecological impacts of MHK devices.

Correction to: Assessing the effect of nitisinone induced hypertyrosinaemia on monoamine neurotransmitters in brain tissue from a murine model of alkaptonuria using mass spectrometry imaging.

The original publication of this article contained an incorrect version that did not include some final reviewers' suggestions, was inadvertently received for production and published. The original article has been corrected.

Assessing the effect of nitisinone induced hypertyrosinaemia on monoamine neurotransmitters in brain tissue from a murine model of alkaptonuria using mass spectrometry imaging.

OBJECTIVE: Nitisinone induced hypertyrosinaemia is a concern in patients with Alkaptonuria (AKU). It has been suggested that this may alter neurotransmitter metabolism, specifically dopamine and serotonin. Herein mass spectrometry imaging (MSI) is used for the direct measurement of 2,4-diphenyl-pyranylium tetrafluoroborate (DPP-TFB) derivatives of monoamine neurotransmitters in brain tissue from a murine model of AKU following treatment with nitisinone. METHODS: Metabolite changes were assessed using MSI on DPP-TFB derivatised fresh frozen tissue sections directing analysis towards primary amine neurotransmitters. Matched tail bleed plasma samples were analysed using LC-MS/MS. Eighteen BALB/c mice were included in this study: HGD-/- (n = 6, treated with nitisinone-4 mg/L, in drinking water); HGD-/- (n = 6, no treatment) and HGD+/- (n = 6, no treatment). RESULTS: Ion intensity and distribution of DPP-TFB derivatives in brain tissue for dopamine, 3-methoxytyramine, noradrenaline, tryptophan, serotonin, and glutamate were not significantly different following treatment with nitisinone in HGD -/- mice, and no significant differences were observed between HGD-/- and HGD+/- mice that received no treatment. Tyrosine (10-fold in both comparisons, p = 0.003; [BALB/c HGD-/- (n = 6) and BALB/c HGD+/- (n = 6) (no treatment) vs. BALB/c HGD-/- (n = 6, treated)] and tyramine (25-fold, p = 0.02; 32-fold, p = 0.02) increased significantly following treatment with nitisinone. Plasma tyrosine and homogentisic acid increased (ninefold, p = < 0.0001) and decreased (ninefold, p = 0.004), respectively in HGD-/- mice treated with nitisinone. CONCLUSIONS: Monoamine neurotransmitters in brain tissue from a murine model of AKU did not change following treatment with nitisinone. These findings have significant implications for patients with AKU as they suggest monoamine neurotransmitters are not altered following treatment with nitisinone.

Trends in depression prevalence in the USA from 2005 to 2015: widening disparities in vulnerable groups.

BACKGROUND: Major depression is associated with significant disability, morbidity, and mortality. The current study estimated trends in the prevalence of major depression in the US population from 2005 to 2015 overall and by demographic subgroups. METHODS: Data were drawn from the National Survey on Drug Use and Health (NSDUH), an annual cross-sectional study of US persons ages 12 and over (total analytic sample N = 607 520). Past-year depression prevalence was examined annually among respondents from 2005 to 2015. Time trends in depression prevalence stratified by survey year were tested using logistic regression. Data were re-analyzed stratified by age, gender, race/ethnicity, income, and education. RESULTS: Depression prevalence increased significantly in the USA from 2005 to 2015, before and after controlling for demographics. Increases in depression were significant for the youngest and oldest age groups, men, and women, Non-Hispanic White persons, the lowest income group, and the highest education and income groups. A significant year × demographic interaction was found for age. The rate of increase in depression was significantly more rapid among youth relative to all older age groups. CONCLUSIONS: The prevalence of depression increased significantly in the USA from 2005 to 2015. The rate of increase in depression among youth was significantly more rapid relative to older groups. Further research into understanding the macro level, micro level, and individual factors that are contributing to the increase in depression, including factors specific to demographic subgroups, would help to direct public health prevention and intervention efforts.

Childhood atopy and mental health: a prospective, longitudinal investigation.

BACKGROUND: Prior studies have suggested a relationship between atopy and mental health, although methodological barriers have limited the generalizability of these findings. The objective of this study was to investigate the relationship between early-life atopy and vulnerability to mental health problems among youth in the community. METHOD: Data were drawn from the Raine Study (N = 2868), a population-based birth cohort study in Western Australia. Logistic regression and generalized estimating equations were used to examine the relationship between atopy at ages 1-5 years [using parent report and objective biological confirmation (sera IgE)], and the range of internalizing and externalizing mental health problems at ages 5-17 years. RESULTS: Atopy appears to be associated with increased vulnerability to affective and anxiety problems, compared to youth without atopy. These associations remained significant after adjusting for a range of potential confounders. No relationship was evident between atopy and attention deficit hyperactivity disorder or externalizing problems. CONCLUSIONS: Findings are the first linking atopy (measured by both parent report and objective verification) with increased vulnerability to affective and anxiety problems. Therefore, replication is required. If replicated, future research aimed at understanding the possible biological and/or social and environmental pathways underlying these links is needed. Such information could shed light on shared pathways that could lead to more effective treatments for both atopy and internalizing mental health problems.

Fish navigation of large dams emerges from their modulation of flow field experience.

Navigating obstacles is innate to fish in rivers, but fragmentation of the world's rivers by more than 50,000 large dams threatens many of the fish migrations these waterways support. One limitation to mitigating the impacts of dams on fish is that we have a poor understanding of why some fish enter routes engineered for their safe travel around the dam but others pass through more dangerous routes. To understand fish movement through hydropower dam environments, we combine a computational fluid dynamics model of the flow field at a dam and a behavioral model in which simulated fish adjust swim orientation and speed to modulate their experience to water acceleration and pressure (depth). We fit the model to data on the passage of juvenile Pacific salmonids (Oncorhynchus spp.) at seven dams in the Columbia/Snake River system. Our findings from reproducing observed fish movement and passage patterns across 47 flow field conditions sampled over 14 y emphasize the role of experience and perception in the decision making of animals that can inform opportunities and limitations in living resources management and engineering design.

Real-life treatment of metastatic colorectal cancer with regorafenib: a single-centre review.

BACKGROUND: Various tyrosine kinase signalling pathways affect the development and progression of colorectal cancer (crc). In clinical trials, regorafenib has been associated with a survival benefit in metastatic crc (mcrc). We assessed the safety and efficacy of regorafenib in real-world patients. METHODS: In a retrospective review of patients with mcrc treated with regorafenib at our institution from 2013 to 2015, patient demographics, treatment, and survival data were collected. Progression-free survival (pfs) and overall survival (os) were estimated using the Kaplan-Meier method. RESULTS: In total, 48 patients were offered regorafenib, and 35 (73%) started treatment. Of the patients who started regorafenib, 57% were men. Median age in the cohort was 61 years, and all patients had a performance status in the range 0-2. Time from diagnosis of mcrc to regorafenib treatment was more than 18 months in 71% of patients. Starting dose was 160 mg in 54% of the patients, 120 mg in 40%, and 80 mg in 6%. Dose reductions occurred in 34% of the patients, and interruptions, in 29%. Best response was progressive disease (60%) and stable disease (17%); response in the rest of the patients was unknown. The most common adverse events on regorafenib (any grade) were fatigue (57%), hyperbilirubinemia (43%), thrombocytopenia (37%), anorexia (31%), and hypertension (31%). The most common grade 3 or 4 adverse events were fatigue (29%), hypophosphatemia (17%), weight loss (11%), and hyperbilirubinemia (9%). Common reasons for discontinuing regorafenib included progressive disease (51%) and toxicity (26%). In patients treated with regorafenib, pfs was 2.4 months (95% confidence interval: 1.8 to 3.3 months) and os was 5.6 months (95% confidence interval: 3.7 to 8.9 months). No factors were associated with survival in univariate or multivariate analysis. CONCLUSIONS: In a real-world setting, regorafenib is associated with survival similar to that reported in the randomized controlled trials, but at the expense of toxicity leading to discontinuation in many patients. Future studies of regorafenib should focus on identifying the patients most likely to benefit and on minimizing toxicity.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

Clinical outcomes of elderly patients receiving neoadjuvant chemoradiation for locally advanced rectal cancer.

BACKGROUND: Studies of clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) are limited. Our aim was to assess the impact of age on clinical outcomes in a large multi-institutional database. PATIENTS AND METHODS: Data for patients diagnosed with LARC who received nCRT and curative-intent surgery between 2005 and 2012 were collected from five major Canadian cancer centers. Age was analyzed as a continuous and dichotomous variable (< 70 versus ≥ 70 years) and correlated with disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Cox regression models were used to adjust for important prognostic factors. RESULTS: Of 1172 patients included, 295 (25%) were ≥ 70 years, and they were less likely to receive adjuvant chemotherapy (ACT; 60% versus 79%, P < 0.0001), oxaliplatin-based ACT (12% versus 31%, P < 0.0001), less likely to complete nCT (76% versus 86%, P < 0.001), and more likely to be anemic at initiation of nCRT (42% versus 30%, P = 0.0004). In multivariate analyses, age ≥ 70 years was associated with similar DFS [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.68-1.26, P = 0.63], similar CSS (HR 0.81, 95% CI 0.46-1.41, P = 0.45), and similar OS (HR 1.28, 95% CI 0.88-1.86, P = 0.20), compared with the younger age group. As a continuous variable, increasing age was not predictive of DFS (HR 1.00, 95% CI 0.99-1.02, P = 0.49) or CSS (HR 1.002, 95% CI 0.98-1.02, P = 0.88); however, it correlated with an inferior OS (HR 1.02, 95% CI 1.00-1.03, P = 0.04). CONCLUSIONS: Elderly patients (≥ 70 years) who receive nCRT followed by surgery appear to have similar outcomes compared with younger patients. Decisions regarding eligibility for nCRT and surgery should not be based on age alone.

Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study.

BACKGROUND: Autoimmune diseases are associated with substantial morbidity and mortality, yet the etiology remains unclear. Depression has been implicated as a risk factor for various immune-related disorders but little is known about the risk of autoimmune disease. This study examined the association between depression and the risk of autoimmune disease, and investigated the temporal and dose-response nature of these relationships. METHOD: A prospective population-based study including approximately 1.1 million people was conducted using linked Danish registries. Depression and autoimmune diseases were diagnosed by physicians and documented in medical records. In total, 145 217 individuals with depression were identified between 1995 and 2012. Survival analyses were used to estimate the relative risk of autoimmune disease among those with, compared to without, depression. Analyses were adjusted for gender, age, and co-morbid mental disorders. RESULTS: Depression was associated with a significantly increased risk of autoimmune disease [incidence rate ratio (IRR) 1.25, 95% CI 1.19-1.31], compared to those without a history of depression. Results suggest a general increased risk of autoimmune diseases following the onset of depression during first year (IRR 1.29, 95% CI 1.05-1.58), which remained elevated for the ensuing 11 years and beyond (IRR 1.53, 95% CI 1.34-1.76). Findings did not support a dose-response relationship. CONCLUSIONS: Depression appears to be associated with an increased risk of a range of autoimmune diseases. Depression may play a role in the etiology of certain autoimmune conditions. If replicated, findings could highlight additional clinical implications in the treatment and management of depression. Future studies are needed to investigate the possible social, genetic, and neurobiological underpinnings of these relationships.

Performance of multinomial designs in comparison with response-based designs in non-randomized phase II trials of targeted cancer agents.

BACKGROUND: In phase II trials of cytotoxic agents, a multinomial phase II design incorporating early progression and response end points was shown to perform more efficiently than designs based only on response. We undertook a study to evaluate the performance of these designs in trials of targeted agents using the actual phase II data. PATIENTS AND METHODS: Using best response data from sequentially enrolled patients in 15 NCIC Clinical Trials Group and 7 European Organization for Research and Treatment of Cancer trials of targeted agents, we determined that trials would have been stopped at the end of stage I of accrual by applying rules generated by the multinomial and Fleming designs. Two variants of the multinomial design were studied: to stop accrual after stage I of enrolment, Variant A required either response or progression criteria to be met, whereas Variant B required that both response and progression criteria to be met. RESULTS: Using early progression, null/alternate hypotheses of 60% and 40% (60/40), the multinomial A variant recommended early stopping more often than the Fleming design. In most of the cases, this recommendation was correct given the final trial outcome. In contrast, the multinomial B variant never led to recommendations for early stopping and changing progression hypotheses did not improve the performance of this design. CONCLUSIONS: The multinomial A design using 60/40 hypotheses carried out better than the Fleming design in appropriately stopping trials of inactive targeted agents early. The multinomial B design was not useful for early stopping decisions. The multinomial A design may be favored over response-based designs in phase II trials of targeted agents.

Motion-guided attention promotes adaptive communications during social navigation.

Animals are capable of enhanced decision making through cooperation, whereby accurate decisions can occur quickly through decentralized consensus. These interactions often depend upon reliable social cues, which can result in highly coordinated activities in uncertain environments. Yet information within a crowd may be lost in translation, generating confusion and enhancing individual risk. As quantitative data detailing animal social interactions accumulate, the mechanisms enabling individuals to rapidly and accurately process competing social cues remain unresolved. Here, we model how motion-guided attention influences the exchange of visual information during social navigation. We also compare the performance of this mechanism to the hypothesis that robust social coordination requires individuals to numerically limit their attention to a set of n-nearest neighbours. While we find that such numerically limited attention does not generate robust social navigation across ecological contexts, several notable qualities arise from selective attention to motion cues. First, individuals can instantly become a local information hub when startled into action, without requiring changes in neighbour attention level. Second, individuals can circumvent speed-accuracy trade-offs by tuning their motion thresholds. In turn, these properties enable groups to collectively dampen or amplify social information. Lastly, the minority required to sway a group's short-term directional decisions can change substantially with social context. Our findings suggest that motion-guided attention is a fundamental and efficient mechanism underlying collaborative decision making during social navigation.

Severity and persistence of asthma and mental health: a birth cohort study.

BACKGROUND: The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link. Method Data were drawn from the Raine Study, a population-based birth cohort study in Western Australia. Logistic regression models and generalized estimating equations were used to examine the relationship between asthma at age 5 years and the range of internalizing and externalizing mental health problems at ages 5-17 years. Analyses were stratified by asthma severity and persistence, and adjusted for a range of potential confounders. RESULTS: More severe and persistent asthma at age 5 was associated with significantly increased odds of affective, anxiety, somatic, oppositional defiant and conduct problems at ages 5-17. Mild asthma and remitted asthma were not associated with heightened vulnerability to mental disorders. CONCLUSIONS: Our results suggest that youth with symptomatic asthma are more likely to suffer from a wide range of mental health problems, and that the likelihood of mental health problems appears to increase as a function of asthma severity. Youth with poorly controlled and/or more severe and persistent asthma may be considered a vulnerable group who might benefit from mental health screening in clinical, school and community settings.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

Eastern Canadian Colorectal Cancer Consensus Conference: standards of care for the treatment of patients with rectal, pancreatic, and gastrointestinal stromal tumours and pancreatic neuroendocrine tumours.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage ii colon cancer.