Mucosal impedance as a diagnostic tool for gastroesophageal reflux disease: an update for clinicians.

Mucosal impedance is a marker of esophageal mucosal integrity and a novel technique for assessing esophageal function and pathology. This article highlights its development and clinical application for gastroesophageal reflux disease (GERD), Barrett's esophagus, and eosinophilic esophagitis. A narrative review of key publications describing the development and use of mucosal impedance in clinical practice was conducted. A low mean nocturnal baseline impedance (MNBI) has been shown to be an independent predictor of response to anti-reflux therapy. MNBI predicts medication-responsive heartburn better than distal esophageal acid exposure time. Patients with equivocal evidence of GERD using conventional methods, with a low MNBI, had an improvement in symptoms following the initiation of PPI therapy compared to those with a normal MNBI. A similar trend was seen in a post fundoplication cohort. Strong clinical utility for the use of mucosal impedance in assessing eosinophilic esophagitis has been repeatedly demonstrated; however, there is minimal direction for application in Barrett's esophagus. The authors conclude that mucosal impedance has potential clinical utility for the assessment and diagnosis of GERD, particularly when conventional investigations have yielded equivocal results.

Impact of Unplanned Intra-Operative Conversions on Outcomes in Minimally Invasive Pancreatoduodenectomy.

BACKGROUND: Minimally-invasive pancreatoduodenectomy (MIPD) is fraught with the risk of complication-related deaths (LEOPARD-2), a significant volume-outcome relationship and a long learning curve. With rates of conversion for MIPD approaching 40%, the impact of these on overall patient outcomes, especially, when unplanned, are yet to be fully elucidated. This study aimed to compare peri-operative outcomes of (unplanned) converted MIPD against both successfully completed MIPD and upfront open PD. METHODS: A systematic review of major reference databases was undertaken. The primary outcome of interest was 30-day mortality. Newcastle-Ottawa scale was used to judge the quality of the studies. Meta-analysis was performed using pooled estimates, derived using random effects model. RESULTS: Six studies involving 20,267 patients were included in the review. Pooled analysis demonstrated (unplanned) converted MIPD were associated with an increased 30-day (RR 2.83, CI 1.62- 4.93, p = 0.0002, I2 = 0%) and 90-day (RR 1.81, CI 1.16- 2.82, p = 0.009, I2 = 28%) mortality and overall morbidity (RR 1.41, CI 1.09; 1.82, p = 0.0087, I2 = 82%) compared to successfully completed MIPD. Patients undergoing (unplanned) converted MIPD experienced significantly higher 30-day mortality (RR 3.97, CI 2.07; 7.65, p < 0.0001, I2 = 0%), pancreatic fistula (RR 1.65, CI 1.22- 2.23, p = 0.001, I2 = 0%) and re-exploration rates (RR 1.96, CI 1.17- 3.28, p = 0.01, I2 = 37%) compared upfront open PD. CONCLUSIONS: Patient outcomes are significantly compromised following unplanned intraoperative conversions of MIPD when compared to successfully completed MIPD and upfront open PD. These findings stress the need for objective evidence-based guidelines for patient selection for MIPD.

Freudian robots: Artificial intelligence and psychodynamics.

OBJECTIVE: Artificial intelligence (AI) is rapidly developing, particularly human-interacting and affective AI systems. Psychodynamic concepts important to human development should be considered in the development of AI systems. CONCLUSION: The development of safe and ethical affective artificial intelligence that remains meaningful and flexible should incorporate psychodynamic concepts. Mental health professionals such as psychiatrists and psychotherapists should be involved in the development of AI to provide expert knowledge in the area of psychodynamics.

Impact of a peer comparison intervention on seasonal influenza vaccine uptake in community pharmacy: A national cluster randomized study.

BACKGROUND: Seasonal influenza vaccine (SIV) uptake in the United States remains suboptimal, requiring new and innovative strategies. OBJECTIVE: To evaluate the impact of a behavioral peer comparison (PC) intervention on SIV uptake in community pharmacies across the United States. METHODS: A cluster randomized study was conducted across a national network of Walmart community pharmacies (> 4500 sites) during the 2019-2020 influenza season. The clusters consisted of 416 markets, each containing an average of 11 pharmacies. All pharmacies in a market were randomly assigned to either no intervention or the PC intervention, a software-delivered communication informing on-site staff, including pharmacists and pharmacy technicians, of their pharmacy's weekly performance, measured as SIV doses administered, compared with that of peer pharmacies within their market. The outcome was the pharmacy-level cumulative SIV doses administered during the intervention period (September 1, 2019,-February 29, 2020). Linear regression models were used to estimate the PC impact, with multiway cluster-robust SEs estimated by market and state. RESULTS: A total of 4589 pharmacies were enrolled in the study, with 2297 (50.1%) randomized to the control group and 2292 (49.9%) randomized to the PC intervention group. Overall, compared with the control pharmacies, the PC pharmacies administered 3.7% (95% CI -0.3% to 7.9%) additional SIV doses. Among large-format pharmacies, the PC pharmacies administered 4.1% (95% CI 0.1%-8.3%) additional SIV doses compared with the controls. Historically low-performing large-format PC pharmacies administered 6.1% (95% CI 0.5%-11.9%) additional SIV doses compared with the controls. No statistically significant treatment effects were observed among small-format pharmacies. CONCLUSION: Our findings demonstrate that PCs can improve SIV uptake among large-format community pharmacies, with historically low-performing pharmacies potentially exhibiting the greatest relative impact. Wide-scale implementation of PCs in community pharmacies may help to further improve SIV uptake in these settings.

Public perception of medicinal and recreational cannabis and its effect on mental health: a survey of a regional Australian town.

OBJECTIVE: To investigate beliefs about treatment capabilities of medicinal cannabis (MC), the effect of recreational cannabis (RC) on mental health and online cannabis search trends. METHOD: Participants (n = 117) completed an online survey, and search engine optimisation software was used to analyse internet search trends. RESULTS: Half the participants perceived RC as harmful to mental health but were uncertain if it impairs treatment for depression or prevents anxiety. Participants believed MC can treat depression and/or anxiety. The Google keyword 'CBD oil' is most popular when seeking cannabis information and provides misinformation. CONCLUSION: Australians are exposed to misinformation about MC online, explaining why participants believed that MC could treat anxiety and/or depression and why there is a reduction in the belief that RC is harmful to mental health. Health authorities should incorporate search engine optimisation strategies to provide accurate information about cannabis.

'I'm just ringing to get a repeat prescription for my contraceptive pill, doctor': developing authentic simulated telephone consultations for medical students.

Within normal surgery hours telephone consultations have been previously shown to make up between 10-20% of patient contacts with General Practitioners (GPs) and to comprise a large proportion of a GP's daily workload. Although obviously very useful, such doctor-patient interactions can be fraught with risk. The General Medical Council (GMC) requires that newly graduated doctors should be adaptable to the challenge of delivering treatment advice and management remotely. Yet, currently, there is limited specific training in telephone consultation skills in both undergraduate and postgraduate curricula.Authentic and properly supervised exposure of medical students to GP telephone consultations can be difficult to achieve in clinical placements. Therefore, we have developed emergency telephone consultations within our primary care Safe and Effective Clinical Outcomes (SECO) clinics which are simulated GP surgeries organised for our final year students. We have expanded the range of patients presenting in these clinics by including trained, simulated patients requesting an urgent telephone consultation with a GP. In doing so we aim to enhance our student's skills and confidence in conducting telephone consultations.This teaching exchange paper aims to describe the ideas behind the construction of simulated patient telephone scripts together with the difficulties and successes encountered in introducing telephone consultations into our GP SECO clinic. We hope these ideas and processes will stimulate and enable others to help students prepare for this challenging area of clinical medicine made increasingly significant by the Covid-19 pandemic.

In Kinematically Aligned Total Knee Arthroplasty, Failure to Recreate Native Tibial Alignment Is Associated With Early Revision.

BACKGROUND: The goal of kinematically aligned (KA) total knee arthroplasty (TKA) is to restore native knee anatomy. However, there are concerns about patellofemoral tracking problems with this technique that lead to early revision. We measured the differences between preoperative anatomic alignment and postoperative component alignment in a consecutive series of KA TKA and evaluated the association between alignment changes and the likelihood of early revision. METHODS: The charts of 219 patients who underwent 275 KA TKA procedures were reviewed. Preoperative anatomic alignment and postoperative tibial and femoral component alignment were measured radiographically. The difference in component alignment compared with preoperative anatomic alignment was compared between patients who underwent aseptic revision and those who did not at a minimum of 12 months of follow-up. Receiver operating characteristic curves were created for statistically significant variables, and the Youden index was used to determine optimal alignment thresholds with regard to likelihood of revision surgery. RESULTS: Change in tibial component alignment compared with native alignment was greater (P = .005) in the revision group (5.0° ± 3.7° of increased varus compared with preoperative anatomic tibial angle) than in the nonrevision group (1.3° ± 4.2° of increased varus). The Youden index indicated that increasing tibial varus by >2.2° or more is associated with increased likelihood of revision. Preoperative anatomic alignment and change in femoral alignment and overall joint alignment (ie, Q angle) were not associated with increased likelihood of revision. CONCLUSION: Small increases in tibial component varus compared with native alignment are associated with early aseptic revision in patients undergoing KA TKA.

An Empirical and Mechanistic Explanation of Abundance-Occupancy Relationships for a Critically Endangered Nomadic Migrant.

The positive abundance-occupancy relationship (AOR) is a pervasive pattern in macroecology. Similarly, the association between occupancy (or probability of occurrence) and abundance is also usually assumed to be positive and in most cases constant. Examples of AORs for nomadic species with variable distributions are extremely rare. Here we examined temporal and spatial trends in the AOR over 7 years for a critically endangered nomadic migrant that relies on dynamic pulses in food availability to breed. We predicted a negative temporal relationship, where local mean abundances increase when the number of occupied sites decreases, and a positive relationship between local abundances and the probability of occurrence. We also predicted that these patterns are largely attributable to spatiotemporal variation in food abundance. The temporal AOR was significantly negative, and annual food availability was significantly positively correlated with the number of occupied sites but negatively correlated with abundance. Thus, as food availability decreased, local densities of birds increased, and vice versa. The abundance-probability of occurrence relationship was positive and nonlinear but varied between years due to differing degrees of spatial aggregation caused by changing food availability. Importantly, high abundance (or occupancy) did not necessarily equate to high-quality habitat and may be indicative of resource bottlenecks or exposure to other processes affecting vital rates. Our results provide a rare empirical example that highlights the complexity of AORs for species that target aggregated food resources in dynamic environments.

Sex ratio bias and shared paternity reduce individual fitness and population viability in a critically endangered parrot.

Sex-biased mortality can lead to altered adult sex ratios (ASRs), which may in turn lead to harassment and lower fitness of the rarer sex and changes in the mating system. Female critically endangered swift parrots (Lathamus discolor) suffer high predation while nesting due to an introduced mammalian predator, the sugar glider (Petaurus breviceps). High predation on females is causing severe population decline alongside strongly biased adult sex ratios (≥73% male). Our 6-year study showed that 50.5% of critically endangered swift parrot nests had shared paternity although the birds remained socially monogamous. Shared paternity increased significantly with the local rate of predation on breeding females, suggesting that rates of shared paternity increased when the ASR became more biased. Nests that were not predated produced fewer fledglings as the local ASR became more male-biased possibly due to higher interference during nesting from unpaired males. Population viability analyses showed that part of the predicted decline in the swift parrot population is due to reduced reproductive success when paternity is shared. The models predicted that the population would decline by 89.4% over three generations if the birds maintained the lowest observed rate of shared paternity. This compares with predicted population reductions of 92.1-94.9% under higher rates of shared paternity. We conclude that biases in the ASR, in this case caused by sex-specific predation from an introduced predator, can lead to changes in the mating system and negative impacts on both individual fitness and long-term population viability.

Faba bean polerovirus 1 (FBPV-1); a new polerovirus infecting legume crops in Australia.

A new polerovirus species with the proposed name faba bean polerovirus 1 (FBPV-1) was found in winter legume crops and weeds in New South Wales, Australia. We describe the complete genome sequence of 5,631 nucleotides, containing all putative open reading frames, from two isolates, one from faba bean (Vicia faba) and one from chickpea (Cicer arietinum). FBPV-1 has a genome organization typical of poleroviruses with six open reading frames. However, recombination analysis strongly supports a recombination event in which the 5' portion of FBPV-1, which encodes for proteins P0, P1 and P1-P2, appears to be from a novel parent with a closest nucleotide identity of only 66% to chickpea chlorotic stunt virus. The 3' portion of FBPV-1 encodes for proteins P3, P4 and P3-P5 and shares 94% nucleotide identity to a turnip yellows virus isolate from Western Australia.

Rigid dressings versus soft dressings for transtibial amputations.

BACKGROUND: Dressings are part of the routine postoperative management of people after transtibial amputation. Two types of dressings are commonly used; soft dressings (e.g. elastic bandages, crepe bandages) and rigid dressings (e.g. non-removable rigid dressings, removable rigid dressings, immediate postoperative protheses). Soft dressings are the conventional dressing choice as they are cheap and easy to apply, while rigid dressings are costly, more time consuming to apply and require skilled personnel to apply the dressings. However, rigid dressings have been suggested to result in faster wound healing due to the hard exterior providing a greater degree of compression to the stump. OBJECTIVES: To assess the benefits and harms of rigid dressings versus soft dressings for treating transtibial amputations. SEARCH METHODS: In December 2018 we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, EBSCO CINAHL Plus, Ovid AMED and PEDro to identify relevant trials. To identify further published, unpublished and ongoing studies, we also searched clinical trial registries, the grey literature, the reference lists of relevant studies and reviews identified in prior searches. We used the Cited Reference Search facility on ThomsonReuters Web of Science and contacted relevant individuals and organisations. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that enrolled people with transtibial amputations. There were no restrictions on the age of participants and reasons for amputation. Trials that compared the effectiveness of rigid dressings with soft dressings were the main focus of this review. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text publications for eligible studies. Two review authors also independently extracted data on study characteristics and outcomes, and performed risk of bias and GRADE assessments. MAIN RESULTS: We included nine RCTs and quasi-RCTs involving 436 participants (441 limbs). All studies recruited participants from acute and/or rehabilitation hospitals from seven different countries (the USA, Australia, Indonesia, Thailand, Canada, France and the UK). In all but one study, it was clearly stated that amputations were secondary to vascular conditions.Primary outcomes Wound healing We are uncertain whether rigid dressings decrease the time to wound healing compared with soft dressings (MD -25.60 days; 95% CI -49.08 to -2.12; one study, 56 participants); very low-certainty evidence, downgraded twice for very high risk of bias and once for serious imprecision. It is not clear whether rigid dressings increase the proportion of wounds healed compared with soft dressings (RR 1.14; 95% CI 0.74 to 1.76; one study, 51 participants); very low-certainty evidence, downgraded twice for very high risk of bias and twice for very serious imprecision.Adverse events It is not clear whether rigid dressings increase the proportion of skin-related adverse events compared with soft dressings (RR 0.65; 95% CI 0.32 to 1.32; I2 = 0%; six studies, 336 participants (340 limbs)); very low-certainty evidence, downgraded twice for very high risk of bias and once for serious imprecision.It is not clear whether rigid dressings increase the proportion of non skin-related adverse events compared with soft dressings (RR 1.09; 95% CI 0.60 to 1.99; I2 = 0%; six studies, 342 participants (346 limbs)); very low-certainty evidence, downgraded twice for very high risk of bias and once for serious imprecision. In addition, we are uncertain whether rigid dressings decrease the time to no pain compared with soft dressings (MD -0.35 weeks; 95% CI -2.11 to 1.41; one study of 23 participants); very low-certainty evidence, downgraded twice for very high risk of bias and twice for very serious imprecision.Secondary outcomesWe are uncertain whether rigid dressings decrease the time to walking compared with soft dressings (MD -3 days; 95% CI -9.96 to 3.96; one study, 56 participants); very low-certainty evidence, downgraded twice for very high risk of bias and twice for very serious imprecision. We are also uncertain whether rigid dressings decrease the length of hospital stay compared with soft dressings (MD -30.10 days; 95% CI -49.82 to -10.38; one study, 56 participants); very low-certainty evidence, downgraded twice for very high risk of bias and once for serious imprecision. It is also not clear whether rigid dressings decrease the time to readiness for prosthetic prescription and swelling compared with soft dressings, as results are based on very low-certainty evidence, downgraded twice for very high risk of bias and once/twice for serious/very serious imprecision. None of the studies reported outcomes on patient comfort, quality of life and cost. AUTHORS' CONCLUSIONS: We are uncertain of the benefits and harms of rigid dressings compared with soft dressings for people undergoing transtibial amputation due to limited and very low-certainty evidence. It is not clear if rigid dressings are superior to soft dressings for improving outcomes related to wound healing, adverse events, prosthetic prescription, walking function, length of hospital stay and swelling. Clinicians should exercise clinical judgement as to which type of dressing they use, and consider the pros and cons of each for patients (e.g. patients with high risk of falling may benefit from the protection offered by a rigid dressing, and patients with poor skin integrity may have less risk of skin breakdown from a soft dressing).

Colony stimulating factor 1 receptor blockade improves the efficacy of chemotherapy against human neuroblastoma in the absence of T lymphocytes.

Tumor-associated macrophages can promote growth of cancers. In neuroblastoma, tumor-associated macrophages have greater frequency in metastatic versus loco-regional tumors, and higher expression of genes associated with macrophages helps to predict poor prognosis in the 60% of high-risk patients who have MYCN-non-amplified disease. The contribution of cytotoxic T-lymphocytes to anti-neuroblastoma immune responses may be limited by low MHC class I expression and low exonic mutation frequency. Therefore, we modelled human neuroblastoma in T-cell deficient mice to examine whether depletion of monocytes/macrophages from the neuroblastoma microenvironment by blockade of CSF-1R can improve the response to chemotherapy. In vitro, CSF-1 was released by neuroblastoma cells, and topotecan increased this release. In vivo, neuroblastomas formed by subcutaneous co-injection of human neuroblastoma cells and human monocytes into immunodeficient NOD/SCID mice had fewer human CD14+ and CD163+ cells and mouse F4/80+ cells after CSF-1R blockade. In subcutaneous or intra-renal models in immunodeficient NSG or NOD/SCID mice, CSF-1R blockade alone did not affect tumor growth or mouse survival. However, when combined with cyclophosphamide plus topotecan, the CSF-1R inhibitor BLZ945, either without or with anti-human and anti-mouse CSF-1 mAbs, inhibited neuroblastoma growth and synergistically improved mouse survival. These findings indicate that depletion of tumor-associated macrophages from neuroblastomas can be associated with increased chemotherapeutic efficacy without requiring a contribution from T-lymphocytes, suggesting the possibility that combination of CSF-1R blockade with chemotherapy might be effective in patients who have limited anti-tumor T-cell responses.

Injury patterns and risk factors for orthopaedic trauma from snowboarding and skiing: a national perspective.

PURPOSE: Alpine skiing and snowboarding are both popular winter sports that can be associated with significant orthopaedic injuries. However, there is a lack of nationally representative injury data for the two sports. METHODS: The National Trauma Data Bank was queried for patients presenting to emergency departments due to injuries sustained from skiing and snowboarding during 2011 and 2012. Patient demographics, comorbidities, and injury patterns were tabulated and compared between skiing and snowboarding. Risk factors for increased injury severity score and lack of helmet use were identified using multivariate logistic regression. RESULTS: Of the 6055 patients identified, 55.2 % were skiers. Sixty-one percent had fractures. Lower extremity fractures were the most common injury and occurred more often in skiers (p < 0.001). Upper extremity fractures were more common in snowboarders, particularly distal radius fractures (p < 0.001). On multivariate analysis, increased injury severity was independently associated with age 18-29, 60-69, 70+, male sex, a positive blood test for alcohol, a positive blood test for an illegal substance, and wearing a helmet. Lack of helmet use was associated with age 18-29, 30-39, smoking, a positive drug test for an illegal substance, and snowboarding. CONCLUSIONS: Young adults, the elderly, and those using substances were shown to be at greater risk of increased injury severity and lack of helmet use. The results of this study can be used clinically to guide the initial assessment of these individuals following injury, as well as for targeting preventive measures and education. LEVEL OF EVIDENCE: Prognostic Level III.

The importance of incorporating functional habitats into conservation planning for highly mobile species in dynamic systems.

The distribution of mobile species in dynamic systems can vary greatly over time and space. Estimating their population size and geographic range can be problematic and affect the accuracy of conservation assessments. Scarce data on mobile species and the resources they need can also limit the type of analytical approaches available to derive such estimates. We quantified change in availability and use of key ecological resources required for breeding for a critically endangered nomadic habitat specialist, the Swift Parrot (Lathamus discolor). We compared estimates of occupied habitat derived from dynamic presence-background (i.e., presence-only data) climatic models with estimates derived from dynamic occupancy models that included a direct measure of food availability. We then compared estimates that incorporate fine-resolution spatial data on the availability of key ecological resources (i.e., functional habitats) with more common approaches that focus on broader climatic suitability or vegetation cover (due to the absence of fine-resolution data). The occupancy models produced significantly (P < 0.001) smaller (up to an order of magnitude) and more spatially discrete estimates of the total occupied area than climate-based models. The spatial location and extent of the total area occupied with the occupancy models was highly variable between years (131 and 1498 km2 ). Estimates accounting for the area of functional habitats were significantly smaller (2-58% [SD 16]) than estimates based only on the total area occupied. An increase or decrease in the area of one functional habitat (foraging or nesting) did not necessarily correspond to an increase or decrease in the other. Thus, an increase in the extent of occupied area may not equate to improved habitat quality or function. We argue these patterns are typical for mobile resource specialists but often go unnoticed because of limited data over relevant spatial and temporal scales and lack of spatial data on the availability of key resources. Understanding changes in the relative availability of functional habitats is crucial to informing conservation planning and accurately assessing extinction risk for mobile resource specialists.