Pediatric Farm Injuries: Morbidity and Mortality

Introduction. Agriculture is an industry where family members oftenlive and work on the same premises. This study evaluated injury patternsand outcomes in children from farm-related accidents. Methods. A 10-year retrospective review of farm-accident relatedinjuries was conducted of patients 17 years and younger. Data collectedincluded demographics, injury mechanism, accident details, injuryseverity and patterns, treatments required, hospitalization details, anddischarge disposition. Results. Sixty-five patients were included; 58.5% were male and themean age was 9.7 years. Median Injury Severity Score and GlasgowComa Scale were 5 and 15, respectively. Accident mechanisms includedanimal-related (43.1%), fall (21.5%), and motor vehicle (21.5%).Soft tissue injuries, concussions and upper extremity fractures werethe most common injuries observed (58.5%, 29.2%, and 26.2%,respectively). Twenty-six patients (40%) required surgical intervention.Mean hospital length of stay was 3.4 ± 4.7 days. The majority ofpatients were discharged to home (n = 62, 95.4%) and two patientssuffered permanent disability. Conclusion. Overall, outcomes for this population were favorable,but additional measures to increase safety, such as fall prevention,animal handling, and driver safety training should be advocated.KS J Med 2017;10(4):92-95

Insomnia disorder

Insomnia disorder affects a large proportion of the population on a situational, recurrent or chronic basis and is among the most common complaints in medical practice. The disorder is predominantly characterized by dissatisfaction with sleep duration or quality and difficulties initiating or maintaining sleep, along with substantial distress and impairments of daytime functioning. It can present as the chief complaint or, more often, co-occurs with other medical or psychiatric disorders, such as pain and depression. Persistent insomnia has been linked with adverse long-term health outcomes, including diminished quality of life and physical and psychological morbidity. Despite its high prevalence and burden, the aetiology and pathophysiology of insomnia is poorly understood. In the past decade, important changes in classification and diagnostic paradigms have instigated a move from a purely symptom-based conceptualization to the recognition of insomnia as a disorder in its own right. These changes have been paralleled by key advances in therapy, with generic pharmacological and psychological interventions being increasingly replaced by approaches that have sleep-specific and insomnia-specific therapeutic targets. Psychological and pharmacological therapies effectively reduce the time it takes to fall asleep and the time spent awake after sleep onset, and produce a modest increase in total sleep time; these are outcomes that correlate with improvements in daytime functioning. Despite this progress, several challenges remain, including the need to improve our knowledge of the mechanisms that underlie insomnia and to develop more cost-effective, efficient and accessible therapies

Fire Suppression Impacts on Fuels and Fire Intensity in the Western U.S.: Insights from Archaeological Luminescence Dating in Northern New Mexico

Here, we show that the last century of fire suppression in the western U.S. has resulted in fire intensities that are unique over more than 900 years of record in ponderosa pine forests (Pinus ponderosa). Specifically, we use the heat-sensitive luminescence signal of archaeological ceramics and tree-ring fire histories to show that a recent fire during mild weather conditions was more intense than anything experienced in centuries of frequent wildfires. We support this with a particularly robust set of optically stimulated luminescence measurements on pottery from an archaeological site in northern New Mexico. The heating effects of an October 2012 CE prescribed fire reset the luminescence signal in all 12 surface samples of archaeological ceramics, whereas none of the 10 samples exposed to at least 14 previous fires (1696–1893 CE) revealed any evidence of past thermal impact. This was true regardless of the fire behavior contexts of the 2012 CE samples (crown, surface, and smoldering fires). It suggests that the fuel characteristics from fire suppression at this site have no analog during the 550 years since the depopulation of this site or the 350 years of preceding occupation of the forested landscape of this region

Myeloma cells down‐regulate adiponectin in bone marrow adipocytes via TNF‐alpha

Multiple myeloma is caused by abnormal plasma cells that accumulate in the bone marrow and interact with resident cells of the bone microenvironment to drive disease progression and development of an osteolytic bone disease. Bone marrow adipocytes (BMAds) are emerging as having important endocrine functions that can support myeloma cell growth and survival. However, how BMAds respond to infiltrating tumor cells remains poorly understood. Using the C57BL/KaLwRij murine model of myeloma, bone marrow adiposity was found to be increased in early stage myeloma with BMAds localizing along the tumor‐bone interface at later stages of disease. Myeloma cells were found to uptake BMAd‐derived lipids in vitro and in vivo, although lipid uptake was not associated with the ability of BMAds to promote myeloma cell growth and survival. However, BMAd‐derived factors were found to increase myeloma cell migration, viability, and the evasion of apoptosis. BMAds are a major source of adiponectin, which is known to be myeloma‐suppressive. Myeloma cells were found to downregulate adiponectin specifically in a model of BMAds but not in white adipocytes. The ability of myeloma cells to downregulate adiponectin was dependent at least in part on TNF‐α. Collectively our data support the link between increased bone marrow adiposity and myeloma progression. By demonstrating how TNF‐α downregulates BMAd‐derived adiponectin, we reveal a new mechanism by which myeloma cells alter the bone microenvironment to support disease progression. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

Nonthermal Hard X-ray Emission and Iron Kalpha Emission from a Superflare on II Pegasi

We report on an X-ray flare detected on the active binary system II~Pegasi with the Swift telescope. The trigger had a 10-200 keV luminosity of 2.2$\times10^{32}$ erg s$^{-1}$-- a superflare, by comparison with energies of typical stellar flares on active binary systems. The trigger spectrum indicates a hot thermal plasma with T$\sim$180 $\times10^{6}$K. X-ray spectral analysis from 0.8--200 keV with the X-Ray Telescope and BAT in the next two orbits reveals evidence for a thermal component (T$>$80 $\times10^{6}$K) and Fe K 6.4 keV emission. A tail of emission out to 200 keV can be fit with either an extremely high temperature thermal plasma (T$\sim3\times10^{8}$K) or power-law emission. Based on analogies with solar flares, we attribute the excess continuum emission to nonthermal thick-target bremsstrahlung emission from a population of accelerated electrons. We estimate the radiated energy from 0.01--200 keV to be $\sim6\times10^{36}$ erg, the total radiated energy over all wavelengths $\sim10^{38}$ erg, the energy in nonthermal electrons above 20 keV $\sim3\times10^{40}$ erg, and conducted energy $<5\times10^{43}$ erg. The nonthermal interpretation gives a reasonable value for the total energy in electrons $>$ 20 keV when compared to the upper and lower bounds on the thermal energy content of the flare. This marks the first occasion in which evidence exists for nonthermal hard X-ray emission from a stellar flare. We investigate the emission mechanism responsible for producing the 6.4 keV feature, and find that collisional ionization from nonthermal electrons appears to be more plausible than the photoionization mechanism usually invoked on the Sun and pre-main sequence stars.Comment: 41 pages, 7 figures, accepted for publication in the Astrophysical Journa

A phase II single-arm study of pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer progressing on enzalutamide alone.

BACKGROUND: Checkpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response. METHODS: We evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg intravenous was given every 3 weeks for four doses with enzalutamide. The primary endpoint was prostate-specific antigen (PSA) decline of ≥50%. Secondary endpoints were objective response, PSA progression-free survival (PFS), time to subsequent treatment, and time to death. Baseline tumor biopsies were obtained when feasible, and samples were sequenced and evaluated for the expression of PD-L1, microsatellite instability (MSI), mutational and neoepitope burdens. RESULTS: Five (18%) of 28 patients had a PSA decline of ≥50%. Three (25%) of 12 patients with measurable disease at baseline achieved an objective response. Of the five responders, two continue with PSA and radiographic response after 39.3 and 37.8 months. For the entire cohort, median follow-up was 37 months, and median PSA PFS time was 3.8 months (95% CI: 2.8 to 9.9 months). Time to subsequent treatment was 7.21 months (95% CI: 5.1 to 11.1 months). Median overall survival for all patients was 21.9 months (95% CI: 14.7 to 28 .4 months), versus 41.7 months (95% CI: 22.16 to not reached (NR)) in the responders. Of the three responders with baseline biopsies, one had MSI high disease with mutations consistent with DNA-repair defects. None had detectable PD-L1 expression. CONCLUSIONS: Pembrolizumab has activity in mCRPC when added to enzalutamide. Responses were deep and durable and did not require tumor PD-L1 expression or DNA-repair defects. TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT02312557)

Development and validation of a non-remission risk prediction model in first episode psychosis:An Analysis of 2 Longitudinal Studies

Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom nonremission in first-episode psychosis. Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 and 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 and 2009 from a further 11 English early intervention services. The one-year nonremission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for nonremission, which was externally validated. The prediction model showed good discrimination C-statistic of 0.73 (0.71, 0.75) and adequate calibration with intercept alpha of 0.12 (0.02, 0.22) and slope beta of 0.98 (0.85, 1.11). Our model improved the net-benefit by 15% at a risk threshold of 50% compared to the strategy of treating all, equivalent to 15 more detected nonremitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases. Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of nonremission at initial clinical contact.</p

Supporting good practice in the provision of services to people with comorbid mental health and alcohol and other drug problems in Australia: describing key elements of good service models

<p>Abstract</p> <p>Background</p> <p>The co-occurrence of mental illness and substance use problems (referred to as "comorbidity" in this paper) is common, and is often reported by service providers as the expectation rather than the exception. Despite this, many different treatment service models are being used in the alcohol and other drugs (AOD) and mental health (MH) sectors to treat this complex client group. While there is abundant literature in the area of comorbidity treatment, no agreed overarching framework to describe the range of service delivery models is apparent internationally or at the national level. The aims of the current research were to identify and describe elements of good practice in current service models of treatment of comorbidity in Australia. The focus of the research was on models of service delivery. The research did not aim to measure the client outcomes achieved by individual treatment services, but sought to identify elements of good practice in services.</p> <p>Methods</p> <p>Australian treatment services were identified to take part in the study through a process of expert consultation. The intent was to look for similarities in the delivery models being implemented across a diverse set of services that were perceived to be providing good quality treatment for people with comorbidity problems.</p> <p>Results</p> <p>A survey was designed based on a concept map of service delivery devised from a literature review. Seventeen Australian treatment services participated in the survey, which explored the context in which services operate, inputs such as organisational philosophy and service structure, policies and procedures that guide the way in which treatment is delivered by the service, practices that reflect the way treatment is provided to clients, and client impacts.</p> <p>Conclusions</p> <p>The treatment of people with comorbidity of mental health and substance use disorders presents complex problems that require strong but flexible service models. While the treatment services included in this study reflected the diversity of settings and approaches described in the literature, the research found that they shared a range of common characteristics. These referred to: service linkages; workforce; policies, procedures and practices; and treatment.</p