Let's TOC Fertility: A stepped wedge cluster randomized controlled trial of the Telehealth Oncofertility Care (TOC) intervention in children, adolescent and young adult cancer survivors.

INTRODUCTION: Children, adolescent, and young adult cancer survivors experience overall increased risks of infertility that are preventable through effective fertility preservation services prior to starting cancer treatment. Oncofertility care is the evidence-based practice of informing newly diagnosed cancer patients about their reproductive risks and supporting shared decision-making on fertility preservation services. Despite longstanding clinical guidelines, oncofertility care delivery continues to be limited and highly variable across adult and pediatric oncology settings. MATERIALS AND METHODS: We describe the design of a stepped wedge cluster randomized clinical trial to evaluate the effectiveness of the multi-component Telehealth Oncofertility Care (TOC) intervention conducted in 20 adult and pediatric oncology clinics across three health systems in Southern California. Intervention components are: 1) electronic health record-based oncofertility needs screen and referral pathway to a virtual oncofertility hub; 2) telehealth oncofertility counseling through the hub; and 3) telehealth oncofertility financial navigation through the hub. We hypothesize the intervention condition will be associated with increased proportions of patients who engage in goal-concordant oncofertility care (i.e., engagement in reproductive risk counseling and fertility preservation services that meet the patient's fertility goals) and improved patient-reported outcomes, compared to the usual care control condition. We will also evaluate intervention implementation in a mixed-methods study guided by implementation science frameworks. DISCUSSION: Our overall goal is to speed implementation of a scalable oncofertility care intervention at cancer diagnosis for children, adolescent and young adult cancer patients to improve their future fertility and quality of life. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05443737.

Implementation of state health insurance benefit mandates for cancer-related fertility preservation: following policy through a complex system.

BACKGROUND: A myriad of federal, state, and organizational policies are designed to improve access to evidence-based healthcare, but the impact of these policies likely varies due to contextual determinants of, reinterpretations of, and poor compliance with policy requirements throughout implementation. Strategies enhancing implementation and compliance with policy intent can improve population health. Critically assessing the multi-level environments where health policies and their related health services are implemented is essential to designing effective policy-level implementation strategies. California passed a 2019 health insurance benefit mandate requiring coverage of fertility preservation services for individuals at risk of infertility due to medical treatments, in order to improve access to services that are otherwise cost prohibitive. Our objective was to document and understand the multi-level environment, relationships, and activities involved in using state benefit mandates to facilitate patient access to fertility preservation services. METHODS: We conducted a mixed-methods study and used the policy-optimized exploration, preparation, implementation, and sustainment (EPIS) framework to analyze the implementation of California's fertility preservation benefit mandate (SB 600) at and between the state insurance regulator, insurer, and clinic levels. RESULTS: Seventeen publicly available fertility preservation benefit mandate-relevant documents were reviewed. Interviews were conducted with four insurers; 25 financial, administrative, and provider participants from 16 oncology and fertility clinics; three fertility pharmaceutical representatives; and two patient advocates. The mandate and insurance regulator guidance represented two "Big P" (system level) policies that gave rise to a host of "little p" (organizational) policies by and between the regulator, insurers, clinics, and patients. Many little p policies were bridging factors to support implementation across levels and fertility preservation service access. Characterizing the mandate's functions (i.e., policy goals) and forms (i.e., ways that policies were enacted) led to identification of (1) intended and unintended implementation, service, and patient outcomes, (2) implementation processes by level and EPIS phase, (3) actor-delineated key processes and heterogeneity among them, and (4) inner and outer context determinants that drove adaptations. CONCLUSIONS: Following the midstream and downstream implementation of a state health insurance benefit mandate, data generated will enable development of policy-level implementation strategies, evaluation of determinants and important outcomes of effective implementation, and design of future mandates to improve fit and fidelity.

Implementation of state health insurance benefit mandates for cancer-related fertility preservation: Following policy through a complex system.

Background: A myriad of federal, state, and organizational policies are designed to improve access to evidence-based healthcare, but the impact of these policies likely varies due to contextual determinants, re-interpretations of and poor compliance with policy requirements throughout implementation. Strategies enhancing implementation and compliance with policy intent can improve population health. Critically assessing the multi-level environments where health policies and their related health services are implemented is essential to designing effective policy-level implementation strategies. California passed a 2019 health insurance benefit mandate requiring coverage of fertility preservation (FP) services for individuals at risk of infertility due to medical treatments to improve access to services that are otherwise cost-prohibitive. Our objective was to document and understand multi-level environment, relationships, and activities involved in using state benefit mandates to facilitate patient access to FP services. Methods: We conducted a mixed-methods study and used the policy-optimized Exploration, Preparation, Implementation, Sustainment (EPIS) framework to analyze implementation of California's fertility preservation benefit mandate (SB 600) at and between the state insurance regulator, insurer and clinic levels. Results: Seventeen publicly available FP benefit mandate-relevant documents were reviewed, and four insurers, 25 financial, administrative and provider participants from 16 oncology and fertility clinics, three fertility pharmaceutical representatives, and two patient advocates were interviewed. The mandate and insurance regulator guidance represented two "Big P" (system level) policies that gave rise to a host of "little p" (organizational) policies by and between the regulator, insurers, clinics, and patients. Many little p policies were bridging factors to support implementation across levels and FP service access. Characterizing the mandate's functions (i.e., policy goals) and forms (i.e., ways that policies were enacted) led to identification of (1) intended and unintended implementation, service, and patient outcomes; (2) implementation processes by level, EPIS phase; (3) actor-delineated key processes and heterogeneity among them; and (4) inner and outer context determinants that drove adaptations. Conclusions: Following the mid- and down-stream implementation of a state health insurance benefit mandate, data generated will enable development of policy level implementation strategies, evaluation of determinants and important outcomes of effective implementation, and design of future mandates to improve fit and fidelity.

Intervening on women's health for rural young breast cancer survivors: A study protocol.

INTRODUCTION: From diagnosis to post-treatment, many young breast cancer survivors (YBCS) experience infertility, limited contraception choices, concern about pregnancy safety, and menopausal symptoms. Clinical guidelines recommend oncofertility care (counseling and/or clinical services that meet fertility, contraception, pregnancy health and/or menopausal symptom management needs) throughout the cancer care continuum. However, significant oncofertility care gaps exist in rural, community oncology settings. MATERIALS AND METHODS: We describe the design of an interrupted time series, effectiveness-implementation hybrid clinical trial that evaluates a multi-component intervention to improve YBCS engagement in oncofertility care. The intervention is comprised of 1) oncology clinic-based oncofertility needs screen; 2) a women's health survivorship care plan in Spanish and English; 3) remote patient navigation; and 4) telehealth oncofertility consultation. During the pre-intervention period (12 months), usual care will be delivered. During the intervention period (15 months), the multi-component intervention will be implemented at two rural oncology clinics with largely Latina, Spanish-speaking populations. The primary outcome of YBCS (n = 135) engagement in oncofertility care will be collected from medical record review. We will also collect validated patient-reported outcomes. Informed by the Exploration Preparation Implementation Sustainment (EPIS) implementation science framework, we will integrate qualitative and quantitative data to explore whether and how the intervention was effective, acceptable, appropriate, and delivered with fidelity. DISCUSSION: Our overall goal is to speed implementation of a scalable oncofertility care intervention for YBCS in underserved areas to reduce disparities and improve reproductive health and quality of life. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05414812.

Changes in Cardiorespiratory Fitness and Probability of Developing Abdominal Obesity at One and Two Years.

Low cardiorespiratory fitness (CRF) is associated with an increased risk of developing abdominal obesity (AO), but it is not known if and/or how changes in CRF affect AO. We examined the relationship between changes in CRF and the risk of developing AO. This is a retrospective observational study of a cohort of 1883 sedentary patients, who had participated in a clinical trial of physical activity promotion carried out in Spain (2003-2007). These data were not used in the clinical trial. At baseline, they were free of cardiovascular disease, hypertension, diabetes, dyslipidemia, and/or AO; with an indirect VO2max measurement; 19-80 years old; and 62% were women. All the measures were repeated at 6, 12, and 24 months. The exposure factor was the change in CRF at 6 or 12 months, categorized in these groups: unfit-unfit, unfit-fit, fit-unfit, and fit-fit. We considered fit and unfit participants as those with VO2max values in the high tertile, and in the moderate or low tertiles, respectively. The main outcome measure was the risk of developing AO at one and two years, as defined by waist circumference >102 (men) and >88 (women) cm. At two years, 10.5% of the participants had developed AO: 13.5% in the unfit-unfit group of change at 6 months; 10.3% in the unfit-fit group (adjusted odds ratio (AOR) 0.86; 95% confidence interval (CI) 0.49-1.52); 2.6% in the fit-unfit group (AOR 0.13; 95%CI 0.03-0.61); and 6.0% in the fit-fit group (AOR 0.47; 95%CI 0.26-0.84). Those who stayed fit at 6 months decreased the probability of developing abdominal obesity at two years.

Vulnerabilidad de la obesidad definida por el índice de masa corporal, perímetro abdominal y porcentaje de grasa corporal / Vulnerability of obesity as defined by body mass index, waist circumference, and body fat percentage

Objetivo: Averiguar en qué medida es posible dejar de tener obesidad (normalizar el índice de masa corporal [IMC], el perímetro abdominal [PA] y/o el porcentaje de grasa corporal [PGC]). Diseño: Estudio de observación longitudinal y retrospectiva. Emplazamiento: Once centros de salud españoles. Participantes: Hombres y mujeres con IMC≥30kg/m2 (n=1.246) u obesidad general (OG), con PA>102cm y >88cm, respectivamente (n=2.122) u obesidad abdominal (OA) y con PGC>25% y >35%, respectivamente (n=2.436) o exceso de grasa corporal (EGC), de la cohorte del Estudio PEPAF de 4.927 participantes de 20 a 80años de edad. Mediciones principales: Datos procedentes del Estudio PEPAF de la captación y de 6, 12 y 24meses: sexo, edad, diagnósticos de diabetes, hipertensión arterial y dislipemia, hábito tabáquico, niveles y cumplimiento de las recomendaciones de actividad física, consumo máximo de oxígeno, peso, talla, PA y tres pliegues grasos cutáneos (torácico, umbilical y muslo anterior para hombres y tríceps, suprailíaco y muslo anterior para mujeres). Resultados: De 2.054 participantes con cualquier tipo de obesidad en la captación y datos válidos a los 2años, 240 (11,6%) habían normalizado todos sus índices diagnósticos de obesidad en ese tiempo. El 19,5% (intervalo de confianza al 95% (IC95%): 17,6-21,4) habían dejado de tener EGC, el 12,0% (IC95%: 10,4-13,7) habían dejado de tener OA y el 10,5% (IC95%: 8,5-12,7) habían dejado de tener OG. Conclusiones: La obesidad se diferencia de las demás enfermedades crónicas en que es posible «curarse» de ella normalizando la cantidad de grasa corporal.(AU)

Aim: To ascertain to what extent it is possible to stop being obese (to normalize body mass index [BMI], waist circumference [WC] and/or body fat percentage [BFP]). Design: Longitudinal observational and retrospective study. Site: Eleven Spanish health centers. Participants: Men and women with BMI≥30kg/m2 (n=1246) or general obesity (GO), with WC>102cm and >88cm, respectively (n=2122) or abdominal obesity (AO) and with BFP>25% and >35%, respectively (n=2436) or excess body fat (EBF), from the PEPAF Study cohort of 4927 participants aged 20-80years. Main measurements: Data from the PEPAF study at baseline and at 6, 12 and 24months: gender, age, diagnoses of diabetes, hypertension and dyslipidemia, smoking, levels of and compliance with physical activity recommendations, maximum oxygen consumption, weigh, height, WC and three skin-folds (thoracic, umbilical and anterior thigh for men and triceps, suprailiac and anterior thigh for women). Results: Of 2054 participants with any type of obesity at baseline and valid data at 2years, 240 (11.6%) had normalized all of their obesity diagnostic indexes. 19.5% (95% confidence interval (95%CI: 17.6-21.4) ceased to have EBF, 12.0% (95%CI: 10.4-13.7) ceased to have AO and 10.5% (95%CI: 8.5-12.7) ceased to have GO. Conclusions: Obesity differs from other chronic diseases in that it can be «cured» by normalizing the amount of body fat.(AU)

[Vulnerability of obesity as defined by body mass index, waist circumference, and body fat percentage]. / Vulnerabilidad de la obesidad definida por el índice de masa corporal, perímetro abdominal y porcentaje de grasa corporal.

AIM: To ascertain to what extent it is possible to stop being obese (to normalize body mass index [BMI], waist circumference [WC] and/or body fat percentage [BFP]). DESIGN: Longitudinal observational and retrospective study. SITE: Eleven Spanish health centers. PARTICIPANTS: Men and women with BMI≥30kg/m2 (n=1246) or general obesity (GO), with WC>102cm and >88cm, respectively (n=2122) or abdominal obesity (AO) and with BFP>25% and >35%, respectively (n=2436) or excess body fat (EBF), from the PEPAF Study cohort of 4927 participants aged 20-80years. MAIN MEASUREMENTS: Data from the PEPAF study at baseline and at 6, 12 and 24months: gender, age, diagnoses of diabetes, hypertension and dyslipidemia, smoking, levels of and compliance with physical activity recommendations, maximum oxygen consumption, weigh, height, WC and three skin-folds (thoracic, umbilical and anterior thigh for men and triceps, suprailiac and anterior thigh for women). RESULTS: Of 2054 participants with any type of obesity at baseline and valid data at 2years, 240 (11.6%) had normalized all of their obesity diagnostic indexes. 19.5% (95% confidence interval (95%CI: 17.6-21.4) ceased to have EBF, 12.0% (95%CI: 10.4-13.7) ceased to have AO and 10.5% (95%CI: 8.5-12.7) ceased to have GO. CONCLUSIONS: Obesity differs from other chronic diseases in that it can be «cured¼ by normalizing the amount of body fat.

Sustained Impact of the Coronavirus Disease 2019 Pandemic on Hepatitis C Virus Treatment Initiations in the United States.

BACKGROUND: Recent reports indicated declines in hepatitis C virus (HCV) testing during the first half of 2020 in the United States due to coronavirus disease 2019 (COVID-19), but the longer-term impact on HCV testing and treatment is unclear. METHODS: We obtained monthly state-level volumes of HCV antibody, RNA and genotype testing, and HCV treatment initiation, stratified by age and gender, spanning January 2019 until December 2020 from 2 large national laboratories. We performed segmented regression analysis for each state from a mixed-effects Poisson regression model with month as the main fixed predictor and state as a random intercept. RESULTS: During the pre-COVID-19 period (January 2019-March 2020), monthly HCV antibody and genotype tests decreased slightly whereas RNA tests and treatment initiations remained stable. Between March and April 2020, there were declines in the number of HCV antibody tests (37% reduction, P < .001), RNA tests (37.5% reduction, P < .001), genotype tests (24% reduction, P = .023), and HCV treatment initiations (31%, P < .001). Starting April 2020 through the end of 2020, there were significant increases in month-to-month HCV antibody (P < .001), RNA (P = .035), and genotype tests (P = .047), but only antibody testing rebounded to pre-COVID-19 levels. HCV treatment initiations remained low after April 2020 throughout the remainder of the year. CONCLUSIONS: HCV testing and treatment dropped by >30% during April 2020 at the start of the COVID-19 pandemic, but although HCV testing increased again later in 2020, HCV treatment rates did not recover. Efforts should be made to link HCV-positive patients to treatment and revitalize HCV treatment engagement by healthcare providers.

Assessment of patient mobility improves the risk stratification of triage with the Emergency Severity Index: a prospective cohort study.

BACKGROUND AND IMPORTANCE: Formal triage may assign a low acuity to patients at high risk of deterioration and mortality. A patient's mobility can be easily assessed at triage. OBJECTIVE: To investigate if a simple assessment of mobility at triage can improve the Emergency Severity Index's (ESI) prediction of adverse outcomes. DESIGN, SETTING AND PARTICIPANTS: Prospective observational study of all patients attending the emergency department (ED) of a single academic hospital in Switzerland over a period of 3 weeks. OUTCOME MEASURES AND ANALYSIS: Triage clinicians classified participants as having normal or impaired mobility at triage. Impaired mobility was defined as the lack of a stable independent gait, regardless of its cause or duration (e.g. any patient who needed help to walk). The primary outcome was 30-day mortality. We performed a survival analysis stratified by mobility and ESI level. We compared the performance of regression models including the ESI alone or in combination with mobility as predictors of mortality using the Bayesian information criterion (BIC). MAIN RESULTS: 2523 patients were included in the study and 880 (34.9%) had impaired mobility. Patients with impaired mobility had a lower median 30-day survival in ESI levels 1-3. Survival of patients with normal mobility was similar regardless of their ESI level. CONCLUSION: The assessment of mobility at triage improves the ESI algorithm's risk stratification.

Assessment of Health Insurance Benefit Mandates for Fertility Preservation Among 11 US States.

Importance: Multiple US states recently passed laws mandating health insurance coverage for fertility preservation (FP) services to improve access to care for patients with cancer, for whom FP service expenses can be prohibitive. Key unanswered questions include how heterogeneous benefit mandate laws and regulations are and how this variation may affect implementation, access, and utilization. Objective: To describe the design of state-level FP health insurance benefit mandate laws and regulations and derive guidance on best practices and implementation needs. Design, Setting, and Population: Legal mapping and implementation science framework-guided analyses were conducted on 11 US state laws that mandate health insurance benefit coverage for FP services for patients at risk of iatrogenic infertility from medical treatments and on related insurer regulations. Design features of laws and regulations and the implementation process were summarized by themes (eg, coverage specification). Exposures: State jurisdiction. Main Outcomes and Measures: Main outcomes were the scope and specificity of mandated FP insurance coverage and the role of clinical practice guidelines and insurer regulations in implementation. Results: Between June 2017 and March 2021, 11 states passed FP benefit mandate laws. States took a median (range) of 283 (0-640) days to implement mandates, and a majority issued regulatory guidance after the law was in effect. While standard-of-care procedures such as embryo cryopreservation require medical evaluation, medications, ultrasonography and laboratory monitoring, oocyte retrieval, embryo derivation, cryopreservation, and storage, there was variation in which services were specified for inclusion or exclusion in the laws and/or regulator guidance. The majority of state laws and regulator guidance reference medical society clinical practice guidelines and federal policies (Affordable Care Act and Health Insurance Portability and Accountability Act). Conclusions and Relevance: In this qualitative assessment of 11 state-level FP benefit mandates, variation that may influence patient access was identified in the design and implementation of the mandates. As clinical stakeholders aim to understand and/or shape these laws and their implementation, key considerations included specificity and flexibility of benefit design to be clinically meaningful, expansion of clinical practice guidelines to inform benefit coverage, inclusion of publicly insured and self-insured populations for universal access, and consistency between state and federal policies.

Emergency department patients with weakness or fatigue: Can physicians predict their outcomes at the front door? A prospective observational study.

BACKGROUND: Generalized weakness and fatigue are underexplored symptoms in emergency medicine. Triage tools often underestimate patients presenting to the emergency department (ED) with these nonspecific symptoms (Nemec et al., 2010). At the same time, physicians' disease severity rating (DSR) on a scale from 0 (not sick at all) to 10 (extremely sick) predicts key outcomes in ED patients (Beglinger et al., 2015; Rohacek et al., 2015). Our goals were (1) to characterize ED patients with weakness and/or fatigue (W|F); to explore (2) to what extent physicians' DSR at triage can predict five key outcomes in ED patients with W|F; (3) how well DSR performs relative to two commonly used benchmark methods, the Emergency Severity Index (ESI) and the Charlson Comorbidity Index (CCI); (4) to what extent DSR provides predictive information beyond ESI, CCI, or their linear combination, i.e., whether ESI and CCI should be used alone or in combination with DSR; and (5) to what extent ESI, CCI, or their linear combination provide predictive information beyond DSR alone, i.e., whether DSR should be used alone or in combination with ESI and / or CCI. METHODS: Prospective observational study between 2013-2015 (analysis in 2018-2020, study team blinded to hypothesis) conducted at a single center. We study an all-comer cohort of 3,960 patients (48% female patients, median age = 51 years, 94% completed 1-year follow-up). We looked at two primary outcomes (acute morbidity (Bingisser et al., 2017; Weigel et al., 2017) and all-cause 1- year mortality) and three secondary outcomes (in-hospital mortality, hospitalization and transfer to ICU). We assessed the predictive power (i.e., resolution, measured as the Area under the ROC Curve, AUC) of the scores and, using logistic regression, their linear combinations. FINDINGS: Compared to patients without W|F (n = 3,227), patients with W|F (n = 733) showed higher prevalences for all five outcomes, reported more symptoms across both genders, and received higher DSRs (median = 4; interquartile range (IQR) = 3-6 vs. median = 3; IQR = 2-5). DSR predicted all five outcomes well above chance (i.e., AUCs > ~0.70), similarly well for both patients with and without W|F, and as good as or better than ESI and CCI in patients with and without W|F (except for 1-year mortality where CCI performs better). For acute morbidity, hospitalization, and transfer to ICU there is clear evidence that adding DSR to ESI and/or CCI improves predictions for both patient groups; for 1-year mortality and in-hospital mortality this holds for most, but not all comparisons. Adding ESI and/or CCI to DSR generally did not improve performance or even decreased it. CONCLUSIONS: The use of physicians' disease severity rating has never been investigated in patients with generalized weakness and fatigue. We show that physicians' prediction of acute morbidity, mortality, hospitalization, and transfer to ICU through their DSR is also accurate in these patients. Across all patients, DSR is less predictive of acute morbidity for female than male patients, however. Future research should investigate how emergency physicians judge their patients' clinical state at triage and how this can be improved and used in simple decision aids.

Ultrasound-guided regional anaesthesia and reduction of distal radius fractures in an emergency department.

OBJECTIVES: Distal radius fractures are among the most common fractures. Ultrasound is gaining importance in the treatment of and as a tool to diagnose distal radius fractures, guide regional anaesthesia and support reductions. Our aim was to demonstrate safety, feasibility and outcome in patients with a distal radius fractures undergoing ultrasound-guided regional anaesthesia (UGRA) with ultrasound-guided reduction (UGR), as compared with procedural sedation for the reduction. METHODS: This retrospective cohort study was carried out in the emergency department of the University Hospital Basel (Switzerland) between February 2014 and October 2017. Adults with an isolated forearm fracture were eligible. The intervention group was treated with UGRA of the brachial plexus and subsequent ultrasound-assisted fracture reduction. Patients in the control group received usual care, which is blind fracture reduction with extension and immobilisation under procedural sedation. RESULTS: 71 patients were enrolled in the intervention group and 142 were to the control group. There was one (1.4%) complication (pneumothorax) in the UGR group. Twenty-five patients (35%) in the intervention group and 67 patients (47%) in the control group underwent surgery. The association between surgery and study group was not significant (p = 0.08). The patient’s age was negatively associated with surgery (p <0.001). The association between surgery and study group was significant in patients ≥60 years (p = 0.035). CONCLUSION: The combination of ultrasound-guided regional anaesthesia and ultrasound-guided reduction of distal radius fractures is feasible. Safety was shown by 70 out of 71 cases of UGRA being without complication. Effectiveness regarding the necessity of subsequent operation was comparable to usual care; in patients over 60 it may be lower with UGR.

Novel Sub-Clustering of Class III Skeletal Malocclusion Phenotypes in a Southern European Population Based on Proportional Measurements.

Current phenotypic characterizations of Class III malocclusion are influenced more by gender or ethnic origin than by raw linear skeletal measurements. The aim of the present research is to develop a Class III skeletal malocclusion sub-phenotype characterization based on proportional cranial measurements using principal component analysis and cluster analysis. Radiometric data from 212 adult subjects (115 women and 96 men) of southern European origin affected by Class III skeletal malocclusion were analyzed. A total of 120 measurements were made, 26 were proportional skeletal measurements, which were used to perform principal component analysis and subsequent cluster analysis. The remaining 94 supplementary measurements were used for a greater description of the identified clusters. Principal component analysis established eight principal components that explained 85.1% of the total variance. The first three principal components explained 51.4% of the variance and described mandibular proportions, anterior facial height proportions, and posterior-anterior cranial proportions. Cluster analysis established four phenotypic subgroups, representing 18.4% (C1), 20.75% (C2), 38.68% (C3), and 22.17% (C4) of the sample. A new sub-clustering of skeletal Class III malocclusions that avoids gender influence is provided. Our results improve clinicians' resources for Class III malocclusion and could improve the diagnostic and treatment approaches for this malocclusion.

Quantifying drought's influence on moist soil seed vegetation in California's Central Valley through remote sensing.

California's Central Valley, USA is a critical component of the Pacific Flyway despite loss of more than 90% of its wetlands. Moist soil seed (MSS) wetland plants are now produced by mimicking seasonal flooding in managed wetlands to provide an essential food resource for waterfowl. Managers need MSS plant area and productivity estimates to support waterfowl conservation, yet this remains unknown at the landscape scale. Also the effects of recent drought on MSS plants have not been quantified. We generated Landsat-derived estimates of extents and productivity (seed yield or its proxy, the green chlorophyll index) of major MSS plants including watergrass (Echinochloa crusgalli) and smartweed (Polygonum spp.) (WGSW), and swamp timothy (Crypsis schoenoides) (ST) in all Central Valley managed wetlands from 2007 to 2017. We tested the effects of water year, land ownership and region on plant area and productivity with a multifactor nested analysis of variance. For the San Joaquin Valley, we explored the association between water year and water supply, and we developed metrics to support management decisions. MSS plant area maps were based on a support vector machine classification of Landsat phenology metrics (2017 map overall accuracy: 89%). ST productivity maps were created with a linear regression model of seed yield (n = 68, R2  = 0.53, normalized RMSE = 10.5%). The Central Valley-wide estimated area for ST in 2017 was 32,369 ha (29,845-34,893 ha 95% CI), and 13,012 ha (11,628-14,396 ha) for WGSW. Mean ST seed yield ranged from 577 kg/ha in the Delta Basin to 365 kg/ha in the San Joaquin Basin. WGSW area and ST seed yield decreased while ST area increased in critical drought years compared to normal water years (Scheffe's test, P < 0.05). Greatest ST area increases occurred in the Sacramento Valley (~75%). Voluntary water deliveries increased in normal water years, and ST seed yield increased with water supply. Z scores of ST seed yield can be used to evaluate wetland performance and aid resource allocation decisions. Updated maps will support habitat monitoring, conservation planning and water management in future years, which are likely to face greater uncertainty in water availability with climate change.

Novel CB1 receptor antagonist BAR-1 modifies pancreatic islet function and clinical parameters in prediabetic and diabetic mice.

BACKGROUDS: Cannabinoid receptor antagonists have been suggested as a novel treatment for obesity and diabetes. We have developed a synthetic cannabinoid receptor antagonist denominated BAR-1. As the function and integrity of a ß-cell cellular structure are important keys for diabetes onset, we evaluated the effects of pharmacological administration of BAR-1 on prediabetic and diabetic rodents. METHODS: CD-1 mice fed a hypercaloric diet or treated with streptozotocin were treated with 10 mg/kg BAR-1 for 2, 4 or 8 weeks. Body weight, oral glucose tolerance test, HbA1c, triglycerides and insulin in serum were measured. In isolated islets, we evaluated stimulated secretion and mRNA expression, and relative area of islets in fixed pancreases. Docking analysis of BAR-1 was complemented. RESULTS: BAR-1 treatment slowed down weight gain in prediabetic mice. Fasting glucose-insulin relation also decreased in BAR-1-treated mice and glucose-stimulated insulin secretion was increased in isolated islets, without effects in oral test. Diabetic mice treated with BAR-1 showed a reduced glucose and a partial recovery of islet integrity. Gene expression of insulin and glucagon showed biphasic behaviour, increasing after 4 weeks of BAR-1 administration; however, after 8 weeks, mRNA abundance decreased significantly. Administration of BAR-1 also prevents changes in endocannabinoid element expression observed in prediabetic mice. No changes were detected in other parameters studied, including the histological structure. A preliminary in-silico study suggests a close interaction with CB1 receptor. CONCLUSIONS: BAR-1 induces improvement of islet function, isolated from both prediabetic and diabetic mice. Effects of BAR-1 suggest a possible interaction with other cannabinoid receptors.

Physicians' Disease Severity Ratings are Non-Inferior to the Emergency Severity Index.

Our objective was to compare informal physicians' disease severity ratings (PDSR) at presentation with the well-established Emergency Severity Index (ESI) in order to test for non-inferiority of the discriminatory ability regarding hospitalization, intensive care, and mortality. We made a prospective observational study with consecutive enrollment. At presentation, the PDSR and subsequently Emergency Severity Index (ESI) levels were recorded. The primary outcome was the non-inferiority of the discriminatory ability (PDSR versus ESI) regarding hospitalization, intensive care, and mortality. The secondary outcomes were the reliability, the predictive validity, and the safety of PDSR. We included 6859 patients. The median age was 51 years (interquartile range (IQR) = 33 to 72 years); 51.4% were males. There were 159 non-survivors (2.4%) at the 30 day follow-up. The PDSR's discriminatory ability was non-inferior to the ESI's discriminatory ability. The safety assessment showed mortality of <0.5% in low-acuity patients in both tools. The predictive validity increased by 3.5 to 7 times if adding high-acuity PDSR to ESI in all categories with mortality of >1%. Our data showed the non-inferiority of PDSR compared with ESI regarding discriminatory ability, a moderate reliability, and an acceptable safety of both tools.

A simple prognostic score predicts one-year mortality of alert and calm emergency department patients: A prospective two-center observational study.

STUDY OBJECTIVE: To derive and validate a prognostic score to predict 1-year mortality using vital signs, mobility and other variables that are readily available at the bedside at no additional cost. METHODS: Post hoc analysis of two independent prospective observational studies in two emergency departments, one in Denmark and the other in Switzerland. PARTICIPANTS: Alert and calm emergency department patients. MEASUREMENTS: The prediction of mortality from presentation to 365 days by vital signs, mobility and other variables that are readily available at the bedside at no additional cost. RESULTS: One thousand six hundred and eighteen alert and calm patients were in the Danish cohort and 1331 in the Swiss cohort. Logistic regression identified age >68 years, abnormal vital signs, impaired mobility and the decision to admit as significant predictors of 365-day mortality. A simple prognostic score awarded one point to each of these predictors. Less than two of these predictors were present in 45.6% of patients, and only 0.4% of these patients died within a year. If two or more of these predictors were present, 365-day mortality increased exponentially. CONCLUSION: Age >68 years, the decision for hospital admission, any vital sign abnormality at presentation and impaired mobility at presentation are equally powerful predictors of 1-year mortality in alert and calm emergency department patients. If validated by others these predictors could be used to discharge patients with confidence since nearly half of these patients had less than two predictors and none of them died within 30 days. However, when two or more predictors were present 365-day mortality increased exponentially.

In vitro conditions for performance evaluation of products for intravascular administration: Developing appropriate test media using Amphotericin B as a model drug.

Currently, there are no compendial in vitro release tests specifically indicated for parenteral formulations. Consideration of biorelevant and clinically relevant test media represents a valuable approach for the development of in vitro tests that ideally can provide information on the formulation performance in vivo. The aim of this study was to investigate the effect of different media components on the solubility of Amphotericin B (a poorly soluble highly protein-bound drug) in order to develop biorelevant and clinically relevant media for future in vitro release testing from its liposomal formulation. Three categories of media were considered in the development approach: Category 1 media: effect of albumin concentration; category 2 media: effect of biorelevant concentrations of plasma components (bile salts, phospholipids, cholesterol, albumin); category 3 media: attaining clinically relevant solubility with biorelevant and synthetic surfactants with and without albumin and setting the basis for the development of a simulated hypoalbuminaemic plasma medium. All the surfactants tested increased Amphotericin B solubility while the simultaneous presence of albumin had a negative effect on solubility. Clinically relevant media with the use of biorelevant or synthetic surfactants and albumin were developed. One medium in which the solubility of Amphotericin B was reduced was identified as potential candidate medium to simulate hypoalbuminaemic plasma. The development of biorelevant and clinically relevant media and understanding the effect of media components and their interactions, supports future development of meaningful in vivo predictive release tests for parenteral formulations.

Clinical Scores and Formal Triage for Screening of Sepsis and Adverse Outcomes on Arrival in an Emergency Department All-Comer Cohort.

BACKGROUND: Early recognition of sepsis remains a major challenge. The clinical utility of the Quick Sepsis-Related Organ Failure Assessment (qSOFA) score is still undefined. Several studies have tested its prognostic value. However, its ability to diagnose sepsis is still unknown. OBJECTIVE: Our aim was to compare the performance of qSOFA, systemic inflammatory response syndrome (SIRS) criteria, National Early Warning Score (NEWS), and formal triage with the Emergency Severity Index (ESI) algorithm to identify patients with sepsis and predict adverse outcomes on arrival in an emergency department (ED) all-comer cohort. METHODS: We included all patients presenting consecutively to the ED during a 3-week period. We used vital signs recorded at triage to calculate the study scores. Two independent assessors retrospectively assigned the primary outcome of sepsis according to Third International Consensus Definitions for Sepsis and Septic Shock criteria in a chart review process. RESULTS: There were 2523 cases included in the analysis and 39 (1.6%) had the primary outcome of sepsis. The area under the curve for sepsis was 0.79 (95% confidence interval [CI] 0.71-0.86) for qSOFA, 0.81 (95% CI 0.73-0.87) for SIRS, 0.85 (95% CI 0.77-0.92) for NEWS, and 0.77 (95% CI 0.70-0.83) for ESI. CONCLUSIONS: qSOFA offered high specificity for the prediction of sepsis and adverse outcomes. However, its low sensitivity does not support widespread use as a screening tool for sepsis. NEWS outperformed qSOFA for prediction of adverse outcomes and screening for sepsis.

Mobility Identifies Acutely Ill Patients at Low Risk of In-Hospital Mortality: A Prospective Multicenter Study.

BACKGROUND: A retrospective study has reported that impaired mobility on presentation (IMOP) enhanced the ability of vital signs to predict mortality in acutely ill patients. This study was designed to further examine the association between IMOP and in-hospital mortality. METHODS: Prospective observational study of three different cohorts of acutely ill patients admitted to hospitals in Esbjerg, Denmark (998 patients), Basel, Switzerland (743 patients), and Kitovu, Uganda (1,622 patients). RESULTS: There were significant differences in age, sex, length of stay, proportion of medical and surgical patients, and in-hospital mortality between the three cohorts. Yet in all three cohorts a National Early Warning Score (NEWS) ≥ 3 when first recorded and IMOP increased the risk of in-hospital mortality to approximately the same extent. IMOP and NEWS ≥ 3 when first recorded were, therefore, used for risk categorization: patients with a NEWS < 3 when first recorded and normal mobility on presentation had the lowest in-hospital mortality risk and those with NEWS ≥ 3 when first recorded and IMOP had the highest risk. The number of these low risk patients ranged from 26% in Kitovu to 42% in Esbjerg, and their in-hospital mortality rates did not significantly differ in all three cohorts, ranging from 0.2% in Esbjerg to 0.4% in Basel. CONCLUSIONS: In this prospective multicenter study IMOP enhanced the risk categorization of acutely ill patients from very different clinical settings. The combination normal mobility on presentation and first recorded NEWS identified a substantial proportion of patients in all cohorts with a low risk of dying while in hospital. TRIAL REGISTRY: The Esbjerg data were collected as part of a trial registered with the US National Library of Medicine (ClinicalTrials.gov; No.: NCT03108807; URL: www.clinicaltrials.gov).