ELEVATE - evaluating Temozolomide and Nivolumab in patients with advanced unresectable previously treated oesophagogastric adenocarcinoma with MGMT methylation: study protocol for a single arm phase II trial.

BACKGROUND: For patients with oesophagogastric adenocarcinoma, surgery is the only curative option and despite the use of multimodality therapy, which combines it with chemotherapy and/or radiotherapy, more than 50% of patients will relapse and die. Many UK patients present with advanced disease which is already inoperable or metastatic at diagnosis. For these patients, standard care chemotherapy only offers them survival of less than a year. Nivolumab, a checkpoint blockade inhibitor, has been found to work in some advanced cancers. It is proposed, for those where immunotherapy hasn't worked, that these immunologically evasive tumours need to be sensitized to immunotherapy drugs to allow them to act. METHODS: ELEVATE is a single arm phase II trial testing the overall response to nivolumab following temozolomide treatment in patients with advanced unresectable previously treated adenocarcinoma which is O6-methylguanine-DNA-methyltransferase (MGMT) methylated. 18 patients are being recruited from UK secondary care sites. To be eligible, participants must have been treated with at least 3 months of platinum and fluoropyrimidine chemotherapy. Participants will receive 50 mg/m2 temozolomide continuously for 3 months. If their disease progresses during the 3 months, they will stop temozolomide and start nivolumab at a dose of 240mg every 2 weeks. If there is no progression after 3 months the participant will continue taking temozolomide in combination with nivolumab. All treatment will stop once the participant progresses on nivolumab. The primary endpoint is the best overall response to nivolumab, using both Response Evaluation Criteria in Solid Tumours version 1.1 and immunotherapy modified Response Evaluation Criteria in Solid Tumours. Secondary endpoints include progression-free survival, overall survival, and quality of life. DISCUSSION: ELEVATE will provide evidence for whether giving nivolumab after temozolomide in patients with previously treated advanced oesophagogastric adenocarcinoma is safe and biologically effective prior to future randomised trials. TRIAL REGISTRATIONS: EudraCT Number: 2020-004771-41 (issued 01 October 2020); ISCRTN11398887 (registered 14 July 2021).

Obstetric Anesthetic Management for Parturients with Hereditary Angioedema: A Case Report and Suggested Protocol.

Hereditary angioedema (HAE) is a disease manifested by repeated episodes of localized submucosal or subcutaneous edematous episodes, potentially triggered by emotional stress, mechanical trauma, or intake of estrogens. We present our experience managing two parturients with HAE. Multidisciplinary care is essential for planning and executing the specialized care of these patients, and management included extensive planning among obstetric, anesthesiology, and allergy and immunology teams. Pregnancy has been shown to have a variable effect on triggering HAE episodes. First-line treatment includes C1 esterase inhibitor concentrate, which can also be used for prophylaxis in high-risk patients. Neuraxial analgesia is recommended to avoid general anesthesia and was established early in both individuals. Vaginal delivery was well tolerated without need for emergent treatment for angioedema symptoms.

Caffeine enhances activity thermogenesis and energy expenditure in rats.

Caffeine and its derivatives have been used, alone and in combination with other phytochemicals, as weight-loss supplements. Caffeine affects several physiological and behavioural aspects of energy balance, including increasing locomotor activity. This study investigates the potential for caffeine to enhance activity thermogenesis and energy expenditure (EE) even when activity level is held constant. To do this, EE and muscle thermogenesis were measured in rats during treadmill walking regimens, with and without caffeine (25 mg/kg, ip). Activity-related EE was significantly increased throughout the treadmill walking protocol. Muscle heat dissipation, on the other hand, was significantly increased by caffeine only at the end of the 25-minute treadmill test. This study demonstrates that caffeine increases the caloric cost of physical activity, compared to the caloric cost of that same physical activity without caffeine, implicating decreased muscle work efficiency. Combined with the known ability of caffeine to increase locomotor activity, the decreased locomotor efficiency imparted by caffeine may further augment the potential for caffeine to enhance caloric expenditure.

Using spatial patterns in illegal wildlife uses to reveal connections between subsistence hunting and trade.

Although most often considered independently, subsistence hunting, domestic trade, and international trade as components of illegal wildlife use (IWU) may be spatially correlated. Understanding how and where subsistence and commercial uses may co-occur has important implications for the design and implementation of effective conservation actions. We analyzed patterns in the joint geographical distribution of illegal commercial and subsistence use of multiple wildlife species in Venezuela and evaluated whether available data were sufficient to provide accurate estimates of the magnitude, scope, and detectability of IWU. We compiled records of illegal subsistence hunting and trade from several sources and fitted a random-forest classification model to predict the spatial distribution of IWUs. From 1969 to 2014, 404 species and 8,340,921 specimens were involved in IWU, for a mean extraction rate of 185,354 individuals/year. Birds were the most speciose group involved (248 spp.), but reptiles had the highest extraction rates (126,414 individuals/year vs. 3,133 individuals/year for birds). Eighty-eight percent of international trade records spatially overlapped with domestic trade, especially in the north and along the coast but also in western inland areas. The distribution of domestic trade was broadly distributed along roads, suggesting that domestic trade does not depend on large markets in cities. Seventeen percent of domestic trade records overlapped with subsistence hunting, but the spatial distribution of this overlap covered a much larger area than between commercial uses. Domestic trade seems to respond to demand from rural more than urban communities. Our approach will be useful for understanding how IWU works at national scales in other parts of the world.

Bullies, bluetongue and bills: 2023 in review.

2023 was a particularly busy year for the veterinary sector, with major changes to RCVS guidance, the re-emergence of a notifiable disease last seen in 2007 and a competitions and markets review. Add to that a new breed banned under the Dangerous Dogs Act, and it's clear the year was anything but quiet. Kathryn Clark reports.

Seeking a sustainable solution to Varroa mite.

Selective breeding may offer a way forward in protecting honey bee colonies from the devastation caused by Varroa mite infestations. Kathryn Clark reports.

2021: a veterinary year in review.

With Covid-19 and Brexit continuing to change the ways in which veterinary teams work, 2021 was another year of uncertainty. Here, Kathryn Clark sums up the year that was.

Understanding Racial-Ethnic Disparities in Wraparound Care for Youths With Emotional and Behavioral Disorders.

OBJECTIVE: Systems of care (SOCs) were developed to increase access to and quality of care for children with emotional and behavioral difficulties and their families through the provision of coordinated, community-based, culturally competent, family-driven services. SOCs focus on wraparound care that is individualized to meet each family's needs. Previous research has illustrated significant disparities in outcomes of nonwraparound care on the basis of youths' race-ethnicity. This study aimed to fill a research gap by examining disparities in outcomes for families receiving wraparound care coordination within an SOC. METHODS: This exploratory study examined racial-ethnic disparities in outcomes observed at intake, during service provision, and at 6-month follow-up among 1,138 youths and their caregivers who participated in wraparound care coordination as part of a statewide SOC between 2016 and 2020. Analyses of variance and regression analyses were executed to investigate whether receiving services and/or the youths' racial-ethnic identity predicted differences in behavioral health outcomes and characteristics of or satisfaction with care. Caregiver-reported outcomes were assessed with the Ohio Scales for Youth, the Child Trauma Screen, and the Caregiver Strain Questionnaire. RESULTS: Results revealed few racial-ethnic disparities in the characteristics and outcomes of care coordination among participants at intake or in family involvement in the wraparound process. Participants across groups reported similar and significant improvement in outcomes. However, the results indicated some disparities in satisfaction with care. CONCLUSIONS: Results revealed the positive impact of care coordination on the health and well-being of youths and caregivers across racial-ethnic groups.

Predictors of 1-year mortality after adult lung transplantation: Systematic review and meta-analyses.

BACKGROUND: Prognostic factors in lung transplantation are those variables that are associated with transplant outcomes. Knowledge of donor and recipient prognostic variables can aid in the optimal allocation of donor lungs to transplant recipients and can also inform post-operative discussions with patients about prognosis. Current research findings related to prognostic factors in lung transplantation are inconsistent and the relative importance of various factors is unclear. This review aims to provide the best possible estimates of the association between putative prognostic variables and 1-year all-cause mortality in adult lung transplant recipients. METHODS: We searched 5 bibliographic databases for studies assessing the associations between putative predictors (related to lung donors, recipients, or the transplant procedure) and 1-year recipient mortality. We pooled data across studies when justified and utilized GRADE methodology to assess the certainty in the evidence. RESULTS: From 72 eligible studies (2002-2020), there were 34 recipient variables, 4 donor variables, 10 procedural variables, and 7 post-transplant complication variables that were amenable to a meta-analysis. With a high degree of certainty in the evidence only post-transplant need for extra-corporeal membrane oxygenation (ECMO) (HR 1.91, 95% CI 1.79-2.04) predicted 1-year mortality. No donor variables appeared to predict transplant outcome with high or even moderate certainty. CONCLUSION: Across the range of contemporary donors and recipients that clinicians accept for lung transplantation, this review, with high certainty, found 1 prognostic factor that predicted 1-year mortality, and 37 additional factors with a moderate degree of certainty. The lack of prognostic significance for some widely accepted factors (e.g., donor smoking, age) likely relates to existing limits in the range of these variables at the time of donor and recipient selection.

Effects of the alpha-2 adrenoceptor agonist guanfacine on attention and working memory in aged non-human primates.

Alpha-2 adrenergic receptors are potential targets for ameliorating cognitive deficits associated with aging as well as certain pathologies such as attention deficit disorder, schizophrenia and Parkinson's disease. Although the alpha-2 agonist guanfacine has been reported to improve working memory in aged primates, it has been difficult to assess the extent to which these improvements may be related to drug effects on attention and/or memory processes involved in task performance. The present study investigated effects of guanfacine on specific attention and memory tasks in aged monkeys. Four Rhesus monkeys (18-21 years old) performed a sustained attention (continuous performance) task and spatial working memory task (self-ordered spatial search) that has minimal demands on attention. Effects of a low (0.0015 mg/kg) and high (0.5 mg/kg) dose of gunafacine were examined. Low-dose guanfacine improved performance on the attention task [i.e. decreased omission errors by 50.8 ± 4.3% (P = 0.001) without an effect on commission errors] but failed to improve performance on the spatial working memory task. The high dose of guanfacine had no effects on either task. Guanfacine may have a preferential effect on some aspects of attention in normal aged monkeys and in doing so may also improve performance on other tasks, including some working memory tasks that have relatively high attention demands.

Establishing IUCN Red List criteria for threatened ecosystems.

The potential for conservation of individual species has been greatly advanced by the International Union for Conservation of Nature's (IUCN) development of objective, repeatable, and transparent criteria for assessing extinction risk that explicitly separate risk assessment from priority setting. At the IV World Conservation Congress in 2008, the process began to develop and implement comparable global standards for ecosystems. A working group established by the IUCN has begun formulating a system of quantitative categories and criteria, analogous to those used for species, for assigning levels of threat to ecosystems at local, regional, and global levels. A final system will require definitions of ecosystems; quantification of ecosystem status; identification of the stages of degradation and loss of ecosystems; proxy measures of risk (criteria); classification thresholds for these criteria; and standardized methods for performing assessments. The system will need to reflect the degree and rate of change in an ecosystem's extent, composition, structure, and function, and have its conceptual roots in ecological theory and empirical research. On the basis of these requirements and the hypothesis that ecosystem risk is a function of the risk of its component species, we propose a set of four criteria: recent declines in distribution or ecological function, historical total loss in distribution or ecological function, small distribution combined with decline, or very small distribution. Most work has focused on terrestrial ecosystems, but comparable thresholds and criteria for freshwater and marine ecosystems are also needed. These are the first steps in an international consultation process that will lead to a unified proposal to be presented at the next World Conservation Congress in 2012.

Associations between state economic and health systems capacities and service use by children with special health care needs.

To examine the relationship between measures of state economic, political, health services, and Title V capacity and individual level measures of the well-being of CSHCN. We selected five measures of Title V capacity from the Title V Information System and 13 state capacity measures from a variety of data sources, and eight indicators of intermediate health outcomes from the National Survey of Children with Special Health Care Needs. To assess the associations between Title V capacity and health services outcomes, we used stepwise regression to identify significant capacity measures while accounting for the survey design and clustering of observations by state. To assess the associations between economic, political and health systems capacity and health outcomes we fit weighted logistic regression models for each outcome, using a stepwise procedure to reduce the models. Using statistically significant capacity measures from the stepwise models, we fit reduced random effects logistic regression models to account for clustering of observations by state. Few measures of Title V and state capacity were associated with health services outcomes. For health systems measures, a higher percentage of uninsured children was associated with decreased odds of receipt of early intervention services, decreased odds of receipt of professional care coordination, and increased odds of delayed or missed care. Parents in states with higher per capita Medicaid expenditures on children were more likely to report receipt of special education services. Only two state capacity measures were associated explicitly with Title V: states with higher generalist physician to population ratios were associated with a greater likelihood of parent report of having heard of Title V and states with higher per capita gross state product were less likely to be associated with a report of using Title V services, conditional on having heard of Title V. The state level measure of family participation in Title V governance was negatively associated with receipt of care coordination and having used Title V services. The measures of state economic, political, health systems, and Title V capacity that we have analyzed are only weakly associated with the well-being of children with special health care needs. If Congress and other policymakers increase the expectations of the states in assuring that the needs of CSHCN and their families are addressed, it is essential to be cognizant of the capacities of the states to undertake that role.

2020: a veterinary year in review.

Covid-19 may have dominated 2020 but, as Kathryn Clark reflects, it was not the only thing that happened last year.

Interaction Time with Electronic Health Records: A Systematic Review.

BACKGROUND: The amount of time that health care clinicians (physicians and nurses) spend interacting with the electronic health record is not well understood. OBJECTIVE: This study aimed to evaluate the time that health care providers spend interacting with electronic health records (EHR). METHODS: Data are retrieved from Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, (Ovid) Embase, CINAHL, and SCOPUS. STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies that describe the use of EHR and include measurement of time either in hours, minutes, or in the percentage of a clinician's workday. Papers were written in English and published between 1990 and 2021. PARTICIPANTS: All physicians and nurses involved in inpatient and outpatient settings. STUDY APPRAISAL AND SYNTHESIS METHODS: A narrative synthesis of the results, providing summaries of interaction time with EHR. The studies were rated according to Quality Assessment Tool for Studies with Diverse Designs. RESULTS: Out of 5,133 de-duplicated references identified through database searching, 18 met inclusion criteria. Most were time-motion studies (50%) that followed by logged-based analysis (44%). Most were conducted in the United States (94%) and examined a clinician workflow in the inpatient settings (83%). The average time was nearly 37% of time of their workday by physicians in both inpatient and outpatient settings and 22% of the workday by nurses in inpatient settings. The studies showed methodological heterogeneity. CONCLUSION: This systematic review evaluates the time that health care providers spend interacting with EHR. Interaction time with EHR varies depending on clinicians' roles and clinical settings, computer systems, and users' experience. The average time spent by physicians on EHR exceeded one-third of their workday. The finding is a possible indicator that the EHR has room for usability, functionality improvement, and workflow optimization.

Outcomes for Implemented Macroeconomic Policy Responses and Multilateral Collaboration Strategies for Economic Recovery After a Crisis: A Rapid Scoping Review.

To promote postpandemic recovery, many countries have adopted economic packages that include fiscal, monetary, and financial policy measures; however, the effects of these policies may not be known for several years or more. There is an opportunity for decision makers to learn from past policies that facilitated recovery from other disease outbreaks, crises, and natural disasters that have had a devastating effect on economies around the world. To support the development of the United Nations Research Roadmap for COVID-19 Recovery, this review examined and synthesized peer-reviewed studies and gray literature that focused on macroeconomic policy responses and multilateral coalition strategies from past pandemics and crises to provide a map of the existing evidence. We conducted a systematic search of academic and gray literature databases. After screening, we found 22 records that were eligible for this review. The evidence found demonstrates that macroeconomic and multilateral coalition strategies have various impacts on a diverse set of countries and populations. Although the studies were heterogeneous in nature, most did find positive results for macroeconomic intervention policies that addressed investments to strengthen health and social protection systems, specifically cash and unconventional/nonstandard monetary measures, in-kind transfers, social security financing, and measures geared toward certain population groups.

Mammographic Surveillance in Older Women With Breast Cancer in Canada and the United States: Are We Choosing Wisely?

PURPOSE: Guidelines on mammographic surveillance after breast cancer treatment have been disseminated internationally and incorporated into Choosing Wisely recommendations to reduce low-value care. However, adherence within different countries before their publication is unknown. METHODS AND MATERIALS: Low-value mammography, defined as "short-interval" (within 6 months of radiation) or "high-frequency" (>1 within 12 months of radiation), was compared in Medicare fee-for-service in the United States and Ontario, Canada. Women ≥65 years diagnosed with breast cancer who underwent breast-conserving therapy with a minimum of 24 months of follow-up were included (n = 19,715 United States; 6479 Ontario). Secondary outcomes were patient and physician characteristics associated with discordance. RESULTS: Short-interval mammography was higher in the United States than in Ontario (55.9% vs 38.0%, P < .001), as was high-frequency (39.6% vs 7.9%, P < .001). In Ontario, younger age (42% ≥85 vs 58% <74 years, P < .001) and chemotherapy (69% vs 51%, P < .001) were associated with short-interval mammography; in the United States, age, earlier diagnosis year, stage, chemotherapy, rurality, and academic center treatment were associated with greater use. Chemotherapy was associated with high-frequency mammography in both countries (13% vs 7% in Ontario, P < .001; 69% vs 51% in United States, P = .02); younger age, earlier diagnosis year, stage, and nonacademic center treatment were associated in the United States. In both countries, radiation oncologists had the highest proportion of providers ordering low-value mammograms. CONCLUSIONS: Despite significant evidence guiding surveillance mammography recommendations, there are high rates of short-interval mammography in both the United States and Ontario, and high rates of high-frequency mammography in the United States. Further international efforts, such as Choosing Wisely, are needed to reduce low-value mammography.

Mortality in patients with cardiogenic shock supported with VA ECMO: A systematic review and meta-analysis evaluating the impact of etiology on 29,289 patients.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is associated with variable outcomes. In this meta-analysis, we evaluated the mortality after VA ECMO across multiple etiologies of cardiogenic shock (CS). METHODS: In June 2019, we performed a systematic search selecting observational studies with ≥10 adult patients reporting on short-term mortality (30-day or mortality at discharge) after initiation of VA ECMO by CS etiology published after 2009. We performed meta-analyses using random effect models and used metaregression to evaluate mortality across CS etiology. RESULTS: We included 306 studies (29,289 patients): 25 studies on after heart transplantation (HTx) (771 patients), 13 on myocarditis (906 patients), 33 on decompensated heart failure (HF) (3,567 patients), 64 on after cardiotomy shock (8,231 patients), 10 on pulmonary embolism (PE) (221 patients), 80 on acute myocardial infarction (AMI) (7,774 patients), and 113 on after cardiac arrest [CA] (7,814 patients). With moderate certainty on effect estimates, we observed significantly different mortality estimates for various etiologies (p < 0.001), which is not explained by differences in age and sex across studies: 35% (95% CI: 29-42) for after HTx, 40% (95% CI: 33-46) for myocarditis, 53% (95% CI: 46-59) for HF, 52% (95% CI: 38-66) for PE, 59% (95% CI: 56-63) for cardiotomy, 60% (95% CI: 57-64) for AMI, 64% (95% CI: 59-69) for post‒in-hospital CA, and 76% (95% CI: 69-82) for post-out‒of-hospital CA. Univariable metaregression showed that variation in mortality estimates within etiology group was partially explained by population age, proportion of females, left ventricle venting, and CA. CONCLUSIONS: Using an overall estimate of mortality for patients with CS requiring VA ECMO is inadequate given the differential outcomes by etiology. To further refine patient selection and management to improve outcomes, additional studies evaluating patient characteristics impacting outcomes by specific CS etiology are needed.