Advocate Health Care

In 2008, Donald Berwick and colleagues provided a framework for the delivery of high value care in the USA, the Triple Aim, that is centred around three overarching goals: improving the individual experience of care; improving the health of populations; and reducing the per capita cost of healthcare.1 The intent is that the Triple Aim will guide the redesign of healthcare systems and the transition to population health. Health systems globally grapple with these challenges of improving the health of populations while simultaneously lowering healthcare costs. As a result, the Triple Aim, although originally conceived within the USA, has been adopted as a set of principles for health system reform within many organisations around the world. The successful achievement of the Triple Aim requires highly effective healthcare organisations. The backbone of any effective healthcare system is an engaged and productive workforce.2 But the Triple Aim does not explicitly acknowledge the critical role of the workforce in healthcare transformation. We propose a modification of the Triple Aim to acknowledge the importance of physicians, nurses and all employees finding joy and meaning in their work. This ‘Quadruple Aim’ would add a fourth aim: improving the experience of providing care. The core of workforce engagement is the experience of joy and meaning in the work of healthcare. This is not synonymous with happiness, rather that all members of the workforce have a sense of accomplishment and meaning in their contributions. By meaning, we refer to the sense of importance of daily work. By joy, we refer to the feeling of success and fulfilment that results from meaningful work. In the UK, the National Health Service has captured this with the notion of an engaged staff that ‘think and act in a positive way about the work they do, the people they …

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

OBJECTIVE: To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD). DESIGN: Prospective cohort study. SETTING: 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). PARTICIPANTS: 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. MAIN OUTCOME MEASURES: The main outcome was development of IBD, including Crohn's disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. RESULTS: Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn's disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn's disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD. CONCLUSIONS: Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods. STUDY REGISTRATION: ClinicalTrials.gov NCT03225586.

BACKGROUND: Low health literacy affects millions of Americans, putting those who are affected at a disadvantage and at risk for poorer health outcomes. Low health literacy can act as a barrier to effective disease self-management; this is especially true for chronic diseases such as heart failure (HF) that require complicated self-care regimens. PURPOSE: This systematic review examined quantitative research literature published between 1999 and 2014 to explore the role of health literacy among HF patients. The specific aims of the systematic review are to (1) describe the prevalence of low health literacy among HF patients, (2) explore the predictors of low health literacy among HF patients, and (3) discuss the relationship between health literacy and HF self-care and common HF outcomes. METHODS: A systematic search of the following databases was conducted, PubMed, CINAHL Plus, Embase, PsycINFO, and Scopus, using relevant keywords and clear inclusion and exclusion criteria. CONCLUSIONS: An average of 39% of HF patients have low health literacy. Age, race/ethnicity, years of education, and cognitive function are predictors of health literacy. In addition, adequate health literacy is consistently correlated with higher HF knowledge and higher salt knowledge. CLINICAL IMPLICATIONS: Considering the prevalence of low health literacy among in the HF population, nurses and healthcare professionals need to recognize the consequences of low health literacy and adopt strategies that could minimize its detrimental effect on the patient's health outcomes.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non-muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non-muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody-drug conjugates for metastatic bladder cancer.

Importance: Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live. Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas. Design, Setting, and Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019. Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview. Main Outcomes and Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality. Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001). Conclusions and Relevance: In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide.

OBJECTIVES: For some people, diagnosis with a serious illness or other adverse life events can precipitate a period of religious struggle. While evidence of the harmful effects of religious struggle is accumulating, less is known about its prevalence or correlates. The aim of this study was to examine the prevalence and correlates of religious struggle in three groups of medical patients. METHODS: Study participants included diabetic outpatients (N= 71), congestive heart failure outpatients (N = 70), and oncology inpatients (N = 97). Participants completed questionnaires which included several measures of religion, including religious struggle, emotional distress or well-being, and demographic characteristics. RESULTS: Half of the total sample (52%) reported no religious struggle, while 15% reported moderate or high levels. In a multi-variate analysis, younger patients (p < 0.001) and CHF patients (p < 0.05) had higher levels of religious struggle. Those with higher levels of positive religious coping also reported higher levels of religious struggle (p < 0.01), while those who attended worship most frequently had lower levels of religious struggle (p < 0.05). Religious struggle was associated with higher levels of depressive symptoms and emotional distress in all three patient groups. CONCLUSIONS: While further research is needed to help clarify the sources, additional correlates, and course of religious struggle, the findings in this study confirm the association between religious struggle and emotional distress in these three groups of medical patients. Clinicians should be attentive to signs of religious struggle. Where patient's responses indicate possible religious struggle, clinicians should consider referral to a trained, professional chaplain or pastoral counselor.

A concerted commitment across research stakeholders is necessary to increase equity, diversity, and inclusion (EDI) and address barriers to cancer clinical trial recruitment and participation. Racial and ethnic diversity among trial participants is key to understanding intrinsic and extrinsic factors that may affect patient response to cancer treatments. This ASCO and Association of Community Cancer Centers (ACCC) Research Statement presents specific recommendations and strategies for the research community to improve EDI in cancer clinical trials. There are six overarching recommendations: (1) clinical trials are an integral component of high-quality cancer care, and every person with cancer should have the opportunity to participate; (2) trial sponsors and investigators should design and implement trials with a focus on reducing barriers and enhancing EDI, and work with sites to conduct trials in ways that increase participation of under-represented populations; (3) trial sponsors, researchers, and sites should form long-standing partnerships with patients, patient advocacy groups, and community leaders and groups; (4) anyone designing or conducting trials should complete recurring education, training, and evaluation to demonstrate and maintain cross-cultural competencies, mitigation of bias, effective communication, and a commitment to achieving EDI; (5) research stakeholders should invest in programs and policies that increase EDI in trials and in the research workforce; and (6) research stakeholders should collect and publish aggregate data on racial and ethnic diversity of trial participants when reporting results of trials, programs, and interventions to increase EDI. The recommendations are intended to serve as a guide for the research community to improve participation rates among people from racial and ethnic minority populations historically under-represented in cancer clinical trials. ASCO and ACCC will work at all levels to advance the recommendations in this publication.

BACKGROUND: Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population. METHODS: This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause. RESULTS: In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease. CONCLUSIONS: In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death. (Funded by the Population Health Research Institute and others.).

PURPOSE: Combination of antiprogrammed cell death protein-1 (PD-1) plus anti-cytotoxic T-cell lymphocyte-4 (anti-CTLA-4) immunotherapy shows greater response rates (RRs) than anti-PD-1 antibody alone in melanoma, but RR after initial anti-PD-1 and programmed death ligand-1 (PD-L1) antibody progression awaits robust investigation. Anti-CTLA-4 antibody alone after anti-PD-1/L1 antibody progression has a historical RR of 13%. We report the results of the first prospective clinical trial evaluating ipilimumab 1 mg/kg plus pembrolizumab following progression on anti-PD-1 immunotherapy. METHODS: Patients with advanced melanoma who had progressed on anti-PD-1/L1 antibody as immediate prior therapy (including non-anti-CTLA-4 antibody combinations) were eligible. Patients received pembrolizumab 200 mg plus ipilimumab 1 mg/kg once every 3 weeks for four doses, followed by pembrolizumab monotherapy. The primary end point was RR by irRECIST. After 35 patients, the trial met the primary end point and was expanded to enroll a total of 70 patients to better estimate the RR. RESULTS: Prior treatments included 60 on anti-PD-1 antibody alone and 10 on anti-PD-1/L1 antibody-based combinations. Thirteen patients had progressed in the adjuvant setting. The median length of prior treatment with anti-PD-1/L1 antibody was 4.8 months. Response assessments included five complete and 15 partial responses, making the irRECIST RR 29% among the entire trial population. The median progression-free survival was 5.0 months, and the median overall survival was 24.7 months. The median duration of response was 16.6 months. There was no difference in median time on prior anti-PD1/L1 or time to PD1 + CTLA4 initiation between responders and nonresponders. Grade 3-4 drug-related adverse events occurred in 27% of patients. Responses occurred in PD-L1-negative, non-T-cell-inflamed, and intermediate tumor phenotypes. CONCLUSION: To our knowledge, this is the first prospective study in melanoma of pembrolizumab plus low-dose ipilimumab after anti-PD-1/L1 immunotherapy failure, demonstrating significant antitumor activity and tolerability.

. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

OBJECTIVE: The authors sought to evaluate 2 approaches with varying time and complexity in engaging adolescents with an Internet-based preventive intervention for depression in primary care. The authors conducted a randomized controlled trial comparing primary care physician motivational interview (MI, 5-10 minutes) + Internet program versus brief advice (BA, 1-2 minutes) + Internet program. SETTING: Adolescent primary care patients in the United States, aged 14 to 21 years. PARTICIPANTS: Eighty-four individuals (40% non-white) at increased risk for depressive disorders (subthreshold depressed mood >3-4 weeks) were randomly assigned to either the MI group (n = 43) or the BA group (n = 40). MAIN OUTCOME MEASURES: Patient Health Questionnaire-Adolescent and Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: Both groups substantially engaged the Internet site (MI, 90.7% vs BA 77.5%). For both groups, CES-D-10 scores declined (MI, 24.0 to 17.0, p < .001; BA, 25.2 to 15.5, p < .001). The percentage of those with clinically significant depression symptoms based on CES-D-10 scores declined in both groups from baseline to 12 weeks, (MI, 52% to 12%, p < .001; BA, 50% to 15%, p < .001). The MI group demonstrated declines in self-harm thoughts and hopelessness and was significantly less likely than the BA group to experience a depressive episode (4.65% vs 22.5%, p = .023) or to report hopelessness (MI group of 2% vs 15% for the BA group, p = .044) by 12 weeks. CONCLUSIONS: An Internet-based prevention program in primary care is associated with declines in depressed mood and the likelihood of having clinical depression symptom levels in both groups. Motivational interviewing in combination with an Internet behavior change program may reduce the likelihood of experiencing a depressive episode and hopelessness.

BackgroundMost studies of long-term exposure to outdoor fine particulate matter (PM2·5) and cardiovascular disease are from high-income countries with relatively low PM2·5 concentrations. It is unclear whether risks are similar in low-income and middle-income countries (LMICs) and how outdoor PM2·5 contributes to the global burden of cardiovascular disease. In our analysis of the Prospective Urban and Rural Epidemiology (PURE) study, we aimed to investigate the association between long-term exposure to PM2·5 concentrations and cardiovascular disease in a large cohort of adults from 21 high-income, middle-income, and low-income countries.MethodsIn this multinational, prospective cohort study, we studied 157 436 adults aged 35–70 years who were enrolled in the PURE study in countries with ambient PM2·5 estimates, for whom follow-up data were available. Cox proportional hazard frailty models were used to estimate the associations between long-term mean community outdoor PM2·5 concentrations and cardiovascular disease events (fatal and non-fatal), cardiovascular disease mortality, and other non-accidental mortality.FindingsBetween Jan 1, 2003, and July 14, 2018, 157 436 adults from 747 communities in 21 high-income, middle-income, and low-income countries were enrolled and followed up, of whom 140 020 participants resided in LMICs. During a median follow-up period of 9·3 years (IQR 7·8–10·8; corresponding to 1·4 million person-years), we documented 9996 non-accidental deaths, of which 3219 were attributed to cardiovascular disease. 9152 (5·8%) of 157 436 participants had cardiovascular disease events (fatal and non-fatal incident cardiovascular disease), including 4083 myocardial infarctions and 4139 strokes. Mean 3-year PM2·5 at cohort baseline was 47·5 μg/m3 (range 6–140). In models adjusted for individual, household, and geographical factors, a 10 μg/m3 increase in PM2·5 was associated with increased risk for cardiovascular disease events (hazard ratio 1·05 [95% CI 1·03–1·07]), myocardial infarction (1·03 [1·00–1·05]), stroke (1·07 [1·04–1·10]), and cardiovascular disease mortality (1·03 [1·00–1·05]). Results were similar for LMICs and communities with high PM2·5 concentrations (>35 μg/m3). The population attributable fraction for PM2·5 in the PURE cohort was 13·9% (95% CI 8·8–18·6) for cardiovascular disease events, 8·4% (0·0–15·4) for myocardial infarction, 19·6% (13·0–25·8) for stroke, and 8·3% (0·0–15·2) for cardiovascular disease mortality. We identified no consistent associations between PM2·5 and risk for non-cardiovascular disease deaths.InterpretationLong-term outdoor PM2·5 concentrations were associated with increased risks of cardiovascular disease in adults aged 35–70 years. Air pollution is an important global risk factor for cardiovascular disease and a need exists to reduce air pollution concentrations, especially in LMICs, where air pollution levels are highest.FundingFull funding sources are listed at the end of the paper (see Acknowledgments).

Importance: Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients. Objective: To develop an evidence-based clinical practice guideline for adults with Down syndrome. Evidence Review: The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence. Findings: From 11 295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome. Conclusions and Relevance: These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.

BACKGROUND: Although several models of evidence-based practice (EBP) exist, there is a paucity of studies that have been conducted to evaluate their implementation in healthcare settings. AIM: The purpose of this study was to examine the impact of the Advancing Research and Clinical practice through close Collaboration (ARCC) Model on organizational culture, clinicians' EBP beliefs and EBP implementation, and patient outcomes at one healthcare system in the western United States. DESIGN: A pre-test, post-test longitudinal pre-experimental study was conducted with follow-up immediately following full implementation of the ARCC Model. SETTING AND SAMPLE: The study was conducted at a 341-bed acute care hospital in the western region of the United States. The sample consisted of 58 interprofessional healthcare professionals. METHODS: The ARCC Model was implemented in a sequential format over 12 months with the key strategy of preparing a critical mass of EBP mentors for the healthcare system. Healthcare professionals' EBP beliefs, EBP implementation, and organizational culture were measured with valid and reliable instruments. Patient outcomes were collected in aggregate from the hospital's medical records. RESULTS: Findings indicated significant increases in clinicians' EBP beliefs and EBP implementation along with positive movement toward an organizational EBP culture. Study findings also indicated substantial improvements in several patient outcomes. LINKING EVIDENCE TO ACTION: Implementation of the ARCC Model in healthcare systems can enhance clinicians' beliefs and implementation of evidence-based care, improve patient outcomes, and move organizational culture toward EBP.

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. The United States Preventive Service Task Force (USPSTF) has developed criteria for prioritizing conditions of public health importance with the potential for providing screening recommendations to improve clinical care. The quality of existing evidence needed to inform clinical guidelines has not been previously reviewed. Using the National Library of Medicine (NLM) database PubMed, we first identified 18 peer reviewed articles that addressed co-occurring medical conditions in adults with DS. Those conditions discussed in over half of the articles were prioritized for further review. Second, we performed detailed literature searches on these specific conditions. To inform the search strategy and review process a series of key questions were formulated a priori. The quality of available evidence was then graded and knowledge gaps were identified. The number of participating adults and the design of clinical studies varied by condition and were often inadequate for answering all of our key questions. We provide data on thyroid disease, cervical spine disease, hearing impairment, overweight-obesity, sleep apnea, congenital heart disease, and osteopenia-osteoporosis. Minimal evidence demonstrates massive gaps in our clinical knowledge that compromises clinical decision-making and management of these medically complex individuals. The development of evidence-based clinical guidance will require an expanded clinical knowledge-base in order to move forward.

PURPOSE: To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS: The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited. RECOMMENDATIONS: ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to < 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines.

OBJECTIVE: To determine whether hip fracture patients, a group at very high risk for additional fragility fractures, are being evaluated and treated effectively for osteoporosis. METHODS: Clinical and bone densitometry (dual x-ray absorptiometry [DXA]) records were reviewed in hip fracture patients at 4 Midwestern US health systems to determine the frequency of DXA use, calcium and vitamin D supplementation, and antiresorptive drug treatment. RESULTS: DXA was performed at the 4 study sites in only 12%, 12%, 13%, and 24% of patients, respectively. Calcium and vitamin D supplements were prescribed in 27%, 1%, 3%, and 25% of the patients at the 4 study sites. Antiresorptive drugs were prescribed in 26%, 12%, 7%, and 37% of the patients with only 2-10% receiving a bisphosphonate. CONCLUSION: Reducing osteoporotic fractures will require more effective approaches to managing hip fracture patients and other high-risk populations.

Although there is a large body of research on mild traumatic brain injury (MTBI), the portion that pertains to acute patients (those less than 1 month postinjury) is relatively small and yields inconsistent findings. The potential contribution of non-neurological factors, such as pain and emotional distress, to the clinical picture in this population is also lacking. To address these issues, the cognitive performance and symptom complaints of 37 hospitalized MTBI subjects were compared to those of 39 hospitalized trauma subjects, averaging 4.5 days postinjury. MTBI subjects performed significantly worse on all cognitive measures, but did not differ from trauma subjects in their report of postconcussive symptoms. Analyses also revealed that cognitive performance was unrelated to pain severity and emotional distress. Postconcussive symptoms were similarly unrelated to pain severity, but were consistently related to emotional distress. Results are discussed in terms of their etiological and treatment implications.

// Heather E. Leeper 1 , Alissa A. Caron 2 , Paul A. Decker 3 , Robert B. Jenkins 5 , Daniel H. Lachance 4 , Caterina Giannini 5 1 Neuro-Oncology, Advocate Medical Group, Park Ridge, IL 60068, USA 2 Experimental Pathology, Mayo Clinic SW, Rochester, MN 55905, USA 3 Biomedical Statistics and Informatics, Mayo Clinic SW, Rochester, MN 55905, USA 4 Neurology, Mayo Clinic SW, Rochester, MN 55905, USA 5 Anatomic Pathology, Mayo Clinic SW, Rochester, MN 55905, USA Correspondence to: Caterina Giannini, e-mail: giannini.caterina@mayo.edu Keywords: diffuse gliomas, WHO grade II, IDH mutation, ATRX, 1p19q codeletion Received: March 12, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: June 22, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: July 03, 2015 ABSTRACT Background: Epigenetic, genetic, and molecular studies have identified several diagnostic and prognostic markers in diffuse gliomas. Their importance for evaluating WHO grade II gliomas has yet to be specifically delineated. Methods: We analyzed markers, including IDH mutation(IDHmut), 1p19q codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression, and outcomes in 159 patients with WHO grade II oligodendroglioma, oligoastrocytoma, and astrocytoma (2003&ndash;2012). Results: IDHmut was found in 141(91%) and ATRX loss in 64(87%) of IDHmut-noncodel tumors ( p = 0.003). All codeleted tumors ( n = 66) were IDHmut. Four subgroups were identified: IDHmut-codel, 66(43%); IDHmut-noncodel-ATRX loss, 60(39%); IDHmut-noncodel-ATRXwt, 9(6%); IDHwt, 14(9%). Median survival among 4 groups was significantly different ( p = 0.038), particularly in IDHmut-codel (median survival 15.6 years) compared to the remaining 3 groups ( p = 0.025). Survival by histology was not significant. Overall (OS), but not progression-free (PFS), survival was significantly longer with gross total resection vs. biopsy only ( p = 0.042). Outcomes for patients with subtotal resection were not significantly different from those with biopsy only. Among these uniformly treated patients, OS far exceeds PFS, particularly in those with 1p/19q codeletion. Conclusions: For WHO grade II diffuse glioma, molecular classification using 1p/19qcodel, IDHmut, and ATRX loss more accurately predicts outcome and should be incorporated in the neuropathologic evaluation.