Cost-Effectiveness of Screening Mammography Beyond Age 75 Years : A Cost-Effectiveness Analysis.

BACKGROUND: The cost-effectiveness of screening mammography beyond age 75 years remains unclear. OBJECTIVE: To estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden. DESIGN: Markov microsimulation model. DATA SOURCES: SEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium. TARGET POPULATION: U.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS). TIME HORIZON: Lifetime. PERSPECTIVE: National health payer. INTERVENTION: Screening mammography to age 75, 80, 85, or 90 years. OUTCOME MEASURES: Breast cancer death, survival, and costs. RESULTS OF BASE-CASE ANALYSIS: Extending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer. RESULTS OF SENSITIVITY ANALYSIS: Costs per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography. LIMITATION: No randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs. CONCLUSION: Although annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer. PRIMARY FUNDING SOURCE: National Cancer Institute and National Institutes of Health.

Mammography adherence in relation to function-related indicators in older women.

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999-2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66-74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9-30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66-70 vs. 71-74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend < 0.01). Similarly, a higher FRI score was associated with longitudinal non-adherence (FRI ≥ 2 vs. 0: aHR = 1.16, 95% CI = 1.11, 1.22, p-trend < 0.01). Effect measures of FRI did not differ substantially by age categories. Older women with a higher burden of functional limitations are less likely to be adherent to screening mammography recommendations.

Response to Toshihide Tsuda, Yumiko Miyano and Eiji Yamamoto [1].

BACKGROUND: In August 2021, we published in Environmental Health a Toolkit for detecting misused epidemiological methods with the goal of providing an organizational framework for transparently evaluating epidemiological studies, a body of evidence, and resultant conclusions. Tsuda et al., the first group to utilize the Toolkit in a systematic fashion, have offered suggestions for its modification. MAIN BODY: Among the suggested modifications made by Tsuda et al., we agree that rearrangement of Part A of the Toolkit to reflect the sequence of the epidemiological study process would facilitate its usefulness. Expansion or adaptation of the Toolkit to other disciplines would be valuable but would require the input of discipline-specific expertise. We caution against using the sections of the Toolkit to produce a tally or cumulative score, because none of the items are weighted as to importance or impact. Rather, we suggest a visual representation of how a study meets the Toolkit items, such as the heat maps used to present risk of bias criteria for studies included in Cochrane reviews. We suggest that the Toolkit be incorporated in the sub-specialty known as "forensic epidemiology," as well as in graduate training curricula, continuing education programs, and conferences, with the recognition that it is an extension of widely accepted ethics guidelines for epidemiological research. CONCLUSION: We welcome feedback from the research community about ways to strengthen the Toolkit as it is applied to a broader assemblage of research studies and disciplines, contributing to its value as a living tool/instrument. The application of the Toolkit by Tsuda et al. exemplifies the usefulness of this framework for transparently evaluating, in a systematic way, epidemiological research, conclusions relating to causation, and policy decisions. POSTSCRIPT: We note that our Toolkit has, most recently, inspired authors with discipline-specific expertise in the field of Conservation Biology to adapt it for use in the Biological Sciences.

Advances in microfabrication technologies in tissue engineering and regenerative medicine.

BACKGROUND: Tissue engineering provides various strategies to fabricate an appropriate microenvironment to support the repair and regeneration of lost or damaged tissues. In this matter, several technologies have been implemented to construct close-to-native three-dimensional structures at numerous physiological scales, which are essential to confer the functional characteristics of living tissues. METHODS: In this article, we review a variety of microfabrication technologies that are currently utilized for several tissue engineering applications, such as soft lithography, microneedles, templated and self-assembly of microstructures, microfluidics, fiber spinning, and bioprinting. RESULTS: These technologies have considerably helped us to precisely manipulate cells or cellular constructs for the fabrication of biomimetic tissues and organs. Although currently available tissues still lack some crucial functionalities, including vascular networks, innervation, and lymphatic system, microfabrication strategies are being proposed to overcome these issues. Moreover, the microfabrication techniques that have progressed to the preclinical stage are also discussed. CONCLUSIONS: This article aims to highlight the advantages and drawbacks of each technique and areas of further research for a more comprehensive and evolving understanding of microfabrication techniques in terms of tissue engineering and regenerative medicine applications.

Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence). LIMITATIONS: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies. CONCLUSION: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).

Mortality in hospitalized patients with cancer and coronavirus disease 2019: A systematic review and meta-analysis of cohort studies.

BACKGROUND: Heterogeneous evidence exists on the effect of coronavirus disease 2019 (COVID-19) on the clinical outcomes of patients with cancer. METHODS: A systematic review was performed using the Medline, Embase, and CENTRAL databases and the World Health Organization Novel Coronavirus website to identify studies that reported mortality and characteristics of patients with cancer who were diagnosed with COVID-19. The primary study outcome was mortality, defined as all-cause mortality or in-hospital mortality within 30 days of initial COVID-19 diagnosis. The pooled proportion of mortality was estimated using a random-effects model, and study-level moderators of heterogeneity were assessed through subgroup analysis and metaregression. RESULTS: Among 2922 patients from 13 primarily inpatient studies of individuals with COVID-19 and cancer, the pooled 30-day mortality rate was 30% (95% CI, 25%-35%). The overall pooled 30-day mortality rate among 624 patients from 5 studies that included a mixture of inpatient and outpatient populations was 15% (95% CI, 9%-22%). Among the hospitalized studies, the heterogeneity (I2 statistic) of the meta-analysis remained high (I2 , 82%). Cancer subtype (hematologic vs solid), older age, male sex, and recent active cancer therapy each partially explained the heterogeneity of mortality reporting. In multivariable metaregression, male sex, along with an interaction between the median patient age and recent active cancer therapy, explained most of the between-study heterogeneity (R2 , 96%). CONCLUSIONS: Pooled mortality estimates for hospitalized patients with cancer and COVID-19 remain high at 30%, with significant heterogeneity across studies. Dedicated community-based studies are needed in the future to help assess overall COVID-19 mortality among the broader population of patients with cancer.

Disparities in H1N1 Vaccination Rates: a Systematic Review and Evidence Synthesis to Inform COVID-19 Vaccination Efforts.

BACKGROUND: Data suggest that there were disparities in H1N1 vaccine uptake, and these may inform COVID-19 vaccination efforts. We conducted a systematic review to evaluate disparities in H1N1 vaccine uptake, factors contributing to disparities, and interventions to reduce them. METHODS: We searched English-language articles in MEDLINE ALL, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from database inception through May 8, 2020. Observational studies examining H1N1 vaccine uptake by race/ethnicity, socioeconomic status, rurality, and disability status in US settings were included. Two reviewers independently assessed study eligibility. Single-reviewer data abstraction was confirmed by a second reviewer. We conducted independent dual quality assessment, and collective strength of evidence assessment. RESULTS: We included 21 studies. African American/Black, Latino, and low-socioeconomic status participants had disproportionately lower H1N1 vaccination rates (low- to moderate-strength evidence). However, Latinos were more likely than Whites to intend to be vaccinated, and African American/Blacks and participants with lower-socioeconomic status were just as likely to intend to be vaccinated as their White and higher-socioeconomic status counterparts (low-strength evidence). Vaccine uptake for other groups has been insufficiently studied. Factors potentially contributing to disparities in vaccine uptake included barriers to vaccine access, inadequate information, and concerns about vaccine safety and efficacy. Studies were largely cross-sectional. Many of the studies are a decade old and were conducted in the context of a different pandemic. The categorization of racial and ethnic groups was not consistent across studies and not all groups were well-studied. DISCUSSION: Efforts to avoid disparities in COVID-19 vaccination uptake should prioritize vaccine accessibility and convenience in African American/Black, Latino, and low-SES communities; engage trusted stakeholders to share vaccine information; and address concerns about vaccine safety and efficacy. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. PROTOCOL REGISTRATION: PROSPERO CRD42020187078.

Toolkit for detecting misused epidemiological methods.

BACKGROUND: Critical knowledge of what we know about health and disease, risk factors, causation, prevention, and treatment, derives from epidemiology. Unfortunately, its methods and language can be misused and improperly applied. A repertoire of methods, techniques, arguments, and tactics are used by some people to manipulate science, usually in the service of powerful interests, and particularly those with a financial stake related to toxic agents. Such interests work to foment uncertainty, cast doubt, and mislead decision makers by seeding confusion about cause-and-effect relating to population health. We have compiled a toolkit of the methods used by those whose interests are not aligned with the public health sciences. Professional epidemiologists, as well as those who rely on their work, will thereby be more readily equipped to detect bias and flaws resulting from financial conflict-of-interest, improper study design, data collection, analysis, or interpretation, bringing greater clarity-not only to the advancement of knowledge, but, more immediately, to policy debates. METHODS: The summary of techniques used to manipulate epidemiological findings, compiled as part of the 2020 Position Statement of the International Network for Epidemiology in Policy (INEP) entitled Conflict-of-Interest and Disclosure in Epidemiology, has been expanded and further elucidated in this commentary. RESULTS: Some level of uncertainty is inherent in science. However, corrupted and incomplete literature contributes to confuse, foment further uncertainty, and cast doubt about the evidence under consideration. Confusion delays scientific advancement and leads to the inability of policymakers to make changes that, if enacted, would-supported by the body of valid evidence-protect, maintain, and improve public health. An accessible toolkit is provided that brings attention to the misuse of the methods of epidemiology. Its usefulness is as a compendium of what those trained in epidemiology, as well as those reviewing epidemiological studies, should identify methodologically when assessing the transparency and validity of any epidemiological inquiry, evaluation, or argument. The problems resulting from financial conflicting interests and the misuse of scientific methods, in conjunction with the strategies that can be used to safeguard public health against them, apply not only to epidemiologists, but also to other public health professionals. CONCLUSIONS: This novel toolkit is for use in protecting the public. It is provided to assist public health professionals as gatekeepers of their respective specialty and subspecialty disciplines whose mission includes protecting, maintaining, and improving the public's health. It is intended to serve our roles as educators, reviewers, and researchers.

Frailty as a mortality predictor in older adults with COVID-19: A systematic review and meta-analysis of cohort studies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the coronavirus diseases 2019 (COVID-19) pandemic, continues to spread rapidly worldwide and is associated with high rates of mortality among older adults, those with comorbidities, and those in poor physiological states. This paper aimed to systematically identify the impact of frailty on overall mortality among older adults with COVID-19. We conducted a systematic review of the literature indexed in 4 databases. A random-effects model with inverse variance-weighted meta-analysis using the odds ratio was used to study the association of frailty levels with clinical outcomes among older adults with COVID-19. Heterogeneity was measured using the I2 statistic and Egger's test. We identified 22 studies that met our inclusion criteria, including 924,520 total patients. Overall, frailty among older adults was associated with high rates of COVID-19-related mortality compared with non-frail older adults (OR [odds ratio]:5.76; 95% confidence interval [95% CI]: 3.85-8.61, I2: 40.5%). Our results show that physical limitations, such as those associated with frailty among older adults, are associated with higher rates of COVID-19-related mortality.

Trends and Patterns of Testosterone Therapy among U.S. Male Medicare Beneficiaries, 1999 to 2014.

PURPOSE: We explored the Medicare database (1999 to 2014) to provide a comprehensive assessment of testosterone therapy patterns in the older U.S. male population. MATERIALS AND METHODS: We estimated annual age-standardized incidence (new users) and prevalence (existing users) of testosterone therapy according to demographic characteristics, comorbidities and potential indications. RESULTS: There were 392,698 incident testosterone therapy users during 88 million person-years. Testosterone therapy users were predominantly younger, white nonHispanic, and located in South and West U.S. Census regions. On average testosterone therapy use increased dramatically during 2007 to 2014 (average annual percent change 15.5%), despite a decrease in 2014. In 2014 the most common recorded potential indications for any testosterone therapy were hypogonadism (48%), fatigue (18%), erectile dysfunction (15%), depression (4%) and psychosexual dysfunction (1%). Laboratory tests to measure circulating testosterone concentrations for testosterone therapy were infrequent with 35% having had at least 1 testosterone test in the 120 days preceding testosterone therapy, 4% the recommended 2 pre-testosterone therapy tests, and 16% at least 1 pre-testosterone therapy test and at least 1 post-testosterone therapy test. CONCLUSIONS: Testosterone therapy remains common in the older U.S. male population, despite a recent decrease. Although testosterone therapy prescriptions are predominantly for hypogonadism, a substantial proportion appear to be for less specific conditions. Testosterone tests among men prescribed testosterone therapy appear to be infrequent.

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

A Systematic Review of Smartphone Applications Available for Corona Virus Disease 2019 (COVID19) and the Assessment of their Quality Using the Mobile Application Rating Scale (MARS).

The global impact of COVID-19 pandemic has led to a rapid development and utilization of mobile health applications. These are addressing the unmet needs of healthcare and public health system including contact tracing, health information dissemination, symptom checking and providing tools for training healthcare providers. Here we provide an overview of mobile applications being currently utilized for COVID-19 and their assessment using the Mobile Application Rating Scale. We performed a systematic review of the literature and mobile platforms to assess mobile applications currently utilized for COVID-19, and a quality assessment of these applications using the Mobile Application Rating Scale (MARS) for overall quality, Engagement, Functionality, Aesthetics, and Information. Finally, we provide an overview of the key salient features that should be included in mobile applications being developed for future use. Our search identified 63 apps that are currently being used for COVID-19. Of these, 25 were selected from the Google play store and Apple App store in India, and 19 each from the UK and US. 18 apps were developed for sharing up to date information on COVID-19, and 8 were used for contact tracing while 9 apps showed features of both. On MARS Scale, overall scores ranged from 2.4 to 4.8 with apps scoring high in areas of functionality and lower in Engagement. Future steps should involve developing and testing of mobile applications using assessment tools like the MARS scale and the study of their impact on health behaviours and outcomes.

Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.

BACKGROUND: CpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis. METHODS: We searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques. RESULTS: The pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21-24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries. CONCLUSION: Although no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.

Ongoing and future directions in the management of metastatic colorectal cancer: Update on clinical trials.

Metastatic colorectal cancer (mCRC) continues to show poor outcomes, with many patients exhausting effective standard-of-care therapy. To explore the current landscape of clinical trials for mCRC, we reviewed over 600 clinical trials that are currently ongoing for mCRC patients. Immunotherapeutic agents form approximately 39% (includes monoclonal antibodies, viruses, vaccines, and immunomodulators) of all agents and targeted therapy forms 45% (tyrosine kinase inhibitors, epigenetic modulators, and others) of all agents being investigated for mCRC.

Caffeine intake is not associated with serum testosterone levels in adult men: cross-sectional findings from the NHANES 1999-2004 and 2011-2012.

OBJECTIVE: The association of caffeine intake with testosterone remains unclear. We evaluated the association of caffeine intake with serum testosterone among American men and determined whether this association varied by race/ethnicity and measurements of adiposity. METHODS: Data were analyzed for 2581 men (≥20 years old) who participated in the cycles of the NHANES 1999-2004 and 2011-2012, a cross-sectional study. Testosterone (ng/mL) was measured by immunoassay among men who participated in the morning examination session. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable weighted linear regression models were conducted. RESULTS: We identified no linear relationship between caffeine intake and testosterone levels in the total population, but there was a non-linear association (pnonlinearity < .01). Similarly, stratified analysis showed nonlinear associations among Mexican-American and Non-Hispanic White men (pnonlinearity ≤ .03 both) and only among men with waist circumference <102 cm and body mass index <25 kg/m2 (pnonlinearity < .01, both). CONCLUSION: No linear association was identified between levels of caffeine intake and testosterone in US men, but we observed a non-linear association, including among racial/ethnic groups and measurements of adiposity in this cross-sectional study. These associations are warranted to be investigated in larger prospective studies.

Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials.

BACKGROUND: Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients. METHODS: We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients. RESULTS: We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients. CONCLUSION: Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management.

Risk and Predictors of Variceal Bleeding in Cirrhosis Patients Receiving Primary Prophylaxis With Non-Selective Beta-Blockers.

OBJECTIVES: Prior studies have demonstrated the efficacy of non-selective beta-blockers (NSBB) in preventing first variceal bleeding in patients with cirrhosis. However, little is known about the overall effectiveness of NSBB in routine clinical care. METHODS: We conducted a retrospective cohort study of cirrhotic patients without prior bleeding who initiated a NSBB (propranolol, nadolol) at any Veterans Administration facility between 2008 and 2013. The primary outcome was variceal bleeding within 12 months. We conducted Cox-proportional hazards analyses to identify demographic, clinical, and NSBB-related (type of NSBB, mean dose, dose change, and heart rate response) factors associated with variceal bleeding. RESULTS: Of 5,775 patients, 678 (11.7%) developed variceal bleeding. Mean daily dose of NSBB was <40 mg in 58.8%, 18.1% had either upward or downward titration in NSBB dose, and 9.8% had hemodynamic response. Patients who were younger, with ascites, greater medical comorbidity, and higher MELD (Model for end-stage liver disease) scores had a higher risk of variceal bleeding. Patients on a higher daily dose (>60 vs. <40 mg, adjusted hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.51-0.81), who had either upward or downward dose titration (adjusted HR 0.69; 95% CI: 0.52-0.90 and 0.64; 95% CI 0.45-0.90, respectively), and those who achieved hemodynamic response (adjusted HR 0.75; 95% CI=0.57-1.0) had lower risk. CONCLUSIONS: Approximately 12% of patients bled while being on NSBB for primary prophylaxis. A higher NSBB dose and dose titration were protective; yet most patients did not have the NSBB dose titrated to the recommended levels. Our data highlight the need for careful monitoring of cirrhotic patients on NSBB.

Local Control Modality and Outcome for Ewing Sarcoma of the Femur: A Report From the Children's Oncology Group.

BACKGROUND: The choice of a local control (LC) modality for Ewing sarcoma (EWS) of the femur is controversial. This study aimed to determine the effect of LC modality on tumor LC and patient outcomes. METHODS: The study reviewed the treatment and outcomes for 115 patients who had EWS of the femur treated with similar chemotherapy in three cooperative group trials. Patient outcomes were analyzed according to the LC modality using the log-rank test and the cumulative incidence of local or distant failure using competing risks regression. RESULTS: The median age of the patients was 13 years. The most common tumor location was the proximal femur followed by the mid femur. For 55 patients with available data, the tumor was larger than 8 cm in 29 patients and 8 cm or smaller in 26 patients. For 84 patients (73 %), surgery only was performed, whereas 17 patients (15 %) had surgery plus radiation, and 14 patients (12 %) had radiation only. The 5-year event-free survival (EFS) rate was 65 % (95 % confidence interval [CI], 55-73 %), and the 5-year overall survival (OS) rate was 70 % (95 % CI, 61-78 %). Patient outcomes did not differ significantly according to tumor location within the femur (proximal, mid or distal) or tumor size (<8 vs ≥8 cm). The findings showed no statistically significant differences in EFS, OS, cumulative incidence of local failure, or cumulative incidence of distant failure according to LC modality (surgery, surgery plus radiation, or radiation). CONCLUSIONS: The LC modality did not significantly affect disease outcome for EWS of the femur. Further study of treatment complications and functional outcome may help to define the optimal LC modality.

A proposed staging system and stage-specific interventions for familial adenomatous polyposis.

BACKGROUND AND AIMS: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis. METHODS: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. RESULTS: The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. CONCLUSIONS: The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.