Patterns of care amongst older adults diagnosed with locally advanced esophageal cancer: A cohort study

Introduction: Since the early 2010s, neoadjuvant chemoradiation followed by esophagectomy (trimodal therapy) has been a recommended treatment for patients diagnosed with locally advanced esophageal cancer. However, it may also add treatment-related toxicity, particularly for older adults with significant comorbidity and frailty burdens. We examined contemporary patterns of care in older adults, which have not been well characterized. Materials and Methods: We used the Surveillance Epidemiology and End Results-Medicare database to identify a cohort of US adults aged 66 years and older diagnosed with incident locally advanced esophageal cancer between 2004 and 2017. Calendar year age-standardized percentages of treatment receipt were calculated. Joinpoint regression was used to detect temporal trends in treatment receipt. Descriptive associations between patient factors and treatment were assessed. Trend analyses quantified how the percentage of trimodal and definitive chemoradiation (no surgery) patients receiving cisplatin-based, carboplatin-based, and other chemotherapy regimens evolved over time. Results: In total, 4332 adults aged ≥66 years with locally advanced esophageal cancer were included. The age-standardized percentage of patients receiving trimodal therapy increased from 16.7% in 2004 to 26.1% in 2017 (annual percent change = 3.5%; 95% confidence interval [CI], 0.7%–6.4%) in adenocarcinomas and from 7.3% in 2004 to 9.1% in 2017 (annual percent change = 0.4%; 95% CI, −4.1%–5.1%) in squamous cell carcinomas. By 2017, definitive chemoradiation became the most frequently used treatment modality for adenocarcinomas (49.8%; 95% CI, 43.5–56.0) and squamous cell carcinomas (59.5%; 95% CI, 50.8–68.2). Patients with higher comorbidity and frailty burdens were less likely to be treated with trimodal therapy. Amongst patients receiving chemoradiation as part of their treatment, a large and swift channeling away from cisplatin and towards carboplatin-based regimens was observed. Discussion: In practice, definitive chemoradiation is the most commonly received treatment by older adults with locally advanced esophageal cancer. Four out of five older adults do not receive trimodal therapy, some of whom are potentially undertreated

Trimodality Therapy vs Definitive Chemoradiation in Older Adults With Locally Advanced Esophageal Cancer

Background: The comparative effectiveness of trimodality therapy vs definitive chemoradiation for treating locally advanced esophageal cancer in older adults is uncertain. Existing trials lack generalizability to older adults, a population with heightened frailty. We sought to emulate a hypothetical trial comparing these treatments using real-world data. Methods: A cohort of adults aged 66-79 years diagnosed with locally advanced esophageal cancer between 2004 and 2017 was identified in the Surveillance Epidemiology and End Results-Medicare database. The clone-censor-weight method was leveraged to eliminate time-related biases when comparing outcomes between treatments. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home. Results: A total of 1240 individuals with adenocarcinomas and 661 with squamous cell carcinomas were identified. For adenocarcinomas, the standardized 5-year risk of mortality was 73.4% for trimodality therapy and 83.8% for definitive chemoradiation (relative risk [RR] = 0.88, 95% confidence interval [CI] = 0.82 to 0.95). Trimodality therapy was associated with mortality risk reduction for squamous cell carcinomas (RR = 0.87, 95% CI = 0.70 to 1.01). The 1-year incidence of functional adverse events was higher in the trimodality group (adenocarcinomas RR = 1.40, 95% CI = 1.22 to 1.65; squamous cell carcinomas RR = 1.21, 95% CI = 1.00 to 1.49). Over 5 years, trimodality therapy was associated with 160 (95% CI = 67 to 229) and 177 (95% CI = 51 to 313) additional home days in individuals with adenocarcinomas and squamous cell carcinomas, respectively. Conclusions: Compared with definitive chemoradiation, trimodality therapy was associated with reduced mortality but increased risk of function-related adverse events. Discussing these tradeoffs may help optimize care plans

Factors influencing common diagnoses made during first-opinion small-animal consultations in the United Kingdom

It is currently unclear how frequently a diagnosis is made during small-animal consultations or how much of a role making a diagnosis plays in veterinary decision-making. Understanding more about the diagnostic process will help direct future research towards areas relevant to practicing veterinary surgeons. The aim of this study was to determine the frequency with which a diagnosis was made, classify the types of diagnosis made (and the factors influencing these) and determine which specific diagnoses were made for health problems discussed during small-animal consultations. Data were gathered during real-time direct observation of small-animal consultations in eight practices in the United Kingdom. Data collected included characteristics of the consultation (e.g. consultation type), patient (e.g. breed), and each problem discussed (e.g. new or pre-existing problem). Each problem discussed was classified into one of the following diagnosis types: definitive; working; presumed; open; previous. A three-level multivariable logistic-regression model was developed, with problem (Level 1) nested within patient (Level 2) nested within consulting veterinary surgeon (Level 3). Problems without a previous diagnosis, in cats and dogs only, were included in the model, which had a binary outcome variable of definitive diagnosis versus no definitive diagnosis. Data were recorded for 1901 animals presented, and data on diagnosis were gathered for 3192 health problems. Previous diagnoses were the most common diagnosis type (n = 1116/3192; 35.0%), followed by open (n = 868/3192; 27.2%) then definitive (n = 660/3192; 20.7%). The variables remaining in the final model were patient age, problem history, consultation type, who raised the problem, and body system affected. New problems, problems in younger animals, and problems raised by the veterinary surgeon were more likely to result in a definitive diagnosis than pre-existing problems, problems in older animals, and problems raised by the owner. The most common diagnoses made were overweight/obese and periodontal disease (both n = 210; 6.6%). Definitive diagnoses are rarely made during small-animal consultations, with much of the veterinary caseload involving management of ongoing problems or making decisions around new problems prior to a diagnosis being made. This needs to be taken into account when considering future research priorities, and it may be necessary to conduct research focused on the approach to common clinical presentations, rather than purely on the common diagnoses made. Examining how making a diagnosis affects the actions taken during the consultation may shed further light on the role of diagnosis in the clinical decision-making process

Common decisions made and actions taken during small-animal consultations at eight first-opinion practices in the United Kingdom

In order for veterinary surgeons to undertake an evidence-based approach to making decisions about theirpatients, it is important that new evidence is generated to support the clinical decision-making process.Many of the decisions are likely to be around the actions taken to treat or manage health problemsdiscussed during the consultation, and little is currently known about the factors which affect the typeof action taken. The aim of this study was to determine the decisions made and actions taken for healthproblems discussed during first-opinion small-animal consultations, as well as identifying factors whichmay affect the decision-making process.Data were gathered during direct observation of small-animal consultations conducted by 62 veterinarysurgeons in eight first-opinion practices in the United Kingdom. For each patient presented, data weregathered on all health problems discussed during the consultation. The decision made (whether an actionwas taken or not) and the action taken where applicable (e.g. therapeutic treatment with antibiotics) wasalso recorded. A three-level multivariable logistic-regression model was developed, with problem (Level1) nested within patient (Level 2) nested within consulting veterinary surgeon (Level 3), and a binaryoutcome variable of action versus no action.At least one action was taken for 69% (n = 2203/3192) of all problems discussed. Therapeutic treatmentwas the most common action taken (n = 1286/3192 problems; 40.3%), followed by management advice(n = 1040/3192; 32.6%) and diagnostic work-up (n = 323/3192; 10.1%). The most common therapeutictreatment was antibiotics (n = 386/1286; 30%), while the most common management advice given wasdietary advice (n = 509/1040; 48.9%). The three explanatory variables remaining in the final model werewhether the problem was a presenting or non-presenting problem, the type of diagnosis made, andthe body system affected. Explanatory variables which did not remain in the final model were patientsignalment, problem history, consultation type, clinical examination type, and who raised the problem(veterinary surgeon or owner).For over two-thirds of problems discussed, an action was taken which suggests these problems maybe seen as important by the veterinary surgeon and/or pet owner. No action was taken for almost a thirdof cases which could represent ‘watchful waiting’, which has been highlighted as important in humanhealthcare. Future research should focus on the common actions taken, further exploring the complexdecision-making process, and examining the effect of the decisions made on long-term patient outcomes

Increased dietary protein in the second trimester of gestation increases live weight gain and carcass composition in weaner calves to 6 months of age

Genetically similar nulliparous Polled Hereford heifers from a closed pedigree herd were used to evaluate the effects of dietary protein during the first and second trimester of gestation upon fetal, placental and postnatal growth. Heifers were randomly allocated into two groups at 35d post AI (35dpc) to a single bull and fed High (15.7%CP) or Low (5.9%CP) protein in the first trimester (T1). At 90dpc, half of each nutritional treatment group changed to a High or Low protein diet for the second trimester until 180dpc (T2). High protein intake in the second trimester increased birthweight in females (P = 0.05) but there was no effect of treatment upon birthweight when taken over both sexes. Biparietal diameter was significantly increased by high protein in the second trimester with the effect being greater in the female (P = 0.02) but also significant overall (P = 0.05). Placental weight was positively correlated with birth weight, fibroblast volume, and relative blood vessel volume (P < 0.05). Placental fibroblast density was increased and trophoblast volume decreased in the high protein first trimester treatment group (P <0.05). There was a trend for placental weight to be increased by high protein in the second trimester (P = 0.06). Calves from heifers fed the high protein treatment in the second trimester weighed significantly more on all occasions preweaning (at one month (P = 0.0004), 2 mths (P = 0.006), 3 mths (P = 0.002), 4 mths (P = 0.01), 5 mths (P = 41 0.03), 6 mths (P = 0.001)), and grew at a faster rate over the 6 month period. By 6 mths of age the calves from heifers fed high nutrition in the second trimester weighed 33kg heavier than those fed the low diet in the second trimester. These results suggest that dietary protein in early pregnancy alters the development of the bovine placenta and calf growth to weaning

Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism

Background & aims: β-hydroxy-β-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) – differences in plasma bioavailability have been reported. We previously reported that ∼3 g oral FA-HMB increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB). The objective of the present study was to quantify muscle protein metabolism responses to oral Ca-HMB. Methods: Eight healthy young males received a primed constant infusion of 1,2 13C2 leucine and 2H5 phenylalanine to assess MPS (by tracer incorporation in myofibrils) and MPB (via arterio-venous (A-V) dilution) at baseline and following provision of ∼3 g of Ca-HMB; muscle anabolic (MPS) and catabolic (MPB) signalling was assessed via immunoblotting. Results: Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 μM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < 0001) and suppressions in MPB (PA: 7.6 ± 1.2 μmol Phe per leg min−1, Ca-HMB: 5.2 ± 0.8 μmol Phe per leg min−1, p < 0.01). Increases in the phosphorylation of mTORc1 substrates i.e. p70S6K1 and RPS6 were also observed, with no changes detected in the MPB targets measured. Conclusions: These findings support the pro-anabolic properties of HMB via mTORc1, and show that despite proposed differences in bioavailability, Ca-HMB provides a comparable stimulation to MPS and suppression of MPB, to FA-HMB, further supporting its use as a pharmaconutrient in the modulation of muscle mass

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters