Population trends in emergency cancer diagnoses: The role of changing patient case-mix

BackgroundDiagnosis of cancer through an emergency presentation is associated with worse clinical and patient experience outcomes. The proportion of patients with cancer who are diagnosed through emergency presentations has consequently been introduced as a routine cancer surveillance measure in England. Welcome reductions in this metric have been reported over more than a decade but whether reductions reflect true changes in how patients are diagnosed rather than the changing case-mix of incident cohorts in unknown.MethodsWe analysed ‘Routes to Diagnosis’ data on cancer patients (2006–2015) and used logistic regression modelling to determine the contribution of changes in four case-mix variables (sex, age, deprivation, cancer site) to time-trends in emergency presentations.ResultsBetween 2006 and 2015 there was an absolute 4.7 percentage point reduction in emergency presentations (23.8%–19.2%). Changing distributions of the four case-mix variables explained 19.0% of this reduction, leaving 81.0% unexplained. Changes in cancer site case-mix alone explained 16.0% of the total reduction.ConclusionChanges in case-mix (particularly that of cancer sites) account for about a fifth of the overall reduction in emergency presentations. This would support the use of adjustment/standardisation of reported statistics to support their interpretation and help appreciate the influence of case-mix, particularly regarding cancer sites with changing incidence. However, most of the reduction in emergency presentations remains unaccounted for, and likely reflects genuine changes during the study period in how patients were being diagnosed.     

Bringing Stem Cell‐Based Therapies for Type 1 Diabetes to the Clinic: Early Insights from Bioprocess Economics and Cost‐Effectiveness Analysis

Differentiation of pluripotent stem cells (PSCs) into β cells could provide insulin independence for type 1 diabetes (T1D) patients. This approach would reduce the clinical complications that most patients managed on intensive insulin therapy (IIT) face. However, bottlenecks of PSC manufacturing and limited engraftment of encapsulated cells hinder the long‐term effectiveness of these therapies. A bioprocess decision‐support tool is combined with a disease state‐transition model to evaluate the cost‐effectiveness of the stem cell‐based therapy against IIT. Clinical effectiveness is assessed in quality‐adjusted life years (QALYs). Manufacturing costs per patient reduce from $430 000 to $160 000 with optimization of batch size and annual demand. For 96% of the patients, cell therapy improves the quality of life compared to IIT. Cost savings are achieved for 2% of the population through prevention of renal disease. The therapy is cost‐effective for 3.4% of patients when a willingness to pay (WTP) of up to $150 000 per QALY is considered. A 75% cost reduction in the cell therapy price increases cost‐effectiveness likelihood to 51% at $100 000 per QALY. This study highlights the need for scalable manufacturing platforms for stem cell therapies, as well as to prioritizing access to the therapy to patients with an increased likelihood of costly complications.     

Influence of N-glycosylation on effector functions and thermal stability of glycoengineered IgG1 monoclonal antibody with homogeneous glycoforms

Glycosylation of the conserved asparagine residue in each heavy chain of IgG in the CH2 domain is known as N-glycosylation. It is one of the most common post-translational modifications and important critical quality attributes of monoclonal antibody (mAb) therapeutics. Various studies have demonstrated the effects of the Fc N-glycosylation on safety, Fc effector functions, and pharmacokinetics, both dependent and independent of neonatal Fc receptor (FcRn) pathway. However, separation of various glycoforms to investigate the biological and functional relevance of glycosylation is a major challenge, and existing studies often discuss the overall impact of N-glycans, without considering the individual contributions of each glycoform when evaluating mAbs with highly heterogeneous distributions. In this study, chemoenzymatic glycoengineering incorporating an endo-β-N-acetylglucosaminidase (ENGase) EndoS2 and its mutant with transglycosylation activity was used to generate mAb glycoforms with highly homogeneous and well-defined N-glycans to better understand and precisely evaluate the effect of each N-glycan structure on Fc effector functions and protein stability. We demonstrated that the core fucosylation, non-reducing terminal galactosylation, sialylation, and mannosylation of IgG1 mAb N-glycans impact not only on FcγRIIIa binding, antibody-dependent cell-mediated cytotoxicity, and C1q binding, but also FcRn binding, thermal stability and propensity for protein aggregation.     

Cancer incidence among Canadian Veterans: A matched cohort study

IntroductionOccupational exposures related to military service may increase the risk of cancer for military Veterans, while high levels of fitness during service may decrease risk. However, few studies have compared this post-career cancer risk directly to the employed general population.MethodsThis retrospective cohort study used linked administrative data. Canadian Armed Forces and Royal Canadian Mounted Police Veterans in Ontario, Canada were matched 1:4 on age, sex, geography, and community-level income to a group of non-Veterans most likely to have been employed during a period similar to the Veterans’ military service. Cancer diagnoses were identified using the Ontario Cancer Registry.ResultsDuring the study period, 642 of 30 576 included Veterans (2.1%) and 3408 of the 122 293 matched general population cohort (2.8%) experienced at least one cancer diagnosis. The crude rate of cancer was 153.5 per 100 000 person-years among Veterans vs. 205.9 per 100 000 person-years for the general population cohort. After adjusting for rurality and matching variables, Veterans had an 27% lower risk of developing any cancer than their matched comparators [hazard ratio = 0.73 (95% CI: 0.67–0.80)]. Among specific cancer types, the risk of lung and colorectal cancer was significantly lower for Veterans relative to the general population cohort; the risk of breast and prostate cancer was similar.DiscussionThis study adds to the growing international evidence suggesting that risk of many cancers among Veterans is lower or similar to the general population. Further understanding of the complex relationships among occupational exposures, environmental factors, and lifestyle factors is needed.     

In vivo glyco-engineered antibody with improved lytic potential produced by an innovative non-mammalian expression system

Recent studies have demonstrated that the reduction of the core fucosylation on N-glycans of human IgGs is responsible for a clearly enhanced antibody-dependent cellular cytotoxicity (ADCC). This finding might give access to improved active therapeutic antibodies. Here, the expression of the tumor antigen-specific antibody IGN311 was performed in a glyco-optimized strain of the moss Physcomitrella patens. Removal of plant specific N-glycan structures in this plant expression host was achieved by targeted knockout of corresponding genes and included quantitative elimination of core fucosylation. Antibodies transiently expressed and secreted by such genetically modified moss protoplasts assembled correctly, showed an unaltered antigen-binding affinity and, in extensive tests, revealed an up to 40-fold enhanced ADCC. Thus, the glyco-engineered moss-based transient expression platform combines a rapid technology with the subsequent analysis of glycooptimized therapeutics with regard to advanced properties.     

Adiposity, physical activity, and physical fitness among children from Aragón, Spain

Objective: The main purpose of this study was to determine the relationship between physical activity (PA) levels and adiposity. The secondary purpose was to assess the effect of physical fitness and living area on adiposity. Research Methods and Procedures: A cross‐sectional study was carried out in a regional representative sample of 1068 children 7 to 12 years of age. Anthropometric and physical fitness values (including BMI, aerobic capacity, strength levels, velocity assessment, and flexibility) were measured in all children. Results: The prevalence of being overweight and obese in the entire sample was 31% and 6%, respectively. No difference between urban and rural children was found. The proportion of boys who were classified as overweight and obese was similar in physically active and sedentary (non‐physically active) groups. However, physically active girls tended to show lower obesity prevalence compared with their sedentary counterparts (p = 0.06). In girls, the sum of the 6 skinfolds thickness (SSF) measurements was lower in the physically active group when compared with the non‐physically active group (p < 0.05); however, this effect was not observed in boys. Multiple regression analysis revealed that the level of physical activity (PA) had a significant effect on BMI and SSF in boys but not in girls, while maximal oxygen uptake (Vo _2max) was significantly related to adiposity in both sexes. Discussion: Regular participation in at least 2 hours per week of sports activities on top of the compulsory education program is associated with better physical fitness and lower whole body adiposity. In the children included in our study, among all physical fitness variables, Vo _2max showed the strongest relationship with BMI and fat mass assessed by means of skinfold measurements.     

Designer schools: the role of school space and architecture in obesity prevention

Spatial features of obesogenic environments studied on a broad community level have been associated with childhood overweight and obesity, but little research has focused on the effects of the design of micro spaces, such as schools, on individual health behaviors. This article aims to generate thinking and research on the link between school space and architecture and obesity prevention by reviewing and synthesizing available literature in architecture, environmental psychology, and obesity research, in an effort to propose promising ideas for school space design and redesign. The school environment is defined through 5 dimensions: physical, legal, policy, social, and cultural domains. Theories underlying environmental interventions and documented associations between the environment and health behaviors and outcomes are reviewed to illustrate how existing environmental research could translate to obesity prevention. Design strategies aimed at promoting physical activity and healthful eating are proposed, with particular emphasis on the design of cafeterias, activity spaces, connectivity with the larger community, and student health centers.     

Effects of a reimbursement incentive on enrollment in a weight control program

Objective: The objective was to examine the effect of offering a reimbursement incentive on the percentage of inquirers who enrolled in a weight control program and on weight loss and program attendance among enrollees. Research Methods and Procedures: We used a sequential control‐intervention design to observe how inquirers of the University of Alabama at Birmingham EatRight Lifestyle Program responded to an enrollment incentive for potential 50% ($150) reimbursement of the total program fee if they attended 10 of 12 classes and lost at least 6% of their current body weight. Inquirers had to be adults with a BMI ≥30 kg/m², seeking information about a weight control program, and informed of the program cost. Outcomes included proportion of inquirers enrolled, overall number of classes attended, and weight loss. Results: Of the 401 people who inquired during the study periods, 24.5% and 25.0% enrolled in the intervention and control periods, respectively. There was a trend toward higher attendance in the intervention group, compared with the control group; there were no differences in percentage of weight loss. The odds of attending ≥10 classes were 2.4 times as high, and both losing >6% body weight and attending ≥10 classes were three times as high in the intervention subjects compared with controls, although non‐significant. Discussion: The potential of earning a performance‐based reimbursement incentive did not affect enrollment in the EatRight Lifestyle Program. Performance‐based incentives may be an ideal mechanism for extending coverage of weight‐loss interventions by insurers because of limited financial risk and improved adherence.     

Fundulus as the premier teleost model in environmental biology: opportunities for new insights using genomics

A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms.     

Relationship between early puberty and the risk of hypertension/overweight at age 50: Evidence for a modified Barker hypothesis among Polish youth

The objective of this paper is to evaluate: (a) the association between BMI in childhood and adolescence and BMI at age 50, and (b) the association between timing of maturation at puberty and BMI at age 50 and the occurrence of high blood pressure. We explore whether differences in somatic and physiological factors observed among children with early or late onset of puberty indicates that this period of life could be critical for appearance of some CVD risk factors later in the life cycle. Our data include 135 males and 148 females, born in 1953, participants in the Wroc?aw Longitudinal Study. Data pertaining to their growth and several indices of sexual and skeletal maturation were collected yearly between age 8 and 18. Subsequently, their anthropometric traits were measured and cardiovascular health status was assessed at age 50. We find that BMI at distinct stages in the life cycle were positively correlated. Also BMI at 50 were positively associated with blood pressure at 50. Moreover, earlier maturation at puberty is associated with higher values of BMI at age 50. We also find that earlier pubertal maturation is an independent factor that influences the appearance of high blood pressure in adulthood.