Real-world outcomes in patients with advanced endometrial cancer: A retrospective cohort study of US electronic health records.

Objectives: To characterize clinical outcomes of women with advanced/recurrent endometrial cancer (AEC) in routine practice using electronic health records from a real-world database.

Methods: Adult women diagnosed with AEC (stage III/IV, or early stage with locoregional/distant recurrence) between January 1, 2013 and September 30, 2020, inclusive, were eligible provided they received platinum-based chemotherapy at any time following diagnosis and had ≥2 clinical visits. Follow-up was from initiation of systemic treatment after advanced diagnosis (index) until March 30, 2021, last available follow-up, or death, whichever occurred first.

Utilization of Poly(ADP-Ribose) Polymerase Inhibitors in Ovarian Cancer: A Retrospective Cohort Study of US Healthcare Claims Data.

Introduction: We aimed to characterize real-world utilization of poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) in women with ovarian cancer (OC).

Methods: This retrospective observational study of claims data from US MarketScan Commercial/Medicare Supplemental databases included women with OC initiating olaparib, niraparib, or rucaparib from January 1, 2017, to May 31, 2019. Patients were observed from first outpatient prescription until at least 30 days' follow-up.

Adverse events in women switching from olaparib capsules to tablets: retrospective observational study of US claims data.

Describe rates of prespecified adverse events in patients who switched from olaparib capsules to tablets. Retrospective, observational cohort analysis using self-controlled, pre-post design. Data on patients with ovarian cancer who switched from olaparib capsules to tablets between January 2015 and February 2019 were obtained from a US claims database.

Rate of Adverse Events and Associated Health Care Costs for the Management of Inflammatory Bowel Disease in Germany.

Purpose: Therapeutic management of inflammatory bowel disease (IBD) is challenging, and available therapies are associated with adverse events (AEs) that may lead to treatment discontinuation. This study evaluated the rate of drug-related AEs of special interest (AESIs) associated with IBD therapies and compare health care costs among patients with IBD who did and did not experience AESIs.

Methods: A retrospective cohort analysis was conducted using claims data from a German Sickness Fund (Allgemeine Ortskrankenkasse PLUS).

Analysis of Safety, Medical Resource Utilization, and Treatment Costs by Drug Class for Management of Inflammatory Bowel Disease in the United States Based on Insurance Claims Data.

Introduction: Conventional pharmaceutical interventions for inflammatory bowel disease (IBD) provide limited disease/symptom control and are associated with an increased risk of adverse events (AEs). These limitations increase patient morbidity, medical resource utilization (MRU), and costs.

Methods: The IQVIA™ Real-World Data Adjudicated Claims-US database was leveraged to identify adult patients (> 18 years) with Crohn's disease (Crohn's) or ulcerative colitis (UC), who were new and chronic users (≥ 60 days) of oral corticosteroids (OCS), immunosuppressants (IS), anti-tumor necrosis factor agents (anti-TNF) or combinations thereof.

Changes in behaviors after diagnosis of type 2 diabetes and 10-year incidence of cardiovascular disease and mortality.

Background: Large changes in health behaviors achieved through intensive lifestyle intervention programs improve cardiovascular disease (CVD) risk factors among adults with type 2 diabetes. However, such interventions are not widely available, and there is limited evidence as to whether changes in behaviors affect risk of CVD events.

Methods: Among 852 adults with screen-detected type 2 diabetes in the ADDITION-Cambridge study, we assessed changes in diet, physical activity, and alcohol use in the year following diabetes diagnosis.

Moderate weight change following diabetes diagnosis and 10 year incidence of cardiovascular disease and mortality.

Aims/hypothesis: Adults with type 2 diabetes are at high risk of developing cardiovascular disease (CVD). Evidence of the impact of weight loss on incidence of CVD events among adults with diabetes is sparse and conflicting. We assessed weight change in the year following diabetes diagnosis and estimated associations with 10 year incidence of CVD events and all-cause mortality.

Change in lifestyle behaviors and diabetes risk: evidence from a population-based cohort study with 10 year follow-up.

Background: Promoting positive changes in lifestyle behavior in the whole population may be a feasible and effective approach to reducing type 2 diabetes burden, but the impact of population shifts of modifiable risk factors remains unclear. Currently most of the evidence on modifiable lifestyle behavior and type 2 diabetes risk on a population level comes from studies of between-individual differences. The objective of the study was to investigate the association and potential impact on disease burden for within-individual change in lifestyle behavior and diabetes risk.

Impact of weight maintenance and loss on diabetes risk and burden: a population-based study in 33,184 participants.

Background: Weight loss in individuals at high risk of diabetes is an effective prevention method and a major component of the currently prevailing diabetes prevention strategies. The aim of the present study was to investigate the public health potential for diabetes prevention of weight maintenance or moderate weight loss on a population level in an observational cohort with repeated measurements of weight and diabetes status.

Methods: Height, weight and diabetes status were objectively measured at baseline and 10 year follow-up in a population-based cohort of 33,184 participants aged 30-60 years between 1990 and 2013 in Västerbotten County, Sweden.

Prospective associations between sedentary time, physical activity, fitness and cardiometabolic risk factors in people with type 2 diabetes.

Aims/hypothesis: The aim of this study was to examine the prospective associations between objectively measured physical activity energy expenditure (PAEE), sedentary time, moderate-to-vigorous-intensity physical activity (MVPA), cardiorespiratory fitness (CRF) and cardiometabolic risk factors over 4 years in individuals with recently diagnosed diabetes.

Methods: Among 308 adults (mean age 61.0 [SD 7.

Medication burden in the first 5 years following diagnosis of type 2 diabetes: findings from the ADDITION-UK trial cohort.

Introduction: Individuals with screen-detected diabetes are likely to receive intensified pharmacotherapy to improve glycaemic control and general cardiometabolic health. Individuals are often asymptomatic, and little is known about the degree to which polypharmacy is present both before, and after diagnosis. We aimed to describe and characterize the pharmacotherapy burden of individuals with screen-detected diabetes at diagnosis, 1 and 5 years post-diagnosis.

Mortality benefits of population-wide adherence to national physical activity guidelines: a prospective cohort study.

We quantified the mortality benefits and attributable fractions associated with engaging in physical activity across a range of levels, including those recommended by national guidelines. Data were from the Allied Dunbar National Fitness Survey, a population-based prospective cohort comprising 1,796 male and 2,122 female participants aged 16-96 years, randomly selected from 30 English constituencies in 1990. Participants were tagged for mortality at the Office for National Statistics.

Healthy behavior change and cardiovascular outcomes in newly diagnosed type 2 diabetic patients: a cohort analysis of the ADDITION-Cambridge study.

Objective: To examine whether improvements in health behaviors are associated with reduced risk of cardiovascular disease (CVD) in individuals with newly diagnosed type 2 diabetes.

Research Design And Methods: Population-based prospective cohort study of 867 newly diagnosed diabetic patients aged between 40 and 69 years from the treatment phase of the ADDITION-Cambridge study. Because the results for all analyses were similar by trial arm, data were pooled, and results were presented for the whole cohort.

Temporal shifts in cardiovascular risk factor distribution.

Background: Complementary strategies to shift risk factor population distributions and target high-risk individuals are required to reduce the burden of type 2 diabetes and cardiovascular disease (CVD).

Purpose: To examine secular changes in glucose and CVD risk factors over 20 years during an individual and population-based CVD prevention program in Västerbotten County, Sweden.

Methods: Population-based health promotion intervention was conducted and annual invitation for individuals turning 40, 50, and 60 years to attend a health assessment, including an oral glucose tolerance test, biochemical measures, and a questionnaire.

Generalism and the evolution of parasite virulence.

The evolution of parasite-imposed host harm (virulence) will be affected by numerous factors, not least the range of hosts that parasites can infect. Here, we consider four ways that parasite host range (generalism) might directly affect observed levels of parasite virulence: costs of generalism, multiplicity of infection, maladaptive virulence, and host availability. Integrating parasite infectivity range with life-history evolution will generate novel general hypotheses for the evolutionary ecology of virulence, as well as explicit predictions about the virulence of emerging diseases resulting from host shifts.

Socio-demographic and behavioural correlates of physical activity perception in individuals with recently diagnosed diabetes: results from a cross-sectional study.

Background: Physical activity (PA) levels in type 2 diabetes mellitus (T2DM) patients are generally low. Poor PA perception may impede healthy behaviour change in this high risk group. We describe (i) objective PA levels, (ii) the difference between objective and self-reported PA ('PA disparity') and the correlates of (iii) PA disparity and (iv) overestimation in recently diagnosed T2DM patients.

The implications of immunopathology for parasite evolution.

By definition, parasites harm their hosts, but in many infections much of the pathology is driven by the host immune response rather than through direct damage inflicted by parasites. While these immunopathological effects are often well studied and understood mechanistically in individual disease interactions, there remains relatively little understanding of their broader impact on the evolution of parasites and their hosts. Here, we theoretically investigate the implications of immunopathology, broadly defined as additional mortality associated with the host's immune response, on parasite evolution.

How can immunopathology shape the evolution of parasite virulence?

Immunopathology (immune-mediated pathology) is a ubiquitous cause of disease during infection, but how will parasite exploitation strategies evolve in its presence? Immunopathology can act to increase parasite fitness if it increases transmission rate, but can equally act to decrease parasite fitness if it increases host mortality. The focus here is on understanding how immunopathology, mediated through different immune mechanisms, can influence parasite fitness and how experimental manipulations of the immune system can be carried out to examine this. A better understanding of how parasite fitness scales with, or responds to, immunopathology is crucial to understanding the nature of selection acting on parasite virulence traits and will allow more informed predictions to be made regarding the trajectory of parasite virulence evolution.

Consequences of immunopathology for pathogen virulence evolution and public health: malaria as a case study.

Evolutionary theories explaining virulence-the fitness damage incurred by infected hosts-often focus on parasite strategies for within-host exploitation. However, much virulence can be caused by the host's own immune response: for example, pro-inflammatory cytokines, although essential for killing malaria parasites, also damage host tissue. Here we argue that immune-mediated virulence, or 'immunopathology,' may affect malaria virulence evolution and should be considered in the design of medical interventions.

Identifying the age cohort responsible for transmission in a natural outbreak of Bordetella bronchiseptica.

Identifying the major routes of disease transmission and reservoirs of infection are needed to increase our understanding of disease dynamics and improve disease control. Despite this, transmission events are rarely observed directly. Here we had the unique opportunity to study natural transmission of Bordetella bronchiseptica--a directly transmitted respiratory pathogen with a wide mammalian host range, including sporadic infection of humans--within a commercial rabbitry to evaluate the relative effects of sex and age on the transmission dynamics therein.

Dynamic models of immune responses: what is the ideal level of detail?

Background: One of the goals of computational immunology is to facilitate the study of infectious diseases. Dynamic modeling is a powerful tool to integrate empirical data from independent sources, make novel predictions, and to foresee the gaps in the current knowledge. Dynamic models constructed to study the interactions between pathogens and hosts' immune responses have revealed key regulatory processes in the infection.

Acellular pertussis vaccination facilitates Bordetella parapertussis infection in a rodent model of bordetellosis.

Despite over 50 years of population-wide vaccination, whooping cough incidence is on the rise. Although Bordetella pertussis is considered the main causative agent of whooping cough in humans, Bordetella parapertussis infections are not uncommon. The widely used acellular whooping cough vaccines (aP) are comprised solely of B.

Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites.

Background: Explaining parasite virulence (harm to the host) represents a major challenge for evolutionary and biomedical scientists alike. Most theoretical models of virulence evolution assume that virulence arises as a direct consequence of host exploitation, the process whereby parasites convert host resources into transmission opportunities. However, infection-induced disease can be immune-mediated (immunopathology).

Blockade of TNF receptor 1 reduces disease severity but increases parasite transmission during Plasmodium chabaudi chabaudi infection.

Reducing host carriage of transmission-stage malaria parasites (gametocytes) is expected to decrease the population-wide burden of malaria. Some malaria disease severity is attributed to the induction of the pro-inflammatory cytokines TNF-alpha and lymphotoxin-alpha (LT-alpha), and we are interested in whether anti-malaria interventions which ameliorate the symptoms induced by those cytokines may have the capacity to alter malaria transmission. As many functions of TNF-alpha and LT-alpha are exerted through TNF receptor 1 (TNFR1), we investigated the effect TNFR1 blockade exerted on parasite transmission using the rodent malaria Plasmodium chabaudi chabaudi.