Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

Urinary incontinence, faecal incontinence and pelvic organ prolapse symptoms 20-26 years after childbirth: A longitudinal cohort study.

OBJECTIVE: To investigate pelvic floor dysfunction (PFD; urinary incontinence (UI), faecal incontinence (FI) and prolapse) ≥20 years after childbirth and their association with delivery mode history and demographic characteristics. DESIGN: Cohort study with long-term follow-up. SETTING: Maternity units in Aberdeen and Birmingham (UK) and Dunedin (NZ). POPULATION: Women giving birth in 1993/1994. METHODS: Postal questionnaires at 20 (New Zealand) or 26 (United Kingdom) years after index birth (n = 6195). Regression analyses investigated associations between risk factors and UI, FI and prolapse symptoms. MAIN OUTCOME MEASURES: Prevalence of self-reported UI, FI, 'something coming down' from or in the vagina (SCD), and the Pelvic Organ Prolapse-Symptom Score, and relationships with delivery method. RESULTS: Thirty-seven per cent (n = 2270) responded at 20/26 years, of whom 61% reported UI (59% of whom reported more severe UI), 22% FI and 17% prolapse symptoms. Having only caesarean section (CS) was associated with a significantly lower risk of UI (OR 0.63, 95% CI 0.46-0.85), FI (OR 0.63, 95% CI 0.42-0.96) and SCD (OR 0.44, 95% CI 0.27-0.74) compared to only spontaneous vaginal deliveries (SVDs). Having any forceps delivery was associated with reporting FI compared to only SVDs (OR 1.29, 95% CI 1.00-1.66), but there was no association for UI (OR 0.95, 95% CI 0.76-1.19) or SCD (OR 1.05, 95% CI 0.80-1.38). Higher current BMI was associated with all PFD outcomes. CONCLUSIONS: Prevalence of PFD continues to increase up to 26 years following index birth, and differences were observed according to delivery mode history. Exclusive CS was associated with less risk of UI, FI and any prolapse symptoms.

Global impacts of COVID-19 pandemic on sexual and reproductive health services: An international comparative study on primary care from the INTRePID Consortium.

OBJECTIVE: To understand how the COVID-19 pandemic has impacted sexual and reproductive health (SRH) visits. DESIGN: An ecological study comparing SRH services volume in different countries before and after the onset of the COVID-19 pandemic. SETTING: Seven countries from the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID) across four continents. POPULATION: Over 3.8 million SRH visits to primary care physicians in Australia, China, Canada, Norway, Singapore, Sweden and the USA. METHODS: Difference in average SRH monthly visits before and during the pandemic, with negative binomial regression modelling to compare predicted and observed number of visits during the pandemic for SRH visits. MAIN OUTCOME MEASURES: Monthly number of visits to primary care physicians from 2018 to 2021. RESULTS: During the pandemic, the average volume of monthly SRH visits increased in Canada (15.6%, 99% CI 8.1-23.0%) where virtual care was pronounced. China, Singapore, Sweden and the USA experienced a decline (-56.5%, 99% CI -74.5 to -38.5%; -22.7%, 99% CI -38.8 to -6.5%; -19.4%, 99% CI -28.3 to -10.6%; and -22.7%, 99% CI -38.8 to -6.5%, respectively); while Australia and Norway showed insignificant changes (6.5%, 99% CI -0.7 to -13.8% and 1.7%, 99% CI -6.4 to -9.8%). The countries that maintained (Australia, Norway) or surpassed (Canada) pre-pandemic visit rates had the greatest use of virtual care. CONCLUSIONS: In-person SRH visits to primary care decreased during the pandemic. Virtual care seemed to counterbalance that decline. Although cervical cancer screening appeared insensitive to virtual care, strategies such as incorporating self-collected samples for HPV testing may provide a solution in a future pandemic.

Condition of surplus dairy calves during marketing: A cross-sectional study.

In North America, surplus dairy calves are sold soon after birth and often marketed through a third party (e.g., live auction, livestock dealer) before entering veal or dairy beef production. Previous work has demonstrated that a percentage of calves have failed transfer of passive immunity (FTPI) and clinical signs of disease on arrival at calf-raising facilities, but little is known regarding calf condition during marketing. The objectives of this cross-sectional study were to (1) estimate the prevalence of FTPI and poor health outcomes in surplus calves on arrival at livestock dealers, and (2) investigate the association between calf-level variables (body weight, sex, source) and health outcomes. Two livestock dealers in Ohio were visited 2 to 3 times per week, with approximately 28 calves enrolled in the study per visit for a total of 1,119 calves. One blood sample per calf was obtained to evaluate FTPI by measuring serum total protein concentrations (using a cutoff <5.1 g/dL). Calves were clinically evaluated for signs of arthritis, broken ribs or tail, dehydration, depression, diarrhea, fever, navel inflammation, and respiratory disease by 2 observers; health outcomes were dichotomized using clinically relevant cut points. Descriptive statistics were used to estimate the prevalence of calves with poor health outcomes. Multivariable logistic regression models were built to investigate the effect of body weight, sex, and source on health outcomes. Nineteen percent (206/1,091) of calves had FTPI.

Interference of the direct and ground-reflected waves in the atmosphere with volumetric scatteringa).

The interference of the direct and ground-reflected sound waves is significantly affected by volumetric scattering in the atmosphere, such as scattering by turbulence and forest. In the present article, the existing theory describing this interference is generalized to three somewhat independent but equally important cases. First, the attenuation of the direct and ground-reflected waves caused by backscattering is addressed. Second, the existing theory is extended for statistically quasi-homogeneous turbulence in which the variances and length scales of the temperature and wind velocity fluctuations depend on the height above the ground. Third, the existing theory, which was previously formulated only for near-horizontal sound propagation, is generalized to slanted sound propagation as pertinent to elevated sound sources. Numerical results for slanted propagation demonstrate that atmospheric turbulence can significantly increase the sound pressure level at the interference minima. The extended theory of the interference of the direct and ground-reflected waves in the atmosphere with volumetric scattering is important for practical applications, such as auralization of flying aircraft and sound propagation in a forest, and can be adapted to radio wave propagation.

Phase-preserving narrow- and wide-angle parabolic equations for sound propagation in moving mediaa).

Parabolic equations are among the most popular numerical techniques in many fields of physics. This article considers extra-wide-angle parabolic equations, wide-angle parabolic equations, and narrow-angle parabolic equations (EWAPEs, WAPEs, and NAPEs, respectively) for sound propagation in moving inhomogeneous media with arbitrarily large variations in the sound speed and Mach number of the (subsonic) wind speed. Within their ranges of applicability, these parabolic equations exactly describe the phase of the sound waves and are, thus, termed the phase-preserving EWAPE, WAPE, and NAPE. Although variations in the sound speed and Mach number are often relatively small, omitting the second-order terms pertinent to these quantities can result in large cumulative phase errors for long propagation ranges. Therefore, the phase-preserving EWAPE, WAPE, and NAPE can be preferable in applications. Numerical implementation of the latter two equations can be performed with minimal modifications to existing codes and is computationally efficient. Numerical results demonstrate that the phase-preserving WAPE and NAPE provide more accurate results than the WAPE and NAPE based on the effective sound speed approximation.

Discussion of sound propagation through the turbulent Martian atmosphere and implications for inference of turbulence spectra.

Chide et al. [J. Acoust. Soc. Am. 155, 420-435 (2024)] provide a first attempt to infer the spectrum of temperature fluctuations on Mars from experimental data on the variances of travel-time and log-amplitude fluctuations recorded by the microphone on board the Perseverance rover. However, the theoretical formulations that were used to interpret the travel-time data have limitations. In addition to explaining those issues, this article also outlines approaches for predicting statistical characteristics of acoustic signals in the Martian atmosphere. In particular, the experimentally observed dependence of the travel-time variance on the propagation range can be attributed to ground-blocking of buoyantly produced turbulent velocity fluctuations and the non-Markov character of phase fluctuations.

Using systems mapping to understand the constraints and enablers of solutions to plastic pollution.

Plastic pollution is now considered globally ubiquitous, irreversible, and a planetary boundary threat. Solutions are urgently needed but their development and application are hampered by the complexity and scale of the issue. System dynamics is a technique used to understand complex behaviours of systems through model building and is useful for conceptualising the relationships between various interacting, dynamic factors, and identifying potential intervention points within the system where specific policies or innovations might have the greatest impact or meet with the greatest resistance. Here, twenty-five participants (all scientific researchers of various career stages, disciplines and nationalities working on plastic pollution) completed a series of exercises through an interactive, iterative group model building exercise during a one-day workshop. The process culminated in the generation of a causal loop diagram, based on participants' perspectives, illustrating the dynamic factors relating to the constraints and enablers of solutions to plastic pollution. A total of 18 factors and seven feedback loops were identified. Key factors influencing the system were Effective legislation, Funding, Public education and awareness, Behaviour change, Innovation, and Effective waste management. Our findings highlight that there is no single driver, or 'silver bullet', for resolving this complex issue and that a holistic approach should be adopted to create effective and systemic change.

An automated faecal egg count system for detection of Ascaridia galli ova in chickens.

Chicken production has increased over the past decade, resulting in a concomitant rise in the demand for more humane options for poultry products including cage-free, free-range, and organic meat and eggs. These husbandry changes, however, have come hand-in-hand with increased prevalence of Ascaridia galli infection, which can cause clinical disease in chickens as well as the occasional appearance of worms in eggs. Additionally, development of anthelmintic resistance in closely related helminths of turkeys highlights the need for closely monitored anthelmintic treatment programs. Manual faecal egg counts (FECs) can be time-consuming and require specialist training. As such, this study sought to validate an automated FEC system for use in detection and quantification of A. galli eggs in chicken faeces. Automated counts using the Parasight System (PS) were compared to traditional manual McMaster counting for both precision and correlation between methods. Overall, ten repeated counts were performed on twenty individual samples for a total of 200 counts performed for each method. A strong, statistically significant correlation was found between methods (R2 = 0.7879, P < 0.0001), and PS counted more eggs and performed with statistically significant higher precision (P = 0.0391) than manual McMaster counting. This study suggests that PS is a good alternative method for performing A. galli FECs and provides a new tool for use in helminth treatment and control programs in chicken operations.

Homogeneity in Motor Competence Among Youths With Intellectual Disability With and Without Down Syndrome.

PURPOSE: To determine if there is a homogeneity of scores for youth with intellectual disability (ID) with and without Down syndrome (DS) in 19 test items of motor competence from the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition (BOT-2). Homogeneity was defined as the means for each of the 19 test items scores by sex and the presence or absence of DS sharing the same population mean. METHOD: Participants were 622 youth with ID aged 6 to 21 years. Items for bilateral coordination, balance, and upper limb coordination were examined using the BOT-2. RESULTS: For all 19 BOT-2 items, means between youth with and without DS did not differ from the population mean. CONCLUSION: These results potentiate the development of expected BOT-2 motor competence scores for youth with ID independent of the presence of DS for clinical practice.

Myonuclear alterations associated with exercise are independent of age in humans.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with the nuclear lamina protein lamin A regulating nuclear shape, nuclear mechanics and ultimately gene expression. Defective lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than those from untrained individuals. Complementary to this, exercise resulted in increased levels of lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.

In-hospital outcomes in patients with and without epilepsy diagnosed with COVID-19-A cohort study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with mortality in persons with comorbidities. The aim of this study was to evaluate in-hospital outcomes in patients with COVID-19 with and without epilepsy. METHODS: We conducted a retrospective study of patients with COVID-19 admitted to a multicenter health system between March 15, 2020, and May 17, 2021. Patients with epilepsy were identified using a validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM case definition. Logistic regression models and Kaplan-Meier analyses were conducted for mortality and non-routine discharges (i.e., not discharged home). An ordinary least-squares regression model was fitted for length of stay (LOS). RESULTS: We identified 9833 people with COVID-19 including 334 with epilepsy. On univariate analysis, people with epilepsy had significantly higher ventilator use (37.70% vs 14.30%, p < .001), intensive care unit (ICU) admissions (39.20% vs 17.70%, p < .001) mortality rate (29.60% vs 19.90%, p < .001), and longer LOS (12 days vs 7 days, p < .001). and fewer were discharged home (29.64% vs 57.37%, p < .001). On multivariate analysis, only non-routine discharge (adjusted odds ratio [aOR] 2.70, 95% confidence interval [CI] 2.00-3.70; p < .001) and LOS (32.50% longer, 95% CI 22.20%-43.60%; p < .001) were significantly different. Factors associated with higher odds of mortality in epilepsy were older age (aOR 1.05, 95% CI 1.03-1.08; p < .001), ventilator support (aOR 7.18, 95% CI 3.12-16.48; p < .001), and higher Charlson comorbidity index (CCI) (aOR 1.18, 95% CI 1.04-1.34; p = .010). In epilepsy, admissions between August and December 2020 or January and May 2021 were associated with a lower odds of non-routine discharge and decreased LOS compared to admissions between March and July 2020, but this difference was not statistically significant. SIGNIFICANCE: People with COVID-19 who had epilepsy had a higher odds of non-routine discharge and longer LOS but not higher mortality. Older age (≥65), ventilator use, and higher CCI were associated with COVID-19 mortality in epilepsy. This suggests that older adults with epilepsy and multimorbidity are more vulnerable than those without and should be monitored closely in the setting of COVID-19.

Preference for and impact of telehealth vs in-person asthma visits among Black and Latinx adults.

BACKGROUND: Black and Latinx adults experience disproportionate asthma-related morbidity and limited specialty care access. The severe acute respiratory syndrome coronavirus 2 pandemic expanded telehealth use. OBJECTIVE: To evaluate visit type (telehealth [TH] vs in-person [IP]) preferences and the impact of visit type on asthma outcomes among Black and Latinx adults with moderate-to-severe asthma. METHODS: For this PREPARE trial ancillary study, visit type preference was surveyed by e-mail or telephone post-trial. Emergency medical record data on visit types and asthma outcomes were available for a subset (March 2020 to April 2021). Characteristics associated with visit type preferences, and relationships between visit type and asthma outcomes (control [Asthma Control Test] and asthma-related quality of life [Asthma Symptom Utility Index]), were tested using multivariable regression. RESULTS: A total of 866 participants consented to be surveyed, with 847 respondents. Among the participants with asthma care experience with both visit types, 42.0% preferred TH for regular checkups, which associated with employment (odds ratio [OR] = 1.61; 95% confidence interval [CI], 1.09-2.39; P = .02), lower asthma medication adherence (OR = 1.06; 95% CI, 1.01-1.11; P = .03), and having more historical emergency department and urgent care asthma visits (OR = 1.10 for each additional visit; 95% CI, 1.02-1.18; P = .02), after adjustment. Emergency medical record data were available for 98 participants (62 TH, 36 IP). Those with TH visits were more likely Latinx, from the Southwest, employed, using inhaled corticosteroid-only controller therapy, with lower body mass index, and lower self-reported asthma medication adherence vs those with IP visits only. Both groups had comparable Asthma Control Test (18.4 vs 18.9, P = .52) and Asthma Symptom Utility Index (0.79 vs 0.84, P = .16) scores after adjustment. CONCLUSION: TH may be similarly efficacious as and often preferred over IP among Black and Latinx adults with moderate-to-severe asthma, especially for regular checkups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02995733.

Influence of ground blocking on the acoustic phase variance in a turbulent atmosphere.

Sound propagation through atmospheric turbulence is important in many applications such as localization of low flying aircraft, sonic boom disturbances, and auralization of aircraft during takeoff and landing. This article extends an isotropic turbulence model in the atmospheric boundary layer to account for ground blocking of buoyancy-produced velocity fluctuations. The extended, anisotropic turbulence model is needed to correctly predict the effect of the largest velocity eddies on the statistical characteristics of sound signals. This model and geometrical acoustics are then employed to derive a closed-form expression for the variance of the phase fluctuations of a spherical sound wave for vertical and slanted propagation, without the use of the Markov approximation. A numerical analysis of this expression indicates significant anisotropy of the phase variance due to the buoyancy-produced velocity fluctuations with ground blocking such that it decreases in the vertical direction and increases in the near-horizontal directions. The newly formulated phase variance is compared with data from an outdoor experiment on vertical and slanted sound propagation. By accounting for ground blocking, much better agreement is obtained between the theoretical predictions and experimental data.

Phase-modulated Rice model for statistical distributions of complex signals.

The basic Rice model is commonly used to describe complex signal statistics from randomly scattered waves. It correctly describes weak (Born) scattering, as well as fully saturated scattering, and smoothly interpolates between these extremes. However, the basic Rice model is unsuitable for situations involving scattering by random inhomogeneities spanning a broad range of spatial scales, as commonly occurs for sound scattering by turbulence in the atmospheric boundary layer and other scenarios. In such scenarios, the phase variations are often considerably stronger than those predicted by the basic Rice model. Therefore, the basic Rice model is extended to include a random modulation in the signal phase, which is attributable to the influence of the largest, most energetic inhomogeneities in the propagation medium. Various joint and marginal distributions for the complex signal statistics are derived to incorporate the phase-modulation effect. Approximations of the phase-modulated Rice model involving the Nakagami distribution for amplitude, and the wrapped normal and von Mises distributions for phase, are also developed and analyzed. The phase-modulated Rice model and various approximations are shown to greatly improve agreement with simulated data for sound propagation in the near-ground atmosphere.

Socioeconomic status associates with worse asthma morbidity among Black and Latinx adults.

BACKGROUND: Asthma disproportionately affects African American/Black (AA/B) and Hispanic/Latinx (H/L) patients and individuals with low socioeconomic status (SES), but the relationship between SES and asthma morbidity within these racial/ethnic groups is inadequately understood. OBJECTIVE: To determine the relationship between SES and asthma morbidity among AA/B and H/L adults with moderate to severe asthma using multidomain SES frameworks and mediation analyses. METHODS: We analyzed enrollment data from the PeRson EmPowered Asthma RElief randomized trial, evaluating inhaled corticosteroid supplementation to rescue therapy. We tested for direct and indirect relationships between SES and asthma morbidity using structural equation models. For SES, we used a latent variable defined by poverty, education, and unemployment. For asthma morbidity, we used self-reported asthma exacerbations in the year before enrollment (corticosteroid bursts, emergency room/urgent care visits, or hospitalizations), and Asthma Control Test scores. We tested for mediation via health literacy, perceived stress, and self-reported discrimination. All models adjusted for age, sex, body mass index, ethnicity, and comorbidities. RESULTS: Among 990 AA/B and H/L adults, low SES (latent variable) was directly associated with hospitalizations (ß = 0.24) and worse Asthma Control Test scores (ß = 0.20). Stress partially mediated the relationship between SES and increased emergency room/urgent care visits and worse asthma control (ß = 0.03 and = 0.05, respectively). Individual SES domains were directly associated with asthma morbidity. Stress mediated indirect associations between low educational attainment and unemployment with worse asthma control (ß = 0.05 and = 0.06, respectively). CONCLUSIONS: Lower SES is directly, and indirectly through stress, associated with asthma morbidity among AA/B and H/L adults. Identification of stressors and relevant management strategies may lessen asthma-related morbidity among these populations.

Equine allergic skin diseases: Clinical consensus guidelines of the World Association for Veterinary Dermatology.

BACKGROUND: Allergic skin diseases are common in horses worldwide. The most common causes are insect bites and environmental allergens. OBJECTIVES: To review the current literature and provide consensus on pathogenesis, diagnosis, treatment and prevention. MATERIALS AND METHODS: The authors reviewed the literature up to November 2022. Results were presented at North America Veterinary Dermatology Forum (2021) and European Veterinary Dermatology Congress (2021). The report was available to member organisations of the World Association for Veterinary Dermatology for feedback. CONCLUSIONS AND CLINICAL RELEVANCE: Insect bite hypersensitivity (IBH) is the best characterised allergic skin disease. An immunoglobulin (Ig)E response against Culicoides salivary antigens is widely documented. Genetics and environmental factors play important roles. Tests with high sensitivity and specificity are lacking, and diagnosis of IBH is based on clinical signs, seasonality and response to insect control. Eosinophils, interleukin (IL)-5 and IL-31 are explored as therapeutic targets. Presently, the most effective treatment is insect avoidance. Existing evidence does not support allergen-specific immunotherapy (ASIT) using commercially available extracts of Culicoides. Hypersensitivity to environmental allergens (atopic dermatitis) is the next most common allergy. A role for IgE is supported by serological investigation, skin test studies and positive response to ASIT. Prospective, controlled, randomised studies are limited, and treatment relies largely on glucocorticoids, antihistamines and ASIT based on retrospective studies. Foods are known triggers for urticaria, yet their role in pruritic dermatitis is unknown. Recurrent urticaria is common in horses, yet our understanding is limited and focussed on IgE and T-helper 2 cell response. Prospective, controlled studies on treatments for urticaria are lacking. Glucocorticoids and antihistamines are primary reported treatments.

Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.

Decision making under risk: framing effects in pigeon risk preferences.

When humans face probabilistic outcomes, their choices often depend on whether the choice is framed in terms of losses or gains. In the present research, we gave pigeons a choice between risky (variable) outcomes and safe (constant) outcomes that resulted in the same net reward. In Experiment 1, in which the outcomes represented a loss, the pigeons preferred the risky alternative. In Experiment 2, in which the outcomes represented a gain, the pigeons were indifferent between the two alternatives. In Experiment 3, in which the outcomes represented neither a gain nor a loss, the pigeons strongly preferred the risky alternative. The results were interpreted in terms of the relative value of gains and losses given to the alternatives by pigeons in the context of a risky and safe choice. In Experiment 4 we tested that hypothesis by giving pigeons a choice between a risky and safe alternative with the same net outcome, in the context of a gain associated with the safe alternative, but no gain or loss associated with the risky alternative. In support of the interpretation of the first three experiments, with the safe alternative associated with a gain, the pigeons now preferred the safe alternative. These results were discussed in terms of economic and foraging theories and were contrasted with the aversion to uncertainty (risk) more typically shown by humans.

COPD Population in US Primary Care: Data From the Optimum Patient Care DARTNet Research Database and the Advancing the Patient Experience in COPD Registry.

PURPOSE: To describe demographic and clinical characteristics of chronic obstructive pulmonary disease patients managed in US primary care. METHODS: This was an observational registry study using data from the Chronic Obstructive Pulmonary Disease (COPD) Optimum Patient Care DARTNet Research Database from which the Advancing the Patient Experience COPD registry is derived. Registry patients were aged ≥35 years at diagnosis. Electronic health record data were collected from both registries, supplemented with patient-reported information/outcomes from the Advancing the Patient Experience registry from 5 primary care groups in Texas, Ohio, Colorado, New York, and North Carolina (June 2019 through November 2020). RESULTS: Of 17,192 patients included, 1,354 were also in the Advancing the Patient Experience registry. Patients were predominantly female (56%; 9,689/17,192), White (64%; 9,732/15,225), current/ex-smokers (80%; 13,784/17,192), and overweight/obese (69%; 11,628/16,849). The most commonly prescribed maintenance treatments were inhaled corticosteroid with a long-acting ß2-agonist (30%) and inhaled corticosteroid with a long-acting muscarinic antagonist (27%). Although 3% (565/17,192) of patitents were untreated, 9% (1,587/17,192) were on short-acting bronchodilator monotherapy, and 4% (756/17,192) were on inhaled corticosteroid monotherapy. Despite treatment, 38% (6,579/17,192) of patients experienced 1 or more exacerbations in the last 12 months. These findings were mirrored in the Advancing Patient Experience registry with many patients reporting high or very high impact of disease on their health (43%; 580/1,322), a breathlessness score 2 or more (45%; 588/1,315), and 1 or more exacerbation in the last 12 months (50%; 646/1,294). CONCLUSIONS: Our findings highlight the high exacerbation, symptom, and treatment burdens experienced by COPD patients managed in US primary care, and the need for more real-life effectiveness trials to support decision making at the primary care level.