Discerning asthma endotypes through comorbidity mapping.

Asthma is a heterogeneous, complex syndrome, and identifying asthma endotypes has been challenging. We hypothesize that distinct endotypes of asthma arise in disparate genetic variation and life-time environmental exposure backgrounds, and that disease comorbidity patterns serve as a surrogate for such genetic and exposure variations. Here, we computationally discover 22 distinct comorbid disease patterns among individuals with asthma (asthma comorbidity subgroups) using diagnosis records for >151 M US residents, and re-identify 11 of the 22 subgroups in the much smaller UK Biobank.

The Impact of Principal Diagnosis on Readmission Risk among Patients Hospitalized for Community-Acquired Pneumonia.

Coding variation distorts performance/outcome statistics not eliminated by risk adjustment. Among 1596 community-acquired pneumonia patients hospitalized from 1998 to 2012 identified using an evidence-based algorithm, the authors measured the association of principal diagnosis (PD) with 30-day readmission, stratified by Pneumonia Severity Index risk class. The 152 readmitted patients were more ill (Pneumonia Severity Index class V 38.

Naloxone Prescriptions Among Commercially Insured Individuals at High Risk of Opioid Overdose.

Importance: As opioid-related mortality continues to increase, naloxone remains a critical intervention in preventing overdose death. Opportunities to expand access through the health care setting should be optimized.

Objective: To determine the characteristics of naloxone prescribing for US patients at high risk of opioid overdose.

Characterizing pediatric inpatient sleep duration and disruptions.

Objective: To contextualize inpatient sleep duration and disruptions in a general pediatric hospital ward by comparing in-hospital and at-home sleep durations to recommended guidelines and to objectively measure nighttime room entries.

Methods: Caregivers of patients four weeks - 18 years of age reported patient sleep duration and disruptions in anonymous surveys. Average at-home and in-hospital sleep durations were compared to National Sleep Foundation recommendations.

The Relative Ability of Comorbidity Ascertainment Methodologies to Predict In-Hospital Mortality Among Hospitalized Community-acquired Pneumonia Patients.

Background: Despite widespread use of comorbidities for population health descriptions and risk adjustment, the ideal method for ascertaining comorbidities is not known. We sought to compare the relative value of several methodologies by which comorbidities may be ascertained.

Methods: This is an observational study of 1596 patients admitted to the University of Chicago for community-acquired pneumonia from 1998 to 2012.

Associations between environmental quality and adult asthma prevalence in medical claims data.

As of 2014, approximately 7.4% of U.S.

Understanding Toxoplasmosis in the United States Through "Large Data" Analyses.

Background: Toxoplasma gondii infection causes substantial morbidity and mortality in the United States, and infects approximately one-third of persons globally. Clinical manifestations vary. Seropositivity is associated with neurologic diseases and malignancies.

Denosumab: a case of MRONJ with resolution.

A patient was referred by a clinical oncologist regarding a non-healing area of bone in the lower jaw. The patient was taking denosumab (Prolia(®), Xgeva(®)) when they had a tooth extracted and the area failed to heal. Following suspension of the drug, the area healed with mucosal coverage.

RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models.

Agents that inhibit estrogen production, such as aromatase inhibitors or those that directly block estrogen receptor (ER) activity, such as selective estrogen receptor modulators and selective estrogen receptor degraders, are routinely used in the treatment of ER-positive breast cancers. However, although initial treatment with these agents is often successful, many women eventually relapse with drug-resistant breast cancers. To overcome some of the challenges associated with current endocrine therapies and to combat the development of resistance, there is a need for more durable and more effective ER-targeted therapies.

Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis.

Context: Abaloparatide is a novel synthetic peptide analog of parathyroid hormone-related protein (PTHrP) that is currently being developed as a potential anabolic agent in the treatment of postmenopausal osteoporosis.

Objective: This study sought to assess the effects of abaloparatide on bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck in postmenopausal women with osteoporosis.

Design: Multi-center, multi-national, double-blind placebo controlled trial in which postmenopausal women were randomly assigned to receive 24 weeks of treatment with daily sc injections of placebo, abaloparatide, 20, 40, or 80 μg, or teriparatide, 20 μg.

The role of statins for primary prevention in non-elderly colorectal cancer patients.

Background: There is conflicting evidence for the role of statins in the primary prevention of colorectal cancer (CRC). We conducted a case control study (N=357,702) in the non-elderly adult US population (age=18-64 years) with the primary objective to examine the association between CRC and statin use.

Patients And Methods: MarketScan® databases were used to identify patients with CRC.

Environmental and state-level regulatory factors affect the incidence of autism and intellectual disability.

Many factors affect the risks for neurodevelopmental maladies such as autism spectrum disorders (ASD) and intellectual disability (ID). To compare environmental, phenotypic, socioeconomic and state-policy factors in a unified geospatial framework, we analyzed the spatial incidence patterns of ASD and ID using an insurance claims dataset covering nearly one third of the US population. Following epidemiologic evidence, we used the rate of congenital malformations of the reproductive system as a surrogate for environmental exposure of parents to unmeasured developmental risk factors, including toxins.

Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.

Background: Women have disproportionately higher mortality rates relative to incidence for bladder cancer. Multiple etiologies have been proposed, including delayed diagnosis and treatment. Guidelines recommend ruling out malignancy in men and women presenting with hematuria.

A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci.

Association of elevated plasminogen activator inhibitor 1 levels with diminished lung function in patients with asthma.

Background: We previously reported that plasminogen activator inhibitor 1 (PAI-1) was upregulated in human asthmatic airways and promotes airway fibrosis in an allergen-challenged murine model of asthma.

Objectives: To examine whether elevated plasma levels of PAI-1 are associated with poor lung function in asthmatic patients.

Methods: Five hundred nineteen adults were eligible for the study, and ultimately 353 adults were enrolled and completed the baseline protocol between January 24, 2004, and July 30, 2005.

Design, Synthesis, and Preclinical Characterization of the Selective Androgen Receptor Modulator (SARM) RAD140.

This report describes the discovery of RAD140, a potent, orally bioavailable, nonsteroidal selective androgen receptor modulator (SARM). The characterization of RAD140 in several preclinical models of anabolic androgen action is also described.

Synthesis of potent, substituted carbazoles as selective androgen receptor modulators (SARMs).

The synthesis and in vitro binding affinity for a novel series of potent androgen receptor modulators is described. One of the more potent compounds (17, RAD35010) was further characterized in vivo where it restored levator ani weight in castrated male rats to near sham level while having no significant effect on prostate weight.

Defining an episode of care for colonoscopy: work of the High Value Health Care Project characterizing episodes and costs of care.

Working with a group of key stakeholders, the authors developed an episode-based resource use measure focused on the use of colonoscopy. This measure is intended to identify differences in health care resource use in a short time frame surrounding the colonoscopy. The ultimate intent in the development of this measure was to pair it with a measure of quality so that both the cost and quality of care can be evaluated together.

Obesity and asthma morbidity in a community-based adult cohort in a large urban area: the Chicago Initiative to Raise Asthma Health Equity (CHIRAH).

Background: Urban minority populations experience increased rates of obesity and increased asthma prevalence and severity. Objective. The authors sought to determine whether obesity, as measured by body mass index (BMI), was associated with asthma quality of life or asthma-related emergency department (ED)/urgent care utilization in an urban, community-based sample of adults.

CXCR4 expression heterogeneity in neuroblastoma cells due to ligand-independent regulation.

Background: CXCR4, the receptor for the chemokine stromal-derived factor 1 (SDF-1), has been shown to mediate many of the processes essential for cancer progression such as tumor cell proliferation, metastasis, and angiogenesis. To understand the role of CXCR4 in the biology of neuroblastoma, a disease that presents with wide spread metastases in over 50% of patients, we screened ten patient derived-neuroblastoma cell-lines for basal CXCR4 expression and sought to identify characteristics that correlate with tumor cell phenotype.

Results: All cell lines expressed CXCR4 mRNA at variable levels, that correlated well with three distinct classes of CXCR4 surface expression (low, moderate, or high) as defined by flow cytometry.

Ethnic disparities in asthma morbidity in Chicago.

Rationale: The role of ethnicity and socioeconomic status in explaining variations in asthma morbidity is unclear.

Objectives: To describe the magnitude of ethnic disparities in asthma morbidity in Chicago and to determine whether differences in socioeconomic status explain these disparities.

Methods: We conducted a survey of 561 school-age children and 353 young adults with asthma and measured their self-reported ethnicity, socioeconomic status (using 11 variables), and asthma morbidity (symptom frequency, asthma-specific quality of life, and frequency of severe asthma exacerbations).

Improving asthma self-efficacy: developing and testing a pilot community-based asthma intervention for African American adults.

Background: Low-income African American adults in Chicago have disproportionately high asthma morbidity and mortality rates. Interventions that improve asthma self-efficacy for appropriate self-management behaviors might ultimately improve asthma control in this population.

Objective: We sought to pilot test an intervention to improve asthma self-efficacy for appropriate self-management behaviors.

The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention.

The menopausal transition is associated with decreased ovarian function and concomitant decline in estrogen production, which may result in physiological effects such as hot flashes, reduced bone mass, and altered lipid profile. It is well established that these unfavorable changes are effectively offset with estrogen therapy (ET) or, in women with a uterus, estrogens in combination with a progestin (hormone therapy). Selective estrogen receptor (ER) modulators (SERMs), which exhibit both ER agonist and antagonist activities depending on the target tissue, have been regarded as offering the potential to provide the benefits of ET and hormone therapy with an improved safety and tolerability profile.

Characterizing community-based asthma knowledge in Chicago and its high risk neighborhoods.

The goal of this study was to characterize asthma knowledge in high risk neighborhoods compared to a random sample of residents in the Chicago area. The Chicago Community Asthma Survey-32 (CCAS-32) was administered to 1006 Chicago-area residents and 388 residents in 4 high-risk Chicago inner-city neighborhoods. There was a significant difference in asthma knowledge between groups.