Chronic Disease Surveillance Using Electronic Health Records From Health Centers in a Large Urban Setting.

OBJECTIVES: To assess the validity of electronic health records (EHRs) from a network of health centers for chronic disease surveillance among an underserved population in an urban setting. DESIGN: EHRs from a network of health centers were used to calculate the prevalence of chronic disease among adult and child patient populations during 2016. Two population-based surveys with local estimates of chronic disease prevalence were compared with the EHR prevalences. SETTING: A network of health centers that provides health care services to an underserved population in a large urban setting. PARTICIPANTS: A total of 187 292 patients who had at least 1 health care visit recorded in the Philadelphia health center network. MAIN OUTCOME MEASURE: Chronic disease indicator (CDI) prevalence of adult obesity, adult smoking, adult diabetes, adult hypertension, child obesity, and child asthma. Health center CDI proportions were compared with survey estimates. RESULTS: Overall consistency between the health center estimates and surveys varied by CDI. With the exception of childhood obesity, all health center CDI proportions fell within the 95% CI for at least 1 comparison survey estimate. Statistically significant differences were observed and varied by CDI. CONCLUSIONS: This analysis presents a novel use of existing EHR data to estimate chronic disease prevalence among underserved populations. With the increased use of EHRs in health centers, data from health center networks may supplement chronic disease surveillance efforts, if used appropriately.

Severe exacerbations in moderate-to-severe asthmatics are associated with increased pro-inflammatory and type 1 mediators in sputum and serum.

BACKGROUND: Asthma is a heterogeneous disease and understanding this heterogeneity will enable the realisation of precision medicine. We sought to compare the sputum and serum inflammatory profiles in moderate-to-severe asthma during stable disease and exacerbation events. METHODS: We recruited 102 adults and 34 children with asthma. The adults were assessed at baseline, 3, 6, and 12-month follow-up visits. Thirty-seven subjects were assessed at onset of severe exacerbation. Forty sputum mediators and 43 serum mediators were measured. Receiver-operator characteristic (ROC) curves were constructed to identify mediators that distinguish between stable disease and exacerbation events. The strongest discriminating sputum mediators in the adults were validated in the children. RESULTS: The mediators that were significantly increased at exacerbations versus stable disease and by ≥1.5-fold were sputum IL-1ß, IL-6, IL-6R, IL-18, CXCL9, CXCL10, CCL5, TNFα, TNF-R1, TNF-R2, and CHTR and serum CXCL11. No mediators decreased ≥1.5-fold at exacerbation. The strongest discriminators of an exacerbation in adults (ROC area under the curve [AUC]) were sputum TNF-R2 0.69 (95% CI: 0.60 to 0.78) and IL-6R 0.68 (95% CI: 0.58 to 0.78). Sputum TNF-R2 and IL-6R were also discriminatory in children (ROC AUC 0.85 [95% CI: 0.71 to 0.99] and 0.80 [0.64 to 0.96] respectively). CONCLUSIONS: Severe asthma exacerbations are associated with increased pro-inflammatory and Type 1 (T1) immune mediators. In adults, sputum TNF-R2 and IL-6R were the strongest discriminators of an exacerbation, which were verified in children.

Personal and Neighborhood Attributes Associated with Cervical and Colorectal Cancer Screening in an Urban African American Population.

INTRODUCTION: Assessing individual social determinants of health in primary care might be complemented by consideration of population attributes in patients' neighborhoods. We studied associations between cervical and colorectal cancer screening and neighborhood attributes among an African American population in Philadelphia. METHODS: We abstracted demographic and cancer screening information from records of patients seen during 2006 at 3 federally qualified health centers and characterized patients' census tracts of residence by using census, survey, and other data to define population metrics for poverty, racial segregation, educational attainment, social capital, neighborhood safety, and violent crime. We used generalized estimating equations to obtain adjusted relative risks of screening associated with individual and census tract attributes. RESULTS: Among 1,708 patients for whom colorectal cancer screening was recommended, screening was up to date for 41%, and among 4,995 women for whom cervical cancer screening was recommended, screening was up to date for 75%. After controlling for age, sex (for colorectal cancer screening), insurance coverage, and clinic site, people living in the most racially segregated neighborhoods were nearly 10% more likely than others to be unscreened for colorectal cancer. Other census tract population attributes were not associated with differences in screening levels for either cancer. CONCLUSIONS: The association between lower rates of colorectal cancer screening and neighborhood racial segregation is consistent with known barriers to colonoscopy among African Americans combined with effects of segregation on health-related behaviors. Recognition of the association between segregation and lower colorectal cancer screening rates might be useful in informing and targeting community outreach to improve screening.

Identifying neighborhood characteristics associated with diabetes and hypertension control in an urban African-American population using geo-linked electronic health records.

For health care providers, information on community-level social determinants of health is most valuable when it is specific to the populations and health outcomes for which they are responsible. Diabetes and hypertension are highly prevalent conditions whose management requires an interplay of clinical treatment and behavioral modifications that may be sensitive to community conditions. We used geo-linked electronic health records from 2016 of African American patients of a network of federally qualified health centers in Philadelphia, PA to examine cross-sectional associations between characteristics of patients' residential neighborhoods and hypertension and diabetes control (n = 1061 and n = 2633, respectively). Hypertension and diabetes control were defined to align with the Health Resources and Services Administration (HRSA) Uniform Data System (UDS) reporting requirements for HRSA-funded health centers. We examined associations with nine measures of neighborhood socioeconomic status (poverty, education, deprivation index), social environment (violent crime, perceived safety and social capital, racial segregation), and built environment (land-use mix, intersection density). In demographics-adjusted log-binomial regression models accounting for neighborhood-level clustering, poor diabetes and hypertension control were more common in highly segregated neighborhoods (i.e., high proportion of African American residents relative to the mean for Philadelphia; prevalence ratio = 1.27 [1.02-1.57] for diabetes, 1.22 [1.12-1.33] for hypertension) and less common in more walkable neighborhoods (i.e., higher retail land use). Neighborhood deprivation was also weakly associated with poor hypertension control. An important consideration in making geographic information actionable for providers is understanding how specific community-level determinants affect the patient population beyond individual-level determinants.

Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma.

BACKGROUND: Several animal studies, and one inoculation study in adult asthmatics have shown that interleukin-33 (IL-33) is a major contributor to type-2 inflammation in acute asthma. However, the link between IL-33 and type-2 inflammation has not been shown in naturally occurring asthma exacerbations. OBJECTIVES: To determine if airway IL-33 is associated with type-2 inflammation measured by type-2 cytokines, FeNO and sputum eosinophils in patients presenting to the Emergency Department with an asthma exacerbations. METHODS: Adult patients hospitalized due to acute asthma were enrolled. Upper airways were sampled with nasal swabs and lower airways with induced sputum. Cytokines were measured at protein level using a Luminex® assay and mRNA expression level using droplet-digital-PCR. Airway sampling was repeated four weeks after exacerbation. RESULTS: At the time of exacerbation, upper airway IL-33 correlated with upper airway IL-5 and IL-13 (R = 0.84, p < 0.01 and R = 0.76, p < 0.01, respectively) and with lower airway IL-13 (R = 0.49, p = 0.03). Similar associations were observed for mRNA expression. Lower airway IL-33 positively correlated with lower airway IL-13 (R = 0.84, p < 0.01). IL-13 and IL-33 were positively correlated with FeNO, and IL-5 with eosinophils. The association between IL-33 and type-2 cytokines were still present four weeks after exacerbation. CONCLUSION: This is the first study to demonstrate that airway IL-33 is associated with type-2 cytokines in naturally occurring asthma exacerbations in adults, providing in vivo evidence supporting that IL-33 may be driving type-2 inflammation in acute asthma. Thus supporting IL-33 as a potential future drug target due to its role, upstream in the immunological cascade.

Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles.

BACKGROUND: Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous. OBJECTIVE: We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations. METHODS: Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters. RESULTS: The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1ß, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes. CONCLUSIONS: A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters.

Sputum Inflammatory Mediators Are Increased in Aspergillus fumigatus Culture-Positive Asthmatics.

Aspergillus fumigatus sensitization and culture in asthma are associated with disease severity and lung function impairment, but their relationship with airway inflammation is poorly understood. We investigated the profile of 24 sputum inflammatory mediators in A. fumigatus culture-positive or-negative moderate-to-severe asthmatics. Fifty-two subjects were recruited from a single center. A. fumigatus was cultured from 19 asthmatics. Asthma control, symptom score, lung function, and sputum cell count were not significantly different between the asthmatics with and without a positive A. fumigatus culture. All of the sputum mediators were numerically increased in subjects with a positive versus negative sputum A. fumigatus culture. Sputum TNF-R2 was significantly elevated (P=0.03) and the mediator that best distinguished A. fumigatus culture-positive from culture-negative subjects (receiver-operator characteristic area under the curve 0.66 [95% CI: 0.51 to 0.82, P=0.045]). A. fumigates-positive culture in moderate-to-severe asthma is associated with increased inflammatory sputum mediators.

A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding.

Affinity- and stability-engineered variants of CTLA4-Ig fusion molecules with enhanced pharmacokinetic profiles could yield improved therapies with the potential of higher efficacy and greater convenience to patients. In this study, to our knowledge, we have, for the first time, used in vitro evolution to simultaneously optimize CTLA4 affinity and stability. We selected for improved binding to both ligands, CD80 and CD86, and screened as dimeric Fc fusions directly in functional assays to identify variants with stronger suppression of in vitro T cell activation. The majority of CTLA4 molecules showing the largest potency gains in primary in vitro and ex vivo human cell assays, using PBMCs from type 1 diabetes patients, had significant improvements in CD80, but only modest gains in CD86 binding. We furthermore observed different potency rankings between our lead molecule MEDI5265, abatacept, and belatacept, depending on which type of APC was used, with MEDI5265 consistently being the most potent. We then created fusions of both stability- and potency-optimized CTLA4 moieties with human Fc variants conferring extended plasma t1/2 In a cynomolgus model of T cell-dependent Ab response, the CTLA4-Ig variant MEDI5265 could be formulated at >100 mg/ml for s.c. administration and showed superior efficacy and significantly prolonged serum t1/2 The combination of higher stability and potency with prolonged pharmacokinetics could be compatible with very infrequent, s.c. dosing while maintaining a similar level of immune suppression to more frequently and i.v. administered licensed therapies.

Biological clustering supports both "Dutch" and "British" hypotheses of asthma and chronic obstructive pulmonary disease.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. OBJECTIVE: We sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the "British" or "Dutch" hypotheses of airway disease pathogenesis. METHODS: We compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines. The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts. Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD). RESULTS: Discriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables. Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic. Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL-1ß expression. Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study. CONCLUSIONS: Sputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses. These findings may contribute to improved patient classification to enable stratified medicine.

Inferior intravitreal injection site associated with a higher incidence of post-injection endophthalmitis / 国际眼科杂志(Guoji Yanke Zazhi)

?AlM:To determine whether inferior injections had a higher incidence of post-injection endophthalmitis than superior injections. The incidence of endophthalmitis is higher for inferior than superior trabeculectomy filtering blebs, possibly due to bacteria pooling in the inferior tear lake. ? METHODS: A practice - wide database of endophthalmitis cases identified 5 occurring during the two-year study period. A retrospective review of 8 672 injections in 1 121 eyes of 909 patients treated during the same two-year study period was performed in order to assess the injection site location. ?RESULTS: Five eyes developed presumed infectious endophthalmitis. Eighty percent of endophthalmitis cases were injected inferiorly, even though 84. 6% of the total cohort was injected superiorly. The odds ratio of infection associated with inferior injection location is 22. 1 (P=0. 006). ? CONCLUSlON: Endophthalmitis after intravitreal injection is rare, occurring in only 0. 025% of injections overall. Avoiding intravitreal injections in the inferior quadrants may further reduce the rate of endophthalmitis.

Coming to our senses: the application of somatic psychology to group psychotherapy.

Somatic psychology, the interplay of the body, the mind, the emotions, and the social context, significantly contributes to the theory and practice of group therapy. The processing of sensory experiences in the here-and-now of the therapy group helps group members to develop self-awareness, the ability to understand their relationships with others, and the capacity for empathy. When group members know what they experience, they can understand how others feel and resonate emotionally with those feelings. Neurobiology, sensory processing, and attachment theories help us to understand how the sense of self develops somatically. Principles of somatic therapies are applied to group therapy practice in working with attachment disorders, transference impasse, and trauma. The importance and implications of the group therapist's embodied attunement are explored.