Care navigation addresses issues of tele-mental health acceptability and uptake in rural and remote Australian communities.

INTRODUCTION: People living in rural and remote areas face substantial barriers to accessing timely and appropriate mental health services. In the Bowen Basin region of Queensland, Australia, barriers include: limited local providers, long waiting lists, unreliable telecommunication, and reluctance to trial telehealth. Isaac Navicare is a new, community co-designed care navigation service which addresses these barriers by coupling care navigation with supported telehealth, and referrals to mental health providers and other supports. We aimed to understand the reach and effectiveness of Isaac Navicare in improving access to mental health services and address an evidence gap on strategies for improving telehealth acceptability. METHODS: This mixed-methods implementation science evaluation used the RE-AIM Framework. It involved a client database review, survey and semi-structured interviews with service users during the 12-month pilot from November 2021. RESULTS: 197 clients (128 adults, 69 minors) were referred to Navicare during the pilot. Half of adult clients were unemployed, meaning referral options were limited to low-cost or bulk-billed services. Participants described Navicare as supportive and effective in helping to access timely and appropriate mental health supports. Most clients who expressed a treatment modality preference selected face-to-face (n = 111, 85.4%), however most referrals were for telehealth (n = 103, 66.0%) due to a lack of suitable alternatives. The rapport and trust developed with the care navigator was critical for increasing willingness to trial telehealth. Barriers to telehealth included privacy issues, technical difficulties, unreliable internet/phone, and perceived difficulties developing therapeutic rapport. The supported telehealth site was under-utilised. The majority (88.3%, n = 182) of referrals to Navicare were from local health or community service providers or schools. DISCUSSION: Coupling supportive, individualised care navigation with tele-mental health provider options resulted in increased uptake and acceptance of telehealth. Many barriers could be addressed through better preparation of clients and improving promotion and uptake of the supported telehealth site. CONCLUSION: Attitudes towards telehealth have changed during the COVID-19 pandemic, however although the need exists, barriers remain to uptake. Telehealth alone is not enough. Coupling telehealth with other supports such as care navigation improves acceptance and uptake.

Screening Non-neutralizing Anti-idiotype Antibodies Against a Drug Candidate for Total Pharmacokinetic and Target Engagement Assay.

Non-neutralizing anti-idiotype antibodies against a therapeutic monoclonal antibody (mAb) play a crucial role in the creation of total pharmacokinetic (PK) assays and total target engagement (TE) assays during both pre-clinical and clinical development. The development of these anti-idiotype antibodies is challenging. In this study, we utilized a hybridoma platform to produce a variety of anti-idiotype antibodies against GSK2857914, a humanized IgG1 anti-BCMA monoclonal antibody. The candidate clones were evaluated using surface plasmon resonance (SPR) and bio-layer interferometry (BLI) for binding affinity, binding profiling, matrix interference, and antibody pairing determination. We discovered that three anti-idiotype antibodies did not prevent BCMA from binding to GSK2857914. All three candidates demonstrated high binding affinities. One of the three exhibited minimal matrix inference and could pair with the other two candidates. Additionally, one of the three clones was biotinylated as a capture reagent for the total PK assay, and another was labeled with ruthenium as a detection reagent for both the total PK assay and total TE assay. The assay results clearly show that these reagents are genuine non-neutralizing anti-idiotypic antibodies and are suitable for total PK and TE assay development. Based on this and similar studies, we conclude that the hybridoma platform has a high success rate for generating non-neutralizing anti-idiotype antibodies. Our methodology for developing and characterizing non-neutralizing anti-idiotype antibodies to therapeutic antibodies can be generally applied to any antibody-based drug candidate's total PK and total TE assay development.

New Frontiers in Diabetes Care: Quality Improvement Study of a Population Health Team in Rural Critical Access Hospitals.

BACKGROUND: Rural populations are older, have higher diabetes prevalence, and have less improvement in diabetes-related mortality rates compared to urban counterparts. Rural communities have limited access to diabetes education and social support services. OBJECTIVE: Determine if an innovative population health program that integrates medical and social care models improves clinical outcomes for patients with type 2 diabetes in a resource-constrained, frontier area. DESIGN/PARTICIPANTS: Quality improvement cohort study of 1764 patients with diabetes (September 2017-December 2021) at St. Mary's Health and Clearwater Valley Health (SMHCVH), an integrated health care delivery system in frontier Idaho. The United States Department of Agriculture's Office of Rural Health defines frontier as sparsely populated areas that are geographically isolated from population centers and services. INTERVENTION: SMHCVH integrated medical and social care through a population health team (PHT), where staff assess medical, behavioral, and social needs with annual health risk assessments and provide core interventions including diabetes self-management education, chronic care management, integrated behavioral health, medical nutritional therapy, and community health worker navigation. We categorized patients with diabetes into three groups: patients with two or more PHT encounters during the study (PHT intervention), one PHT encounter (minimal PHT), and no PHT encounters (no PHT). MAIN MEASURES: HbA1c, blood pressure, and LDL over time for each study group. KEY RESULTS: Of the 1764 patients with diabetes, mean age was 68.3 years, 57% were male, 98% were white, 33% had three or more chronic conditions, and 9% had at least one unmet social need. PHT intervention patients had more chronic conditions and higher medical complexity. Mean HbA1c of PHT intervention patients significantly decreased from baseline to 12 months (7.9 to 7.6%, p < 0.01) and sustained reductions at 18 months, 24 months, 30 months, and 36 months. Minimal PHT patients decreased HbA1c from baseline to 12 months (7.7 to 7.3%, p < 0.05). CONCLUSION: The SMHCVH PHT model was associated with improved hemoglobin A1c among less well-controlled patients with diabetes.

Trust Dynamics of Community Health Workers in Frontier Food Banks and Pantries: a Qualitative Study.

BACKGROUND: Medical mistrust has had devastating consequences during the COVID-19 pandemic, particularly in rural communities. Community Health Workers (CHWs) have been shown to build trust, but there is little research on trust-building by CHWs in rural communities. OBJECTIVE: This study aims to understand the strategies that CHWs use to build trust with participants of health screenings in frontier Idaho. DESIGN: This is a qualitative study based on in-person, semi-structured interviews. PARTICIPANTS: We interviewed CHWs (N=6) and coordinators of food distribution sites (FDSs; e.g., food banks and pantries) where CHWs hosted a health screening (N=15). APPROACH: Interviews were conducted with CHWs and FDS coordinators during FDS-based health screenings. Interview guides were initially designed to assess facilitators and barriers to health screenings. Trust and mistrust emerged as dominant themes that determined nearly every aspect of the FDS-CHW collaboration, and thus became the focus of interviews. KEY RESULTS: CHWs encountered high levels of interpersonal trust, but low institutional and generalized trust, among the coordinators and clients of rural FDSs. When working to reach FDS clients, CHWs anticipated confronting mistrust due to their association with the healthcare system and government, especially if CHWs were perceived as "outsiders." Hosting health screenings at FDSs, which were trusted community organizations, was important for CHWs to begin building trust with FDS clients. CHWs also volunteered at FDS locations to build interpersonal trust before hosting health screenings. Interviewees agreed that trust building was a time- and resource-intensive process. CONCLUSIONS: CHWs build interpersonal trust with high-risk rural residents, and should be integral parts of trust building initiatives in rural areas. FDSs are vital partners in reaching low-trust populations, and may provide an especially promising environment to reach some rural community members. It is unclear whether trust in individual CHWs also extends to the broader healthcare system.

Predictors of compassion satisfaction and compassion fatigue in health care workers providing health and rehabilitation services in rural and remote locations: A scoping review.

INTRODUCTION: A better understanding of the predictors of compassion satisfaction and compassion fatigue in health care workers in rural and remote communities is needed to inform preventative interventions for this sector of the health workforce. OBJECTIVE: To identify predictors of compassion satisfaction and compassion fatigue in health care workers providing health and rehabilitation services in rural and remote locations. DESIGN: A scoping review informed by Arksey and O'Malley's five-stage framework and the scoping review protocol of the PRISMA-ScR statement. FINDINGS: The search yielded 946 articles, and 34 full texts were screened for eligibility, leaving 12 studies meeting the inclusion criteria. No studies on workers providing rehabilitation services were identified. Three studies assessed possible predictors of compassion satisfaction and compassion fatigue in health care workers, and all studies evaluated burnout. The most studied predictor variables were age, gender, profession and workload. DISCUSSION: This study identified potential risk and protective factors for health care workers that are likely relevant to those providing rehabilitation services in rural locations. Little is known about possible predictors of compassion satisfaction and compassion fatigue in professionals working in rural and remote areas outside of medicine and nursing or health care workers in rural community-based settings. CONCLUSION: Research examining predictors of compassion satisfaction and compassion fatigue in rehabilitation health care workers working in rural and remote locations is scant. Research that identifies risk and protective factors in this rapidly growing sector of the health care workforce is needed to inform the development of interventions that promote professional quality of life.

Technology-facilitated care coordination in rural areas: What is needed?

BACKGROUND: Health is poorer in rural areas and a major challenge is care coordination for complex chronic conditions. The HITECH and 21st Century Cure Acts emphasize health information exchange which underpins activities required to improve care coordination. OBJECTIVE AND METHODS: Using semi-structured interviews and surveys, we examined how providers experience electronic health information exchange during care coordination since these Acts were implemented, with a focus on rural settings where health disparities exist. We used a purposive sample that included primary care, acute care hospitals, and community health services in the United States. FINDINGS: We identified seven themes related to care coordination and information exchange: 'insufficient trust of data'; 'please respond'; 'just fax it'; 'care plans'; 'needle in the haystack'; 're-documentation'; and 'rural reality'. These gaps were magnified when information exchange was required between unaffiliated electronic health records (EHRs) about shared patients, which was more pronounced in rural settings. CONCLUSION: Policy and incentive modifications are likely needed to overcome the observed health information technology (HIT) shortcomings. Rural settings in the United States accentuate problems that can be addressed through international medical informatics policy makers and the implementation and evaluation of interoperable HIT systems.

Internet-Based Monitoring in the Severe Asthma Research Program Identifies a Subgroup of Patients With Labile Asthma Control.

BACKGROUND: We designed an Internet-Based Monitoring Systems (IBS) survey to facilitate monitoring of asthma symptoms and asthma exacerbations in the Severe Asthma Research Program (SARP). Our objective was to evaluate compliance with the IBS survey tool and to explore how data from an IBS tool can inform understanding of asthma phenotypes. METHODS: We invited adult subjects in the SARP III cohort (N = 528) to complete a monthly IBS asthma control survey. We compared the characteristics of subjects who did and those who did not participate in the IBS survey tool. Among subjects who participated in the IBS (IBS+), we identified participants with low, medium, and high Asthma Control Test (ACT) score variability, and we explored asthma morbidity in these three participant subgroups. RESULTS: Two hundred fifty-nine subjects participated in the IBS (IBS+) survey. Compared with subjects who did not engage with the IBS (IBS-) survey, IBS+ subjects were older and more likely to be white, college educated, and have an annual household income > $25,000, and have controlled asthma. Among IBS+ participants, the subgroup with the highest ACT score variability was more likely to have severe asthma, with a lower ACT score at baseline and increased asthma-related health-care use (often precipitated by cold and flulike illnesses). Participants with high ACT variability were also characterized by metabolic dysfunction, as evidenced by obesity and hypertension. CONCLUSIONS: Active participation with an Internet-based symptom survey tool in patients with severe asthma is influenced by race, socioeconomic status, and asthma control. Among survey participants, a group with highly variable (labile) asthma control is identifiable as a specific subgroup with unmet treatment needs. The association of asthma lability, increased susceptibility to adverse asthma effects of cold and flulike illnesses, and metabolic dysfunction provides clues for potentially effective intervention strategies.

The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture.

A carefully timed coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum yielded eight new 16-membered-ring macrolides, berkeleylactones A-H (1, 4, 6-9, 12, 13), as well as the known antibiotic macrolide A26771B (5), patulin, and citrinin. There was no evidence of the production of the berkeleylactones or A26771B (5) by either fungus when grown as axenic cultures. The structures were deduced from analyses of spectral data, and the absolute configurations of compounds 1 and 9 were determined by single-crystal X-ray crystallography. Berkeleylactone A (1) exhibited the most potent antimicrobial activity of the macrolide series, with low micromolar activity (MIC = 1-2 µg/mL) against four MRSA strains, as well as Bacillus anthracis, Streptococcus pyogenes, Candida albicans, and Candida glabrata. Mode of action studies have shown that, unlike other macrolide antibiotics, berkeleylactone A (1) does not inhibit protein synthesis nor target the ribosome, which suggests a novel mode of action for its antibiotic activity.

Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts.

BACKGROUND: Severe asthma is a complex heterogeneous disease associated with older age and obesity. The presence of eosinophilic (type 2) inflammation in some but not all patients with severe asthma predicts responsiveness to current treatments, but new treatment approaches will require a better understanding of non-type 2 mechanisms of severe asthma. We considered the possibility that systemic inflammation, which arises in subgroups of obese and older patients, increases the severity of asthma. Interleukin-6 (IL-6) is a biomarker of systemic inflammation and metabolic dysfunction, and we aimed to explore the association between IL-6 concentrations, metabolic dysfunction, and asthma severity. METHODS: In this cross-sectional analysis, patients were recruited from two cohorts: mainly non-severe asthmatics from the University of California San Francisco (UCSF) and mainly severe asthmatics from the Severe Asthma Research Program (SARP). We generated a reference range for plasma IL-6 in a cohort of healthy control patients. We compared the clinical characteristics of asthmatics with plasma IL-6 concentrations above (IL-6 high) and below (IL-6 low) the upper 95% centile value for plasma IL-6 concentration in the healthy cohort. We also compared how pulmonary function, frequency of asthma exacerbations, and frequency of severe asthma differed between IL-6 low and IL-6 high asthma populations in the two asthma cohorts. FINDINGS: Between Jan 1, 2005, and Dec 31, 2014, we recruited 249 patients from UCSF and between Nov 1, 2012, and Oct 1, 2014, we recruited 387 patients from SARP. The upper 95th centile value for plasma IL-6 concentration in the healthy cohort (n=93) was 3·1 pg/mL, and 14% (36/249) of UCSF cohort and 26% (102/387) of the SARP cohort had plasma IL-6 concentrations above this upper limit. The IL-6 high patients in both asthma cohorts had a significantly higher average BMI (p<0·0001) and a higher prevalence of hypertension (p<0·0001) and diabetes (p=0·04) than the IL-6 low patients. IL-6 high patients also had significantly worse lung function and more frequent asthma exacerbations than IL-6 low patients (all p values <0·0001). Although 80% (111/138) of IL-6 high asthmatic patients were obese, 62% (178/289) of obese asthmatic patients were IL-6 low. Among obese patients, the forced expiratory volume in 1 s (FEV1) was significantly lower in IL-6 high than in IL-6 low patients (mean percent predicted FEV1=70·8% [SD 19·5] vs 78·3% [19·7]; p=0·002), and the percentage of patients reporting an asthma exacerbation in the past 1-2 years was higher in IL-6 high than in IL-6 low patients (66% [73/111] vs 48% [85/178]; p=0·003). Among non-obese asthmatics, FEV1 values and the frequency of asthma exacerbations within the past 1-2 years were also significantly worse in IL-6 high than in IL-6 low patients (mean FEV1 66·4% [SD 23·1] vs 83·2% [20·4] predicted; p<0·0001; 59% [16/27] vs 34% [108/320]; p=0·01). INTERPRETATION: Systemic IL-6 inflammation and clinical features of metabolic dysfunction, which occur most commonly in a subset of obese asthma patients but also in a small subset of non-obese patients, are associated with more severe asthma. These data provide strong rationale to undertake clinical trials of IL-6 inhibitors or treatments that reduce metabolic dysfunction in a subset of patients with severe asthma. Plasma IL-6 is a biomarker that could guide patient stratification in these trials. FUNDING: NIH and the Parker B Francis Foundation.

The thioredoxin system in breast cancer cell invasion and migration.

Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1) in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1) expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS) or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS) levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation.

Treatment of acute cardiac ischemia focuses on reestablishment of blood flow in coronary arteries. However, impaired microvascular perfusion damages peri-infarct tissue, despite arterial patency. Identification of cytokines that induce microvascular dysfunction would provide new targets to limit microvascular damage. Pro-nerve growth factor (NGF), the precursor of NGF, is a well characterized cytokine in the brain induced by injury. ProNGF activates p75 neurotrophin receptor (p75(NTR)) and sortilin receptors to mediate proapoptotic responses. We describe induction of proNGF by cardiomyocytes, and p75(NTR) in human arterioles after fatal myocardial infarction, but not with unrelated pathologies. After mouse cardiac ischemia-reperfusion (I-R) injury, rapid up-regulation of proNGF by cardiomyocytes and p75(NTR) by microvascular pericytes is observed. To identify proNGF actions, we generated a mouse expressing a mutant Ngf allele with impaired processing of proNGF to mature NGF. The proNGF-expressing mouse exhibits cardiac microvascular endothelial activation, a decrease in pericyte process length, and increased vascular permeability, leading to lethal cardiomyopathy in adulthood. Deletion of p75(NTR) in proNGF-expressing mice rescues the phenotype, confirming the importance of p75(NTR)-expressing pericytes in the development of microvascular injury. Furthermore, deficiency in p75(NTR) limits infarct size after I-R. These studies identify novel, nonneuronal actions for proNGF and suggest that proNGF represents a new target to limit microvascular dysfunction.

A large subgroup of mild-to-moderate asthma is persistently noneosinophilic.

RATIONALE: Airway eosinophilia is typical of asthma, and many controller treatments target eosinophilic disease. Asthma is clinically heterogeneous, however, and a subgroup of people with asthma do not have airway eosinophilia. The size of this subgroup is uncertain because prior studies have not examined repeated measures of sputum cytology to determine when people with asthma have intermittent versus persistent sputum eosinophila and when they are persistently noneosinophilic. OBJECTIVES: To determine the prevalence and clinical characteristics of the noneosinophilic asthma phenotype. METHODS: We analyzed sputum cytology data from 995 subjects with asthma enrolled in clinical trials in the Asthma Clinical Research Network where they had undergone sputum induction and measures of sputum cytology, often repeatedly, and assessment of responses to standardized asthma treatments. MEASUREMENTS AND MAIN RESULTS: In cross-sectional analyses, sputum eosinophilia (≥2% eosinophils) was found in only 36% of subjects with asthma not taking an inhaled corticosteroid (ICS) and 17% of ICS-treated subjects with asthma; an absence of eosinophilia was noted frequently, even in subjects with asthma whose disease was suboptimally controlled. In repeated measures analyses of people with asthma not taking an ICS, 22% of subjects had sputum eosinophilia on every occasion (persistent eosinophilia); 31% had eosinophilia on at least one occasion (intermittent eosinophilia); and 47% had no eosinophilia on every occasion (persistently noneosinophilic). Two weeks of combined antiinflammatory therapy caused significant improvements in airflow obstruction in eosinophilic asthma, but not in persistently noneosinophilic asthma. In contrast, bronchodilator responses to albuterol were similar in eosinophilic and noneosinophilic asthma. CONCLUSIONS: Approximately half of patients with mild-to-moderate asthma have persistently noneosinophilic disease, a disease phenotype that responds poorly to currently available antiinflammatory therapy.

The H antigen at epithelial surfaces is associated with susceptibility to asthma exacerbation.

RATIONALE: Acute asthma exacerbations, precipitated by viral infections, are a significant cause of morbidity, but not all patients with asthma are equally susceptible. OBJECTIVES: To explore susceptibility factors for asthma exacerbations, we considered a role for histoblood group antigens because they are implicated in mechanisms of gastrointestinal viral infection, specifically the O-secretor mucin glycan phenotype. We investigated if this phenotype is associated with susceptibility to asthma exacerbation. METHODS: We performed two consecutive case-control studies in subjects with asthma who were either prone or resistant to asthma exacerbations. Exacerbation-prone cases had frequent use of prednisone for an asthma exacerbation and frequent asthma-related healthcare utilization, whereas exacerbation-resistant control subjects had rarely reported asthma exacerbations. The frequency of different mucin glycan phenotypes, defined by the presence or absence of H (O), A, B, or AB antigens, was compared in cases and control subjects. MEASUREMENTS AND MAIN RESULTS: In an initial study consisting of 49 subjects with asthma (23 cases and 26 control subjects), we found that having the O-secretor phenotype was associated with a 5.8-fold increase in the odds of being a case (95% confidence interval, 1.7-21.0; P = 0.006). In a replication study consisting of 204 subjects with asthma (101 cases and 103 control subjects), we found that having the O-secretor phenotype was associated with a 2.3-fold increased odds of being a case (95% confidence interval, 1.2-4.4; P = 0.02). CONCLUSIONS: The O-secretor mucin glycan phenotype is associated with susceptibility to asthma exacerbation. Clinical trial registered at www.clinicaltrials.gov (NCT00201266).

Objective airway monitoring improves asthma control in the cold and flu season: a cluster randomized trial.

BACKGROUND: The goals of asthma care are reductions in risk and impairment, but achieving these goals requires collaborative work between patients and their clinicians. The purpose of this study was to improve inhaled corticosteroid (ICS) adherence and asthma control by cueing therapeutic communication between patients with asthma and their primary care clinicians. METHODS: We conducted a prospective, cluster-randomized, controlled effectiveness trial to assess the effect of providing visually standardized, interpreted peak flow graphs (CUE intervention) to patients and their clinicians on ICS adherence and asthma control. Asthma control outcomes were analyzed by season to account for seasonal variations in exacerbation frequency. RESULTS: Although mean log-transformed ICS adherence was not significantly different between the two groups, there was a trend toward preserved adherence in the intervention group over time (P = .16). Intervention patients required fewer courses of oral steroids during winter (9% vs 23%, P < .001) and spring (3% and 17%, P < .001) compared with control subjects. Intervention patients also had fewer periods of worsening symptoms (65% vs 89%, P < .001) and fewer urgent care visits (10% vs 23%, P < .001) during winter compared with control subjects. Post hoc analysis showed significant improvement in the intervention group with respect to ICS adherence during winter months (P < .05), the likely explanation for the reduction in prednisone use and symptoms. Day-to-day peak flow variability in the intervention group fell consistently throughout the study from an average of 32% at baseline to 23% at final measurement (P < .001), indicating less airway reactivity over time. CONCLUSIONS: Our findings provide evidence of the value of peak flow monitoring for patients with asthma during seasons of greatest vulnerability, the cold/flu season. The peak flow information apparently led to improvements in ICS adherence resulting in less need for prednisone rescue and fewer episodes of worsening symptoms.

Barriers to patient-clinician collaboration in asthma management: the patient experience.

OBJECTIVE: To describe what adult patients with asthma report about their experiences with their own self-management behavior and working with their clinicians to control asthma. METHODS: The study sample consisted of 104 patients with persistent asthma participating in a clinical trial on asthma monitoring. All subjects were seen by primary care clinicians of a large, academic medical center. This qualitative post hoc analysis examined the views of adults with asthma about their asthma-related health care. Patients attended monthly visits as part of their study participation, during which data were derived from semistructured interviews. All patients included in this analysis participated in the study for 1 year. At the end of study participation, patients were asked to complete an evaluation of their clinician's communication behavior. All study clinicians were also asked to complete a self-evaluation of their own communication behavior. RESULTS: Five major themes of barriers to successful self-management were identified, including personal constraints, social constraints, communication failures, medication issues, and health care system barriers to collaboration with their clinicians. Patients most frequently reported lack of communication surrounding issues relating to day-to-day management of asthma (31%) and home management of asthma (24%). Clinicians generally rated themselves well for consistency in showing nonverbal attentiveness (89%) and maintaining interactive conversations (93%). However, only 30% of clinicians reported consistency in helping patients make decisions about asthma management and only 33% of clinicians reported consistency in tailoring medication schedules to the patient's routines. CONCLUSION: These findings emphasize the difficulties of establishing and maintaining a therapeutic partnership between patients and clinicians. The results underscore the need for system-wide interventions that promote the success of a therapeutic patient-clinician relationship in order to achieve long-term success in chronic disease management.

Morphological characteristics of cardiac calcium release units in animals with metabolic and circulatory disorders.

Metabolic and circulatory disorders such as diabetes and hypertension are associated with cardiac dysfunction. Research on these types of experimental animals has observed abnormal calcium (Ca(2+)) sparks and waves in cells; a potential mechanism altering excitation-contraction (e-c) coupling in the myocardium. The e-c coupling depends on the intricate spatial relationship between the sarcolemma and sarcoplasmic reticulum calcium release units (CRU's). The objective of this study was to assess for a presence or absence of abnormalities in CRU's from type II diabetic and hypertensive rat models. Myocardial tissue underwent perfusion fixation followed by selective staining of the CRU's and the features observed using a high voltage electron microscope. Results revealed both diabetic groups had significant increases in body weight, a tendency toward an enlarged heart, and a significant disruption of the CRU's and displacement of transverse (t)-tubules in a longitudinal direction. The hypertensive model characteristically showed a dramatic increase in heart size, a significant increase in disrupted CRU's and a tendency towards longitudinal t-tubule orientation. We propose the two disorders of diabetes and hypertension have a similar etiology of cardiomyopathy resulting, in part, from an increase in the number of incomplete CRU's, due to a morphological change in the architecture and orientation of the t-tubules. These architectural changes could potentially explain the impaired calcium signaling previously observed in diabetic and hypertensive cardiomyopathy.

Improving chronic care of type 2 diabetes using teams of interprofessional learners.

PURPOSE: To improve the care and outcomes of adult patients with type 2 diabetes by teaching interprofessional teams of learners the principles and practices of the Improving Chronic Illness Care Model. METHOD: The study population consisted of 384 adult patients with type 2 diabetes. The study design was a nonrandomized, parallel-group, clinical trial conducted during 18 months in the University of California, San Francisco internal medicine clinics. Interprofessional team care provided by primary care internal medicine residents, nurse practitioner students, and pharmacy students was compared with usual care by internal medicine residents only. Processes of care, clinical status, and health utilization were measured in both patient groups. Learner outcomes also were assessed and compared. RESULTS: At study completion, intervention patients more frequently received assessments of glycosolated hemoglobin (79% versus 67%; P=.01), LDL-C (69% versus 55%; P=.009), blood pressure (86% versus 79%; P=.08), microalbuminuria (40% versus 30%; P=.05), smoking status assessment (43% versus 31%; P=.02), and foot exams (38% versus 20%; P=.0005). Intervention patients had more planned general medicine visits (7.9+/-6.2 versus 6.2+/-5.7; P=.006) than did control patients. Interprofessional learners rated themselves significantly higher on measures of accomplishment, preparation, and success for chronic care than did the usual care learners. CONCLUSIONS: Interprofessional team care by learners was effective in improving quality of care for adult patients with diabetes treated in general medicine clinics. The chronic illness framework resulted in more appropriate health care utilization.

Translation factors direct intrinsic ribosome dynamics during translation termination and ribosome recycling.

Characterizing the structural dynamics of the translating ribosome remains a major goal in the study of protein synthesis. Deacylation of peptidyl-tRNA during translation elongation triggers fluctuations of the pretranslocation ribosomal complex between two global conformational states. Elongation factor G-mediated control of the resulting dynamic conformational equilibrium helps to coordinate ribosome and tRNA movements during elongation and is thus a crucial mechanistic feature of translation. Beyond elongation, deacylation of peptidyl-tRNA also occurs during translation termination, and this deacylated tRNA persists during ribosome recycling. Here we report that specific regulation of the analogous conformational equilibrium by translation release and ribosome recycling factors has a critical role in the termination and recycling mechanisms. Our results support the view that specific regulation of the global state of the ribosome is a fundamental characteristic of all translation factors and a unifying theme throughout protein synthesis.