Island medicine longitudinal cohort study: Rapid rise in chronic kidney disease in rural and remote communities.

AIM: To determine the change in incidence and prevalence of chronic kidney disease (CKD) in rural and remote communities over the last decade. METHODS: We examined the change in age-standardized incidence and prevalence in Tasmania between 2010 and 2020, using a linked dataset that included any adult with a creatinine test taken in a community laboratory during the study period (n = 581 513; 87.8% of the state's adult population). We defined CKD as two measures of eGFR <60 mL/min per 1.73 m2, at least 3 months apart. RESULTS: State-wide age-standardized prevalence of CKD increased by 28% in the decade to 2020, from 516 to 659 per 10 000 population. Prevalence in men increased 31.3% and women 24.8%. The greatest increase in age-standardized prevalence was seen in rural or remote communities with an increase of 36.6% overall, but with considerable variation by community (range + 0.4% to +88.3%). The increase in the actual number of people with CKD in the decade to 2020 was 67%, with the number of women increasing by 58% and men by 79%. CONCLUSION: The age-standardized prevalence of CKD in rural and remote regions has increased considerably over the past decade, likely compounded by limited access to primary and secondary healthcare. These findings highlight the need to ensure healthcare resources are directed to areas of greatest need.

Micrococcin P1 and P2 from Epibiotic Bacteria Associated with Isolates of Moorea producens from Kenya.

Epibiotic bacteria associated with the filamentous marine cyanobacterium Moorea producens were explored as a novel source of antibiotics and to establish whether they can produce cyclodepsipeptides on their own. Here, we report the isolation of micrococcin P1 (1) (C48H49N13O9S6; obs. m/z 1144.21930/572.60381) and micrococcin P2 (2) (C48H47N13O9S6; obs. m/z 1142.20446/571.60370) from a strain of Bacillus marisflavi isolated from M. producens' filaments. Interestingly, most bacteria isolated from M. producens' filaments were found to be human pathogens. Stalked diatoms on the filaments suggested a possible terrestrial origin of some epibionts. CuSO4·5H2O assisted differential genomic DNA isolation and phylogenetic analysis showed that a Kenyan strain of M. producens differed from L. majuscula strain CCAP 1446/4 and L. majuscula clones. Organic extracts of the epibiotic bacteria Pseudoalteromonas carrageenovora and Ochrobactrum anthropi did not produce cyclodepsipeptides. Further characterization of 24 Firmicutes strains from M. producens identified extracts of B. marisflavi as most active. Our results showed that the genetic basis for synthesizing micrococcin P1 (1), discovered in Bacillus cereus ATCC 14579, is species/strain-dependent and this reinforces the need for molecular identification of M. producens species worldwide and their epibionts. These findings indicate that M. producens-associated bacteria are an overlooked source of antimicrobial compounds.

The 2021 Association Research Circulation Osseous Classification for Early-Stage Osteonecrosis of the Femoral Head to Computed Tomography-Based Study.

BACKGROUND: The Association Research Circulation Osseous developed a novel classification for early-stage (precollapse) osteonecrosis of the femoral head (ONFH). We hypothesized that the novel classification is more reliable and valid when compared to previous 3 classifications: Steinberg, modified Kerboul, and Japanese Investigation Committee classifications. METHODS: In the novel classification, necrotic lesions were classified into 3 types: type 1 is a small lesion, where the lateral necrotic margin is medial to the femoral head apex; type 2 is a medium-sized lesion, with the lateral necrotic margin being between the femoral head apex and the lateral acetabular edge; and type 3 is a large lesion, which extends outside the lateral acetabular edge. In a derivation cohort of 40 early-stage osteonecrotic hips based on computed tomography imaging, reliabilities were evaluated using kappa coefficients, and validities to predict future femoral head collapse by chi-squared tests and receiver operating characteristic curve analyses. The predictability for future collapse was also evaluated in a validation cohort of 104 early-stage ONFH. RESULTS: In the derivation cohort, interobserver reliability (k = 0.545) and intraobserver agreement (63%-100%) of the novel method were higher than the other 3 classifications. The novel classification system was best able to predict future collapse (P < .05) and had the best discrimination between non-progressors and progressors in both the derivation cohort (area under the curve = 0.692 [0.522-0.863], P < .05) and the validation cohort (area under the curve = 0.742 [0.644-0.841], P = 2.46 × 10-5). CONCLUSION: This novel classification is a highly reliable and valid method of those examined. Association Research Circulation Osseous recommends using this method as a unified classification for early-stage ONFH. LEVEL OF EVIDENCE: Level III, diagnostic study.

Direct electrochemical observation of glucosidase activity in isolated single lysosomes from a living cell.

The protein activity in individual intracellular compartments in single living cells must be analyzed to obtain an understanding of protein function at subcellular locations. The current methodology for probing activity is often not resolved to the level of an individual compartment, and the results provide an extent of reaction that is averaged from a group of compartments. To address this technological limitation, a single lysosome is sorted from a living cell via electrophoresis into a nanocapillary designed to electrochemically analyze internal solution. The activity of a protein specific to lysosomes, ß-glucosidase, is determined by the electrochemical quantification of hydrogen peroxide generated from the reaction with its substrate and the associated enzymes preloaded in the nanocapillary. Sorting and assaying multiple lysosomes from the same cell shows the relative homogeneity of protein activity between different lysosomes, whereas the protein activity in single lysosomes from different cells of the same type is heterogeneous. Thus, this study for the analysis of protein activity within targeted cellular compartments allows direct study of protein function at subcellular resolution and provides unprecedented information about the homogeneity within the lysosomal population of a single cell.

Single Cell Titration-Type Assay for Plasma Membrane Cholesterol Chemical Potential.

In this paper, a titration-type assay is described that determines the minimum concentration of cholesterol in solution that is required to drive net influx of cholesterol to the plasma membrane and thus increase the cholesterol concentration. The increase in cholesterol in the plasma membrane is detected by cholesterol diffusion at the site of contact by a cholesterol oxidase-modified microelectrode. In the presented thermodynamic model, the minimum solution phase cholesterol concentration that drives influx to the plasma membrane is a close approximation of the true solution-phase equilibrium concentration of cholesterol produced from cellular cholesterol efflux and as such it is a quantitative measure of the chemical potential of cholesterol in the cellular plasma membrane. This assay provides a measure of cholesterol chemical potential in the living cellular plasma membrane through reference to a solution concentration which avoids invoking classic kinetic theory to relate a rate to a specific thermodynamic activity and which avoids uncertainty associated with mass transfer phenomena.

Characteristics of State Policies Impact Health Care Delivery: An Analysis of Mammographic Dense Breast Notification and Insurance Legislation.

BACKGROUND: Increased breast tissue density may mask cancer and thus decrease the diagnostic sensitivity of mammography. A patient group advocacy led to the implementation of laws to increase the awareness of breast tissue density and to improve access to supplemental imaging in many states. Given limited evidence about best practices, variation exists in several characteristics of adopted policies. OBJECTIVE: To identify which characteristics of state-level policies with regard to dense breast tissue were associated with increased use of downstream breast ultrasound. RESEARCH DESIGN: This was a retrospective series of monthly cross-sections of screening mammography procedures before and after implementation of laws. SUBJECTS: A sample of 13,481,554 screening mammography procedures extracted from the MarketScan Research database performed between 2007 and 2014 on privately insured women aged 40-64 years that resided in a state that had implemented relevant legislation during that period. MEASURES: The outcome was an indicator of whether breast ultrasound imaging followed a screening mammography procedure within 30 days. The main independent variables were policy characteristics indicators. RESULTS: Notification of patients about issues surrounding increased breast density was associated with increased follow-up by ultrasound by 1.02 percentage points (P=0.016). Some policy characteristics such as the explicit suggestion of supplemental imaging or mandated coverage of supplemental imaging by health insurance augmented that effect. Other policy characteristics moderated the effect. CONCLUSIONS: The heterogeneous effect of state legislation with regard to dense breast tissue on screening mammography follow-up by ultrasound may be explained by specific and unique characteristics of the approaches taken by a variety of states.

Veteran-centered barriers to VA mental healthcare services use.

BACKGROUND: Some veterans face multiple barriers to VA mental healthcare service use. However, there is limited understanding of how veterans' experiences and meaning systems shape their perceptions of barriers to VA mental health service use. In 2015, a participatory, mixed-methods project was initiated to elicit veteran-centered barriers to using mental healthcare services among a diverse sample of US rural and urban veterans. We sought to identify veteran-centric barriers to mental healthcare to increase initial engagement and continuation with VA mental healthcare services. METHODS: Cultural Domain Analysis, incorporated in a mixed methods approach, generated a cognitive map of veterans' barriers to care. The method involved: 1) free lists of barriers categorized through participant pile sorting; 2) multi-dimensional scaling and cluster analysis for item clusters in spatial dimensions; and 3) participant review, explanation, and interpretation for dimensions of the cultural domain. Item relations were synthesized within and across domain dimensions to contextualize mental health help-seeking behavior. RESULTS: Participants determined five dimensions of barriers to VA mental healthcare services: concern about what others think; financial, personal, and physical obstacles; confidence in the VA healthcare system; navigating VA benefits and healthcare services; and privacy, security, and abuse of services. CONCLUSIONS: These findings demonstrate the value of participatory methods in eliciting meaningful cultural insight into barriers of mental health utilization informed by military veteran culture. They also reinforce the importance of collaborations between the VA and Department of Defense to address the role of military institutional norms and stigmatizing attitudes in veterans' mental health-seeking behaviors.

Contribution of patient, physician, and environmental factors to demographic and health variation in colonoscopy follow-up for abnormal colorectal cancer screening test results.

BACKGROUND: Patient, physician, and environmental factors were identified, and the authors examined the contribution of these factors to demographic and health variation in colonoscopy follow-up after a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) screening. METHODS: In total, 76,243 FOBT/FIT-positive patients were identified from 120 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011 and were followed for 6 months. Patient demographic (race/ethnicity, sex, age, marital status) and health characteristics (comorbidities), physician characteristics (training level, whether primary care provider) and behaviors (inappropriate FOBT/FIT screening), and environmental factors (geographic access, facility type) were identified from VHA administrative records. Patient behaviors (refusal, private sector colonoscopy use) were estimated with statistical text mining conducted on clinic notes, and follow-up predictors and adjusted rates were estimated using hierarchical logistic regression. RESULTS: Roughly 50% of individuals completed a colonoscopy at a VHA facility within 6 months. Age and comorbidity score were negatively associated with follow-up. Blacks were more likely to receive follow-up than whites. Environmental factors attenuated but did not fully account for these differences. Patient behaviors (refusal, private sector colonoscopy use) and physician behaviors (inappropriate screening) fully accounted for the small reverse race disparity and attenuated variation by age and comorbidity score. Patient behaviors (refusal and private sector colonoscopy use) contributed more to variation in follow-up rates than physician behaviors (inappropriate screening). CONCLUSIONS: In the VHA, blacks are more likely to receive colonoscopy follow-up for positive FOBT/FIT results than whites, and follow-up rates markedly decline with advancing age and comorbidity burden. Patient and physician behaviors explain race variation in follow-up rates and contribute to variation by age and comorbidity burden. Cancer 2017;123:3502-12. Published 2017. This article is a US Government work and is in the public domain in the USA.

Can Composite Measures Provide a Different Perspective on Provider Performance Than Individual Measures?

BACKGROUND: Composite measures, which aggregate performance on individual measures into a summary score, are increasingly being used to evaluate facility performance. There is little understanding of the unique perspective that composite measures provide. OBJECTIVE: To examine whether high/low (ie, high or low) performers on a composite measures are also high/low performers on most of the individual measures that comprise the composite. METHODS: We used data from 2 previous studies, one involving 5 measures from 632 hospitals and one involving 28 measures from 112 Veterans Health Administration (VA) nursing homes; and new data on hospital readmissions for 3 conditions from 131 VA hospitals. To compare high/low performers on a composite to high/low performers on the component measures, we used 2-dimensional tables to categorize facilities into high/low performance on the composite and on the individual component measures. RESULTS: In the first study, over a third of the 162 hospitals in the top quintile based on the composite were in the top quintile on at most 1 of the 5 individual measures. In the second study, over 40% of the 27 high-performing nursing homes on the composite were high performers on 8 or fewer of the 28 individual measures. In the third study, 20% of the 61 low performers on the composite were low performers on only 1 of the 3 individual measures. CONCLUSIONS: Composite measures can identify as high/low performers facilities that perform "pretty well" (or "pretty poorly") across many individual measures but may not be high/low performers on most of them.

Practical application of opt-out recruitment methods in two health services research studies.

BACKGROUND: Participant recruitment is an ongoing challenge in health research. Recruitment may be especially difficult for studies of access to health care because, even among those who are in care, people using services least often also may be hardest to contact and recruit. Opt-out recruitment methods (in which potential participants are given the opportunity to decline further contact about the study (opt out) following an initial mailing, and are then contacted directly if they have not opted out within a specified period) can be used for such studies. However, there is a dearth of literature on the effort needed for effective opt-out recruitment. METHODS: In this paper we describe opt-out recruitment procedures for two studies on access to health care within the U.S. Department of Veterans Affairs. We report resource requirements for recruitment efforts (number of opt-out packets mailed and number of phone calls made). We also compare the characteristics of study participants to potential participants via t-tests, Fisher's exact tests, and chi-squared tests. RESULTS: Recruitment rates for our two studies were 12 and 21%, respectively. Across multiple study sites, we had to send between 4.3 and 9.2 opt-out packets to recruit one participant. The number of phone calls required to arrive at a final status for each potentially eligible Veteran (i.e. study participation or the termination of recruitment efforts) were 2.9 and 6.1 in the two studies, respectively. Study participants differed as expected from the population of potentially eligible Veterans based on planned oversampling of certain subpopulations. The final samples of participants did not differ statistically from those who were mailed opt-out packets, with one exception: in one of our two studies, participants had higher rates of mental health service use in the past year than did those mailed opt-out packets (64 vs. 47%). CONCLUSIONS: Our results emphasize the practicality of using opt-out methods for studies of access to health care. Despite the benefits of these methods, opt-out alone may be insufficient to eliminate non-response bias on key variables. Researchers will need to balance considerations of sample representativeness and feasibility when designing studies investigating access to care.

Myopic and Forward Looking Behavior in Branded Oral Anti-Diabetic Medication Consumption: An Example from Medicare Part D.

We evaluate consumption responses to the non-linear Medicare Part D prescription drug benefit. We compare propensity-matched older patients with diabetes and Part D Standard or low-income-subsidy (LIS) coverage. We evaluate monthly adherence to branded oral anti-diabetics, with high end-of-year donut hole prices (>$200) for Standard patients and consistent, low (≤$6) prices for LIS. As an additional control, we examine adherence to generic anti-diabetics, with relatively low, consistent prices for Standard patients. If Standard patients are forward looking, they will reduce branded adherence in January, and LIS-Standard differences will be constant through the year. Contrary to this expectation, branded adherence is lower for Standard patients in January and diverges from LIS as the coverage year progresses. Standard-LIS generic adherence differences are minimal. Our findings suggest that seniors with chronic conditions respond myopically to the nonlinear Part D benefit, reducing consumption in response to high deductible, initial coverage and gap prices. Thus, when the gap is fully phased out in 2020, cost-related nonadherence will likely remain in the face of higher spot prices for more costly branded medications. These results contribute to studies of Part D plan choice and medication adherence that suggest that seniors may not make optimal healthcare decisions. Copyright © 2016 John Wiley & Sons, Ltd.

Understanding collaborative care implementation in the Department of Veterans Affairs: core functions and implementation challenges.

BACKGROUND: The collaborative care model is an evidence-based practice for treatment of depression in which designated care managers provide clinical services, often by telephone. However, the collaborative care model is infrequently adopted in the Department of Veterans Affairs (VA). Almost all VA medical centers have adopted a co-located or embedded approach to integrating mental health care for primary care patients. Some VA medical centers have also adopted a telephone-based collaborative care model where depression care managers support patient education, patient activation, and monitoring of adherence and progress over time. This study evaluated two research questions: (1) What does a dedicated care manager offer in addition to an embedded-only model? (2) What are the barriers to implementing a dedicated depression care manager? METHODS: This study involved 15 qualitative, multi-disciplinary, key informant interviews at two VA medical centers where reimbursement options were the same- both with embedded mental health staff, but one with a depression care manager. Participant interviews were recorded and transcribed. Thematic analysis was used to identify descriptive and analytical themes. RESULTS: Findings suggested that some of the core functions of depression care management are provided as part of embedded-only mental health care. However, formal structural attention to care management may improve the reliability of care management functions, in particular monitoring of progress over time. Barriers to optimal implementation were identified at both sites. Themes from the care management site included finding assertive care managers to hire, cross-discipline integration and collaboration, and primary care provider burden. Themes from interviews at the embedded site included difficulty getting care management on leaders' agendas amidst competing priorities and logistics (staffing and space). CONCLUSIONS: Providers and administrators see depression care management as a valuable healthcare service that improves patient care. Barriers to implementation may be addressed by team-building interventions to improve cross-discipline integration and communication. Findings from this study are limited in scope to the VA healthcare system. Future investigation of whether alternative barriers exist in implementation of depression care management programs in non-VA hospital systems, where reimbursement rates may be a more prominent concern, would be valuable.

Factors Associated With Missed and Cancelled Colonoscopy Appointments at Veterans Health Administration Facilities.

BACKGROUND & AIMS: Cancelled and missed colonoscopy appointments waste resources, increase colonoscopy delays, and can adversely affect patient outcomes. We examined individual and organizational factors associated with missed and cancelled colonoscopy appointments in Veteran Health Administration facilities. METHODS: From 69 facilities meeting inclusion criteria, we identified 27,994 patients with colonoscopy appointments scheduled for follow-up, on the basis of positive fecal occult blood test results, between August 16, 2009 and September 30, 2011. We identified factors associated with colonoscopy appointment status (completed, cancelled, or missed) by using hierarchical multinomial regression. Individual factors examined included age, race, sex, marital status, residence, drive time to nearest specialty care facility, limited life expectancy, comorbidities, colonoscopy in the past decade, referring facility type, referral month, and appointment lead time. Organizational factors included facility region, complexity, appointment reminders, scheduling, and prep education practices. RESULTS: Missed appointments were associated with limited life expectancy (odds ratio [OR], 2.74; P = .0004), no personal history of polyps (OR, 2.74; P < .0001), high facility complexity (OR, 2.69; P = .007), dual diagnosis of psychiatric disorders and substance abuse (OR, 1.82; P < .0001), and opt-out scheduling (OR, 1.57; P = .02). Cancelled appointments were associated with age (OR, 1.61; P = .0005 for 85 years or older and OR, 1.44; P < .0001 for 65-84 years old), no history of polyps (OR, 1.51; P < .0001), and opt-out scheduling (OR, 1.26; P = .04). Additional predictors of both outcomes included race, marital status, and lead time. CONCLUSIONS: Several factors within Veterans Health Administration clinic control can be targeted to reduce missed and cancelled colonoscopy appointments. Specifically, developing systems to minimize referrals for patients with limited life expectancy could reduce missed appointments, and use of opt-in scheduling and reductions in appointment lead time could improve both outcomes.

What Works in Readmissions Reduction: How Hospitals Improve Performance.

BACKGROUND: Hospitals across the United States are pursuing strategies to reduce avoidable readmissions but the evidence on how best to accomplish this goal is mixed, with no specific clinical practice shown to reduce readmissions consistently. Changes to hospital organizational practices, a key component of context, also may be critical to improving performance on readmissions, but this has not been studied. OBJECTIVE: The aim of this study was to understand how high-performing hospitals improved risk-stratified readmission rates, and whether their changes to clinical practices and organizational practices differed from low-performing hospitals. DESIGN: This was a qualitative study of 10 hospitals in which readmission rates had decreased (n=7) or increased (n=3). PARTICIPANTS: A total of 82 hospital staff drawn from hospitals that had participated in the State Action on Avoidable Readmissions quality improvement initiative. RESULTS: High-performing hospitals were distinguished by several organizational practices that facilitated readmissions reduction, that is, collective habits of action or interpretation shared by organization members. First, high-performing hospitals reported focused efforts to improve collaboration across hospital departments. Second, they helped postacute providers improve care by sharing the hospital's clinical and quality improvement expertise and data. Third, high performers enthusiastically engaged in trial and error learning to reduce readmissions. Fourth, they emphasized that readmissions represented bad outcomes for patients, de-emphasizing the role of financial penalties. Both high-performing and low-performing hospitals had implemented most clinical practice changes commonly recommended to reduce readmissions. CONCLUSIONS: Our findings highlight several organizational practices that hospitals may be able to use to enhance the effectiveness of their readmissions reduction efforts.

Communication-Microelectrode Detection of Cholesterol Efflux from the Human Buccel Mucosa.

It has previously demonstrated that cholesterol efflux from the cell plasma membrane is increased in a mouse model of cystic fibrosis (CF) compared to a wild-type control. A noninvasive means of characterizing plasma membrane cholesterol efflux at the surface of airway tissue of CF patients is needed to extend the trends found in animal models of CF to the human disease state. Microelectrode-induced cholesterol efflux from the plasma membrane of cells at the surface of tissue is proposed as a strategy to demonstrate increased cholesterol efflux for CF in human subjects. Data demonstrating detection of cholesterol efflux from the human buccal mucosa is reported as proof-of-concept for an in vivo diagnostic assay.

Relationships between Medicare Advantage contract characteristics and quality-of-care ratings: an observational analysis of Medicare Advantage star ratings.

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) publishes star ratings on Medicare Advantage (MA) contracts to measure plan quality of care with implications for reimbursement and bonuses. OBJECTIVE: To investigate whether MA contract characteristics are associated with quality of care through the Medicare plan star ratings. DESIGN: Retrospective study of MA star ratings in 2010. Unadjusted and adjusted multivariable linear regression models assessed the relationship between 5-star rating summary scores and plan characteristics. SETTING: CMS MA contracts nationally. PARTICIPANTS: 409 (71%) of a total of 575 MA contracts, covering 10.56 million Medicare beneficiaries (90% of the MA population) in the United States in 2010. MEASUREMENTS: The MA quality ratings summary score (stars range from 1 to 5) is a quality measure based on 36 indicators related to processes of care, health outcomes, access to care, and beneficiary satisfaction. RESULTS: Nonprofit, larger, and older MA contracts were more likely to receive higher star ratings. Star ratings ranged from 2 to 5. Nonprofit contracts received an average 0.55 (95% CI, 0.42 to 0.67) higher star ratings than for-profit contracts (P  < 0.001) after controls were set for contract characteristics. LIMITATION: The study focused on persons aged 65 years or older covered by MA. CONCLUSION: In 2010, nonprofit MA contracts received significantly higher star ratings than for-profit contracts. When comparing health plans in the future, the CMS should give increasing attention to for-profit plans with lower quality ratings and consider developing programs to assist newer and smaller plans in improving their care for Medicare beneficiaries. PRIMARY FUNDING SOURCE: None.

Characterizing Pressure and Flow Rate for Aqueous Immersion Surgery.

Hemorrhage control during surgery remains a major clinical challenge for surgeons. Bleeding can affect the safety and efficacy of any surgical procedure. There are well-established methods to address this side-effect of surgery, but all current technologies require the surgeon to direct attention to hemostasis rather than the continuance of the procedure. We have developed a novel surgical method, titled aqueous immersion surgery (AIS), that is able to sustain a bloodless surgical field by providing a controlled hydraulic pressure (immersion pressure) on the bleeding site. Together with the replenishment of an immersion fluid (immersion flow rate), AIS maintains optical clarity of the surgical field. This numerical study was undertaken to investigate the influence of the rate exchange of the immersion fluid on the concentration of blood, hence optical clarity therein. A 3-dimensional multicomponent simulation was performed to evaluate the mixing of blood from an idealized arterial bleeding vessel under pulsatile conditions. With an increase in immersion pressure, bleeding was reduced and increased perfusion was observed. Additionally, the magnitude and direction of the flow field affected the deflection of the bleeding trajectory and, in turn, affected the removal rate of blood from the surgical field. For an idealized case, an optimal immersion flow rate was found for immersion pressures of 100 and 110 mm Hg. From this study, fluid dynamic guidelines are postulated to support future development of AIS.

Role of Exchange Protein Activated by cAMP 1 in Regulating Rates of Microtubule Formation in Cystic Fibrosis Epithelial Cells.

The regulation of microtubule dynamics in cystic fibrosis (CF) epithelial cells and the consequences of reduced rates of microtubule polymerization on downstream CF cellular events, such as cholesterol accumulation, a marker of impaired intracellular transport, are explored here. It is identified that microtubules in both CF cell models and in primary CF nasal epithelial cells repolymerize at a slower rate compared with respective controls. Previous studies suggest a role for cAMP in modulating organelle transport in CF cells, implicating a role for exchange protein activated by cAMP (EPAC) 1, a regulator of microtubule elongation, as a potential mechanism. EPAC1 activity is reduced in CF cell models and in Cftr(-/-) mouse lung compared with respective non-CF controls. Stimulation of EPAC1 activity with the selective EPAC1 agonist, 8-cpt-2-O-Me-cAMP, stimulates microtubule repolymerization to wild-type rates in CF cells. EPAC1 activation also alleviates cholesterol accumulation in CF cells, suggesting a direct link between microtubule regulation and intracellular transport. To verify the relationship between transport and microtubule regulation, expression of the protein, tubulin polymerization-promoting protein, was knocked down in non-CF human tracheal (9/HTEo(-)) cells to mimic the microtubule dysregulation in CF cells. Transduced cells with short hairpin RNA targeting tubulin polymerization-promoting protein exhibit CF-like perinuclear cholesterol accumulation and other cellular manifestations of CF cells, thus supporting a role for microtubule regulation as a mechanism linking CFTR function to downstream cellular manifestation.

How personal and standardized coordination impact implementation of integrated care.

BACKGROUND: Integrating health care across specialized work units has the potential to lower costs and increase quality and access to mental health care. However, a key challenge for healthcare managers is how to develop policies, procedures, and practices that coordinate care across specialized units. The purpose of this study was to identify how organizational factors impacted coordination, and how to facilitate implementation of integrated care. METHODS: Semi-structured interviews were conducted in August 2009 with 30 clinic leaders and 35 frontline staff who were recruited from a convenience sample of 16 primary care and mental health clinics across eight medical centers. Data were drawn from a management evaluation of primary care-mental health integration in the US Department of Veterans Affairs. To protect informant confidentiality, the institutional review board did not allow quotations. RESULTS: Interviews identified antecedents of organizational coordination processes, and highlighted how these antecedents can impact the implementation of integrated care. Overall, implementing new workflow practices were reported to create conflicts with pre-existing standardized coordination processes. Personal coordination (i.e., interpersonal communication processes) between primary care leaders and staff was reported to be effective in overcoming these barriers both by working around standardized coordination barriers and modifying standardized procedures. DISCUSSION: This study identifies challenges to integrated care that might be solved with attention to personal and standardized coordination. A key finding was that personal coordination both between primary care and mental health leaders and between frontline staff is important for resolving barriers related to integrated care implementation. CONCLUSION: Integrated care interventions can involve both new standardized procedures and adjustments to existing procedures. Aligning and integrating procedures between primary care and specialty care requires personal coordination amongst leaders. Interpersonal relationships should be strengthened between staff when personal connections are important for coordinating patient care across clinical settings.

A probability metric for identifying high-performing facilities: an application for pay-for-performance programs.

BACKGROUND: Two approaches are commonly used for identifying high-performing facilities on a performance measure: one, that the facility is in a top quantile (eg, quintile or quartile); and two, that a confidence interval is below (or above) the average of the measure for all facilities. This type of yes/no designation often does not do well in distinguishing high-performing from average-performing facilities. OBJECTIVE: To illustrate an alternative continuous-valued metric for profiling facilities--the probability a facility is in a top quantile--and show the implications of using this metric for profiling and pay-for-performance. METHODS: We created a composite measure of quality from fiscal year 2007 data based on 28 quality indicators from 112 Veterans Health Administration nursing homes. A Bayesian hierarchical multivariate normal-binomial model was used to estimate shrunken rates of the 28 quality indicators, which were combined into a composite measure using opportunity-based weights. Rates were estimated using Markov Chain Monte Carlo methods as implemented in WinBUGS. The probability metric was calculated from the simulation replications. RESULTS: Our probability metric allowed better discrimination of high performers than the point or interval estimate of the composite score. In a pay-for-performance program, a smaller top quantile (eg, a quintile) resulted in more resources being allocated to the highest performers, whereas a larger top quantile (eg, being above the median) distinguished less among high performers and allocated more resources to average performers. CONCLUSION: The probability metric has potential but needs to be evaluated by stakeholders in different types of delivery systems.