Transplant size mismatch in restrictive lung disease.

To maximize the benefit of lung transplantation, the effect of size mismatch on survival in lung transplant recipients with restrictive lung disease (RLD) was examined. All single and bilateral RLD lung transplants from 1987 to 2011 in the United Network for Organ Sharing (UNOS) Database were identified. Donor predicted total lung capacity (pTLC):Recipient pTLC ratio (pTLCr) quantified mismatch. pTLCr was segregated into five strata. A Cox proportional hazards model evaluated the association of pTLCr with mortality hazard. To identify a critical pTLCr, a Cox model using a restricted cubic spline for pTLCr was used. A total of 6656 transplants for RLD were identified. Median pTLCr for single orthotopic lung transplant (SOLT) and bilateral orthotopic lung transplant (BOLT) was 1.0 (0.69-1.47) and 0.98 (0.66-1.45). Examination of pTLCr as a categorical variable revealed that undersizing (pTLCr <0.8) for SOLT and moderate oversizing (pTLCr = 1.1-1.2) for SOLT and BOLT had a harmful survival effect [for SOLT pTLC <0.8: HR 1.711 (95% CI 1.146-2.557), P = 0.01 and for BOLT pTLC 1.1-1.2: HR 1.717 (95% CI 1.112-2.651), P = 0.02]. Spline analysis revealed significant changes in SOLT mortality by variation of pTLCr between 0.8-0.9 and 1.1-1.2. RLD patients undergoing SOLT are susceptible to detriments of an undersized lung. RLD patients undergoing BOLT have higher risk of mortality when pTLCr falls between 1.1 and 1.2.

Postdischarge monitoring using interactive voice response system reduces 30-day readmission rates in a case-managed Medicare population.

BACKGROUND: Automated home monitoring systems have been used to coordinate care to improve patient outcomes and reduce rehospitalizations, but with little formal study of efficacy. The Geisinger Monitoring Program (GMP) interactive voice response protocol is a post-hospital discharge telemonitoring system used as an adjunct to existing case management in a primary care Medicare population to reduce emergency department visits and hospital readmissions. OBJECTIVES: To determine if use of GMP reduced 30-day hospital readmission rates among case-managed patients. RESEARCH DESIGN: A pre-post parallel quasi-experimental study. METHODS: A total of 875 Medicare patients who were enrolled in the combined case-management and GMP program were compared with 2420 matched control patients who were only case managed. Claims data were used to document an acute care admission followed by a readmission within 30 days in the preintervention and postintervention periods (ie, before and during 2009). Regression modeling was used to estimate the within-patient effect of the intervention on readmission rates. RESULTS: The use of GMP with case management was associated with a 44% reduction in 30-day readmissions in the study cohort (95% confidence interval, 23%-60%, P=0.0004), when using the control group to control for secular trends. Similar estimates were obtained when using different propensity score adjustment methods or different approaches to handling dropout observations. CONCLUSIONS: Investing in automated monitoring systems may reduce hospital readmission rates among primary care case-managed patients. Evidence from this quasi-experimental study demonstrates that the combination of telemonitoring and case management, as compared with case management alone, may significantly reduce readmissions in a Medicare Advantage population.

It still takes a village: Advocating healthy living medicine for communities through social justice action.

Countless individuals in the United States continue to experience effects related to the coronavirus disease 2019 (COVID-19) pandemic, such as job/business instability, the breaking down of school systems, isolation, and negative health consequences. There are, however, certain populations and communities that continue to be disproportionately affected, resulting in severe health outcomes, decreased quality of life, and alarmingly high death rates. These populations typically live in historically excluded communities and identify as persons of color. To advance health equity in these communities, healthy living (HL) strategies are paramount. In fact HL Medicine - getting sufficient physical activity, practicing good nutrition, maintaining a healthy body weight, and not smoking, can be a viable solution. Applying these concepts, particularly the promotion of physical activity, through community collaboration can advance the goals of social justice action.

Physics-Based Modelling and Simulation of Multibeam Echosounder Perception for Autonomous Underwater Manipulation.

One of the key distinguishing aspects of underwater manipulation tasks is the perception challenges of the ocean environment, including turbidity, backscatter, and lighting effects. Consequently, underwater perception often relies on sonar-based measurements to estimate the vehicle's state and surroundings, either standalone or in concert with other sensing modalities, to support the perception necessary to plan and control manipulation tasks. Simulation of the multibeam echosounder, while not a substitute for in-water testing, is a critical capability for developing manipulation strategies in the complex and variable ocean environment. Although several approaches exist in the literature to simulate synthetic sonar images, the methods in the robotics community typically use image processing and video rendering software to comply with real-time execution requirements. In addition to a lack of physics-based interaction model between sound and the scene of interest, several basic properties are absent in these rendered sonar images-notably the coherent imaging system and coherent speckle that cause distortion of the object geometry in the sonar image. To address this deficiency, we present a physics-based multibeam echosounder simulation method to capture these fundamental aspects of sonar perception. A point-based scattering model is implemented to calculate the acoustic interaction between the target and the environment. This is a simplified representation of target scattering but can produce realistic coherent image speckle and the correct point spread function. The results demonstrate that this multibeam echosounder simulator generates qualitatively realistic images with high efficiency to provide the sonar image and the physical time series signal data. This synthetic sonar data is a key enabler for developing, testing, and evaluating autonomous underwater manipulation strategies that use sonar as a component of perception.

Immunocrit, colostrum intake, and preweaning body weight gain in piglets after split suckling based on birth weight or birth order.

Preweaning survival and growth are compromised in litters with larger numbers of piglets. We evaluated two approaches for altering initial nursing with the goal to improve access to colostrum by groups of piglets that are known to have reduced access to colostrum. Therefore, we temporarily (1.5 h) removed either the heaviest six piglets in the litter (WT) or the first half of the piglets born (ORD) to provide a short period of nursing with reduced competition for the remaining piglets. We found that WT piglets were heavier (P ≤ 0.05) at 7 d after farrowing and gained more body weight (BW) from farrowing to day 7 than control (CON) piglets which were raised in litters with ad libitum nursing during the same period. Further, we found that the heaviest piglets consumed more (P < 0.001) colostrum and gained more (P < 0.001) BW during the preweaning period but did not have (P > 0.10) greater immunocrits. Although ORD piglets had similar colostrum intake, immunocrits, and preweaning weights as controls, we found that overall the piglets born in the first half of litters had greater (P < 0.01) immunocrits than piglets born in the last half of the litter. Therefore, both birth weight and birth order have effects on traits that are important for prenatal growth and survival, but they differ in that birth weight is more closely related to colostrum intake and birth order affects immunocrit.

Birth weight threshold for identifying piglets at risk for preweaning mortality.

Several studies have suggested there is a critical relationship between piglet birth weight and preweaning mortality. Thus, the objective of the current work was to identify a birth weight threshold value for preweaning mortality. Birth weight and survival data from two studies involving a combined total of 4,068 piglets from 394 litters on four commercial farms (three European, one U.S.) were compiled for a pooled, multistudy analysis. Overall preweaning mortality across the two studies was 12.2%. Key variables used in the analysis were piglet birth weight (measured within 24 h of birth) and corresponding survival outcome (dead or live) by weaning at 3-4 wk of age. A mixed effects logistic regression model was fit to estimate the relationship between preweaning mortality and birth weight. A random effect of study was included to account for overall differences in mortality between the two studies. A piecewise linear predictor was selected to best represent the drastic decrease in preweaning mortality found as birth weight increased in the range of 0.5-1.0 kg and the less extreme change in weight above 1.0 kg. The change point of the birth weight and preweaning mortality model was determined by comparing model fit based on maximizing the likelihood over the interval ranging from 0.5 to 2.3 kg birth weight. Results from the analysis showed a curvilinear relationship between birth weight and preweaning mortality where the birth weight change point value or threshold value was 1.11 kg. In the combined data set, 15.2% of pigs had birth weights ≤1.11 kg. This subpopulation of pigs had a 34.4% preweaning mortality rate and represented 43% of total preweaning mortalities. These findings imply interventions targeted at reducing the incidence of piglets with birth weights ≤1.11 kg have potential to improve piglet survivability. Additional research is needed to validate 1.11 kg as the birth weight threshold for increased risk of preweaning mortality.

Intercellular transfer of mitochondria rescues virus-induced cell death but facilitates cell-to-cell spreading of porcine reproductive and respiratory syndrome virus.

Our recent study showed that intercellular tunneling nanotubes (TNTs) serve as an alternative pathway for cell-to-cell spreading of infectious materials of porcine reproductive and respiratory syndrome virus (PRRSV). In this study, we found that PRRSV infection could induce the formation of TNTs between infected and uninfected cells. Co-culturing PRRSV-infected cells with uninfected cells, including porcine umbilical cord stem cells, rescued PRRSV-induced cell death. Mitochondrion, an important regulator of cell survival/death, was observed transferring from uninfected to PRRSV-infected cells. Importantly, impaired formation of nanotube or defective mitochondrion was unable to rescue infected cells from apoptosis/necrosis. Certain PRRSV proteins were detected to associate with mitochondria and transport from infected to uninfected cells through TNTs. Our results suggest that TNTs-transfer of functional mitochondria rescued PRRSV-infected cells from apoptosis/necrosis in the early stage of infection. On the other hand, mitochondria could be utilized as a vehicle to transport viral materials for spreading the infection.

Porcine Wharton's jelly cells distribute throughout the body after intraperitoneal injection.

BACKGROUND: Wharton's jelly cells (WJCs) have multiple differentiation potentials and are easily harvested in large numbers. WJCs are well tolerated in allogeneic environments and there is a growing list of their therapeutic effects. Most therapies require administering large numbers of cells and this is generally accomplished by intravenous injection. Here, we studied the locations of porcine WJCs in immune-competent, allogeneic hosts after intraperitoneal (IP) injection. METHODS: Male porcine WJCs were administered to female neonatal piglets by IP injection. The location of transplanted cells was examined at 6 h, 24 h, and 7 days after administration using confocal microscopy and polymerase chain reaction (PCR). Transplanted cells were also retrieved from the intestines of recipients and were cultured. Previously transplanted cells were identified by fluorescence in-situ hybridization (FISH) using a Y-chromosome probe. RESULTS: Allogeneic cells were identified in the small and large intestine, stomach, liver, spleen, diaphragm, omentum, kidney, pancreas, mesenteric lymph nodes, heart, lungs, uterus, bladder, and skeletal muscle. Male cells (SRY positive) were found in cultures of cells harvested from the intestinal mucosa 1 week after administration of male porcine WJCs. CONCLUSIONS: Our results show that porcine WJCs distribute widely to the organs in immunocompetent allogeneic hosts after IP administration. They may distribute through the lymphatics initially, and a prominent site of incorporation is the mucosa of the gastrointestinal tract. In that location they could function in the niche of endogenous stem cells and provide secretory products to cells in the tissue damaged by intestinal disease.

Expression of early transcription factors Oct-4, Sox-2 and Nanog by porcine umbilical cord (PUC) matrix cells.

BACKGROUND: Three transcription factors that are expressed at high levels in embryonic stem cells (ESCs) are Nanog, Oct-4 and Sox-2. These transcription factors regulate the expression of other genes during development and are found at high levels in the pluripotent cells of the inner cell mass. The downregulation of these three transcription factors correlates with the loss of pluripotency and self-renewal, and the beginning of subsequent differentiation steps. The roles of Nanog, Oct-4 and Sox-2 have not been fully elucidated. They are important in embryonic development and maintenance of pluripotency in ESCs. We studied the expression of these transcription factors in porcine umbilical cord (PUC) matrix cells. METHODS: Cells were isolated from Wharton's jelly of porcine umbilical cords (PUC) and histochemically assayed for the presence of alkaline phosphatase and the presence of Nanog, Oct-4 and Sox-2 mRNA and protein. PCR amplicons were sequenced and compared with known sequences. The synthesis of Oct-4 and Nanog protein was analyzed using immunocytochemistry. FACS analysis was utilized to evaluate Hoechst 33342 dye-stained cells. RESULTS: PUC isolates were maintained in culture and formed colonies that express alkaline phosphatase. FACS analysis revealed a side population of Hoechst dye-excluding cells, the Hoechst exclusion was verapamil sensitive. Quantitative and non-quantitative RT-PCR reactions revealed expression of Nanog, Oct-4 and Sox-2 in day 15 embryonic discs, PUC cell isolates and porcine fibroblasts. Immunocytochemical analysis detected Nanog immunoreactivity in PUC cell nuclei, and faint labeling in fibroblasts. Oct-4 immunoreactivity was detected in the nuclei of some PUC cells, but not in fibroblasts. CONCLUSION: Cells isolated from PUC express three transcription factors found in pluripotent stem cell markers both at the mRNA and protein level. The presence of these transcription factors, along with the other characteristics of PUC cells such as their colony-forming ability, Hoechst dye-excluding side population and alkaline phosphatase expression, suggests that PUC cells have properties of primitive pluripotent stem cells. Furthermore, PUC cells are an easily and inexpensively obtained source of stem cells that are not hampered by the ethical or legal issues associated with ESCs. In addition, these cells can be cryogenically stored and expanded.

The value of value-based insurance design: savings from eliminating drug co-payments.

OBJECTIVES: To estimate the cost impact of a $0 co-pay prescription drug program implemented by a large healthcare employer as a part of its employee wellness program. STUDY DESIGN: A $0 co-pay program that included approximately 200 antihypertensive, antidiabetic, and antilipid medications was offered to Geisinger Health System (GHS) employees covered by Geisinger Health Plan (GHP) in 2007. Claims data from GHP for the years 2005 to 2011 were obtained. The sample was restricted to continuously enrolled members with Geisinger primary care providers throughout the study period. METHODS: The intervention group, defined as 2251 GHS employees receiving any of the drugs eligible for $0 co-pay, was propensity score matched based on 2 years of pre-intervention claims data to a comparison group, which was defined as 3857 non-GHS employees receiving the same eligible drugs at the same time. Generalized linear models were used to estimate differences in terms of per-member-per-month (PMPM) claims amounts related to prescription drugs and medical care. RESULTS: Total healthcare spending (medical plus prescription drug spending) among the GHS employees was lower by $144 PMPM (13%; 95% CI, $38-$250) during the months when they were taking any of the eligible drugs. Considering the drug acquisition cost and the forgone co-pay, the estimated return on investment over a 5-year period was 1.8. CONCLUSIONS: This finding suggests that VBID implementation within the context of a wider employee wellness program targeting the appropriate population can potentially lead to positive cost savings.

Reduced acute inpatient care was largest savings component of Geisinger Health System's patient-centered medical home.

Early evidence suggests that the patient-centered medical home has the potential to improve patient outcomes while reducing the cost of care. However, it is unclear how this care model achieves such desirable results, particularly its impact on cost. We estimated cost savings associated with Geisinger Health System's patient-centered medical home clinics by examining longitudinal clinic-level claims data from elderly Medicare patients attending the clinics over a ninety-month period (2006 through the first half of 2013). We also used these data to deconstruct savings into its main components (inpatient, outpatient, professional, and prescription drugs). During this period, total costs associated with patient-centered medical home exposure declined by approximately 7.9 percent; the largest source of this savings was acute inpatient care ($34, or 19 percent savings per member per month), which accounts for about 64 percent of the total estimated savings. This finding is further supported by the fact that longer exposure was also associated with lower acute inpatient admission rates. The results of this study suggest that patient-centered medical homes can lead to sustainable, long-term improvements in patient health outcomes and the cost of care.

Impact of a value-based insurance design for back pain on health plan member satisfaction and its implications for patient outcomes.

Back pain is one of the most common reasons for seeking care, and physical therapy (PT) can be an effective treatment option. However, PT coverage for back pain varies widely among private health plans, usually requiring high cost sharing, thereby potentially leading to member dissatisfaction and worse outcomes. In this study, a quasi-experimental design was used to estimate the impact of a new value-based insurance design for back pain-related PT on selected Consumer Assessment of Healthcare Providers and Systems survey items. Under this design, eligible members receive a bundle of 5 PT sessions for a 1-time co-payment; if deemed necessary, the bundle is renewable for 1 additional co-payment. The results indicate that the proportion of members reporting the highest satisfaction rating was higher by about 6 to 10 percentage points among those who received the PT bundle. The data also indicate that those PT bundle members who reported the highest satisfaction rating had improvements in their functional status scores that were roughly 3 to 4 times higher than those who reported a lower satisfaction rating. These findings suggest that providing a value-based insurance design for back pain-related PT can potentially improve health plan members' care experiences and their overall satisfaction. Further study is needed to determine its impact on back pain-related medical care utilization and cost of care.

Primary care diabetes bundle management: 3-year outcomes for microvascular and macrovascular events.

OBJECTIVES: To determine whether a system of care with an all-or-none bundled measure for primary-care management of diabetes mellitus reduced the risk of microvascular and macrovascular complications compared with usual care. STUDY DESIGN: A parallel pre-post observational design was used. In 2006, a system of care for diabetes was implemented for some members of the Geisinger Health Plan. A total of 4095 primary-care patients were in the Diabetes System of Care group (DS) and compared with a propensity score-matched cohort of 4095 primary care patients not in the system of care (non-Diabetes System of Care [NDS]). METHODS: Cumulative hazard rate was measured over a 3-year period for retinopathy, amputation, stroke, and myocardial infarction (MI). RESULTS: The adjusted hazard ratios (HRs) for MI (HR, 0.77; 95% CI, 0.65- 0.90), stroke (HR, 0.79; CI, 0.65-0.97), and retinopathy (HR, 0.81; CI, 0.68-0.97) were all significantly lower among DS patients. The adjusted HR for major amputations (HR, 1.32; CI, 0.45-3.85) did not differ between groups, but only 17 major amputations occurred during the follow-up period. The necessary number of patients to treat in order to prevent 1 event over 3 years was 82 for MI, 178 for stroke, and 151 for retinopathy. CONCLUSIONS: A system of care with an all-or-none bundled measure used in primary care for patients with diabetes may reduce the risk of MI, stroke, and retinopathy over a 3-year period.

Improving patient experience by transforming primary care: evidence from Geisinger's patient-centered medical homes.

Patient-centered medical homes (PCMHs) have the potential to improve patient experience of care. Since 2006, Geisinger Health System has implemented its own version of an advanced PCMH model, referred to as ProvenHealth Navigator (PHN). To evaluate the impact of PHN on patient experience of care, the authors conducted a survey of patients whose primary care clinics had been transformed to "PHN sites" and were under case management at the time of the survey. A comparable survey of patients from non-PHN sites also was conducted for comparison. The results suggest that patients in PHN sites were significantly more likely to report positive changes in their care experience and quality; moreover, they were more likely to cite the physician's office as their usual source of care rather than the emergency room (83% vs. 68% for physician's office; 11% vs. 23% for emergency room). However, the results also suggest that there was no significant difference between PHN and non-PHN patients in their perceptions of access to care or primary care physician performance in terms of patient-centered care (eg, listening, explaining, involving patients in decision making). These findings are consistent with the expectation that transformation of primary care into PCMH can lead to improved patient experience of care.

Can a patient-centered medical home lead to better patient outcomes? The quality implications of Geisinger's ProvenHealth Navigator.

One of the primary goals of the patient-centered medical home (PCMH) is to provide higher quality care that leads to better patient outcomes. Currently, there is only limited evidence regarding the ability of PCMHs to achieve this goal. This article demonstrates the effect of PCMHs in improving certain clinical outcomes, as shown by the ProvenHealth Navigator (PHN), an advanced PCMH model developed and implemented by Geisinger Health System. In this study, the authors examined the claims data from Geisinger Health Plan between 2005 and 2009 and estimated the effect of PHN on reducing amputation rates among patients with diabetes, end-stage renal disease, myocardial infarction, and stroke. The results show that, despite its relatively short period of existence, PHN has led to significant improvements in certain outcomes, further illustrating its potential as a care delivery model to be adopted on a wider scale.

Value-based reengineering: twenty-first century chronic care models.

The need for improved models of chronic care is great and will become critical over the next years as the Medicare-aged population doubles. Many promising models have been developed by outstanding groups across the country. This article reviews key strategies used by successful models in chronic disease management and discusses in detail how Geisinger has evolved and organized its cohesive delivery model.

Reducing long-term cost by transforming primary care: evidence from Geisinger's medical home model.

OBJECTIVES: To estimate cost savings associated with ProvenHealth Navigator (PHN), which is an advanced model of patient-centered medical homes (PCMHs) developed by Geisinger Health System, and determine whether those savings increase over time. STUDY DESIGN: A retrospective claims data analysis of 43 primary care clinics that were converted into PHN sites between 2006 and 2010. The study population included Geisinger Health Plan's Medicare Advantage plan enrollees who were 65 years or older treated in these clinics (26,303 unique members). METHODS: Two patient-level multivariate regression models (with and without interaction effects between prescription drug coverage and PHN exposure) with member fixed effects were used to estimate the effect of members' exposure to PHN on per-member per-month total cost, controlling for member risk, seasonality, yearly trend, and a set of baseline clinic characteristics. RESULTS: In both models, a longer period of PHN exposure was significantly associated with a lower total cost. The total cumulative cost savings over the study period was 7.1% (95% confi dence interval [CI] 2.6-11.6) using the model with the prescription drug coverage interaction effects and 4.3% (95% CI 0.4-8.3) using the model without the interaction effects. Corresponding return on investment was 1.7 (95% CI 0.3-3.0) and 1.0 (95% Cl -0.1 to 2.0), respectively. CONCLUSIONS: Our finding suggests that PCMHs can lead to significant and sustainable cost savings over time.

Non-random tissue distribution of human naïve umbilical cord matrix stem cells.

AIM: To determine the tissue and temporal distribution of human umbilical cord matrix stem (hUCMS) cells in severe combined immunodeficiency (SCID) mice. METHODS: For studying the localization of hUCMS cells, tritiated thymidine-labeled hUCMS cells were injected in SCID mice and tissue distribution was quantitatively determined using a liquid scintillation counter at days 1, 3, 7 and 14. Furthermore, an immunofluorescence detection technique was employed in which anti-human mitochondrial antibody was used to identify hUCMS cells in mouse tissues. In order to visualize the distribution of transplanted hUCMS cells in H&E stained tissue sections, India Black ink 4415 was used to label the hUCMS cells. RESULTS: When tritiated thymidine-labeled hUCMS cells were injected systemically (iv) in female SCID mice, the lung was the major site of accumulation at 24 h after transplantation. With time, the cells migrated to other tissues, and on day three, the spleen, stomach, and small and large intestines were the major accumulation sites. On day seven, a relatively large amount of radioactivity was detected in the adrenal gland, uterus, spleen, lung, and digestive tract. In addition, labeled cells had crossed the blood brain barrier by day 1. CONCLUSION: These results indicate that peripherally injected hUCMS cells distribute quantitatively in a tissue-specific manner throughout the body.

How Geisinger's advanced medical home model argues the case for rapid-cycle innovation.

The Patient Protection and Affordable Care Act of 2010 provides for a number of major payment and delivery system initiatives. These potential changes need to be tested, scaled, and adapted with an urgency not evident in previous demonstration projects of the Centers for Medicare and Medicaid Services. We discuss lessons learned from our iterative tests of care reengineering at Geisinger--specifically, through our advanced medical home model, ProvenHealth Navigator, and the way we continuously modified the model to improve quality and value. We hypothesize that the most important ingredient in our model has been the embedding of nurse case managers into our community practices and the real-time feedback of data on the use of health services by the most complex patients.

Value and the medical home: effects of transformed primary care.

BACKGROUND: The primary care medical home has been promoted to integrate and improve patient care while reducing healthcare spending, but with little formal study of the model or evidence of its efficacy. ProvenHealth Navigator (PHN), an intensive multidimensional medical home model that addresses care delivery and financing, was introduced into 11 different primary care practices. The goals were to improve the quality, efficiency, and patient experience of care. OBJECTIVE: To evaluate the ability of a medical home model to improve the efficiency of care for Medicare beneficiaries. STUDY DESIGN: Observational study using regression modeling based on preintervention and postintervention data and a propensity-selected control cohort. METHODS: Four years of claims data for Medicare patients at 11 intervention sites and 75 control groups were analyzed to compute hospital admission and readmission rates, and the total cost of care. Regression modeling was used to establish predicted rates and costs in the absence of the intervention. Actual results were compared with predicted results to compute changes attributable to the PHN model. RESULTS: ProvenHealth Navigator was associated with an 18% (P <.01) cumulative reduction in inpatient admissions and a 36% (P = .02) cumulative reduction in readmissions across the total population over the study period. CONCLUSIONS: Investing in the capabilities of primary care practices to serve as medical homes may increase healthcare value by improving the efficiency of care. This study demonstrates that the PHN model is capable of significantly reducing admissions and readmissions for Medicare Advantage members.