US hospital engagement in cross-sector partnerships for population health improvement in socioeconomically distressed counties.

OBJECTIVES: This study identifies the internal characteristics of hospitals located in counties with poor socioeconomic conditions that develop collaborative partnerships with a wide range of community organizations, including non-health organizations. STUDY DESIGN: Cross-sectional study that conducted Chi-square and logistic regression analyses. METHODS: Chi-square tests and logistic regression analyses were performed in this cross-sectional research to identify the internal hospital characteristics associated with non-health sector partnership development for hospitals located in U.S. counties in the worst quartile of performance across three socioeconomic conditions. The 2015 American Hospital Association Population Health Survey provided data on hospitals' collaborative arrangements and internal characteristics, including hospital size, teaching status, ownership type, and system affiliation (n = 1,238). The 2014 County Health Rankings were used to identify counties in the worst quartile of performance on educational attainment, unemployment, and child poverty. RESULTS: Chi-square analyses show that larger hospitals, teaching hospitals, hospitals that belong to a system, and not-for profit hospitals are significantly and positively correlated with non-health sector collaborative partnerships across one or more of the county indicators of poor socioeconomic conditions. Logistic regression results show that the only significant internal hospital characteristic associated with such partnerships is hospital size, in counties with poor educational attainment and those with high child poverty. CONCLUSION: Larger hospitals are more likely to have the resources and strategic perspectives to address community health in counties with poor socioeconomic conditions.

Mindfulness based cognitive therapy for youth with inflammatory bowel disease and depression - Findings from a pilot randomised controlled trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising adjunctive treatment for adolescents and young adults (AYAs) with Inflammatory Bowel Disease (IBD) and comorbid depression. OBJECTIVES: This pilot randomised controlled trial (RCT) aimed to evaluate feasibility and efficacy of an adapted MBCT program for AYA, aged 16-29, with IBD. METHODS: Sixty-four AYAs were randomly allocated to MBCT (n = 33) or treatment as usual (TAU) (n = 31). Primary outcome measure was the depression score on Depression, Anxiety and Stress Scale. Secondary outcomes included anxiety, stress, IBD-related quality of life, coping, mindfulness, post-traumatic growth, medication adherence, IBD activity, inflammatory markers, microbiome characteristics and brain functional connectivity. RESULTS: Study recruitment rate was 75%, retention rate 70%, and session attendance 92%. Intention to treat analyses revealed that, compared to TAU group, MBCT group had significantly lower depression (∆ = -6.0; 95%CI = -10.8 to -1.2; P = 0.015) and stress (∆ = -5.1; 95%CI = -10.1 to -0.0; P = 0.049), higher active coping (∆ = 1.0;95%CI = 0.1-1.9; P = 0.022), and total mindfulness scores (∆ = 10.9;95%CI = 1.1-20.8; P = 0.030) at 8 weeks (post-therapy), and improved coping by positive reframing (∆ = 1.1;95%CI = 0.0-2.2; P = 0.043) and planning (∆ = 0.9;95%CI = 0.0-1.9; P = 0.045), mindful awareness (∆ = 5.2.;95%CI = 2.0-8.5; P = 0.002) and total mindfulness scores (∆ = 10.8.;95%CI = 0.4-21.1; P = 0.042) at 20 weeks. On per protocol analysis, MBCT group had significantly lower depression (∆ = -6.3; 95%CI = -11.4 to -1.2; P = 0.015), stress (∆ = -6.0; 95%CI = -11.2 to -0.5; P = 0.032), increased active coping (∆ = 0.9;95%CI = 0-1.7; P = 0.05) at 8 weeks, and mindful awareness (∆ = 5.4; 95%CI = 2.1-8.6; P = 0.001) at 20 weeks. CONCLUSION: In AYAs with IBD, MBCT is feasible and beneficial in improving depression, stress, mindfulness and adaptive coping. It holds promise as an important component of integrated IBD care. Trial registration number ACTRN12617000876392, U1111-1197-7370; Pre-results.

Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases.

BACKGROUND: Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. AIM: To develop evidence-based consensus statements for TDM-guided anti-TNF therapy in IBD. METHODS: A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. RESULTS: 22/24 statements met criteria for consensus. For anti-TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3-8 and 5-12 µg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints-such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision-making. In stable clinical response, TDM-guided dosing may avoid future relapse. Data indicate drug-tolerant anti-drug antibody assays do not offer an advantage over drug-sensitive assays. Further data are required prior to recommending TDM for non-anti-TNF biological agents. CONCLUSION: Consensus statements support the role of TDM in optimising anti-TNF agents to treat IBD, especially in situations of treatment failure.

Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism.

OBJECTIVE: Mercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG). DESIGN: C57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water. Disease activity was scored daily. At sacrifice, colonic histology, cytokine message, caecal luminal and mucosal microbiomes were analysed. RESULTS: Oral and intrarectal TG but not MP rapidly ameliorated spontaneous chronic colitis in Winnie mice (point mutation in Muc2 secretory mucin). TG ameliorated dextran sodium sulfate-induced chronic colitis in wild-type (WT) mice and in mice lacking T and B lymphocytes. Remarkably, colitis improved without immunosuppressive effects in the absence of host hypoxanthine (guanine) phosphoribosyltransferase (Hprt)-mediated conversion of TG to active drug, the thioguanine nucleotides (TGN). Colonic bacteria converted TG and less so MP to TGN, consistent with intestinal bacterial conversion of TG to so reduce inflammation in the mice lacking host Hprt. TG rapidly induced autophagic flux in epithelial, macrophage and WT but not Hprt-/- fibroblast cell lines and augmented epithelial intracellular bacterial killing. CONCLUSIONS: Treatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation.

The impact of center accreditation on hematopoietic cell transplantation (HCT).

There are two voluntary center-accrediting organizations in the USA, the Foundation for the Accreditation of Cellular Therapy (FACT) and core Clinical Trial Network (CTN) certification, that are thought to improve and ensure hematopoietic cell transplantation (HCT) center quality care and certify clinical excellence. We sought to observe whether there are differences in outcomes between HLA-matched and -mismatched HCT by CTN and FACT status. Using the 2008-2010 Center for International Blood & Marrow Transplant Research data we created three center categories: non-FACT centers (24 centers), FACT-only certified centers (106 centers) and FACT and core clinical trial network (FACT/CTN) certified centers (32 centers). We identified patient characteristics within these centers and the relationship between FACT certification and survival. Our cohort consisted of 12 993 transplants conducted in 162 centers. After adjusting for patient and center characteristics we found that FACT/CTN centers had consistently superior results relative to non-FACT and FACT-only centers (P<0.05) especially for more complex HCT. However, non-FACT centers were comparable to FACT-only centers for matched related and unrelated patients. Although FACT status is an important standard of quality control that begins to define improved OS, our results indicate that FACT status alone is not an indicator for superior outcomes.

Crystal structure of an Xrcc4-DNA ligase IV complex.

A complex of two proteins, Xrcc4 and DNA ligase IV, plays a fundamental role in DNA non-homologous end joining (NHEJ), a cellular function required for double-strand break repair and V(D)J recombination. Here we report the crystal structure of human Xrcc4 bound to a polypeptide that corresponds to the DNA ligase IV sequence linking its two BRCA1 C-terminal (BRCT) domains. In the complex, a single ligase chain binds asymmetrically to an Xrcc4 dimer. The helical tails of Xrcc4 undergo a substantial conformational change relative to the uncomplexed protein, forming a coiled coil that unwinds upon ligase binding, leading to a flat interaction surface. A buried network of charged hydrogen bonds surrounded by extensive hydrophobic contacts explains the observed tightness of the interaction. The strong conservation of residues at the interface between the two proteins provides evidence that the observed mode of interaction has been maintained in NHEJ throughout evolution.

Getting the adrenaline going: crystal structure of the adrenaline-synthesizing enzyme PNMT.

BACKGROUND: Adrenaline is localized to specific regions of the central nervous system (CNS), but its role therein is unclear because of a lack of suitable pharmacologic agents. Ideally, a chemical is required that crosses the blood-brain barrier, potently inhibits the adrenaline-synthesizing enzyme PNMT, and does not affect other catecholamine processes. Currently available PNMT inhibitors do not meet these criteria. We aim to produce potent, selective, and CNS-active PNMT inhibitors by structure-based design methods. The first step is the structure determination of PNMT. RESULTS: We have solved the crystal structure of human PNMT complexed with a cofactor product and a submicromolar inhibitor at a resolution of 2.4 A. The structure reveals a highly decorated methyltransferase fold, with an active site protected from solvent by an extensive cover formed from several discrete structural motifs. The structure of PNMT shows that the inhibitor interacts with the enzyme in a different mode from the (modeled) substrate noradrenaline. Specifically, the position and orientation of the amines is not equivalent. CONCLUSIONS: An unexpected finding is that the structure of PNMT provides independent evidence of both backward evolution and fold recruitment in the evolution of a complex enzyme from a simple fold. The proposed evolutionary pathway implies that adrenaline, the product of PNMT catalysis, is a relative newcomer in the catecholamine family. The PNMT structure reported here enables the design of potent and selective inhibitors with which to characterize the role of adrenaline in the CNS. Such chemical probes could potentially be useful as novel therapeutics.

Managed care, vertical integration strategies and hospital performance.

OBJECTIVE: The purpose of this study is to examine the association of managed care with hospital vertical integration strategies, as well as to observe the relationships of different types of vertical integration with hospital efficiency and financial performance. DATA AND METHODS: The sample consists of 363 California short-term acute care hospitals in 1994. Linear structure equation modeling is used to test six hypotheses derived from the strategic adaptation model. Several organizational and market factors are controlled statistically. PRINCIPAL FINDINGS: Results suggest that managed care is a driving force for hospital vertical integration. In terms of performance, hospitals that are integrated with physician groups and provide outpatient services (backward integration) have better operating margins, returns on assets, and net cash flows (p < 0.01). These hospitals are not, however, likely to show greater productivity. Forward integration with a long-term-care facility, on the other hand, is positively and significantly related to hospital productivity (p < 0.001). Forward integration is negatively related to financial performance (p < 0.05), however, opposite to the direction hypothesized. CONCLUSIONS: Health executives should be responsive to the growth of managed care in their local market and should probably consider providing more backward integrated services rather than forward integrated services in order to improve the hospital's financial performance in today's competitive health care market.

Factors underlying organizational change in local health care markets, 1982-1995.

This article examines the association between characteristics of local health care market areas in 1982 and the penetration of new organizational forms in those markets in 1995. The Northeast and South exhibit less organizational form development than the West. Local markets with higher population size and greater density of specialty physicians in 1982 are associated with greater proportions of the markets being covered by a wide variety of organizational forms in 1995.

Diversity in health administration doctoral education: alternative scenarios for the future.

Doctoral programs in health administration are characterized by extreme diversity in focus, format, content, and market. The observed diversity reflects two key structural attributes of health administration as a doctoral field of study: 1) its multidisciplinary base, and 2) its small size. These attributes leave doctoral programs vulnerable to a host of external pressures. The field lacks structure and organizing principles at the national or international level, and students, employers, and other stakeholders suffer some damaging consequences. Pressures from the institutional environment are weak and splintered (among the constituent disciplines of health administration), while the technical environment (economic forces such as competition for students and research funding) produces a powerful set of incentives that shape the form and substance of health administration doctoral education. As alternatives to the current hybrid nature of the field, two additional future scenarios are considered: Integration with Health Services Research, and Integration with Business Administration. The future of health administration doctoral education is interdependent with 1) the continued differentiation of health administration as a master's field of study; 2) trends in research funding; and 3) economies in the delivery of small-scale or individually customized doctoral education. At the least, programs and students currently would benefit from more information classifying program breadth and goals and reporting outcomes; more adequate information on careers and placement; and a modicum of workforce planning.

Benchmarking organ procurement organizations: a national study.

OBJECTIVE: An exploratory examination of the technical efficiency of organ procurement organizations (OPOs) relative to optimal patterns of production in the population of OPOs in the United States. DATA SOURCES: A composite data set with the OPO as the unit of analysis, constructed from a 1995 national survey of OPOs (n = 64), plus secondary data from the Association of Organ Procurement Organizations and the United Network for Organ Sharing. STUDY DESIGN: The study uses data envelopment analysis (DEA) to evaluate the technical efficiency of all OPOs. PRINCIPAL FINDINGS: Overall, six of the 22 larger OPOs (27 percent) are classified as inefficient, while 23 of the 42 smaller OPOs (55 percent) are classified as inefficient. Efficient OPOs recover significantly more kidneys and extrarenal organs; have higher operating expenses; and have more referrals, donors, extrarenal transplants, and kidney transplants. The quantities of hospital development personnel and other personnel, and formalization of hospital development activities in both small and large OPOs, do not significantly differ. CONCLUSIONS: Indications that larger OPOs are able to operate more efficiently relative to their peers suggest that smaller OPOs are more likely to benefit from technical assistance. More detailed information on the activities of OPO staff would help pinpoint activities that can increase OPO efficiency and referrals, and potentially improve outcomes for large numbers of patients awaiting transplants.

Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease.

High-resolution crystal structures are described for seven macrocycles complexed with HIV-1 protease (HIVPR). The macrocycles possess two amides and an aromatic group within 15-17 membered rings designed to replace N- or C-terminal tripeptides from peptidic inhibitors of HIVPR. Appended to each macrocycle is a transition state isostere and either an acyclic peptide, nonpeptide, or another macrocycle. These cyclic analogues are potent inhibitors of HIVPR, and the crystal structures show them to be structural mimics of acyclic peptides, binding in the active site of HIVPR via the same interactions. Each macrocycle is restrained to adopt a beta-strand conformation which is preorganized for protease binding. An unusual feature of the binding of C-terminal macrocyclic inhibitors is the interaction between a positively charged secondary amine and a catalytic aspartate of HIVPR. A bicyclic inhibitor binds similarly through its secondary amine that lies between its component N-terminal and C-terminal macrocycles. In contrast, the corresponding tertiary amine of the N-terminal macrocycles does not interact with the catalytic aspartates. The amine-aspartate interaction induces a 1.5 A N-terminal translation of the inhibitors in the active site and is accompanied by weakened interactions with a water molecule that bridges the ligand to the enzyme, as well as static disorder in enzyme flap residues. This flexibility may facilitate peptide cleavage and product dissociation during catalysis. Proteases [Aba67,95]HIVPR and [Lys7,Ile33,Aba67,95]HIVPR used in this work were shown to have very similar crystal structures.

Hospital-physician relationships in the integrated delivery system: an ethical analysis.

The need to compete for managed care contracts is causing hospitals and physicians to dramatically change how they do business with each other. Most significant is the formation of integrated delivery health-care systems. The emergence of these systems creates an enhanced need for physicians and administrators to better understand what the other actually does. This article examines the new health-care marketplace from both perspectives and how integrated delivery systems affect individual and community patient care, and it offers guidelines for effective hospital-physician relationships within integrated delivery systems.

Strategic adaptation of US rural hospitals during an era of limited financial resources: a longitudinal study, 1983 to 1993.

This research investigated the competing effects of environmental and organizational pressures on rural hospitals' revenue-enhancing and cost-containment strategies from 1993 to 1993. In general, organizational pressures (multihospital system membership and non-government control) exerted more influence than environmental ones. Also, strategies generally were sustained over time and were particularly interdependent with hospitals' maintenance of staffed beds. Strategies did respond to environmental pressures, however, with revenue enhancement associated with local market competition and munificence, and cost containment associated with pressures from Medicare reimbursement.

Strategic cycling: shaking complacency in healthcare strategic planning.

As the conditions affecting business and healthcare organizations in the United States have become more turbulent and uncertain, strategic planning has decreased in popularity. Strategic planning is criticized for stiffling creative responses to the new marketplace and for fostering compartmentalized organizations, adherence to outmoded strategies, tunnel vision in strategy formulation, and overemphasis on planning to the detriment of implementation. However, effective strategic planning can be a force for mobilizing all the constituents of an organization, creating discipline in pursuit of a goal, broadening an organization's perspective, improving communication among disciplines, and motivating the organization's workforce. It is worthwhile for healthcare organizations to preserve these benefits of strategic planning at the same time recognizing the many sources of turbulence and uncertainty in the healthcare environment. A model of "strategic cycling" is presented to address the perceived shortcomings of traditional strategic planning in a dynamic environment. The cycling model facilitates continuous assessment of the organization's mission/values/vision and primary strategies based on feedback from benchmark analysis, shareholder impact, and progress in strategy implementation. Multiple scenarios and contingency plans are developed in recognition of the uncertain future. The model represents a compromise between abandoning strategic planning and the traditional, linear model of planning based on progress through predetermined stages to a masterpiece plan.

Crystallization and preliminary X-ray analysis of thiaminase I from Bacillus thiaminolyticus: space group change upon freezing of crystals.

Thiaminase I (Mr = 42 100) from B. thiaminolyticus, expressed in E. coli, has been crystallized by the vapor-diffusion method. Three crystal forms, two of which grew from 0.1 M sodium acetate (pH = 4.6), 0.2 M ammonium sulfate and 30%(w/v) PEG 2000, have been examined by X-ray analysis. One crystal form diffracted to 2.5 A at room temperature, was orthorhombic, and had unit-cell edges of a = 87.7, b = 120.5 and c = 76.7 A with space group P212121. A self-Patterson map showed a strong peak indicating noncrystallographic translational pseudosymmetry with (u, v, w) = (0.03, 0.0, 0.5). When these crystals were frozen at liquid-nitrogen temperatures, a second crystal form was observed which had unit-cell dimensions a = 85.5, b = 117.5 and c = 36.6 A with space group P21212. A third crystal form grew from 0.1 M Tris (pH = 8.5), 0.2 M sodium acetate trihydrate and 28%(w/v) PEG 6000 to produce orthorhombic crystals of space group P212121 with cell edges of a = 114.4, b = 123.1 and c = 92.5 A.

Hospital development and the performance of organ procurement organizations.

With more than 56,000 patients on the national waiting list for organ transplants and relatively little growth in the number of donors, organ procurement organizations now recognize the need to aggressively market their services and the range of donor procurement opportunities to hospital personnel. This study examines the types and levels of hospital development activities being conducted by organ procurement organizations, the characteristics of organ procurement organizations that are more involved in hospital development, and the relationship between hospital development and organ procurement. Results from a national survey indicate that, as of the mid-1990s, organ procurement organizations had not made major investments in hospital development despite an increased recognition of the importance of these activities. Organ procurement organizations whose directors were more committed to hospital development exhibited higher levels of hospital development activity. Efforts to formalize hospital development activities through the establishment of a hospital development department and evaluation standards were associated with more organs procured per donor.

Hospital response to the implementation of prospective payment.

This research examined the competing effects of regulatory intensity (Prospective Payment System) and inertial pressure on US hospitals' cost of medical materials, shifting of services from inpatient to outpatient settings, size of the administrative component, and use of new technology. Among the expected findings, regulatory intensity was associated with reduced medical material costs, less new technology and a greater administrative component. Inertial pressures were associated with higher medical material costs, more new technology and less shifting of services from inpatient to outpatient settings. It was concluded that US hospitals respond to regulatory pressures within the context of strong inertial forces. The stronger the inertial forces, the less dramatic a hospital's response to regulatory pressures is likely to be.