The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis.

Augmenting hippocampal neurogenesis represents a potential new strategy for treating depression. Here we test this possibility by comparing hippocampal neurogenesis in depression-prone ghrelin receptor (Ghsr)-null mice to that in wild-type littermates and by determining the antidepressant efficacy of the P7C3 class of neuroprotective compounds. Exposure of Ghsr-null mice to chronic social defeat stress (CSDS) elicits more severe depressive-like behavior than in CSDS-exposed wild-type littermates, and exposure of Ghsr-null mice to 60% caloric restriction fails to elicit antidepressant-like behavior. CSDS resulted in more severely reduced cell proliferation and survival in the ventral dentate gyrus (DG) subgranular zone of Ghsr-null mice than in that of wild-type littermates. Also, caloric restriction increased apoptosis of DG subgranular zone cells in Ghsr-null mice, although it had the opposite effect in wild-type littermates. Systemic treatment with P7C3 during CSDS increased survival of proliferating DG cells, which ultimately developed into mature (NeuN+) neurons. Notably, P7C3 exerted a potent antidepressant-like effect in Ghsr-null mice exposed to either CSDS or caloric restriction, while the more highly active analog P7C3-A20 also exerted an antidepressant-like effect in wild-type littermates. Focal ablation of hippocampal stem cells with radiation eliminated this antidepressant effect, further attributing the P7C3 class antidepressant effect to its neuroprotective properties and resultant augmentation of hippocampal neurogenesis. Finally, P7C3-A20 demonstrated greater proneurogenic efficacy than a wide spectrum of currently marketed antidepressant drugs. Taken together, our data confirm the role of aberrant hippocampal neurogenesis in the etiology of depression and suggest that the neuroprotective P7C3-compounds represent a novel strategy for treating patients with this disease.

Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury.

Nerve injuries cause pain, paralysis and numbness that can lead to major disability, and newborns often sustain nerve injuries during delivery that result in lifelong impairment. Without a pharmacologic agent to enhance functional recovery from these injuries, clinicians rely solely on surgery and rehabilitation to treat patients. Unfortunately, patient outcomes remain poor despite application of the most advanced microsurgical and rehabilitative techniques. We hypothesized that the detrimental effects of traumatic neonatal nerve injury could be mitigated with pharmacologic neuroprotection, and tested whether the novel neuroprotective agent P7C3 would block peripheral neuron cell death and enhance functional recovery in a rat neonatal nerve injury model. Administration of P7C3 after sciatic nerve crush injury doubled motor and sensory neuron survival, and also promoted axon regeneration in a dose-dependent manner. Treatment with P7C3 also enhanced behavioral and muscle functional recovery, and reversed pathological mobilization of spinal microglia after injury. Our findings suggest that the P7C3 family of neuroprotective compounds may provide a basis for the development of a new neuroprotective drug to enhance recovery following peripheral nerve injury.

Multi-institutional arrangements: relationships between governing boards and hospital chief executive officers.

This investigation focuses on the impact of multi-institutional arrangements on the role of governing boards in limiting or enhancing the managerial autonomy of individual hospitals. Data from a 1979 Special Survey by the American Hospital Association (N = 4213) are used to examine governing board-administrator relationships as a function of the degree of autonomy and scope of responsibility of the hospital governing board. It is hypothesized that governing boards responsible for multiple hospitals or for multiple nonhospital organizations and those boards accountable to a higher organizational authority will exercise more formal control over hospital chief executive officers (CEOs) than will boards of single or autonomous hospitals. The analysis assumes that formal control by the governing board over the management function of the individual hospital is exercised partly through soliciting or limiting participation by hospital administrators in key policy decisions and through the evaluation of administrative performance. Therefore, it is anticipated that hospitals governed by boards with multiple responsibilities as well as hospitals governed by boards accountable to a higher authority will be (1) less likely to have CEOs who are members of the governing board executive committee, (2) more likely to have annual performance reviews of the CEO by the governing board, and (3) more likely to have such reviews conducted according to preestablished criteria. Study results provide general support for the hypotheses with respect to hospital boards with multiple responsibilities: the data suggest that such boards do exercise greater control over hospital administrators and these effects do appear to be stronger for hospitals in the private sector. Hospitals governed by boards accountable to a higher authority, however, are more likely to have CEOs who are members of the governing board executive committee--a pattern in direct opposition to that hypothesized. Furthermore, these boards are no more likely to conduct annual CEO performance reviews than are boards with more autonomy. Boards accountable to higher authorities are more likely, however, to use preestablished criteria when such reviews are conducted. This general pattern is similar whether hospital boards are accountable to religious authorities, to investor-owned corporate boards, or to the boards of not-for-profit multi-institutional systems. A different pattern emerges, however, for boards accountable to a state, county, or local government authority.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of corporate restructuring on hospital policymaking.

Hospital corporate restructuring is the segmentation of assets or functions of the hospital into separate corporations. While these functions are almost always legally separated from the hospital, their impact on hospital policymaking may be far more direct. This study examines the effects of corporate restructuring by community hospitals on the structure, composition, and activity of hospital governing boards. In general, we expect that the policymaking function of the hospital will change to adapt to the multicorporate structure implemented under corporate restructuring, as well as the overlapping boards and diversified business responsibilities of the new corporate entity. Specifically, we hypothesize that the hospital board under corporate restructuring will conform more to the "corporate" model found in the business/industrial sector and less to the "philanthropic" model common to most community hospitals to date. Analysis of survey data from 1,037 hospitals undergoing corporate restructuring from 1979-1985 and a comparison group of 1,883 noncorporately restructured hospitals suggests general support for this hypothesis. Implications for health care governance and research are discussed.

Hospital board effectiveness: relationships between governing board composition and hospital financial viability.

OBJECTIVE: Two theories--agency and managerialism--are compared with respect to their usefulness in explaining the role of insiders on the hospital board: whether their participation enhances or impairs board financial decision making. DATA SOURCES/STUDY SETTING: The study used 1985 hospital financial and governing board data for a representative sample of acute care California hospitals. STUDY DESIGN: Relationships were examined cross-sectionally between the presence or absence of insiders on the board and measures of hospital financial viability while controlling for the organizational factors of system affiliation, ownership, size, region, and corporate restructuring. PRINCIPAL FINDINGS: Multiple regression analysis found significant relationships between insider (CEO, medical staff) participation and hospital viability. CONCLUSIONS: These results support the managerial theory of governance by suggesting that the CEO and medical staff provide informational advantages to the hospital governing board. However, the cross-sectional design points to the need for future longitudinal studies in order to sequence these relationships between insider participation and improved hospital viability.

The implications of affiliations between Catholic and non-Catholic health care organizations for availability of reproductive health services.

Four case studies of successfully negotiated affiliations between Catholic and non-Catholic organizations reveal the strategies employed to address a range of reproductive health services.

PIP: This article summarizes multiple case studies on decision-making with regard to reproductive health services in affiliations between Catholic and non-Catholic organizations. A database on the number and types of affiliations was compiled during 1990-1996 to provide a national profile of such organizations. Findings of case studies revealed that affiliations between Catholic and non-Catholic health care organizations are diverse in structure, motivated by market and financial issues, and display diverse strategies with regards to reproductive health services. In addition, strategies for providing more comprehensive women's health care were evident in 3 of the 4 case studies. Availability of contraceptive services, female and male sterilization, and infertility services generally was unchanged as a result of affiliations. This shows that affiliations themselves did not significantly affect policies or practices with regards to their provision. Successful negotiations between Catholic and non-Catholic partners involve explicit strategies concerning reproductive health services, some of which curtail specific services and some of which enhance services. Finally, policy-makers have an important role in ensuring that communities receive full disclosure of the nature of affiliations and their possible impact on availability of services.

Impact of divergent evaluations by physicians and patients of patients' complaints.

Physicians' estimates of patients' anxiety, discomfort or pain, and activity limitation were compared with reports by their patients on the same dimensions. The data were collected as part of a series of quality assessment studies at a prepaid group practice serving 19,000 people in a Mid-Atlantic metropolitan area. Analysis of the data showed that physicians underestimated the three dimensions 35 percent of the time and that activity limitation was the dimension most often underestimated. Patients whose physicians correctly estimated their discomfort or pain were more likely to receive prescriptions than patients whose physicians underestimated their discomfort or pain. Patients whose physicians underestimated their activity limitation were most likely to report dissatisfaction with the treatment given. The results are consistent with a growing body of evidence suggesting that physicians who show concern about their patients and a desire to understand their problems establish better therapeutic relationships.

Rural hospital-based alcohol and chemical abuse services: availability and adoption, 1983-1988.

Data from a 1983-88 retrospective panel study of 797 rural (non-Metropolitan Statistical Area) U.S. hospitals revealed that less than one in five (18.7%) had any alcohol and chemical abuse (ACA) service. About one-third of both inpatient and outpatient services had been established during the study period, but few hospitals not offering these services planned to offer them in the immediate future. These findings support other studies that the availability of such services may not meet population need or demand, although non-hospital-sponsored services might partially fill the gap. Bivariate analysis showed that hospital locations in counties that were more densely populated, had higher per capita income and had more physicians per 1,000 population were positively associated with ACA services. Hospitals that were in the New England, Mid-Atlantic, East North Central census divisions, and were large according to number of beds, presence of psychiatric services, availability of psychiatrists and other nonphysician personnel, certain organizational arrangements and strategic management activities were positively associated with ACA services. Multivariable logistic regression suggested the presence of psychiatric services as a key correlate of ACA services, and the scarcity of psychiatric personnel in rural areas appears to have been a major reason for the infrequency of rural hospital-sponsored ACA services.

America's rural hospitals: a selective review of 1980s research.

We review 1980s research on American rural hospitals within the context of a decade of increasing restrictiveness in the reimbursement and operating environments. Areas addressed include rural hospital definitions, organizational and financial performance, and strategic management activities. The latter category consists of hospital closure, diversification and vertical integration, swing-bed conversion, sole community provider designation, horizontal integration and multihospital system affiliation, marketing, and patient retention. The review suggests several research needs, including: developing more meaningful definitions of rural hospitals, engaging in methodologically sound work on the effects of innovative programs and strategic management activities--including conversion of the facility itself--on rural hospital performance, and completing studies of the effects of rural hospital closure or conversion on the health of the communities served.

Strategic activity and financial performance of U.S. rural hospitals: a national study, 1983 to 1988.

This study examines the effect of 13 strategic management activities on the financial performance of a national sample of 797 U.S. rural hospitals during the period of 1983-1988. Controlled for environment-market, geographic-region, and hospital-related variables, the results show almost no measurable effect of strategic adoption on rural hospital profitability and liquidity. Where statistically significant relationships existed, they were more often negative than positive. These findings were not expected; it was hypothesized that positive effects across a broad range of strategies would emerge, other things being equal. Discussed are possible explanations for these findings as well as their implication for a rural health policy relying on individual rural hospital strategic adaptation to environmental change.

Horizontal and vertical integration-diversification in rural hospitals: a national study of strategic activity, 1983-1988.

This study examines both the magnitude of and factors influencing the adoption of 13 horizontal and vertical integration and diversification strategies in a national sample of 797 U.S. rural hospitals during the period 1983-1988. Using organization theory, hypotheses were posed relating environmental and market factors, geographic location, and hospital characteristics to the adoption of horizontal and vertical integration and diversification. Results indicate that only one of 13 strategies was adopted by more than 50 percent of all rural hospitals during the study period, and that most of the directional hypotheses were not confirmed using Cox's proportional hazards models. In particular, environmental and market factors were unrelated to the strategies studied. Issues of methodology and theory are discussed; however, during an historically turbulent period, both relatively low levels of rural hospital strategic activities and lack of predictive power of the theory suggest caution in relying heavily on a policy for rural hospital survival that is dependent on individual market-oriented strategic behavior.

NICU medication errors: identifying a risk profile for medication errors in the neonatal intensive care unit.

OBJECTIVE: To identify a risk profile for harmful medication errors in the neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective cross-sectional study on NICU medication error reports submitted to MEDMARX between 1 January 1999, and 31 December 2005. The Rao-Scott modified chi(2) test was used for analysis. RESULT: 6749 NICU medication error reports were submitted by 163 health-care facilities. Administering errors accounted for approximately one half of errors, and human factors were the most frequently cited cause of error. Patient age was not associated with an increased likelihood of an error being harmful (P=0.11). Error reports involving Institute for Safe Medication Practices (ISMP) High-Alert Medications, occurring in the prescribing phase of medication processing, or involving equipment/delivery device failures were more likely to be harmful (P< or =0.05). CONCLUSION: Risk factors for harmful medication error reports include use of ISMP High-Alert Medications, the prescribing phase of the medication use process, and failure of equipment/delivery devices.

Models of governance in multihospital systems. Implications for hospital and system-level decision-making.

This study utilizes data from a national survey of 159 multihospital systems in order to describe the types of governance structures currently being utilized, and to compare the policy making process for various types of decisions in systems with different approaches to governance. Survey results indicate that multihospital systems most often use one of three governance models. Forty-one percent of the systems (including 33% of system hospitals) use a parent holding company model in which there is a system-wide corporate governing board and separate governing boards for each member hospital. Twenty-two percent of systems in the sample (but 47% of all system hospitals) utilize what we have termed a modified parent holding company model in which there is one system-wide governing board, but advisory boards are substituted for governing boards at the local hospital level. Twenty-three percent of the sampled systems (including 11% of system hospitals) use a corporate model in which there is one system-wide governing board but no other governing or advisory boards at either the divisional, regional or local hospital levels. A comparison of systems using these three governance approaches found significant variation in terms of system size, ownership and the geographic proximity of member hospitals. In order to examine the relationship between alternative approaches to governance and patterns of decision-making, the three model types were compared with respect to the percentages of systems reporting that local boards, corporate management and/or system-wide corporate boards have responsibility for decision-making in a number of specific issue areas. Study results indicate that, regardless of model type, corporate boards are most likely to have responsibility for decisions regarding the transfer, pledging and sale of assets; the formation of new companies; purchase of assets greater than $100,000; changes in hospital bylaws; and the appointment of local board members. In contrast corporate management is relatively uninvolved in these issues, again regardless of governance model type. There is substantial variation in the locus of decision-making responsibility by governance model type for a variety of other issues, however, including: hospital-level service additions and deletions; operating and capital budgets; medical staff privileges, hospital-level long-range planning; hospital CEO performance evaluation and the appointment of hospital CEOs.(ABSTRACT TRUNCATED AT 400 WORDS)

CEO-board relationships under hospital corporate restructuring.

Corporate restructuring has been increasing among the nation's hospitals, but little research has been devoted to assessing how, if at all, this phenomenon affects hospital management and policymaking. This study examines CEO-board relationships in corporately restructured hospitals in relation to more traditionally structured institutions. Analysis of survey responses from 1,179 restructured and 2,010 nonrestructured hospitals indicates that boards of restructured hospitals provide CEOs with greater operational flexibility and control but, at the same time, hold them more accountable for their performance.

Hospital board effectiveness: relationships between board training and hospital financial viability.

This study examined whether hospital governing boards that invest in board education and training are more informed and effective decision-making bodies. Measures of hospital financial viability (i.e., selected financial ratios and outcomes) are used as indicators of hospital board effectiveness. Board participation in educational programs was significantly associated with improved profitability, liquidity, and occupancy levels, suggesting that investment in the education of directors is likely to enhance hospital viability and thus increase board effectiveness.

Does the hospital board need a doctor? The influence of physician board participation on hospital financial performance.

In this study, the authors attempted to determine if physician board participation enhances or impairs the operational performance of a hospital. Two theories--managerialism and agency theory--are compared to determine if participation on the hospital board by inside (i.e., medical staff) and outside physicians provides informational advantages (managerialism) or poses the threat for opportunism (agency theory). Using hospital operating margin to measure hospital performance for a 4-year period (1985-1988), the findings indicate that boards with inside physician (medical staff) participation had significantly better performance than those without such physician participation. Supportive of the managerialist perspective, the findings strongly suggest that medical staff board participation can enhance operational performance. Implications of physician-hospital relations for future hospital strategies as well as health care reform issues are discussed.

Diffusion and adoption of CDC guidelines for the prevention and control of nosocomial infections in US hospitals.

Since 1981, the Centers for Disease Control (CDC) has been publishing Guidelines for the Prevention and Control of Nosocomial Infections as a useful reference tool in infection control. The extent to which practices recommended by CDC to reduce hospital-acquired infections have been successfully diffused and adopted were evaluated in a stratified random sample of 445 US hospitals that were sent a questionnaire in 1985. The data suggest that over 84% of infection control practitioner respondents (78% response rate) are aware of each guideline, although small hospitals (less than 50 beds) are least likely to be aware of the guidelines or to have reviewed them thoroughly. Adoption of the recommendations remains far from universal, ranging from 23% to 75% for 16 specific recommendations investigated. Smaller hospitals were significantly less likely than large hospitals to have adopted each suggested policy. Recommendations that carried Category I rankings were more likely to be adopted, as were those procedures that had cost-savings implications.