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PubMed1995

Quality initiatives and the power of the database: what they are and how they run.

The criteria by which healthcare is judged or measured are quality, accessibility, and cost effectiveness. To evaluate these criteria it is important to have a database. There are many strengths and weakness to large databases. They can be used as an indicator of the level of performance or quality, for clinical decision making, and as a measurement of cost effectiveness. They can also be useful in the evaluation and development of treatment algorithms and critical pathways for patients with entry level disease. In addition, they can measure patient access to healthcare and the appropriateness of care. It is important for these databases to appropriately adjust for preoperative risk factors that may influence outcome. Outcome in most of the databases is measured by mortality, but morbidity, functional status, quality of life, cost of care, length of stay, return to work, and patient satisfaction are also important outcomes. Factors that can influence the quality of the outcome data are the methods by which the data are collected, standardization of definitions, the currentness of the database, adequate numbers of patients and outcomes, and appropriate analytic techniques. It is important to feed back the data to the healthcare providers in a timely enough fashion so that processes and structures of care can be modified to improve treatment and results. The reliability of the databases and the validity must be substantiated for the healthcare provider to have confidence in the database.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1998

Design, testing, and results of an outcomes-managed approach to patients requiring prolonged mechanical ventilation.

BACKGROUND: Outcomes management that uses critical pathways may decrease costs while improving outcomes for patients who require prolonged mechanical ventilation. OBJECTIVE: To study the efficacy of an outcomes-managed approach to weaning patients from prolonged (more than 3 days) mechanical ventilation. METHODS: A method of multidisciplinary care delivery was designed that included an outcomes manager, a care pathway for patients receiving mechanical ventilation, and weaning protocols. Data collection consisted of three parts: a retrospective review of 124 patients who required prolonged ventilation during a 1-year period before implementation of the care model, a 6-month prospective study in which 91 patients were alternately assigned by month to an outcomes-managed approach or a non-outcomes-managed approach, and a 6-month prospective study of 90 patients in which an outcomes-managed approach without alternate-month assignment was used. RESULTS: Outcomes management had no significant effect on total duration of mechanical ventilation or length of stay in the hospital, days of mechanical ventilation without tracheostomy, days of mechanical ventilation with tracheostomy, or outcome (weaned, withdrawal from mechanical ventilation, death, or transfer without weaning). However, duration of mechanical ventilation was 1.3 days shorter, length of stay in the hospital was 2.1 days shorter, and the cost per case was $ 3341 less for patients in the outcomes-managed group than for patients in the non-outcomes-managed group. CONCLUSION: Outcomes-managed care did not have a significant effect on duration of ventilation, length of stay in the hospital, or outcome in patients receiving long-term mechanical ventilation.

Adult↗
PubMed1997

Building a framework for multiple improvement initiatives.

BACKGROUND: As health care organizations struggle to compete and even survive in today's turbulent marketplace, they often juggle a variety of initiatives addressing cost reduction, quality improvement, critical pathways, accreditation, clinical guidelines, strategic planning, and organizational development-each with its own priorities, advocates, methods, and language. EXAMPLE: One large health care system that had adopted continuous quality improvement (CQI) as a major strategy then responded to significant cost pressures with additional initiatives in reengineering, cost reduction, and physician guidelines, with varying connections to the quality language, principles, and methods. The senior leadership committee for the quality initiative undertook the development of a framework to explain the connections among the diverse projects and approaches-a framework still in use after two years. SUMMARY AND CONCLUSION: In this period of enormous change, health care leaders must quickly and effectively mobilize all available resources to optimize organizational effectiveness. Too often, management's response patterns have overemphasized a "splitting" tactic, managing multiple distinct initiatives. The creation of integrated delivery systems, mergers, acquisitions, and alliance exacerbates this problem, as the number of initiatives multiplies in the new organizations. Development and application of an integrating management framework will accelerate the pace of organizational improvement by increasing shared understanding of the current desired states of the organization; linking strategic, cultural, and method needs and behaviors; aligning various management initiatives in relation to organizational goals and one another; increasing the fit of management methods with specific situations; and providing a unifying perspective and language for organizational members to act and learn collaboratively.

Cost Control↗
PubMed1998

Standardized perioperative care protocols and reduced length of stay after colon surgery.

BACKGROUND: Recent studies have suggested that critical pathways and standard order sets decrease hospital length of stay and improve quality of care. A recently conducted prospective, randomized study at our institution found that patients undergoing elective colon resections had earlier return of bowel function if perioperative epidural anesthesia and analgesia were provided. All patients in the study were also placed on a standardized perioperative regimen. We hypothesized that the standardized perioperative protocol used in this study contributed to early return of bowel function and hospital discharge compared with similar patients managed off protocol. STUDY DESIGN: To test this hypothesis, we performed a case-controlled study comparing the hospital courses of 36 study patients to 36 control patients undergoing colorectal surgery by the same surgeons during the same calendar year. The distribution of types of operations and anesthetic techniques was similar in both groups. RESULTS: As dictated by the protocol, all study patients had their nasogastric tubes removed, were started on a low fat liquid diet, and ambulated in the first postoperative day. Nasogastric tubes were removed in control patients and study patients 2.2 +/- 0.9 (mean value +/- SD) and 1.0 +/- 0.0 days postoperatively, respectively. Control patients were started on an oral diet, usually clear liquids, an average of 2.9 +/- 1.1 days postoperatively, a specific liquid diet was started 1.0 day postoperatively in study patients (p < 0.001). Return of bowel function, as determined by bowel tones, flatus, and bowel movements, occurred approximately 1 day earlier in study patients. Study patients were discharged 1 day sooner than control patients. CONCLUSIONS: Our results suggest that the return of bowel function and the length of stay of patients undergoing colon surgery are improved if patients are entered into a standardized protocol that eliminates variation in intraoperative and postoperative anesthesia and postoperative surgical care. We believe these results can be reproduced in routine clinical surgery by having a clearly outlined protocol for perioperative care similar to that used in this study.

Analgesia, Epidural↗
PubMed2000

Factors predicting prolonged length of stay after carotid endarterectomy.

BACKGROUND: Over the last several years, implementation of critical pathways in patients undergoing carotid endarterectomy has decreased postoperative length of stay significantly. Discharge the day after surgery has become commonplace in many centers, including our own. Unfortunately, managed care may interpret this refinement as a standard of care and limit reimbursement or even disallow admissions extending beyond 1 day. We therefore examined our carotid registry to identify risk factors associated with postoperative length of stay exceeding 1 day. METHODS: We retrospectively reviewed all patients undergoing carotid endarterectomy at our academic center from May 1996 through April 1999. Combined procedures and patients undergoing subsequent noncarotid-related procedures on those admissions were excluded. The charts were inspected for atherosclerosis risk factors, including sex and age, specific attending surgeon, side of the surgery, use of intravenous vasoactive drugs, actual preoperative blood pressure, and presence of neurologic symptoms or postoperative complications. Multiple regression analysis was performed on all collected variables. Statistical significance was inferred for P less than.05. RESULTS: A total of 188 patients met the study criteria and had complete, retrievable medical records. A mean postoperative length of stay of 1.65 +/- 0.08 days and a mean total length of stay of 2.17 +/- 0.14 days were observed. Fifty-seven percent of patients went home the day after surgery. There was a 1.6% stroke-mortality rate. Significant predictors of a prolonged stay, listed in order of decreasing importance on the basis of their calculated contribution to prolonging the postoperative length of stay, are as follows (P value; beta coefficient): postoperative complications (<.0001; 1.03), age > 79 years (.008; 0.547), diabetes mellitus (.011; 0.407), female sex (.007; 0.398), and intravenous vasodilator requirement (. 035; 0.382). Other atherosclerosis risk factors, prior neurologic symptoms, the postoperative use of vasopressors, and reoperative surgery did not contribute to extended length of stay. CONCLUSIONS: Discharge on the first postoperative day is feasible in many, but not all, patients undergoing carotid endarterectomy. Our data help define subsets of patients at risk for prolonged postoperative stay. Targeting these subsets for preoperative medical and social interventions may allow safe early discharge more frequently.

Aged↗
PubMed1999

The Brigham integrated computing system (BICS): advanced clinical systems in an academic hospital environment.

The Brigham integrated computing system (BICS) provides nearly all clinical, administrative, and financial computing services to Brigham and Women's Hospital, an academic tertiary-care hospital in Boston. The BICS clinical information system includes a very wide range of data and applications, including results review, longitudinal medical records, provider order entry, critical pathway management, operating-room dynamic scheduling, critical-event detection and altering, dynamic coverage lists, automated inpatient summaries, and an online reference library. BICS design emphasizes direct physician interaction and extensive clinical decision support. Impact studies have demonstrated significant value of the system in preventing adverse events and in saving costs, particularly for medications.

Computer Security↗
PubMed2006

p53 biological network: at the crossroads of the cellular-stress response pathway and molecular carcinogenesis.

p53 as a key molecular node in the stress response pathway, including inflammation. p53 is involved in several critical pathways including cell cycle arrest, apoptosis, DNA repair, and cellular senescence, which are essential for normal cellular homeostasis and maintaining genome integrity. The alteration of the TP53 gene or posttranslational modification in the p53 protein can alter its response to cellular stress. The molecular archaeology of the TP53 mutation spectrum generates hypotheses concerning the etiology and molecular pathogenesis of human cancer. The spectrum of somatic mutations in the TP53 gene implicates environmental carcinogens, and both endogenous agents and processes in the etiology of human cancer.

Apoptosis↗
PubMed2004

Carcinoma of the prostate: inherited susceptibility, somatic gene defects and androgen receptors.

Multiple factors contribute to the development of prostate carcinoma (PCa) and to its progression to an androgen-independent state. In addition to the expected role of androgens and their receptors in facilitating the development of PCa, mutations in a growing number of candidate hereditary prostate cancer loci and genes, such as RNASEL and MSR1, have been detected, suggesting that defects in critical pathways involving DNA damage response, apoptosis and innate immunity may have a particularly important role in the initiation of PCa. Many somatic mutations, gene deletions, gene amplifications, chromosomal rearrangements, and changes in DNA methylation are detectable in PCa cells at the time of diagnosis. The identification of key molecular alteration cells implicates carcinogen defenses, including GSTP1, growth factor signaling pathways (such as PTEN and p27) and androgens as critical determinants of the phenotype of PCa.

Adenocarcinoma↗
PubMed2001

Indirect exposure assessment at the United States Environmental Protection Agency.

In the early 1980s, exposures and subsequent health impact assessments from contaminants emitted into the air from stationary sources focused on the inhalation pathway. This 'direct' pathway of exposure was thought to be the most critical pathway, as it is for many contaminants. However, by the latter 1980s, the focus at the Environmental Protection Agency (EPA) shifted to contaminants that would persist in the environment and could bioaccumulate up the food chain. Consumption of impacted food products, and other 'indirect' pathways of exposure, such as soil-related exposures, were shown to result in exposures that exceeded inhalation exposures by two to up to four orders of magnitude. A historical background of indirect exposure assessment at EPA is provided in this paper, followed by an overview of modeling methodologies commonly used in indirect exposure assessments. These methodologies are demonstrated on a contaminant of primary focus for indirect exposure impact, dioxins. Two examples are provided. In the first, an air-to-beef model validation exercise is described. In the second, an indirect exposure assessment on a municipal solid waste incinerator in Ohio conducted by the EPA is summarized. This incinerator emitted very large amounts of dioxin, more than any single source known to EPA. Models were used to predict the movement of dioxins from the stack to a nearby hypothetical farm, where individuals in the farm family were exposed to dioxins from consumption of home-produced beef and milk. The predicted lifetime cancer risk of 2.8 x 10(-4) based on these food pathways was used by EPA's Region 5 to initiate regulatory activity on this incinerator.

Agriculture↗
PubMed2003

Military use of depleted uranium: assessment of prolonged population exposure.

This work is an exposure assessment for a population living in an area contaminated by the use of depleted uranium (DU) weapons. RESRAD 5.91 code was used to evaluate the average effective dose at depths of 1, 10, 20 cm of contaminated soil, in a residential farming scenario. Critical pathways and groups are identified in soil inhalation and ingestion; critical group is identified in children playing with the soil. From the available information on DU released at targeted sites, both critical and average exposure can produce toxicological hazards. The annual dose limit for the population can be exceeded within a few years from DU deposition for soil inhalation. As a result, clean up at targeted sites must be planned on the basis of measured concentration, when available, while special measures must be adopted anyway to reduce unaware exposures.

Agriculture↗
PubMed2003

Phospholipase D and choline kinase: their role in cancer development and their potential as drug targets.

Malignant cells result from the accumulation of genetic alterations that impinge into the components of signal transduction pathways controlling cell growth, differentiation and apoptosis. One of the critical pathways is related to the regulation of the phospholipid homeostasis. The identification of the molecular components involved in normal cell growth regulation altered upon transformation is required for the development of chemotherapeutic interventions against transformed cells. Discovery of new chemotherapeutic agents is one of the most promising ways to improve our success against cancer, and rational drug design is a key factor to achieve this goal. Evidence supporting choline kinase and phospholipase D as such novel targets is provided.

Animals↗
PubMed2026

Watershed-scale risk assessment of cadmium contamination in Chinese cropland soils: Dual pathways of irrigation input and flood-driven transport.

Irrigation and flood events serve as critical pathways for the transport of cadmium (Cd) from industrial sources into cropland soils at the watershed scale, constituting a major driver of widespread Cd contamination in China's cropland soil. This study evaluated the risk of Cd contamination in cropland soils across China's nine major river basins at the watershed scale, focusing on the contributions of irrigation and flood events, and conducted a sensitivity analysis of key risk factors. The assessment was conducted within a framework that considered factors including hazard, exposure, and vulnerability. The results revealed that numerous watersheds in southeastern China are exposed to dual pressures of Cd contamination risks in cropland soils, driven by both irrigation practices and flood events. Watersheds categorized as High-High, High-Moderate, or Moderate-High risk, reflecting combined Cd contamination risks from irrigation and flood, are vital to China's grain production, contributing 67.1 % of the national cropland area and 66.4 % of the grain yield. The study suggests localized strategies for managing cropland soils Cd contamination risks from irrigation and flood at the watershed scale in China, alongside strengthened cross-regional collaboration in southeastern China.

Cadmium↗
PubMed2002

The Wnt signaling pathway in bipolar disorder.

The Wnt signaling pathway is a highly conserved pathway critical for proper embryonic development. However, recent evidence suggests that this pathway and one of its key enzymes, glycogen synthase kinase 3beta, may play important roles in regulating synaptic plasticity, cell survival, and circadian rhythms in the mature CNS-all of which have been implicated in the pathophysiology and treatment of bipolar disorder. Furthermore, two structurally highly dissimilar medications used to treat bipolar disorder, lithium and valproic acid, exert effects on components of the Wnt signaling pathway. Together, these data suggest that the Wnt signaling pathway may play an important role in the treatment of bipolar disorder. Here, the authors review the modulation of the Wnt/GSK-3beta signaling pathway by mood-stabilizing agents, focusing on two therapeutically relevant aspects: neuroprotection and modulation of circadian rhythms. The future development of selective GSK-3beta inhibitors may have considerable utility not only for the treatment of bipolar disorder but also for a variety of classical neurodegenerative disorders.

Animals↗
PubMed2006

Signal transduction pathways of inflammatory gene expressions and therapeutic implications.

Intercellular adhesion molecule-1 (ICAM-1), an inducible cell adhesion glycoprotein of the immunoglobulin supergene family and cyclooxygenase-2 (COX-2), an inducible prostaglandin G/H synthase, are overexpressed by proinflammatory mediators in a wide variety of cell types. These stimuli increase ICAM-1 or COX-2 expression primarily through activation of ICAM-1 or COX-2 gene transcription. The architecture of the ICAM-1 or COX-2 promoter is complex, containing a large number of binding site for inducible transcription factors, the most important of which is NF-kB. NF-kB acts in concert with other transcription factors or transcriptional coactivators which facilitate the assembly of distinct stereospecific transcription complexes on the ICAM-1 or COX-2 promoter. These transcription complexes presumably mediate the induction of ICAM-1 or COX-2 expression in different cell types and in response to different stimuli. In this review, I summarize the current understanding of ICAM-1 and COX-2 gene regulation with a particular emphasis on the transcription factors or coactivators, and signal transduction pathways critical for their expression. A PKC-dependent c-Src pathway activating NF-kB or GAS to enhance ICAM-1 or COX-2 gene expression is discussed. Furthermore, natural products and novel agents targeting on the transcription factor with potential anti-inflammation and anti-tumor activity are also discussed.

Animals↗
PubMed2005

Wnt signaling in lung cancer.

Wnt signaling has recently emerged as a critical pathway in lung carcinogenesis as already demonstrated in many cancers and particularly in colorectal cancer. We critically discuss in this review the individual components of the Wnt pathway and their role in lung cancer development. We propose that activation of the Wnt-mediated signal occurs in a different manner in lung cancer than in colorectal cancer. In lung cancer, mutations of APC or beta-catenin are rare and the Wnt pathway appears to be activated upstream of beta-catenin. We identified at least three mechanisms of activation: overexpression of Wnt effectors such as Dvl, activation of a non-canonical pathway involving JNK and repression of Wnt antagonists such as WIF-1. The respective relevance of each event and their likely relationship remain unclear. Nevertheless, we propose that many of the studied components of the Wnt pathway may serve as potential targets in the search for therapeutic agents and we can reasonably argue that blockade of Wnt pathway may lead to new treatment strategies in lung cancer.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Health impacts of large releases of radionuclides. Interactions with human nutrition and other indices of population health.

The consumption of food is an important pathway involved in the internal contamination of humans. The site-related critical foodstuffs can be grouped into three main categories: dairy products; aquatic animals, such as fish, molluscs and crustaceans; and other typical foods. The concentration factor plays a more important role than the amount of a certain food consumed. Semi-natural and natural ecosystems are of special interest in this context because they can provide critical pathways for radionuclide transfer to humans, and they can also act as temporary sinks or long-term sources for radionuclides deposited from the atmosphere. From the viewpoint of population health, another important role is played by the countermeasures. The reference values commonly adopted in radiation protection are conservative and they have been established for planning practices that could provide future sources of irradiation. After a large release of radionuclides, the evaluation of the problem must be as realistic as possible, otherwise the countermeasures will imply consequences worse than those produced by the accident itself (without any further intervention). This criterion was clearly stated by the International Commission on Radiological Protection but it was frequently neglected after the Chernobyl accident. The results of a survey on the number of induced abortions following this incident are reported. These suggest that moral and ethical problems are involved above and beyond any economical implications.

Abortion, Spontaneous↗
PubMed2002

Regulation of choline kinase activity by Ras proteins involves Ral-GDS and PI3K.

Ras proteins are molecular switches that control signaling pathways critical in the onset of a variety of human cancers. The signaling pathways activated by Ras proteins are those controlled by its direct effectors such as the serine-threonine protein kinase Raf-1, the exchange factor for other GTPases Ral-GDS, and the lipid kinase PI3K. As a consequence of Ras activation, a number of additional enzymes are affected, including several members of the serine-threonine intracellular proteins kinases as well as enzymes related to phospholipid metabolism regulation such as phospholipases A2 and D, and choline kinase. The precise mechanisms by which ras oncogenes impinge into these later molecules and their relevance to the onset of the carcinogenic process is still not fully understood. Here we have investigated the mechanism of regulation of choline kinase by Ras proteins and found no direct link between PLD and choline kinase activation. We provide evidence that Ras proteins regulate the activity of choline kinase through its direct effectors Ral-GDS and PI3K, while the Raf pathways seems to be not relevant in this process. The importance of Ras-dependent activation of choline kinase is discussed.

3T3 Cells↗
PubMed2005

Wnt signaling in stem cells and non-small-cell lung cancer.

Evidence suggests that stem cells may be the source of mutant cells that cause cancers to develop and proliferate. Wnt signaling has been shown to promote self-renewal in gut epithelial and hematopoietic stem cells and to trigger critical pathways in carcinogenesis. In this review, we highlight the progress in understanding how the Wnt pathway contributes to stem cell maintenance and its role in lung carcinogenesis. Although the function of stem cells in solid tumor development is unclear, the Wnt pathway's role in determining the fate and self-renewal potential of cancer stem cells suggests a critical role in carcinogenesis and that developing drugs to inhibit this pathway may be of therapeutic interest.

Carcinoma, Non-Small-Cell Lung↗