Cross Disciplinary Role Agreement is Needed When Coordinating Long-Term Opioid Prescribing for Cancer: a Qualitative Study.

BACKGROUND: Cancer pain is highly prevalent and often managed in primary care or by oncology providers in combination with primary care providers. OBJECTIVES: To understand interdisciplinary provider experiences coordinating opioid pain management for patients with chronic cancer-related pain in a large integrated healthcare system. DESIGN: Qualitative research. PARTICIPANTS: We conducted 20 semi-structured interviews with interdisciplinary providers in two large academically affiliated VA Medical Centers and their associated community-based outpatient clinics. Participants included primary care providers (PCPs) and oncology-based personnel (OBPs). APPROACH: We deductively identified 94 examples of care coordination for cancer pain in the 20 interviews. We secondarily used an inductive open coding approach and identified themes through constant comparison coming to research team consensus. RESULTS: Theme 1: PCPs and OBPs generally believed one provider should handle all opioid prescribing for a specific patient, but did not always agree on who that prescriber should be in the context of cancer pain. Theme 2: There are special circumstances where having multiple prescribers is appropriate (e.g., a pain crisis). Theme 3: A collaborative process to opioid cancer pain management would include real-time communication and negotiation between PCPs and oncology around who will handle opioid prescribing. Theme 4: Providers identified multiple barriers in coordinating cancer pain management across disciplines. CONCLUSIONS: Our findings highlight how real-time negotiation about roles in opioid pain management is needed between interdisciplinary clinicians. Lack of cross-disciplinary role agreement may result in delays in clinically appropriate cancer pain management.

The presenilins turned inside out: implications for their structures and functions.

The presenilin (PS) proteins are polytopic integral membrane proteins that are critically involved in the development of Alzheimer's disease. The topography of the PS molecule in the endoplasmic reticulum membrane is widely accepted as exhibiting eight-hydrophobic-transmembrane (8-TM) helices. We have previously provided evidence, however, that the intact PS molecule is also present in the cell surface where it exhibits exclusively a 7-TM topography, which differs in significant structural features from the 8-TM model. This evidence, however, has been disparaged and generally rejected by researchers in Alzheimer's disease. The 7-TM model is definitively demonstrated in the present study for PS-1 at the surfaces of PS-1-transfected cells and for endogenous PS-1 at the surfaces of untransfected cells, by immunofluorescence studies using mAbs. These studies force substantial revision of current views of the structural and functional properties of the PS proteins.

The culture of safety: results of an organization-wide survey in 15 California hospitals.

OBJECTIVE: To understand fundamental attitudes towards patient safety culture and ways in which attitudes vary by hospital, job class, and clinical status. DESIGN: Using a closed ended survey, respondents were questioned on 16 topics important to a culture of safety in health care or other industries plus demographic information. The survey was conducted by US mail (with an option to respond by Internet) over a 6 month period from April 2001 in three mailings. SETTING: 15 hospitals participating in the California Patient Safety Consortium. SUBJECTS: A sample of 6312 employees generally comprising all the hospital's attending physicians, all the senior executives (defined as department head or above), and a 10% random sample of all other hospital personnel. The response rate was 47.4% overall, 62% excluding physicians. Where appropriate, responses were weighted to allow an accurate comparison between participating hospitals and job types and to correct for non-response. MAIN OUTCOME MEASURES: Frequency of responses suggesting an absence of safety culture ("problematic responses" to survey questions) and the frequency of "neutral" responses which might also imply a lack of safety culture. Responses to each question overall were recorded according to hospital, job class, and clinician status. RESULTS: The mean overall problematic response was 18% and a further 18% of respondents gave neutral responses. Problematic responses varied widely between participating institutions. Clinicians, especially nurses, gave more problematic responses than non-clinicians, and front line workers gave more than senior managers. CONCLUSION: Safety culture may not be as strong as is desirable of a high reliability organization. The culture differed significantly, not only between hospitals, but also by clinical status and job class within individual institutions. The results provide the most complete available information on the attitudes and experiences of workers about safety culture in hospitals and ways in which perceptions of safety culture differ among hospitals and between types of personnel. Further research is needed to confirm these results and to determine how senior managers can successfully transmit their commitment to safety to the clinical workplace.

Computational analysis of the potential energy surfaces of glycerol in the gas and aqueous phases: effects of level of theory, basis set, and solvation on strongly intramolecularly hydrogen-bonded systems.

The 126 possible conformations of 1,2,3-propanetriol (glycerol) have been studied by ab initio molecular orbital and density functional theory calculations in the gas and aqueous phases at multiple levels of theory and basis sets. The partial potential energy surface for glycerol as well as an analysis of the conformational properties and hydrogen-bonding trends in both phases have been obtained. In the gas phase at the G2(MP2) and CBS-QB3 levels of theory, the important, low-energy conformers are structures 100 and 95. In the aqueous phase at the SM5.42/HF/6-31G* level of theory, the lowest energy conformers are structures 95 and 46. Boltzmann distributions have been determined from these high-level calculations, and good agreement is observed when these distributions are compared to the available experimental data. These calculations indicate that the enthalpic and entropic contributions to the Gibbs free energy are important for an accurate determination of the conformational and energetic preferences of glycerol. Different levels of theory and basis sets were used in order to understand the effects of nonbonded interactions (i.e., intramolecular hydrogen bonding). The efficiency of basis set and level of theory in dealing with the issue of intramolecular hydrogen bonding and reproducing the correct energetic and geometrical trends is discussed, especially with relevance to practical computational methods for larger polyhydroxylated compounds, such as oligosaccharides.

Scaling theory for two-dimensional systems with competing interactions.

We derive an analytic scaling theory for a two-dimensional system in which spontaneous patterns of stripes, bubbles, and intermediately shaped domains arise due to the competition of short-range attractions and long-range dipolar repulsions. The theory predicts temperature and domain-size scaling as a function of the relative repulsion strength eta, the ratio of the repulsive to the attractive coupling constant in the system's Hamiltonian. As eta decreases, the domain size explodes exponentially and the melting temperature for a system of ordered stripes increases. Our findings shed new light on the phase diagram and critical excitations for the dipolar Ising ferromagnet or lattice gas and their continuum analogs. We show that the features described by the scaling theory are insensitive to details like cutoffs for the dipolar interactions and, therefore, should be widely applicable. Our corresponding states analysis explains the experimentally observed stripe melting upon compression in a Langmuir monolayer. A phenomenological extension of the analytic scaling theory describes how the system's behavior is modified in the presence of magnetization or density fluctuations. Fluctuations are found to suppress domain size and the stripe melting temperature. In regimes where fluctuations are important, we predict that domain size will decrease with increasing temperature.

Congestive heart failure associated with itraconazole.

Itraconazole is a synthetic antifungal agent approved in the USA for the treatment of onychomycosis and serious systemic fungal infections. Animal and clinical pharmacology studies suggest negative inotropic effects with itraconazole. Data from the US Food and Drug Administration's Adverse Event Reporting System suggest that use of itraconazole is associated with congestive heart failure. We summarise the details of 58 cases suggestive of congestive heart failure in association with the use of itraconazole. Labelling of itraconazole has been changed to alert physicians to this new finding.

Uterine artery malformation as a hidden cause of severe uterine bleeding. A case report.

BACKGROUND: Uterine artery malformations are rare, life-threatening conditions. Clinical suspicion is essential for a prompt diagnosis and treatment. CASE: A 29-year-old woman was evaluated for severe uterine bleeding that started abruptly two weeks after elective termination of pregnancy. She underwent dilatation and curettage of the uterine cavity for retained products of conception. The patient presented to the emergency room two weeks later with abrupt onset of profuse vaginal bleeding that would spontaneously subside. Magnetic resonance angiography revealed a left uterine artery malformation that was successfully embolized. CONCLUSION: Uterine artery malformations should be suspected when heavy vaginal bleeding occurs in spite of medical or surgical treatment.

Specific intercellular binding of the beta-amyloid precursor protein to the presenilins induces intercellular signaling: its significance for Alzheimer's disease.

Genetic evidence has implicated three proteins, the beta-amyloid precursor protein (beta-APP) and the two homologous presenilins (PS-1 and PS-2), in the etiology of Alzheimer's disease (AD). How these three proteins jointly contribute to AD, however, is not clear. Nor is any of their normal physiological functions known. Herein, we demonstrate, confirming a prediction made earlier, that beta-APP and either PS-1 or PS-2 act as a specific membrane-bound ligand binding intercellularly with either of its two membrane receptors. This results in a cell-cell adhesion, after which rapid transient increases in protein tyrosine kinase activity and protein tyrosine phosphorylation occur coordinately inside one or both of the two adherent cells. The spectrum of proteins modified by tyrosine phosphorylation differs depending on whether PS-1 or PS-2 is involved in the specific intercellular binding to beta-APP, which implies that PS-1 and PS-2 have distinct, rather than redundant, functions in normal physiology. The relevance of this intercellular interaction and signaling process to AD is discussed.

The managed care backlash and the task force in California.

Signs of a managed care backlash in California are increasing. This paper reports and interprets the recently completed work of the California Managed Health Care Improvement Task Force, focusing on the managed care backlash and the state's regulatory response. Although cost containment was a contributing factor, the causes of and solutions to the backlash differ among consumers, physicians, health care workers, politicians, and health plans. The recommendations of the task force could improve the market for health insurance. However, lasting solutions to the profound problems causing the backlash will require fundamental cultural and systemic change.

Economists' perspectives on health care delivery in California as of 1995.

The health care delivery system is made up of providers--hospitals and doctors--increasingly organized into medical groups. Medical groups interact with payors, primarily health maintenance organizations, that increasingly pass through both risk and prices from increasingly demanding purchasers. This article summarizes the present and future prospects for each of these groups.

Cell surface expression of the Alzheimer disease-related presenilin proteins.

The presenilin proteins PS-1 and PS-2 are crucially involved in Alzheimer disease (AD), but their molecular functions are not known. They are integral membrane proteins, but whether they can be expressed at the surface of cells has been in dispute. Here we show by immunofluorescence experiments, using anti-peptide antibodies specific for either PS-1 or PS-2, that live cultured DAMI cells and differentiated human NT2N neuronal cells are specifically immunolabeled for their endogenous as well as transfected presenilins, although the cells cannot be immunolabeled for their intracellular tubulin, unless they are first fixed and permeabilized. These and other results establish that portions of the presenilins are indeed expressed at the surfaces of these cells. These findings support our previous proposal that the presenilins on the surface of a cell engage in intercellular interactions with the beta-amyloid precursor protein on the surface of a neighboring cell, as a critical step in the molecular and cellular mechanisms that lead to AD.

The seven-transmembrane spanning topography of the Alzheimer disease-related presenilin proteins in the plasma membranes of cultured cells.

To ascertain the membrane topography of the multi-transmembrane spanning presenilin proteins PS-1 and PS-2, anti-peptide antibodies were raised to several specific amino acid sequences in the two proteins, and, after their specificity was ascertained, the anti-peptide antibodies were used in immunofluorescent labeling of live PS-transfected, cultured DAMI cells, which are impermeable to the antibodies, as well as of their fixed and permeabilized counterparts. In such experiments, antibodies that specifically stain the intact live cells must label epitopes of the PS proteins that are on the exterior face of the plasma membrane whereas those antibodies that do not stain the live cells but do stain the fixed and permeabilized cells must label epitopes that face the cytoplasmic side of the membrane. The results obtained were entirely in accord with the predictions of the seven-transmembrane spanning topography (like that of rhodopsin and the beta-adrenergic receptor) and were totally inconsistent with the expectations for either the six- or eight-transmembrane topographies that have been proposed.

On the spurious endoproteolytic processing of the presenilin proteins in cultured cells and tissues.

It has been widely reported that the presenilin proteins PS-1 and PS-2 in extracts derived from a variety of cultured cells and from tissues are fragmented extensively by endoproteolytic processing events. It generally has been presumed that this endoproteolysis is a physiologically normal intracellular event following presenilin expression, which might play an important role in the still unknown functions of these molecules in connection with Alzheimer disease. We demonstrate herein, however, that, if a variety of cultured cells and several mouse tissues are examined under conditions minimizing cell trauma, the presenilin molecules in the extracts are found to be intact but that, if the cells and tissues are prepared under somewhat more stressful conditions, the endoproteolytic fragments are then observed. We conclude that these particular endoproteolytic events are not the result of physiologically normal processing of the presenilins but are rather artifacts occurring during the common procedures of specimen preparation.