[Consensus validation of a tool to identify inappropriate prescribing in pediatrics (POPI)]. / Validation par consensus d'un outil d'identification de prescriptions inappropriées en pédiatrie (POPI).

OBJECTIVE: Medication errors including inappropriate prescriptions and drug omissions are one of the causes of adverse drug events in children. Our aim was to develop a preliminary screening tool to detect omissions and inappropriate prescriptions in pediatrics based on French and international guidelines. MATERIEL AND METHODS: Disease classification was based on the prevalence rate of pathology and hospital statistics. The criteria were obtained by reviewing many French and international references. The Delphi consensus technique was used to establish the content validity of POPI. The level of agreement and the proposals of healthcare professionals was noted on a nine-point Likert scale. RESULTS: The criteria were categorized according to the main physiological systems (gastroenterology, respiratory infections, pain, neurology, dermatology, and miscellaneous). They were distributed to 16 French pediatric panelists (eight pharmacists, eight pediatricians who were hospital-based [50%] or working in the community [50%]). After two rounds of the Delphi process, 101 of 108 criteria were chosen with strong consensus (76 inappropriate prescriptions and 25 omissions). CONCLUSIONS: POPI is the first screening tool to detect inappropriate prescriptions and omissions in pediatrics. It is now necessary to conduct a prospective study to determine inter-rater reliability and the tool's detection capacity.

Self-assembling oligothiophene-bolaamphiphiles for loading and controlled release of doxorubicin into living cells.

Design and synthesis of symmetric mannose-functionalized oligothiophenes is reported. Self-organization of these bolaamphiphiles in solution and in the solid state was investigated by optical and AFM experiments. Fluorescence measurements revealed efficient loading and pH-dependent release of the anti-cancer drug doxorubicin. Delivery and release of the active drug into viable A549 cells as well as chirality-dependent cellular toxicity of the bolaamphiphilic transporter were evident from in vitro experiments.

Detection of a few metallo-protein molecules using color centers in nanodiamonds.

Nanometer-sized diamonds containing nitrogen-vacancy defect centers (NV) are promising nanosensors in biological environments due to their biocompatibility, bright fluorescence, and high magnetic sensitivity at ambient conditions. Here we report on the detection of ferritin molecules using magnetic noise induced by the inner paramagnetic iron as a contrast mechanism. We observe a significant reduction of both coherence and relaxation time due to the presence of ferritin on the surface of nanodiamonds. Our theoretical model is in excellent agreement with the experimental data and establishes this method as a novel sensing technology for proteins.

mGluR5, but not mGluR1, antagonist modifies MK-801-induced locomotor activity and deficit of prepulse inhibition.

Hypoglutamatergic theory of schizophrenia is substantiated by observation that high affinity uncompetitive antagonists of NMDA receptors such as PCP can induce psychotic symptoms in humans. Recently, metabotropic glutamate receptors of the mGluR5 type have also been discussed as possible players in this disease. However, less is known about the potential contribution of mGluR1 in schizophrenia. Therefore, the aim of the present study was to compare the effect of selective mGluR1 antagonist EMQMCM, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist (MTEP ([(2-methyl-1, 3-thiazol-4-yl) ethynyl] pyridine) either alone or in combination with (+)MK-801 in a prepulse inhibition (PPI) model and locomotor activity tests. Additionally, the effect of both mGluR1 and mGluR5 antagonists on (+)MK-801-evoked ataxia was tested. In contrast to (+)MK-801, which induced disruption of PPI, neither MTEP (1.25-5 mg/kg) nor EMQMCM (0.5-4 mg/kg) altered the PPI. However, MTEP, but not EMQMCM, enhanced disruption of PPI induced by (+)MK-801. Although neither mGluR1 nor mGluR5 antagonists given alone changed locomotor activity of rats, MTEP at 5 mg/kg potentiated the effect of (+)MK-801 while EMQMCM (up to 4 mg/kg) turned out to be ineffective. On the other hand, EMQMCM, but not MTEP, enhanced ataxia evoked by MK-801. The present results demonstrate that blockade of mGluR1 and mGluR5 evokes different effects on behavior induced by NMDA receptor antagonists.

Direct proof of electron transfer in a rigid first generation triphenyl amine core dendrimer substituted with a peryleneimide acceptor.

The combination of nanosecond transient absorption experiments and single photon timing experiments proved the occurrence of an electron transfer process in the triphenyl amine core dendrimer, N1P1, by demonstrating the presence of an ion-pair absorption for N1P1 in solvents of medium polarity. By means of femtosecond transient absorption measurements the rise time of this ion-pair absorption dominated by the radical anion absorption could be determined, resulting in a value of 180 ps in MeTHF and 138 ps in THF. Furthermore, in femtosecond fluorescence upconversion as well as in monochromatic femtosecond transient absorption, a few ps component was resolved which was assigned to a vibrational and solvent relaxation process of the locally excited singlet state of the peryleneimide.

Polyphenylene dendrimers with different fluorescent chromophores asymmetrically distributed at the periphery.

A new synthetic approach leading to asymmetrically substituted polyphenylene dendrimers is presented. Following this method, polyphenylene dendrimers decorated with an increasing number of chromophores at the periphery have been obtained up to the second generation. Especially the synthesis of a polyphenylene dendrimer bearing three donor chromophores and one acceptor chromophore has been realized. Intramolecular energy transfer within this molecule is demonstrated by applying absorption and fluorescence measurements.

Intramolecular energy hopping and energy trapping in polyphenylene dendrimers with multiple peryleneimide donor chromophores and a terryleneimide acceptor trap chromophore.

Intramolecular Förster-type excitation energy transfer (FRET) processes in a series of first-generation polyphenylene dendrimers substituted with spatially well-separated peryleneimide chromophores and a terryleneimide energy-trapping chromophore at the rim were investigated by steady-state and time-resolved fluorescence spectroscopy. Energy-hopping processes among the peryleneimide chromophores are revealed by anisotropy decay times of 50--80 ps consistent with a FRET rate constant of k(hopp) = 4.6 ns(-1). If a terryleneimide chromophore is present at the rim of the dendrimer together with three peryleneimide chromophores, more than 95% of the energy harvested by the peryleneimide chromophores is transferred and trapped in the terryleneimide. The two decay times (tau(1) = 52 ps and tau(2) = 175 ps) found for the peryleneimide emission band are recovered as rise times at the terryleneimide emission band proving that the energy trapping of peryleneimide excitation energy by the terryleneimide acceptor occurs via two different, efficient pathways. Molecular- modeling-based structures tentatively indicate that the rotation of the terryleneimide acceptor group can lead to a much smaller distance to a single donor chromophore, which could explain the occurrence of two energy-trapping rate constants. All energy-transfer processes are quantitatively describable with Förster energy transfer theory, and the influence of the dipole orientation factor in the Förster equation is discussed.

Fiscal options for America's best hospitals.

A review of America's "best" teaching hospitals shows a huge disparity in their fiscal positions. Among the 15 hospitals studied, roughly half experience some fiscal distress. However, a somewhat similar fiscal analysis of the nation's largest investor-owned hospital chains, HMOs, and physician practice management corporations shows an even more serious weakness in operating margins and debt-equity ratios. Aside from raising possible ethical, quality, and cost issues, this financial analysis suggests that conversion from nonprofit to for-profit ownership of America's top teaching hospitals might not guarantee an improvement in their long-term fiscal outlook.

Diffuse alveolar hemorrhage after clopidogrel use.

Pulmonary hemorrhage following percutaneous coronary intervention is a very rare complication that has been previously reported in association with abciximab and tirofiban, but not with clopidogrel. We report the case of a 56-year-old man who developed diffuse alveolar hemorrhage after receiving clopidogrel for placement of a coronary stent. Since clopidogrel is a commonly used medication, clinicians should be aware of this potentially life-threatening complication.

Polyfluorenes with polyphenylene dendron side chains: toward non-aggregating, light-emitting polymers.

A polyfluorene 12 has been prepared in which bulky polyphenylene dendrimer substituents suppress formation of long wavelength emitting aggregates, thus giving a polymer with pure blue emission. Absorption- and emission spectra and molecular modeling confirm that the bulky dendrimer side chains do not cause extra torsion between the fluorene units. New polyfluorenes with 9,9-diaryl substituents have been prepared to determine the minimum size of substituent necessary for aggregation suppression. An LED using 12 has been demonstrated to produce blue emission with onset voltages below 4 V.

Commentary: public disclosure in the health field: is there a relevant option?

Steadily increasing numbers of private, not-for-profit, and public agencies are releasing quality of care and financial information to enhance the market power of those purchasing America's health services. These sources range widely from the Health Plan Employer Data and Information Set (HEDIS) to the federal Securities and Exchange Commission (SEC). A growing interest in publicly disclosing performance information that concerns providers, as recently recommended by the Institute of Medicine (IOM) report on patient safety, until now has only achieved a modest impact. A major exception is in those metropolitan areas where acute-care facilities experience intense competition for patient admissions. Although the comparative quality and cost information currently available is for the most part in the public interest, it is concluded that, in the foreseeable future, these report cards as now structured will not result in any significant enhancement in access, improvement in quality, or reduction in cost. Options to encourage more public disclosure explored in this paper are Congress potentially passing legislation (a) to establish a Center for Patient Safety within the US Department of Health and Human Services as recommended by the recent Institute of IOM study, or (b) empowering the SEC beyond its current mandate to collect and disseminate all pertinent quality of care and cost information on every provider in the United States. The latter alternative would include user-friendly, comparative analyses to be provided on the Internet and elsewhere and would make readily available information from HEDIS, the Joint Commission on the Accreditation of Healthcare Organization (JCAHO), coronary artery bypass graft (CABG) surgery studies, cost comparisons based on Medicare cost reports and SEC filings, and other similar sources.

Polyphenylene dendrimers with perylene diimide as a luminescent core.

A novel synthesis is presented of a fourfold ethynyl-substituted perylene diimide dye 4, which acts as a core molecule for the buildup of polyphenylene dendrimers. Around the luminescent core 4, a first-generation (5), a second-generation (6), and a third-generation (7) polyphenylene dendritic environment consisting of pentaphenylbenzene building blocks are constructed. The dendrimers 5 and 6 are synthesized by an exclusively divergent route, whereas for 7, a combination of a divergent and convergent approaches is applied. Absorption and emission spectra of 5-7 in different solvents and in a film have been measured and compared to a nondendronized model compound 13. In solution, the internal chromophore is scarcely influenced by the dendritic scaffold; however, in the solid state, aggregation of the perylene diimide is prevented very effectively by the four rigid dendrons. Additionally, fluorescence quantum yields in solution have been determined for 5-7 and 13; they decrease as the number of generation increases.

Is vertical integration adding value to health systems?

Vertical integration is a concept used by health systems when attempting to achieve economies of scale, greater coordination of services, and improved market penetration. This article focuses on the actual outcomes of utilizing vertical integration in the health field and then compares these findings with those reported in other industries. This analysis concludes that this organizational model does not work particularly well in the health industry, as illustrated by health alliances' poor fiscal performance when they acquire physician practices or when they start their own HMO plans.

Management of integrated delivery systems in the next decade.

In an attempt to find some remedies within what is already a highly competitive and politically charged environment, this article's purpose is to specify some major steps that the management of integrated delivery systems might heed in the next decade to curtail their expenditures and better position themselves for the future.

How to enhance the efficacy of health network growth.

In almost every American metropolitan area, health executives are busily enhancing the efficacy of their health networks by corporately restructuring so that their organization can become a fiscally and politically powerful oligopoly or a regulated monopoly. When the formation of these alliances are initially announced by the local media, they are reported to be vehicles to enhance access, social equity and quality of care, and to reduce costs. Since an increasing number of these health networks are currently experiencing fiscal, cultural and other difficulties, it is critical to study: (a) what factors should be considered when developing an effective and efficient health network?; (b) what are the practical issues in their strategic formation and management so they eventually achieve their full potential?; and (c) why will some divestitures among these health networks occur and how will these corporate 'spin offs' impact on consumers, providers, insurers and governmental agencies? Within the next decade the United States will face some inevitable economic difficulties. At that time, enhancing access and reducing costs will become more critical issues for health networks. These alliances may then need to become more responsive to consumer pressures as the Americans shift their political proclivities from the current quasi-competitive to a more quasi-regulatory position. In this context, the use of global budgetary targets is discussed as a possible option in the United States to constrain costs, an approach used in almost all other western industrialized nations.

A variation of noncontingent reinforcement in the treatment of aberrant behavior.

We examined the effectiveness of a variation of noncontingent reinforcement (NCR) that incorporated a stimulus-delay procedure in the reduction of aberrant behavior maintained by positive reinforcement. Functional analyses for three individuals diagnosed with developmental disabilities indicated that their behaviors were maintained by positive reinforcement: one in the form of access to a tangible item, another by attention, and the third by physical contact. We implemented NCR with the delay procedure with two participants using reversal designs to evaluate effects. We also compared this NCR variation and DRO with the third participant to evaluate reinforcer-delivery rates. The variation of NCR was successful in reducing all aberrant behavior to near-zero levels. A comparison of reinforcer delivery between NCR with the stimulus-delay procedure and DRO demonstrated that the participant accessed more reinforcement with NCR. Results are discussed in the context of enhancing decelerative interventions with emphases on minimizing response effort for caregivers and maximizing access to reinforcement for the individuals.

Horizontal mergers in the United States health field: some practical realities.

During the past decade, 'merger mania' has been a striking trend in the US health field as a strategy to improve the integration of services, to reduce expenses, and to increase the ability of providers to manage risk-based payment. However, during the past quarter of a century limited operational and fiscal evidence has been published in both the health and general management literature that strongly supports the efficacy of horizontal mergers. This article further argues that a likely scenario over the next decade, in spite of disappointments among these mergers in effecting significant cost reductions, is for the US health networks to continue acquiring additional providers and insurers. After these alliances gain significant market penetration, they are expected to behave as oligopolists. For these mergers to eventually achieve their earlier projected savings, the health field's leadership will be forced to implement cost-cutting measures such as: more vigorously coordinating the network's key clinical services to reduce competition for revenues among the partners within an alliance, closing superfluous hospitals and centralizing expensive tertiary services, encouraging surplus physicians to relocate to under-served areas, and providing direction to carefully integrate the best elements of what the competitive and regulatory strategies are able to offer to improve access, social equity, quality of care, and to reduce total health expenditures.