Experience with central venous access devices (CVADs) in the Canadian hemophilia primary prophylaxis study (CHPS).

INTRODUCTION: Haemophilia A treatment with factor VIII concentrates requires frequent venipunctures; a central venous access device (CVAD) may be required to facilitate reliable venous access, especially in young children. While CVADs provide reliable venous access, complications such as infection and thrombosis may occur. AIM: The aim of this study was to assess CVAD use in the Canadian Hemophilia Primary Prophylaxis Study (CHPS), a single-arm, multi-centre prospective study whereby factor use is tailored to individual prophylactic need. METHODS: Participants received a tailored, escalating dose, prophylaxis regimen of increasing frequency of FVIII infusions: step-1: 50 IU kg(-1) once weekly; step-2: 30 IU kg(-1) twice weekly; and step-3: 25 IU kg(-1) on alternate days, according to their level of bleeding. CVAD insertion was at the discretion of the local health care team. Details regarding CVAD use during this protocol were analysed. RESULTS: Fifty six boys were enrolled, 21 required 25 CVADs due to difficult venous access. CVADs were inserted at a median age of 1.3 years (range: 0.6-2.1) and were removed at a median age of 8.7 years (range 6.3-11.8). Six participants experienced non-life threatening CVAD-complications, the most frequent being device malfunction requiring CVAD replacement (n = 4). Two boys were shown to have CVAD-associated thrombosis detected on routine imaging; one required removal due to infusion difficulties and the other was asymptomatic and did not require device removal. No CVAD-related infections were documented. CONCLUSION: Our study shows that the CHPS tailored prophylaxis regimen is associated with a decreased requirement for CVADs and with few device-related complications.

Propranolol and central nervous system function: potential implications for paediatric patients with infantile haemangiomas.

Given its improved safety profile compared with systemic corticosteroids, propranolol has become the mainstay treatment of infantile haemangioma (IH) worldwide. There is evidence, mainly from adult volunteer studies, that propranolol use is associated with central nervous system (CNS) effects. Impairment to short- and long-term memory, psychomotor function, sleep quality and mood with relatively low doses and durations of treatment have been reported. The exact magnitude of CNS effects resulting from propranolol use, especially in the early developmental stages and for prolonged periods of use, is not currently known. These effects may not be readily recognizable and require specialized assessment of cognitive function not routinely performed. Furthermore, there may be a delay between exposure and cognitive defects. The evidence to date provides a strong rationale to proceed with caution when prescribing propranolol for IH: treatment should be used only when indicated (in the presence of ulceration, impairment of a vital function or risk of permanent disfigurement) and for a limited duration, and the benefits of treatment should be weighed carefully against potential adverse events before treatment is initiated. This narrative review describes the evidence for an effect of propranolol use on CNS function from volunteer and patient studies, including IH.

Observation of a long-wavelength hosing modulation of a high-intensity laser pulse in underdense plasma.

We report the first experimental observation of a long-wavelength hosing modulation of a high-intensity laser pulse. Side-view images of the scattered optical radiation at the fundamental wavelength of the laser reveal a transverse oscillation of the laser pulse during its propagation through underdense plasma. The wavelength of the oscillation λ(hosing) depends on the background plasma density n(e) and scales as λ(hosing)∼n(e)(-3/2). Comparisons with an analytical model and two-dimensional particle-in-cell simulations reveal that this laser hosing can be induced by a spatiotemporal asymmetry of the intensity distribution in the laser focus which can be caused by a misalignment of the parabolic focusing mirror or of the diffraction gratings in the pulse compressor.

Electron bunch length measurements from laser-accelerated electrons using single-shot THz time-domain interferometry.

Laser-plasma wakefield-based electron accelerators are expected to deliver ultrashort electron bunches with unprecedented peak currents. However, their actual pulse duration has never been directly measured in a single-shot experiment. We present measurements of the ultrashort duration of such electron bunches by means of THz time-domain interferometry. With data obtained using a 0.5 J, 45 fs, 800 nm laser and a ZnTe-based electro-optical setup, we demonstrate the duration of laser-accelerated, quasimonoenergetic electron bunches [best fit of 32 fs (FWHM) with a 90% upper confidence level of 38 fs] to be shorter than the drive laser pulse, but similar to the plasma period.

Excited ions in intense femtosecond laser pulses: laser-induced recombination.

Electron-ion recombination in a laser-induced electron recollision is of fundamental importance as the underlying mechanism responsible for the generation of high-harmonic radiation and hence for the production of attosecond pulse trains in the extreme ultraviolet and soft x-ray spectral regions. By using an ion beam target, remotely prepared to be partially in long-lived excited states, the recombination process has for the first time been directly observed and studied.

Comparison of experimental and simulated Kalpha yield for 400 nm ultrashort pulse laser irradiation.

Ti Kalpha emission yields from foils irradiated with approximately 45 fs, p-polarized pulses of a frequency-doubled Ti:sapphire laser are presented. A simple model invoking vacuum heating to predict absorption and hot electron temperature was coupled with the cross section for K -shell ionization of Ti and the Bethe-Bloch stopping power equation for electrons. The peak predicted Kalpha emission was in generally good agreement with experiment. This contrasts strongly with previous work at the fundamental frequency. Similar predictions using particle-in-cell (PIC) code simulation to estimate the number and temperature of hot electrons also gave good agreement for yield.

Kalpha yields from Ti foils irradiated with ultrashort laser pulses.

We have studied the emission of Kalpha radiation from Ti foils irradiated with ultrashort (45 fs) laser pulses. We utilized the fundamental (800 nm) light from a Ti:sapphire laser on bare foils and foils coated with a thin layer of parylene E (CH). The focusing was varied widely to give a range of intensities from approximately 10(15) - 10(19) W cm(-2). Our results show a conversion efficiency of laser to Kalpha energy of approximately 10(-4) at tight focus for both types of targets. In addition, the coated targets exhibited strong secondary peaks of conversion at large defocus, which we believe are due to modification of the extent of preformed plasma due to the dielectric nature of the plastic layer. This in turn affects the level of resonance absorption. A simple model of Kalpha production predicts a much higher conversion than seen experimentally and possible reasons for this are discussed.

Monoenergetic beams of relativistic electrons from intense laser-plasma interactions.

High-power lasers that fit into a university-scale laboratory can now reach focused intensities of more than 10(19) W cm(-2) at high repetition rates. Such lasers are capable of producing beams of energetic electrons, protons and gamma-rays. Relativistic electrons are generated through the breaking of large-amplitude relativistic plasma waves created in the wake of the laser pulse as it propagates through a plasma, or through a direct interaction between the laser field and the electrons in the plasma. However, the electron beams produced from previous laser-plasma experiments have a large energy spread, limiting their use for potential applications. Here we report high-resolution energy measurements of the electron beams produced from intense laser-plasma interactions, showing that--under particular plasma conditions--it is possible to generate beams of relativistic electrons with low divergence and a small energy spread (less than three per cent). The monoenergetic features were observed in the electron energy spectrum for plasma densities just above a threshold required for breaking of the plasma wave. These features were observed consistently in the electron spectrum, although the energy of the beam was observed to vary from shot to shot. If the issue of energy reproducibility can be addressed, it should be possible to generate ultrashort monoenergetic electron bunches of tunable energy, holding great promise for the future development of 'table-top' particle accelerators.

The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease.

OBJECTIVE: To determine the efficacy of donepezil in the treatment of neuropsychiatric symptoms in patients with Alzheimer disease (AD) in a randomized withdrawal study. METHOD: Patients with mild to moderate AD with marked neuropsychiatric symptoms at baseline (Neuropsychiatric Inventory [NPI] > 11 points) were treated openly with donepezil 5 mg daily for 6 weeks followed by 10 mg daily for a further 6 weeks. Patients were then randomized (60:40) to either placebo or 10 mg donepezil daily. All patients were assessed at 6 weeks and provided there was no marked cognitive deterioration their blinded treatment was continued for a further 6 weeks. NPI and carer distress were assessed at 6 weekly intervals throughout the study. RESULTS: A total of 134 patients participated. Following randomization patients who continued on donepezil 10 mg for 12 weeks had improvements in NPI compared with the placebo group (mean change -2.9 vs 3.3 points; ITT-LOCF p = 0.02) and in NPI-Distress scores (median change -2.0 vs 1.0 points; ITT-LOCF p = 0.01). During the open-label phase the total NPI and NPI-Distress scores were lower after 12 weeks treatment with open label donepezil compared with baseline (total NPI 22 points vs13 points; ITT-LOCF p < 0.0001; NPI-Distress 13.5 vs 7.9 points; ITT-LOCF p < 0.0001). In the open-label phase all domains of the NPI (with the exception of elation) were improved (all p < 0.05 after Bonferroni correction). CONCLUSIONS: Donepezil has significant efficacy in the treatment of neuropsychiatric symptoms in patients with mild to moderate AD.

Experimental study of proton emission from 60-fs, 200-mJ high-repetition-rate tabletop-laser pulses interacting with solid targets.

Measurements of proton emission have been made from a variety of solid targets irradiated by a 60-fs, 200-mJ, 7 x 10(18)-W cm(-2) laser system operating at 2 Hz. Optimum target conditions were found in terms of target material and thickness. For Mylar targets of thickness 20-40 microm, a maximum proton energy of 1.5 MeV was measured. For aluminum targets, a maximum energy of 950 keV was measured for 12 microm, and for copper, 850 keV for 12.5 microm.

Suppression of multiple ionization of atomic ions in intense ultrafast laser pulses.

The interaction of an intense laser field with a beam of atomic ions has been investigated experimentally for the first time. The ionization dynamics of Ar+ ions and Ar neutrals in a 60 fs, 790 nm laser pulse have been compared and contrasted at intensities up to 10(16) W cm-2. Our results show that nonsequential ionization from an Ar+ target is strongly suppressed compared with that from the corresponding neutral target. We have also observed for the first time the strong field ionization of high lying target metastable levels in the Ar+ beam.

Trabecular bone density in premenopausal rheumatoid arthritis patients.

OBJECTIVE: This study was undertaken to compare trabecular bone mineral density (BMD) in premenopausal rheumatoid arthritis (RA) patients and normal age-matched controls. METHOD: A protocol was designed to record age, duration of disease, use of corticosteroids (CS) and/or slow-acting antirheumatic drug (SAARD) therapy together with duration of such therapy. BMD was measured using the Hologic QDR 1,000 dual energy X-ray absorptiometer. The first four lumbar vertebrae and the left femur were measured in 56 RA patients and 165 controls. Height and weight were measured. Comparisons were made between RA patients and controls, as well as between subgroups of RA patients based on CS therapy. RESULTS: Patients with RA had significantly lower BMD (P < 0.05) at all the sites than the normal controls. The mean duration of RA at the time of study was 60 months (standard deviation 58 months). Thirteen RA patients had used CS in doses less than 10 mg daily for 6 months or longer (mean 19 months), while 25 patients had been on SAARD for an excess of 6 months (mean 23 months). The CS-treated patients had significantly lower BMD than untreated subjects at the femoral neck and inter-trochanteric region (P < 0.05), but not at the lumbar spine. However, when compared with normal controls, the CS-treated subgroups had significantly lower BMD at the lumbar spine and all femoral areas. Trochanteric BMD was the best determinant of the RA group, with a sensitivity of 65% and specificity of 77%. The positive predictive value was 16%, while the negative predictive value was 10%. Using Bayes' theorem, the prevalence of osteopenia in RA was found to be 6%. CONCLUSION: We conclude that generalised bone loss is a systemic feature of RA and that loss at the spine and femur may be aggravated by CS therapy.

Counterintuitive alignment of H2(+) in intense femtosecond laser fields.

The multiphoton ionization of H2 has been studied using laser pulses of 266 nm wavelength, 250 fs duration, and 5x10(13) W/cm(2) peak intensity. Dissociation of H2(+) via one-photon absorption proceeds through two channels with markedly different proton angular distributions. The lower-energy channel (2.6 eV kinetic energy release) is produced in the bond softening mechanism, which generates parallel alignment. The higher-energy channel (3.5 eV) originates from population trapping in a light-induced bound state, where bond hardening generates orthogonal, counterintuitive alignment.

Fear in children and adolescents: relations with negative life events, attributional style, and avoidant coping.

In this study, we explored relations among negative life events, negative attributional style, avoidant coping, and level of fear in 99 children who had survived residential fires. Overall, negative life events, negative attributional style, and avoidant coping were found to be predictive of levels of fear. However, the relation between negative life events and fear was moderated by mother's level of education such that this prediction was obtained only for those children whose mothers were low in education level. Age, ethnicity, and sex did not moderate these relations. In addition, negative attributional style and avoidant coping were related to levels of fear in those children whose mothers were high in education levels but not those whose mothers were low in education level. Results are discussed within a stress and coping framework.

Teaching medical faculty how to apply continuous quality improvement to medical education.

BACKGROUND: An eight-hour workshop was conducted at a professional meeting in 1996 to introduce medical faculty to the principles of continuous quality improvement (CQI) as they relate to change in medical education and to provide participants with opportunities to use specific tools for applications to education. Four two-hour sessions focused on an introduction to CQI, understanding and mapping processes, identifying change ideas, and testing a change for improvement. TESTING A CHANGE FOR IMPROVEMENT: The goals of the final session were to plan a pilot test of an improvement, identify the steps of the plan-do-study-act (PDSA) cycle, and consider change for improvement in the context of one's own organization. Working in small groups, participants chose a specific change one might try in the following example: improving student performance in a neuroscience course. POSTSESSION EVALUATION AND FOLLOW-UP: Immediately following the workshop sessions, participants represented by administrators in medical education and clinical and basic science teaching faculty completed evaluations on the usefulness and likelihood of their using CQI tools. One year later, of the 32 workshop registrants who were mailed surveys, 15 respondents rated their change in understanding of CQI and their use of CQI techniques. More than 60% of the respondents reported application of CQI principles at their organizations. CQI methods used most frequently included structured team meetings, prioritizing opportunities, and brainstorming. CONCLUSION: The significant application of CQI principles and methods reported by participants one year after a brief intervention supports a need and utility for CQI principles and tools in medical education.

A conceptual framework for the analysis of health care organizations' performance.

Organizational performance remains an elusive concept despite its importance to health care organizations' (HCOs') management and analysis. This paper uses Parsons' social system action theory to develop a comprehensive theoretically grounded framework by which to overcome the current fragmented approach to HCO performance management. The Parsonian perspective focuses on four fundamental functions that an HCO needs to ensure its survival. Organizational performance is determined by the dynamic equilibrium resulting from the continual interaction of, and interchange among, these four functions. The alignment interchanges allow the creation of bridges between traditional models of organizational performance that are usually used as independent and competing models. The attraction of the Parsonian model lies in its capacity to: (1) embody the various dominant models of organizational performance; (2) present a strong integrative framework in which the complementarity of various HCO performance perspectives are well integrated while their specificity is still well preserved; and (3) enrich the performance concept by making visible several dimensions of HCO performance that are usually neglected. A secondary objective of this paper is to lay the foundation for an integrative process of arbitration among competing indicators and perspectives which is absolutely necessary to make operational the Parsonian model of HCO performance. In this matter, we make reference to the theory of communicative action elaborated by Habermas. It offers, we think, a challenging and refreshing perspective on how to manage HCO performance evaluation processes.