Protocol for assessing mortality reduction with the early use of noninvasive ventilation in prehospital emergency services: A multicentre, observational cohort study in Madrid, Spain.

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.

Biallelic PDX1 (insulin promoter factor 1) mutations causing neonatal diabetes without exocrine pancreatic insufficiency.

AIMS: Recessive PDX1 (IPF1) mutations are a rare cause of pancreatic agenesis, with three cases reported worldwide. A recent report described two cousins with a homozygous hypomorphic PDX1 mutation causing permanent neonatal diabetes with subclinical exocrine insufficiency. The aim of our study was to investigate the possibility of hypomorphic PDX1 mutations in a large cohort of patients with permanent neonatal diabetes and no reported pancreatic hypoplasia or exocrine insufficiency. METHODS: PDX1 was sequenced in 103 probands with isolated permanent neonatal diabetes in whom ABCC8, KCNJ11 and INS mutations had been excluded. RESULTS: Sequencing analysis identified biallelic PDX1 mutations in three of the 103 probands with permanent neonatal diabetes (2.9%). One proband and his affected brother were compound heterozygotes for a frameshift and a novel missense mutation (p.A34fsX191; c.98dupC and p.P87L; c.260C>T). The other two probands were homozygous for novel PDX1 missense mutations (p.A152G; c.455C>G and p.R176Q; c.527G>A). Both mutations affect highly conserved residues located within the homeobox domain. None of the four cases showed any evidence of exocrine pancreatic insufficiency, either clinically, or, where data were available, biochemically. In addition a heterozygous nonsense mutation (p.C18X; c.54C>A) was identified in a fourth case. CONCLUSIONS: This study demonstrates that recessive PDX1 mutations are a rare but important cause of isolated permanent neonatal diabetes in patients without pancreatic hypoplasia/agenesis. Inclusion of the PDX1 gene in mutation screening for permanent neonatal diabetes is recommended as a genetic diagnosis reveals the mode of inheritance, allows accurate estimation of recurrence risks and confirms the requirement for insulin treatment.

Physical characteristics of the M.D. Anderson Hospital clinical neutron beam.

The physical characteristics of the M.D. Anderson Hospital (MDAH) clinical neutron beam are presented. The central-axis percent depth-dose values are intermediate between a 4 and 6 MV X-ray beam. The build-up curves reach a depth of maximum dose at 1.2 cm and have surface dose values of approximately 30%. Teflon flattening filters are employed to flatten the beam at the depth of the 75% dose level. Two wedges are available for shaping the beam; they are made of Teflon and produce wedge angles of 31 degrees and 45 degrees as defined by the ICRU. Output factors ranged from 0.88 for a 4 x 4 cm field to 1.12 for a 20 x 20 cm field. Tungsten blocks reduced the dose received at Dmax to 25% of the unblocked value but only 52% of the unblocked value at a depth of 22.8 cm.

Measurement of dose distributions using film in therapeutic electron beams.

The feasibility of using film dosimetry data as the input data for patient treatment planning was evaluated. The central-axis depth dose and the off-axis ratios obtained from film measurements in a solid phantom were compared with those of ion-chamber measurements in water. Two techniques were used to generate isodose distributions. The first technique used only the film data, i.e., the central-axis depth dose and the off-axis ratios used for the reconstruction were determined from the film optical density (corrected for film nonlinearity). In the second technique, the central-axis depth dose measured by an ion chamber in a water phantom was combined with the off-axis ratios measured using film in the "solid water" phantom. The resulting isodose distributions from both techniques were compared with the ion-chamber measurements in water for 7-, 12-, and 18-MeV electrons, and the second technique showed better agreement with the ion-chamber measurements than did the first technique. The differences were within a clinically acceptable range.

Effects of filters and wedges on skin sparing and gamma/neutron dose ratios in neutron teletherapy.

The effects of skin sparing and the gamma/neutron dose ratios in the clinical situations presently in use at the TAMVEC neutron teletherapy facility are not appreciably affected by the presence of filters and/or wedges. It is also shown that if skin sparing is lost due to close proximity of a hydrogenous scattering source, it can be restored by the use of thin lead filters.

Design of flattening filters for the fast-neutron beam at TAMVEC by use of decrement lines.

Isodose distributions in a tissue-equivalent phantom produced by fast neutrons from 50-MeV deuterons incident on a thick beryllium target exhibit strong forward peaking, particularly for large fields. The design by use of decrement lines and the construction of polyethylene filters used to "flatten" those distributions are discussed and the results are illustrated. Also, the compromises of central-axis attenuation versus effective filter width and of off-axis peaking versus depth of "flattening" are discussed.

Dosimetry of effective wedge fields produced by an internal wedge.

A procedure is described to calculate the monitor unit ratios required to produce effective wedge fields having a desired wedge angle by combining an internal 60 degrees wedge with an open field. Complementary procedures are derived and demonstrated for calculating the effective wedge dose distributions with wedge angles of 15 degrees, 30 degrees, and 45 degrees using the central axis depth dose data and off-axis ratios of the open field and the 60 degrees wedged field. Measurements at five points on and off the central axis within each field and measurements of the effective wedge factor demonstrated that the calculated wedge distributions were correctly delivered to within 2% in all cases.

Skin-sparing effects of neutron beam filtering materials.

The skin-sparing effects of several filtering materials for fast neutron beams were studied under various conditions. A parallel-plate ionization chamber was used for the measurements. The parameters which were studied included field size, distance from filter to ion chamber, filter material, and filter thickness. On the basis of this work, Teflon (polytetrafluoroethylene) was chosen for fabrication of flattening filters and wedges.

Dosimetric characteristics of wedges mounted beyond the blocking tray.

In a beam accessory configuration for a linear accelerator using a prototype multileaf collimator, newly designed wedges were mounted beyond the blocking tray. The isodose curves, depth of maximum dose, surface dose, and wedge transmission factors were measured for the wedges designed for this unique configuration. The same set of wedges was used for both 6- and 18-MV x rays. The shape of the wedged isodose curves was essentially unchanged from those produced by the conventional wedges located above the blocking tray. The isodose curves exhibited the desired wedge angles over the range of field sizes from 5 x 5 to 15 x 40 cm. In the 10 x 10-cm field, the average difference between the observed wedge angle and the desired wedge angle was 3.8 degrees. The surface doses ranged from 18% to 35% for the wedged 10 x 10-cm fields as compared with about 15% for the same open field. Dosimetrically the wedges were acceptable for clinical use.

Neutron energy spectra of d(49)-Be and p(41)-Be neutron radiotherapy sources.

Zero-degree neutron energy spectra for the p(41)-Be and d(49)-Be reactions were measured by time-of-flight for neutrons with energies above 1.9 and 1.4 MeV, respectively. Spectral changes resulting from the addition of copper, aluminum, and polyethylene filters to unfiltered beams were determined. Integral yields, average energies, filter material attenuation coefficients, and kerma fractions were computed for these spectra. Calculated spectra for neutron beams filtered by various thicknesses of polyethylene compared favorably with experimental results

Fast-neutron dose rate vs energy for the d+Be reaction--a reanalysis.

The differences in the published information concerning tissue kerma in air vs deuteron energy for the d+Be reaction are analyzed in light of some recent measurements. The reason for the discrepancy is determined to be a lack of electron suppression on the Be target in some earlier measurements, and the relation ln(tissue kerma)=ln(1.356 X 10(-4)+2.97lnE is found to fit the measured data over the deuteron energy range 11-50 MeV.

Modification of the 50% maximum dose depth for 41-MeV (p+,Be) neutrons by use of filtration and/or transmission targets.

Several target configurations for the 41-MeV (p+,Be) reaction have been evaluated for the characteristics of the radiation field produced; depth dose, dose rate per microA, From analysis, it is concluded that to achieve the desired 13.2-cm depth for 50% of maximum dose and acceptable dose rate at a target-to-skin distance (TSD) of 125-150 cm, the neutron spectra must be filtered to preferentially absorb the lower-energy neutrons. Further increases in depth of 50% of maximum dose and a significant reduction in beryllium heating problems result if a partial transmission target is used with the terminal 30% of proton energy being deposited in a copper target backing.

Computer dosimetry for flattened and wedged fast-neutron beams.

Beam flattening by the use of polyethylene filters has been developed for the 50-MeV d in equilibrium Be fast-neutron therapy beam at the Texas A&M Variable-Energy Cyclotron (TAMVEC) as a result of the need for a more uniform dose distribution at depth within the patient. A computer algorithm has been developed that allows the use of a modified decrement line method to calculate dose distributions; standards decrement line methods do not apply because of off-axis peaking. The dose distributions for measured flattened beams are transformed into distributions that are physically equivalent to an unflattened distribution. In the transformed space, standard decrement line theory yields a distribution for any field size which, by applying the inverse transformation, generates the flattened dose distribution, including the off-axis peaking. A semiempirical model has been constructed that allows the calculation of dose distributions for wedged beams from open-beam data.

Comprehensive analysis of electron beam central axis dose for a radiotherapy linear accelerator.

This work evaluates the application of AAPM task group 25 (TG25) methodology for determination of central axis depth dose for a radiotherapy linear accelerator, whose dual scattering foil system and applicators were recently modified. The percent depth dose (%DD) and the dose output factor have been measured for square and rectangular fields at 100- and 110-cm source-to-surface distance (SSDs). At 100-cm SSD, results showed that %DD for a specific energy and field size can vary with applicator, the largest variation being for the 20-MeV, 10 x 10-cm field where a spread of +/- 2.5% or +/- 3 mm about the mean %DD is observed. The square-root method determines rectangular field %DD within 1%. Output factors for rectangular fields are calculated from square field values more accurately using a square-root method than the equivalent-square method recommended by TG25. At 110-cm SSD, the %DD calculated from that at 100-cm SSD using an inverse square factor does not agree with measured values for all fields. The maximum difference observed for the 20-MeV, 6 x 6-cm field was 5.5% or 10 mm. Output data at the 110-cm SSD show that the square-root method is suitable for determination of the air-gap correction factors of rectangular fields. In summary, the recommendations of TG25 work reasonably well for central axis electron beam dosimetry for this version of a radiotherapy linear accelerator, except in limited cases where applicator-scattered electrons apparently cause minor but clinically significant discrepancies.

Composition of A-150 tissue-equivalent plastic.

In recent years, the use of tissue-equivalent materials has become quite common in fast-neutron dosimetry, with the A-150 plastic developed by Shonka et al. probably the most popular. Information on this specific plastic is scantily reported in the literature and as a consequence a preponderance of authors unknowingly reference an article by Shonka describing an early version of a tissue substitute plastic but having a different elemental composition than the present A-150 formulation. We have reviewed the results of 21 chemical analyses which have occurred over a time span of four years on a total of 14 samples of A-150 plastic and based on these data and the formulation of the plastic, have arrived at a suggested composition for A-150 tissue-equivalent plastic. The ambiguities of water absorption by nylon, one of the components of the plastic, and the uncertainty this reflects in the composition of the plastic were evaluated.

Dosimetric evaluation of a two-dimensional, arc electron, pencil-beam algorithm in water and PMMA.

The accuracy of dose calculations from a pencil-beam algorithm developed specifically for arc electron beam therapy was evaluated at 10 and 15 MeV. Mid-arc depth-doses were measured for 0 degrees and 90 degrees arcs using 12 and 15 cm radius cylindrical water phantoms. Calculated depth-doses for the 90 degrees arced beams in the build-up region were as much as 3% less than measured values; the maximum dose was similar in magnitude but at a greater depth; and the therapeutic depth, R80, was 2-4 mm deeper. Calculated values of output (dose per monitor unit) at the depth of the maximum calculated dose were compared with measured values; for arcs ranging from 0-90 degrees, 12 and 15 cm radius water phantoms, and collimator widths of 4, 5 and 6 cm, results showed differences as great as 7%. Isodose countours for a 90 degrees arc were also measured in a 15 cm radius PMMA phantom. At the depth of maximum dose the algorithm predicted doses in the penumbral regions, both with and without collimation, which agreed within a few per cent of measured values. The largest discrepancies were 5%, which occurred in the penumbral portion of the depth-dose fall-off region. Differences between measurement and calculation are not believed to be clinically significant and are believed to be primarily due to the fact that the algorithm models neither large-angle scattering nor the effects of range straggling on the pencil-beam dose distribution.

The Clatterbridge high-energy neutron facility: dosimetry intercomparisons.

Dosimetry intercomparisons have been performed between the Clatterbridge high-energy neutron facility and the following institutions, all employing beams with similar neutron energies: Université Catholique de Louvain, Belgium; University of Washington, Seattle, USA; MD Anderson Hospital, Houston, USA; and Fermi National Accelerator Laboratory, Batavia, USA. The purpose of the intercomparison was to provide a basis for the exchange of dose-response data and to facilitate the involvement of Clatterbridge in collaborative clinical trials. Tissue-equivalent ionization chambers were used by the participants in each intercomparison to compare measurements of total (neutron plus gamma) absorbed dose in the host institution's neutron beam, following calibration of the chambers in a reference photon beam. The effects of differences in exposure standards, chamber responses in the neutron beams and protocol-dependent dosimetry factors were all investigated. It was concluded that the overall difference in the measurement of absorbed dose relative to that determined by the Clatterbridge group was less than 2%.