A Randomized Placebo-Controlled N-of-1 Trial: The Effect of Proton Pump Inhibitor in the Management of Gastroesophageal Reflux Disease.

Background: Gastroesophageal reflux disease (GERD) is the most frequent chronic gastrointestinal disorder. It is defined as a condition developed when the reflux of gastric contents causes troublesome symptoms (heartburn and regurgitation). This requires adequate treatment since it can lead to long-term complications including esophagus adenocarcinoma. Proton pump inhibitors (PPI) are generally used to treat GERD due to their high-security profile and efficiency on most patients. However, recurrent reflux despite initial treatment is frequent. N-of-1 trial is a study that allows the identification of the best treatment for each patient. The objective of this study is to compare the efficacy of standard dose with double dosage of esomeprazole, to improve the GERD symptoms in a single patient. Methods: A single-patient trial, placebo-controlled, randomized, double-blind, was carried out from September 25th, 2012, to April 26th, 2013. It included one outpatient at the gastroenterology service in a fourth-level hospital, diagnosed with nonerosive reflux disease (NERD). Yet, his symptoms were heartburn and reflux, and his endoscopic results were normal esophageal mucosa, without hiatal hernia, though pathological pH values. A no-obese male without any tobacco or alcohol usage received esomeprazole 40 mg/day and 40 mg/bid for 24 weeks. A standardized gastroesophageal reflux disease questionnaire (GerdQ) was used weekly to evaluate symptom frequency and severity. The consumption of 90% of the capsules was considered as an adequate treatment adherence. D'agostino-Pearson and Wilcoxon test were used to determine normal or nonnormal distribution and compare both treatments, respectively, both with a significant statistical difference of p < 0.05. Results: The patient completed the study with 96% of adherence. The double dosage of esomeprazole did not improve the control of symptoms compared with the standard dosage. Mean symptomatic score was 9.5±0.5 and 10.2±0.6 for each treatment, respectively (p > 0.05). Conclusion: There was no significant improvement in the patient GERD symptoms increasing the dose of oral esomeprazole during the 6 months of study. N-of-1 trials in chronic pathologies including GERD are recommended due to their potential value as systematic methods that evaluate therapies without strong scientific evidence.

Radiation characterisation and dosimetric measurements of a femtosecond pulsed laser ablation system.

This work describes the radiation characterisation and dosimetric measurements performed on the low-energy micromachining station of the femtosecond STELA (Santiago TErawatt LAser) at the University of Santiago de Compostela (Spain). For this aim, ionisation chambers, solid state detectors, and radiochromic films were used. The results show the emission of pulsed x-ray produced by laser-accelerated electrons from the ablated material exhibiting both bremsstrahlung and characteristic radiation. Although this radiation was produced unintentionally, a high superficial dose rate can be achieved. This radiation can be successfully stopped using small shielding to protect personnel from its effects. Based on the results of this work, the yearly dose equivalent after installing the shielding was negligible.

Recombination in liquid-filled ionization chambers beyond the Boag limit.

PURPOSE: The high mass density and low mobilities of charge carriers can cause important recombination in liquid-filled ionization chambers (LICs). Saturation correction methods have been proposed for LICs. Correction methods for pulsed irradiation are based on Boag equation. However, Boag equation assumes that the charge ionized by one pulse is fully collected before the arrival of the next pulse. This condition does not hold in many clinical beams where the pulse repetition period may be shorter than the charge collection time, causing overlapping between charge carriers ionized by different pulses, and Boag equation is not applicable there. In this work, the authors present an experimental and numerical characterization of collection efficiencies in LICs beyond the Boag limit, with overlapping between charge carriers ionized by different pulses. METHODS: The authors have studied recombination in a LIC array for different dose-per-pulse, pulse repetition frequency, and polarization voltage values. Measurements were performed in a Truebeam Linac using FF and FFF modalities. Dose-per-pulse and pulse repetition frequency have been obtained by monitoring the target current with an oscilloscope. Experimental collection efficiencies have been obtained by using a combination of the two-dose-rate method and ratios to the readout of a reference chamber (CC13, IBA). The authors have also used numerical simulation to complement the experimental data. RESULTS: The authors have found that overlap significantly increases recombination in LICs, as expected. However, the functional dependence of collection efficiencies on the dose-per-pulse does not change (a linear dependence has been observed in the near-saturation region for different degrees of overlapping, the same dependence observed in the nonoverlapping scenario). On the other hand, the dependence of collection efficiencies on the polarization voltage changes in the overlapping scenario and does not follow that of Boag equation, the reason being that changing the polarization voltage also affects the charge collection time, thus changing the amount of overlapping. CONCLUSIONS: These results have important consequences for saturation correction methods for LICs. On one hand, the two-dose-rate method, which relies on the functional dependence of the collection efficiencies on dose-per-pulse, can also be used in the overlapping situation, provided that the two measurements needed to feed the method are performed at the same pulse repetition frequency (monitor unit rate). This result opens the door to computing collection efficiencies in LICs in many clinical setups where charge overlap in the LIC exists. On the other hand, correction methods based on the voltage-dependence of Boag equation like the three-voltage method or the modified two-voltage method will not work in the overlapping scenario due to the different functional dependence of collection efficiencies on the polarization voltage.

Evaluation of chamber response function influence on IMRT verification using 2D commercial detector arrays.

This work is devoted to studying the influence of chamber response functions on the standard IMRT verification for the different detector technologies available on commercial devices. We have tested three of the most used 2D detector arrays for radiotherapy dosimetry verification, based on air-ionization chambers and diode detectors. The response function has been carefully simulated using the Monte Carlo method and measured through slit and pinhole collimators. Although the response function of air-ionization detectors is considerably different with respect to that of standard diodes, the impact on a verification based in the gamma function with tolerances 3 mm and 3% is quite limited. The results show that the standard air-ionization detector arrays perform in a similar way whenever the tolerances for the gamma function are not lowered below 1.5 mm and 1.5%. Additionally, the sensitivity of these devices to fluence perturbations was measured by intentionally modifying some leaf positions in the multileaf collimator. The wider response function of air-ionization chamber arrays made them slightly more sensitive to random fluence perturbations, although silicon diode arrays are more accurate to describe the dose distribution in a point by point basis.

A convolution model for obtaining the response of an ionization chamber in static non standard fields.

PURPOSE: This work contains an alternative methodology for obtaining correction factors for ionization chamber (IC) dosimetry of small fields and composite fields such as IMRT. The method is based on the convolution/superposition (C/S) of an IC response function (RF) with the dose distribution in a certain plane which includes chamber position. This method is an alternative to the full Monte Carlo (MC) approach that has been used previously by many authors for the same objective. METHODS: The readout of an IC at a point inside a phantom irradiated by a certain beam can be obtained as the convolution of the dose spatial distribution caused by the beam and the IC two-dimensional RF. The proposed methodology has been applied successfully to predict the response of a PTW 30013 IC when measuring different nonreference fields, namely: output factors of 6 MV small fields, beam profiles of cobalt 60 narrow fields and 6 MV radiosurgery segments. The two-dimensional RF of a PTW 30013 IC was obtained by MC simulation of the absorbed dose to cavity air when the IC was scanned by a 0.6 × 0.6 mm(2) cross section parallel pencil beam at low depth in a water phantom. For each of the cases studied, the results of the IC direct measurement were compared with the corresponding obtained by the C/S method. RESULTS: For all of the cases studied, the agreement between the IC direct measurement and the IC calculated response was excellent (better than 1.5%). CONCLUSIONS: This method could be implemented in TPS in order to calculate dosimetry correction factors when an experimental IMRT treatment verification with in-phantom ionization chamber is performed. The miss-response of the IC due to the nonreference conditions could be quickly corrected by this method rather than employing MC derived correction factors. This method can be considered as an alternative to the plan-class associated correction factors proposed recently as part of an IAEA work group on nonstandard field dosimetry.

A liquid-filled ionization chamber for high precision relative dosimetry.

Radiosurgery and intensity modulated radiation therapy (IMRT) treatments are based on the delivery of narrow and/or irregularly shaped megavoltage photon beams. This kind of beams present both lack of charged particle equilibrium and steep dose gradients. Quality assurance (QA) measurements involved in these techniques must therefore be carried out with a dosimeter featuring high small volume. In order to obtain a good signal to noise ratio, a relatively dense material is needed as active medium. Non-polar organic liquids were proposed as active mediums with both good tissue equivalence and showing high signal to noise ratio. In this work, a liquid-filled ionization chamber is presented. Some results acquired with this detector in relative dosimetry are studied and compared with results obtained with unshielded diode. Medium-term stability measurements were also carried out and its results are shown. The liquid-filled ionization chamber presented here shows its ability to perform profile measurements and penumbrae determination with excellent accuracy. The chamber features a proper signal stability over the period studied.

The determination of beam quality correction factors: Monte Carlo simulations and measurements.

Modern dosimetry protocols are based on the use of ionization chambers provided with a calibration factor in terms of absorbed dose to water. The basic formula to determine the absorbed dose at a user's beam contains the well-known beam quality correction factor that is required whenever the quality of radiation used at calibration differs from that of the user's radiation. The dosimetry protocols describe the whole ionization chamber calibration procedure and include tabulated beam quality correction factors which refer to 60Co gamma radiation used as calibration quality. They have been calculated for a series of ionization chambers and radiation qualities based on formulae, which are also described in the protocols. In the case of high-energy photon beams, the relative standard uncertainty of the beam quality correction factor is estimated to amount to 1%. In the present work, two alternative methods to determine beam quality correction factors are prescribed-Monte Carlo simulation using the EGSnrc system and an experimental method based on a comparison with a reference chamber. Both Monte Carlo calculations and ratio measurements were carried out for nine chambers at several radiation beams. Four chamber types are not included in the current dosimetry protocols. Beam quality corrections for the reference chamber at two beam qualities were also measured using a calorimeter at a PTB Primary Standards Dosimetry Laboratory. Good agreement between the Monte Carlo calculated (1% uncertainty) and measured (0.5% uncertainty) beam quality correction factors was obtained. Based on these results we propose that beam quality correction factors can be generated both by measurements and by the Monte Carlo simulations with an uncertainty at least comparable to that given in current dosimetry protocols.

A new method for output factor determination in MLC shaped narrow beams.

A new method for the measurement of output factors of narrow beams is presented in this work. By combining a new large area parallel plane ionization chamber (PTW model T34070) with a relative film dosimetry the output factors of small square fields of a 6 MV beam shaped by a MLC were measured. Several detectors (three ionization chambers, two solid state detectors and film) and Monte Carlo simulation were also employed to validate this new methodology and also to determine those detectors more suitable for narrow beam output factor determination. The proposed method for output factor measurement has shown to be in a very good agreement with diamond, diode and Monte Carlo results while it is insensitive to position displacements. Several uncertainties associated to the process of narrow beam dosimetry have also been addressed.