Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis

BACKGROUND: In numerous clinical trials, proton pump inhibitors have demonstrated potent acid suppression and healing of erosive oesophagitis, as well as successful symptom relief for the entire spectrum of gastro-oesophageal reflux disease. AIM: The 'Future of Acid Suppression Therapy' (FAST) trial evaluated, in actual clinical practice, the timing of symptom relief, changes in symptom severity, health-related quality of life and safety in endoscopically confirmed erosive gastro-oesophageal reflux disease treated with rabeprazole. METHODS: This open-label, multicentre study enrolled 2579 patients to receive rabeprazole treatment using 20 mg once daily for 8 weeks. Between two clinical visits (at enrollment and week 8), patients used an interactive voice response system to rate gastro-oesophageal reflux disease symptoms. Subgroup analyses of efficacy were conducted for gender, age, Hetzel-Dent grade, presence of Barrett's oesophagus and for patients reporting previously ineffective symptom relief with omeprazole or lansoprazole. RESULTS: On day 1, rabeprazole significantly decreased daytime and night-time heartburn severity, regurgitation and belching. Complete relief of daytime and night-time heartburn was achieved in 64.0% and 69.2% of symptomatic patients, respectively, on day 1, and in 81.1% and 85.7% of patients, respectively, on day 7. Patients with moderate or severe heartburn symptoms at baseline achieved an even greater degree of satisfactory symptom relief (none or mild) from day 1 onwards. The median time to satisfactory heartburn relief was 2 days. Subgroup analyses showed no consistent differences in efficacy compared to the overall population treated. Health-related quality of life in patients was significantly lower than that of the US general population and improved significantly after 8 weeks of rabeprazole therapy. Rabeprazole was well tolerated, with headache as the most common adverse event, reported by less than 2% of the study population. CONCLUSIONS: In this large, open-label trial, rabeprazole rapidly and effectively relieved gastro-oesophageal reflux disease symptoms in most patients with erosive oesophagitis. Substantial symptom relief was noted on day 1; improvement continued over the first week and at week 4. By week 8, the health-related quality of life had also improved vs. baseline.     

Reference values for pulsed Doppler signals from the blood flow on both sides of the aortic valve

Pulsed Doppler signals were recorded in 215 healthy subjects,120 males and 95 females, between 1 and 65 years of age. Themeasurements were performed in the left ventricular outflowtract (LVOT) and in the ascending aorta (AAO). Amplitude spectrafrom the Doppler signals were stored in digital form togetherwith adjustment data for the instrument, the simultaneouslyregistered ECG and respiration signal. The maximum velocity(V_max, the maximum acceleration (A_max) and the width of thevelocity distribution around V_max (width) were derived fromthese spectra and used for the characterization of the signals.These parameters were computed without observer interactionusing a computer program. Effects of age, sex, body surfacearea, heart rate and respiration were studied. Reference rangeswere calculated. The following conclusions can be drawn: V_maxand A_max in the AAO decrease clearly with increasing age fromapproximately 100 to 60 cm s^-1 and from 2000 to 1000 cm s^-2(medians), respectively. The variation of the width in the AAOis greater for people over 45 years. V_max, A_maxand width inthe LVOT increase slightly with advancing age from approximately60 to 80 cm s^-1, 800 to 1000 cm s^-2 and 12 to 15 cm s^-1 (medians),respectively. These parameters of flow were either unrelatedor only weakly related to other physiological variables in thisstudy group.     

Reference values for pulsed Doppler signals from the blood flow velocity on both sides of the pulmonary valve

Pulsed Doppler signals were recorded from the pulmonary arteryand the right ventricular outflow tract in 215 healthy subjects(120 males, 95 females; 1–65 years). Amplitude spectrafrom these Doppler signals were stored in digital form togetherwith adjustment data for the instrument and the simultaneouslyrecorded ECG. From these Doppler spectra the median of the maximalvelocity ( V_max), the maximal acceleration (A_max) and the dispersionof the velocity distribution around V_max (width) were calculated.These three median values were used to characterize the Dopplerspectra and to define normal values for bloodflow velocities.Thus, calculations were made without observer interaction usinga well-defined computer program. The effect of age, gender,body surface area and heart rate were studied. Reference rangeswere calculated. There is a slight decrease of the median value of V_max and A_maxin the pulmonary artery during lifetime from 80 to 70 cm s^–1and from 1200 to 800 cms^–2, respectively. On the otherhand, there is no correlation between age and V_max and A_maxin the right ventricular outflow tract. The width of the spectraincreases with age at both sites. No significant changes withage were seen with the other variables.     

Normal diastolic filling patterns of the left ventricle

Pulsed Doppler measurements on both sides of the mitral valveand M-mode left ventricular echocardiograms were performed in215 healthy subjects, 120 males and 95 females, between oneand 65 years old, in order to evaluate normal diastolic fillingpatterns of the left ventricle. The relation between the maximumblood velocity during early passive filling (Ewave) and duringatrial contraction (A wave) was computed from the Doppler spectraobtained proximal and distal to the mitral valve, resultingin the EA ratio. The influence on the EA ratio of age, gender,body surface area, blood pressure, heart rate, PR interval,respiration, wall thickness and basal wall mass of the leftventricle was investigated. The study showed that the EA ratio measured proximal to themitral valve (in the left atrium) was significantly smallerthan the EA ratio measured distal (in the left ventricle) andthat the only prominent relations with the EA ratio were thosewith age and heart rate. The EA ratio declines with age: proximalto the mitral valve from approximately (medians) 2.5 to 1 anddistal to it from 3.5 to 1.5. All other physiological variablesare weakly related or unrelated to the EA ratio in this groupof healthy subjects.     

Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation?

Background and Purpose

Large breast size is associated with an increased risk of late adverse effects after breast conservation surgery and radiotherapy, even when 3D dosimetry is used. The purpose of this study is to test the hypothesis that residual dose inhomogeneity is sufficient to explain the association.

Methods

Patients previously treated after breast conservation surgery with whole breast radiotherapy using 3D dosimetry and followed up in the UK FAST hypofractionation trial were selected for this analysis. The residual level of dose inhomogeneity across the whole breast treatment volume was used to test for association between residual dosimetry and post-treatment change in breast appearance at 2 years post-radiotherapy.

Results

At 2 years, 201/279 (72%) of women had no change in photographic breast appearance, 61 (22%) had mild change and 17 (6%) had marked change. Breast size and dosimetry were both significantly associated with late effects in univariate analyses, but only breast size remained an independent significant risk factor for change in breast appearance when included in a multiple regression model together with other prognostic factors (p = 0.006 for trend).

Conclusion

Large-breasted women are more likely to suffer change in breast size and shape after whole breast radiotherapy delivered using 3D dosimetry, but residual dose inhomogeneity is insufficient to explain the association.