A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia

Abstract  Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and ¹³C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation ( P  = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating ( P  = 0.001) and overall symptom score ( P  = 0.022), and at week 3 for bloating ( P  = 0.008) and heartburn ( P  = 0.041). 100 mg was also better than placebo for QOL (physical function) ( P  = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.     

Significance of cross-cultural experience for young psychiatrists--learning from "The Joint Workshop for Psychiatric Residents of Korea and Japan"]

Korea and Japan are geographically very close, and a variety of cultural exchanges have taken place in recorded history. However, Korea and Japan have been enriched by the influence of Western cultures along with modernization, and mutual exchanges between the two countries have thus decreased in numerous fields including mental health and psychiatry. Prof. Masahisa Nishizono and Prof. Byun-Kun Min, who are leaders in the field of psychiatry in both Japan and Korea, have established "The Joint Workshop for Psychiatric Residents of Korea and Japan", which has been held alternately in Fukuoka or Seoul every summer since 2000. This Joint Workshop provides young psychiatrists with real experiences and many opportunities to learn about transcultural psychiatry regarding both countries. The participants are able to obtain a better mutual understanding of psychiatric epidemiology, recent developments in biological psychiatry while also learning about different concepts regarding the stigma of mental disorders. All participants could also increase their knowledge about the traditional culture and social changes related to the field of psychiatry in both countries. The workshop has helped to build friendship and mutual cooperation between both nations. Contemporary societies are continually becoming more and more diversified and complicated. For young psychiatrists who have to treat patients with modern difficulties and various complicated problems, such cross-cultural experiences may be useful for establishing potentially new and effective treatments for such patients. Psychiatrists and mental health experts have tried to reduce of stigma and discrimination against people with mental disorders, but even today such stigma and discrimination continues to strongly exist. The author thinks that such cross-cultural experiences by the psychiatrists themselves may help to reduce such notions. The author would like to explore the role of cross-cultural experiences in the field of psychiatry.     

Changes in metacarpal bone mineral density with age and menopause using computed X-ray densitometry in Japanese women: Cross-sectional and longitudinal study

Background: Bone mineral density (BMD) loss with age and menopause is widely accepted in elderly women. However, only a few studies have utilized a multiple regression model that includes physical characteristics to assess comprehensive lifetime changes in BMD.

Objective: A prospective study was conducted to characterize the normal patterns in metacarpal BMD changes in Japanese women, and to assess the applicability of a fitting model using cross-sectional data compared with longitudinal variability.

Subjects and methods: The study consisted of 5422 healthy women in cross-sectional data and a 1-year follow-up of 359 women. The metacarpal BMD was measured by computed X-ray densitometry. Multiple linear and nonlinear regression analyses were performed in cross-sectional subjects. Nonparametric analysis was used to compare percentage rates of BMD changes between actual and estimated values.

Results: The cross-sectional data showed that the best-fit equation was a nonlinear change model using the variables of age and height in premenopausal women, and years since menopause (YSM), age and height in postmenopausal women. The results of longitudinal data indicated the following. In premenopausal women, the actual BMD changes were greater in the 30–39 age group than the 20–29 age group and were less in the 50–59 group than the 40–49 group. The rates of annual change in BMD between the actual value and estimated value by change model were very similar. In postmenopausal women, the actual changes in BMD indicated that the rapid rate of reduction observed was over 3% at 0–5 YSM and 1.5% at 6–10 YSM, and thereafter showed a slower rate of decline at 11 YSM. The change model represented the trend of actual change in BMD for postmenopausal women, whereas the rates of estimated BMD loss underestimated the actual changes at 1–10 YSM.

Conclusion: The change model for premenopausal women using cross-sectional data is beneficial in evaluating the actual metacarpal BMD variability, whereas that for postmenopausal women is insufficient in estimating the longitudinal BMD variability.

Résumé. Arrière plan: On accepte communément que les femmes âgées aient connu une perte de densité minérale osseuse (DMO) avec l’âge et la ménopause, cependant seulement un petit nombre d’études ont utilisé un modèle de régression multiple, qui inclut des caractéristiques physiques afin de suivre de manière adéquate les changements de DMO au cours de la vie

Objectif: Une étude prospective a été menée afin de caractériser les modalités normales du changement de la DMO métacarpienne chez les femmes japonaises et pour estimer la possibilité d’appliquer un modèle d’ajustement utilisant des données transversales comparées avec la variabilité longitudinale.

Sujets et méthodes: L’étude consiste en sonnées transversales de 5422 femmes en bonne santé et d’un suivi d’un an pour 359 femmes. La DMO métacarpienne a été mesurée par densitométrie radiographique calculée par ordinateur. Des analyses de régression linéaires multiples et non linéaires, ont été effectuées sur les données transversales. Une analyse non paramétrique a été utilisée pour comparer les pourcentages de changement de DMO entre valeurs estimées et valeurs observées.

Résultats: Les données transversales indiquent que la meilleure équation ajustée est un modèle non linéaire employant les variables d’âge et de stature des femmes avant la ménopause, les années depuis la ménopause (ADM) et l’âge et la stature après la ménopause. Les résultats des données longitudinales indiquent qu’avant la ménopause, le changement en DMO est plus élevé dans le groupe d’âge 30–39 ans que dans le groupe d’âge 20–29 ans et ceux-ci sont inférieurs aux valeurs de des groupes 40–49 et 50–59 ans. Les taux annuels de changement de DMO que ce soit par les valeurs mesurées ou par les valeurs estimées sont similaires. Chez les femmes ménopausées, les changements en DMO observés indiquent que le rapide taux de réduction est supérieur à 3% entre 0 et 5 ans après la ménopause, puis de 1,5% entre 6 et 10 ans après la ménopause et décline à un rythme plus lent à partir de 11 ans après la ménopause. Le modèle de changement coïncide avec les changements en DMO observés chez les femmes ménopausées, tandis que les taux de perte de DMO du modèle sous estiment les changements effectifs entre 1 et 10 ans après la ménopause.

Zusammenfassung. Hintergrund: Es ist allgemein bekannt, dass bei älteren Frauen die Knochendichte (bone mineral density, BMD) im Alter und mit der Menopause abnimmt. Allerdings haben nur wenige Studien ein multiples Regressionsmodell benutzt, das körperliche Merkmale einschließt, um die komplexen Änderungen der Knochendichte im Verlauf des Lebens zu erfassen.

Ziel: Es wurde eine prospektive Studie durchgeführt, um das normale Muster von Mittelhandknochendichte-Änderungen bei Japanischen Frauen zu charakterisieren und um unter vergleichender Verwendung von Quer- und Längsschnittsdaten die Anwendbarkeit eines rechnerischen Anpassungsmodells zu prüfen.

Probanden und Methoden: Die Studie umfasste Querschnittsdaten von 5422 gesunden Frauen und eine Einjahres-Nachuntersuchung von 359 Frauen. Die Mittelhandknochendichte wurde radiologisch mittels Rechner-Densitometrie gemessen. Multiple lineare und nicht-lineare Regressionsanalysen wurden an den Querschnittsdaten durchgeführt. Eine nicht-parametrische Analyse wurde benutzt, um die prozentuale Veränderung der Knochendichte zwischen tatsächlich gemessenen und geschätzten Werten zu vergleichen.

Ergebnisse: Die Querschnittsdaten zeigten, dass die beste rechnerische Anpassung durch ein nicht-lineares Modell unter Verwendung der Variablen Alter und Körperhöhe bei Frauen vor der Menopause erzielt wurde, und unter Verwendung der Variablen Jahren seit der Menopause (years since menopause, YSM), Alter und Körperhöhe bei Frauen nach der Menopause. Die Ergebnisse der longitudinalen Daten zeigten folgendes. Bei Frauen vor der Menopause waren die tatsächlichen Knochendichteänderungen in der Gruppe der 30–39-jährigen größer als in der Gruppe der 20–29-jährigen und geringer in der Gruppe der 50–59-jährigen als in der der 40–49-jährigen. Das prozentuale Ausmaß der jährlichen Veränderung der Knochendichte zwischen den tatsächlich gemessenen und den über das Anpassungsmodell geschätzten Werten war sehr ähnlich. Bei Frauen nach der Menopause zeigten die tatsächlich gemessenen Veränderungen der Knochendichte, dass die beobachtbare Abnahmerate der Knochendichte 0 bis 5 Jahre nach der Menopause größer als 3% war, 6 bis 10 Jahre nach der Menopause 1,5% betrug, und erst 11 Jahre nach Menopause langsamer wurde. Das rechnerische Anpassungsmodell zeigte zwar den Trend der tatsächlichen Knochendichteänderung bei Frauen nach der Menopause, unterschätzte allerdings die tatsächlichen Knochendichteänderungen in den ersten 10 Jahren nach der Menopause.

Resumen. Antecedentes: La pérdida de densidad mineral ósea (BMD) con la edad y en la menopausia está ampliamente reconocida en las mujeres ancianas. Sin embargo, muy pocos estudios han utilizado un modelo de regresión múltiple que tuviera en cuenta características físicas para evaluar los cambios globales que se producen lo largo de la vida en la BMD.

Objetivo: Se realizó un estudio prospectivo para caracterizar los patrones normales de cambio en la BMD de los metacarpos en mujeres japonesas y para estimar la aplicabilidad de un modelo ajustado, utilizando datos transversales comparados con la variabilidad longitudinal.

Sujetos y métodos: Se obtuvieron datos transversales de 5422 mujeres sanas y se realizó un seguimiento de 359 mujeres durante 1 año. La BMD de los metacarpos se determinó mediante densitometría de rayos X computerizada. Se realizaron análisis de regresión lineal y no lineal múltiple en los sujetos de la muestra transversal. Se utilizó un análisis no paramétrico para comparar las tasas porcentuales de los cambios en la BMD entre los valores reales y los estimados.

Resultados: Los datos transversales mostraron que la ecuación con el mejor ajuste era un modelo de cambio no lineal, que usaba como variables la edad y la estatura en las mujeres premenopaúsicas, y los años que habían transcurrido desde la menopausia (YSM), así como la edad y la estatura, en las mujeres postmenopaúsicas. Los resultados de los datos longitudinales indicaron lo siguiente: en las mujeres premenopaúsicas, los cambios reales en la BMD fueron mayores en el grupo de 30–39 años de edad que en el de 20–29 años, y menores en el grupo de 50–59 años que en el de 40–49. Las tasas de cambio anual de la BMD entre el valor real y el estimado por el modelo de cambio eran muy similares. En las mujeres postmenopaúsicas, los cambios reales en la BMD indicaban que la rápida tasa de reducción observada era superior al 3% a los 0–5 YSM y del 1,5% a los 6–10 YSM; posteriormente, mostraban una menor tasa de disminución a los 11 YSM. El modelo de cambio representaba la tendencia del cambio real en la BMD en las mujeres postmenopaúsicas, mientras que las tasas estimadas de pérdida de la BMD subestimaban los verdaderos cambios a los 1–10 YSM.     

Evaluation of socket healing in patients undergoing bisphosphonate therapy: Experience of a single Institution

Objective: To assess the clinical features of exodontias performed in cancer patients who have been receiving intravenous bisphosphonates (BPs). Study Design: This is a retrospective cohort study using a sample of 20 patients receiving BPs who had 62 teeth extracted. An univariate analysis was applied to calculate socket healing time (HT), comparing among exodontias performed according to cause, such as periodontal disease or caries, type of BP, and use of corticosteroid. In order to analyze the influence of each variable on HT, multiple statistical analyses were performed through logistic multiple regression. Results: From the 62 tooth extractions performed, 5 exodontias had evolved to 4 sites of bisphosphonate-related osteonecrosis of the jaws (BOJ). Of another 57 exodontias without development of BOJ, HT was significantly better for tooth extraction performed in patients receiving corticosteroid (p= .01), for tooth extracted due to caries (p= .04), and for extractions under pamidronate (p= .03). Sockets after exodontias due to periodontal diseases had OR= 5.22 (95% CI 1.73-133.66, p=0.01) for delayed HT, exodontias performed under corticosteroid use had OR=0.04 (95% CI 0.01-0.40, p<0.001), and exodontias performed under zoledronate had OR=0.31 (95% CI 0.08-1.25, p=0.10). Conclusions: Exodontias performed in patients under BP therapy had a low rate of BOJ occurrence. Zoledronate and periodontal diseases influence delayed socket healing. Adjuvant antibiotics could be relevant procedures aimed at reducing the risk of BOJ development. Key words:Bisphosphonate; tooth extraction; osteonecrosis; jaw osteonecrosis; bisphosphonate-related osteonecrosis; socket healing.