Translation and Linguistic Validation of the Allergy-CONTROL-ScoreTM for Use in Japan.

BACKGROUND: Symptom and medication scores are recommended to measure the primary outcome on allergies. The Allergy Control Score was proved to be a valid and reliable instrument to assess allergy severity in clinical trials and may be used in observational studies of respiratory allergic diseases in many countries. We translated the Allergy Control Score and adapted it for use in Japan. METHODS: We translated the original English version into Japanese according to the Mapi approach to linguistic validation: conceptual definition, forward translation by two native Japanese speakers, reconciliation, backtranslation by an independent translator, review in consultation with original developer, and pilot testing on 12 patients of an allergy clinic and 3 volunteers with seasonal/non-seasonal allergic rhinitis and/or asthma. RESULTS: Two of the ten back-translated items needed slight modifications and some words were revised. In the pilot test, the average time required to complete the questionnaire was 55 seconds for the section on symptoms and 25 seconds for the section on medication. All participants were able to self-complete the questionnaire. CONCLUSIONS: By applying the Mapi approach to linguistic validation, we ensured a close match between the Japanese and English versions of the Allergy Control Score. The Allergy Control Score Japanese version is accessible and acceptable to persons with respiratory allergic symptoms in Japan.

Translation and linguistic validation of the Allergy-CONTROL-ScoreTM for use in Japan.

BACKGROUND: Symptom and medication scores are recommended to measure the primary outcome on allergies. The Allergy Control Score was proved to be a valid and reliable instrument to assess allergy severity in clinical trials and may be used in observational studies of respiratory allergic diseases in many countries. We translated the Allergy Control Score and adapted it for use in Japan. METHODS: We translated the original English version into Japanese according to the Mapi approach to linguistic validation: conceptual definition, forward translation by two native Japanese speakers, reconciliation, back-translation by an independent translator, review in consultation with original developer, and pilot testing on 12 patients of an allergy clinic and 3 volunteers with seasonal/non-seasonal allergic rhinitis and/or asthma. RESULTS: Two of the ten back-translated items needed slight modifications and some words were revised. In the pilot test, the average time required to complete the questionnaire was 55 seconds for the section on symptoms and 25 seconds for the section on medication. All participants were able to self-complete the questionnaire. CONCLUSIONS: By applying the Mapi approach to linguistic validation, we ensured a close match between the Japanese and English versions of the Allergy Control Score. The Allergy Control Score Japanese version is accessible and acceptable to persons with respiratory allergic symptoms in Japan.

Synthesis and evaluation of 3-amino-6-aryl-pyridazines as selective CB(2) agonists for the treatment of inflammatory pain.

A series of 3-amino-6-aryl-pyridazines have been identified as CB(2) agonists with high efficacy and selectivity against the CB(1) receptor. Details of the investigation of structure-activity relationships (SAR) are disclosed, which led to the identification of pyridazine analogue 35, a compound with high potency in an in vivo model of inflammatory pain.

Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor.

A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies.

A model of learning clinical reasoning at a US-based workshop: interactive reasoning.

BACKGROUND: Since 2001 the University of Hawaii School of Medicine has conducted a 5-day workshop on clinical reasoning for Japanese medical students. To determine how Japanese medical students learn clinical reasoning at a US-based educational workshop. MATERIAL/METHODS: This qualitative study used 20 semi-structured interviews with students, non-participant observation, and videotapes of 40 standardized-patient encounters. RESULTS: Participants initially struggled with linguistic and cultural differences, then acquired an understanding of medical interviewing. Students understood clinical reasoning as a process of connecting with the patient using rapport building in order to gather information necessary to form a differential diagnosis and test hypotheses in conjunction with the physical examination. These findings supported a model of Interactive Reasoning. CONCLUSIONS: Our findings suggest that foreign medical students can overcome linguistic and cultural barriers at a US-based workshop and acquire an understanding of medical interviewing and clinical reasoning.

2-Amino-5-aryl-pyridines as selective CB2 agonists: synthesis and investigation of structure-activity relationships.

2-Amino-5-aryl-pyridines, exemplified by compound 1, had been identified as a synthetically tractable series of CB(2) agonists from a high-throughput screen of the GlaxoSmithKline compound collection. Described herein are the results of an investigation of the structure-activity relationships (SAR) which led to the identification a number of potent and selective agonists.

Pyridine-3-carboxamides as novel CB(2) agonists for analgesia.

We describe herein the medicinal chemistry approach which led to the discovery of a novel pyridine-3-carboxamide series of CB(2) receptor agonists. The SAR of this new template was evaluated and culminated in the identification of analogue 14a which demonstrated efficacy in an in vivo model of inflammatory pain.

Barriers to vaccination among Japanese medical students: focus group interviews.

BACKGROUND: To date, medical schools and clinical training hospitals in Japan that require students to show immunity for measles, mumps, rubella, varicella (chickenpox), and hepatitis B prior to the commencement of residency are limited. METHODS: This qualitative study used focus group interviews to elucidate why medical students do not undergo vaccination. A total of three groups were identified and interviewed: group A (two men, three women), group B (two men, two women), group C (three men, two women). All recorded interviews were transcribed verbatim and analyzed according to the constant comparative method with a series of codes and categories. RESULTS: Findings elucidated that vaccination for medical students is not mandatory in Japan. Analysis found that the factors that influence willingness to be vaccinated can be divided into three dimensions (individual level, university/regional hospital level, governmental level) and two primary categories (cost of vaccination, awareness of vaccination) consisting of 10 codes. These factors did not exist in isolation, but have mutually overlapping areas. CONCLUSIONS: Vaccination against vaccine-preventable diseases is essential to a hospital's infectious-disease countermeasures and cannot continue to be overlooked by physicians (at the individual level), by universities and residency programs (at the community level) nor by the government (at the national level).

Discovery of 2-[(2,4-dichlorophenyl)amino]-N-[(tetrahydro- 2H-pyran-4-yl)methyl]-4-(trifluoromethyl)- 5-pyrimidinecarboxamide, a selective CB2 receptor agonist for the treatment of inflammatory pain.

Selective CB2 receptor agonists are promising potential therapeutic agents for the treatment of inflammatory and neuropathic pain. A focused screen identified a pyrimidine ester as a partial agonist at the CB2 receptor with micromolar potency. Subsequent lead optimization identified 35, GW842166X, as the optimal compound in the series. 35 has an oral ED50 of 0.1 mg/kg in the rat FCA model of inflammatory pain and was selected as a clinical candidate for this indication.

An eight-year follow-up national study of medical school and general hospital ethics committees in Japan.

BACKGROUND: Ethics committees and their system of research protocol peer-review are currently used worldwide. To ensure an international standard for research ethics and safety, however, data is needed on the quality and function of each nation's ethics committees. The purpose of this study was to describe the characteristics and developments of ethics committees established at medical schools and general hospitals in Japan. METHODS: This study consisted of four national surveys sent twice over a period of eight years to two separate samples. The first target was the ethics committees of all 80 medical schools and the second target was all general hospitals with over 300 beds in Japan (n = 1457 in 1996 and n = 1491 in 2002). Instruments contained four sections: (1) committee structure, (2) frequency of annual meetings, (3) committee function, and (4) existence of a set of guidelines for the refusal of blood transfusion by Jehovah's Witnesses. RESULTS: Committee structure was overall interdisciplinary. Frequency of annual meetings increased significantly for both medical school and hospital ethics committees over the eight years. The primary activities for medical school and hospital ethics committees were research protocol reviews and policy making. Results also showed a significant increase in the use of ethical guidelines, particularly those related to the refusal of blood transfusion by Jehovah's Witnesses, among both medical school and hospital ethics committees. CONCLUSION: Overall findings indicated a greater recognized degree of responsibilities and an increase in workload for Japanese ethics committees.

Four physician communication styles in routine Japanese outpatient medical encounters.

BACKGROUND: Few studies have explored how physicians approach medical encounters in Japan. OBJECTIVE: This study examined how Japanese physicians conduct routine medical encounters in the context of outpatient care to patients with nonmalignant disorders. DESIGN: Qualitative study using semi-structured interviews and direct observation. SETTING: The outpatient department of a general hospital located in an urban area of Japan. PARTICIPANTS: Physicians and nurses providing care and patients receiving care for nonmalignant disorders. RESULTS: A 2-dimensional model was developed, with patient communication (how physician interacted with patients) along 1 axis, and nurse communication (how physicians collaborated with nursing staff) along the other axis. Four physician communication styles (individually adaptive, individually defined, collaboratively adaptive, and collaboratively defined) were identified as typical ways in which the Japanese physicians in the sample interacted with patients and nurses during routine medical encounters. CONCLUSIONS: Results suggest the need for a multiprovider-patient model of medical communication among physician, nurse, and patient. Further research is needed to establish the applicability of this model to the communication styles of physicians in other countries.

Informed consent revisited: Japan and the U.S.

Informed consent, decision-making styles and the role of patient-physician relationships are imperative aspects of clinical medicine worldwide. We present the case of a 74-year-old woman afflicted with advanced liver cancer whose attending physician, per request of the family, did not inform her of her true diagnosis. In our analysis, we explore the differences in informed-consent styles between patients who hold an "independent" and "interdependent" construal of the self and then highlight the possible implications maintained by this position in the context of international clinical ethics. Finally, we discuss the need to reassess informed-consent styles suitable to the needs of each patient regardless of whether he or she resides in the United States or in Japan.

Professional approaches to stroke treatment in Japan: a relationship-centred model.

RATIONALE: To examine how stroke professionals in Japan approach rehabilitation therapy. METHODS: This qualitative study was based on Grounded Theory. Data collection included (1) non-participatory observation, (2) non-structured interviews, and (3) semi-structured interviews. A national hospital located in an urban area of the prefecture of Kanagawa in Japan specializing in the treatment of stroke and other neurological disorders. Stroke professionals (doctors, nurses, clinical psychologists, physiotherapists, occupational therapists and speech therapists), patients and patients' families. RESULTS: (1) Professionals recognized patient motivation as a factor related to rehabilitation outcome, but believed it to be a direct product of fostered fiduciary relationships and effective patient interaction. (2) Professionals regarded fiduciary relationships as the most important determinant of rehabilitation outcome. (3) Professionals adapted their behaviour and communication style in aims of fostering fiduciary relationships. These findings informed a three-component model of care: the Relationship-centred Model. CONCLUSIONS: The Relationship-centred Model describes how stroke professionals in Japan approach rehabilitative therapy. This model of care may be preferred by patients in other countries who also favour a family-centred approach to decision making.

Perspectives on advance directives in Japanese society: A population-based questionnaire survey.

BACKGROUND: In Japan, discussion concerning advance directives (ADs) has been on the rise during the past decade. ADs are one method proposed to facilitate the process of communication among patients, families and health care providers regarding the plan of care of a patient who is no longer capable of communicating. In this paper, we report the results of the first in-depth survey on the general population concerning the preferences and use of ADs in Japan. METHOD: A self-administered questionnaire was sent via mail to a stratified random sampling of 560 residents listed in the residential registry of one district of Tokyo, Japan (n = 165,567). Association between correlating factors and specific preferences toward ADs was assessed using contingency table bivariate analysis and multivariate regression model to estimate independent contribution. RESULTS: Of the 560 questionnaires sent out, a total of 425 participants took part in the survey yielding a response rate of 75.9 %. The results of the present study indicate that: 1) the most important components to be addressed are the specifics of medical treatment at the end of life stage and disclosure of diagnosis and prognosis; 2) the majority of participants found it suitable to express their directives by word to family and/or physician and not by written documentation; 3) there is no strong need for legal measures in setting up an AD; 4) it is permissible for family and physician to loosely interpret one's directives; 5) the most suitable proxy is considered to be a family member, relative, or spouse. Multivariate analysis found the following five factors as significantly associated with preferences: 1) awareness regarding living wills, 2) experience with the use of ADs, 3) preferences for end-of-life treatment, 4) preferences for information disclosure, and 5) intentions of creating a will. CONCLUSIONS: Written ADs might be useful in the Japanese setting when the individual either wishes: 1) to not provide a lot of leeway to surrogates and/or caregivers, and/or 2) to ensure his or her directives in the cases of terminal illness, brain death, and pain treatment, as well as regarding information disclosure.

The development of a brief and objective method for evaluating moral sensitivity and reasoning in medical students.

BACKGROUND: Most medical schools in Japan have incorporated mandatory courses on medical ethics. To this date, however, there is no established means of evaluating medical ethics education in Japan. This study looks 1) To develop a brief, objective method of evaluation for moral sensitivity and reasoning; 2) To conduct a test battery for the PIT and the DIT on medical students who are either currently in school or who have recently graduated (residents); 3) To investigate changes in moral sensitivity and reasoning between school years among medical students and residents. METHODS: Questionnaire survey: Two questionnaires were employed, the Problem Identification Test (PIT) for evaluation of moral sensitivity and a portion of the Defining Issues Test (DIT) for moral reasoning. Subjects consisted of 559 medical school students and 272 residents who recently graduated from the same medical school located in an urban area of Japan. RESULTS: PIT results showed an increase in moral sensitivity in 4th and 5th year students followed by a decrease in 6th year students and in residents. No change in moral development stage was observed. However, DIT results described a gradual rising shift in moral decision-making concerning euthanasia between school years. No valid correlation was observed between PIT and DIT questionnaires. CONCLUSION: This study's questionnaire survey, which incorporates both PIT and DIT, could be used as a brief and objective means of evaluating medical students' moral sensitivity and reasoning in Japan.

The blueprint for stress can be found in invertebrates.

Through an extremely complicated equilibrium called homeostasis, all living organisms maintain their survival in the face of both externally and internally generated "stimuli". This apparent harmony is constantly challenged. Survival through successful adaptation is maintained as close to steady state as possible by adaptive responses, which may also be called perturbation responses since they have a constitutively defined dynamic capacity, i.e., an immediate limit, in a series of balancing and feedback activities reflecting an astounding array of biological, psychological and sociological behaviors. The broad spectrum of stimuli capable of engaging this protective response is remarkable. We define stress as a type of stimulation that is stronger and lasts for a longer duration, upsetting a typical perturbation response given its dynamic parameters. The stress response, which evolves out of the perturbation response, involves inducible signal molecules, i.e., cytokines. We surmise that the ability to exist in an ever-changing environment was a requirement for all life forms, including invertebrates and single celled organisms. It would be expected that these organisms exhibit both perturbation and stress responses. In this regard, we demonstrate that these organisms have mammalian-like signal molecule systems, i.e., opioid, and corresponding behaviors that are similar to those found in mammals with regard to both perturbation and stress responses. Thus, it would appear that these responses evolved first in simpler organisms and were then maintained and enhanced during evolution.