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.

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.

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.

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.

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.

Discovery of 1-[4-(3-chlorophenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-7-yl]-1-morpholin-4-ylmethanone (GSK554418A), a brain penetrant 5-azaindole CB2 agonist for the treatment of chronic pain.

We report the synthesis and SAR of a series of novel azaindole CB(2) agonists. 6-Azaindole 18 showed activity in an acute pain model but was inactive in a chronic model. 18 is a Pgp substrate with low brain penetration. The template was redesigned, and the resulting 5-azaindole 36 was a potent CB(2) agonist with high CNS penetration. This compound was efficacious in the acute model and the chronic joint pain model.

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.

Characteristics of qualitative studies in influential journals of general medicine: a critical review.

Although qualitative studies have increased since the 1990s, some reports note that relatively few influential journals published them up until 2000. This study critically reviewed the characteristics of qualitative studies published in top tier medical journals since 2000. We assessed full texts of qualitative studies published between 2000 and 2004 in the Annals of Internal Medicine, BMJ, JAMA, Lancet, and New England Journal of Medicine. We found 80 qualitative studies, of which 73 (91%) were published in BMJ. Only 10 studies (13%) combined qualitative and quantitative methods. Sixty-two studies (78%) used only one method of data collection. Interviews dominated the choice of data collection. The median sample size was 36 (range: 9-383). Thirty-three studies (41%) did not specify the type of analysis used but rather described the analytic process in detail. The rest indicated the mode of data analysis, in which the most prevalent methods were the constant comparative method (23%) and the grounded theory approach (22%). Qualitative data analysis software was used by 33 studies (41%). Among influential journals of general medicine, only BMJ consistently published an average of 15 qualitative study reports between 2000 and 2004. These findings lend insight into what qualities and characteristics make a qualitative study worthy of consideration to be published in an influential journal, primarily BMJ.

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).

Evaluation of a program to celebrate seasonal events for Japanese hospice patients.

OBJECTIVE: Palliative care of the terminally ill requires not only treatment of physical pain, but also care for a patient's spiritual and social needs. In Japan, where many customs correlate closely with the seasons of fall, winter, spring, and summer, seasonal events carry significance for patients who have reached a terminal stage of disease. This study determined how Japanese hospice patients evaluate a program that celebrates seasonal events and considers the modality and significance of season events at hospices. METHODS: A questionnaire survey was conducted for 1 year between August 2000 and July 2001 at a hospice located in the suburbs of Tokyo, Japan. Of the original 48 instruments, a total of 43 instruments were returned (response rate: 89.6%). RESULTS: Results showed that 72.1% of respondents participated in seasonal events, and the majority of participants positively evaluated their experiences of seasonal events. Positive aspects included being able to get a feeling for the seasons (74.2%) and being able to interact with staff and volunteers (51.6%). Negative aspects included that the events were too long (9.7%) and tiring (6.5%), and that the events made one feel sad (6.5%). Reasons for participating in seasonal events included seeming fun (71.0%), recreative (58.1%), and being entertaining (48.4%). SIGNIFICANCE OF RESULTS: Overall findings suggest that there is significance in celebrating the seasons with a monthly event at hospices. Further research is needed on the modality and experiences of celebrating the seasons at hospices in other nations.

A template for informed consent forms in medical examination and treatment: an intervention study.

BACKGROUND: There are few studies to use a template to ensure that information provided to the patient in the process of informed consent is consistent. To examine the differences between informed consent forms based on a template and those not based on a template. MATERIAL/METHODS: An intervention study using a template for informed consent forms that could be modified according to test/treatment, specialty, setting and patient. Our sample included 22 departments at the University of Tokyo Hospital, a 1100-bed care referral center. Twelve items in each informed consent form were scored. Items included diagnosis and current condition, purpose of procedure, details and nature of procedure, effectiveness, patient specific information, changing one's mind, and the use of illustrations and figures. The 36 possible points for each form were summed for a total possible score of 108 points. Total scores and scores for each item were then compared between pre- and post-test forms. RESULTS: Total number of points significantly increased from 70.9 to 96.9 between pre- and post intervention (p<0.001, paired t test). Internal medicine (pre: 68.6 to post: 101.9) showed a more significant increase in score than surgery (71.9 to 95.2) (ANOVA, pre-post: F(1,106)=324.8 p<0.001; interaction: F(1,106)=11.2, p<0.01). There was no difference in the rate of improvement between treatment and examination forms (ANOVA, pre-post: F(1, 106)=253.3, p<0.001; interaction: F(1,106)=2.8, p=0.1). CONCLUSIONS: A template can increase the number of items described and the thoroughness in which they are described.

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.

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.

Eye on religion: considering the influence of Buddhist and Shinto thought on contemporary Japanese bioethics.

Religious traditions can play a significant role in the shaping of bioethical thought. In Japan, traditional Buddhist and Shinto thought continue to influence contemporary bioethical perspectives. To better define this relationship, this paper examines the correlation between Japanese bioethical perspectives and Buddhist and Shinto thought. An in-depth discussion explores how Buddhist and Shinto scholars have used fundamental concepts with each religious tradition to agree and disagree with the disclosure of an incurable disease to a patient, brain death, and brain-dead organ transplantation.

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.