title: Derivation of gender and age-specific reference intervals from fully normal Japanese individuals and the implications for health screening.
abstract: BACKGROUND
  With nationwide standardization of laboratory tests among institutions for health screening in Japan, common reference intervals (RIs) were derived from records of 1,500,000 health check attendees.
  
  
  METHODS
  Targets were 20 basic laboratory tests including body mass index (BMI) and systolic and diastolic blood pressures (SBP, DBP). Individuals fulfilling the following strict criteria were chosen: SBP<130, DBP<85mmHg, BMI<25kg/m(2), non-smoking, ethanol consumption<20g/day and under no mediation with no remarkable current/past illnesses. The latent abnormal values exclusion (LAVE) method was applied to ensure fully normal results. RIs were derived by parametric method using modified Box-Cox power transformation.
  
  
  RESULTS
  Among all attendees, 23% fulfilled the criteria. Application of the LAVE method further reduced the dataset by 40%-50%. Age-related charts of test results differed greatly between genders in almost all tests. Comparison of derived RIs with clinical decision limits (CDLs) revealed that the upper limits of RIs differed from CDLs according to gender and age.
  
  
  CONCLUSIONS
  Implementation of gender and age-specific RIs derived from individuals with fully normal health attributes will (1) enable appropriate interpretation of test results in health screening and (2) promote judicious application of CDLs for therapeutic intervention, taking into account gender, age and other health attributes.
authors.affiliation: Department of Nursing, Ashikaga Institute of Technology, 268-1 Ohmae-cho, Ashikaga, Tochigi 326-8558, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yamakado
authors.affiliation: Department of Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube 755-8505, Japan. Electronic address: RXK03567@nifty.com.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ichihara
authors.affiliation: National Federation of Health Insurance Societies, 1-24-4 Minamiaoyama, Minato-ku, Tokyo 107-8558, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Mizuho Health Insurance Society, Otemachi Medical Center, 1-5-5 Otemachi Chiyoda-ku, Tokyo 100-8176, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Diseases, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.affiliation: National Federation of Health Insurance Societies, 1-24-4 Minamiaoyama, Minato-ku, Tokyo 107-8558, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Komatsubara
authors.affiliation: Medical Corporation Doyukai, 1-15-10 Nishikata, Bunkyo-ku, Tokyo 113-0024, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Takaya
authors.affiliation: Kansai Occupational Health Association, 3-1-1 Umeda, Kita-ku, Osaka 530-0001, Japan.
authors.forename: Shohken
authors.initials: S
authors.lastname: Tomita
authors.affiliation: Department of Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube 755-8505, Japan; Clinical Research Center, Yamaguchi University Hospital, 1-1-1 Minamikogushi, Ube 755-8505, Japan.
authors.forename: Reo
authors.initials: R
authors.lastname: Kawano
authors.affiliation: Department of Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube 755-8505, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takada
authors.affiliation: Tokyo Center for Laboratory Medicine, 6-3-17 Shimomeguro, Meguro-ku, Tokyo 153-0064, Japan.
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000066491:Clinical Decision-Making; D005260:Female; D006262:Health / Q000592:standards*; D006801:Humans; D007564:Japan; D008297:Male; D008403:Mass Screening / Q000592:standards*; D008875:Middle Aged; D012016:Reference Values; D012737:Sex Factors
keywords: Clinical decision limit; Clinical guideline; Health screening; Reference individual; Reference interval