Peter Felding (Copenhagen):

 

"Criteria for including and excluding reference individuals"

(in NORIP)

 

 

Recruitment

Reference individuals could be recruited from

  • the laboratory personnel
  • and their relatives
  • or acquaintances,
  • from new blood donors or ones that seldom donate blood.

In fact potentially from any one fulfilling the criteria.

Equal sex and age distributions were sought according to the protocol.

 

Note:

  • The individuals were not recruited randomly from age and sex groups in a given population as in the Skåne study (1999)1 or in the Vejle –glucose study (2001)2
  • Potential reference individuals excluded themselves before entering the study if they did not fulfill the inclusion criteria.

 

1: Back SE, Nilsson JE, Fex G, Jeppson JO, Rosen U, Tryding N, von Schenck H, Norlund L. Towards common reference intervals in clinical chemistry. An attempt at harmonization between three hospital laboratories in Skane, Sweden. Clin Chem Lab Med 1999 May;37(5):573-92.

2: Jorgensen LG, Stahl M, Brandslund I, Hyltoft Petersen P, Borch-Johnsen K, de Fine Olivarius N.

Plasma glucose reference interval in a low-risk population. 2. Impact of the new WHO and ADA recommendations on the diagnosis of diabetes mellitus.Scand J Clin Lab Invest 2001 May;61(3):181-90.

 

Criteria for inclusion

The reference individual should

  • be feeling subjectively well
  • have reached the age of 18
  • not be pregnant or breast-feeding
  • not have been an in-patient in a hospital nor been subjectively dangerously ill during the last month
  • not have had more than 2 measures of alcohol (24 g) in the last 24 hours
  • not have given blood as a donor in the last five months
  • not have taken prescribed drugs other than the P-pill or estrogens (female sex hormone) during the last two weeks
  • not have smoked in the last hour prior to blood sampling

 

Exclusions of values from reference individuals can originate from exclusion of:

  1. Whole individuals based on their personal properties or habits.

    2. (main issue of present talk)

  2. Analytical series from laboratories
  3. Single results
  1. as outliers (will be done in NORIP if appropiate)
  2. because of certain disease ( Is not done in NORIP (yet) . Is used in the Skåne study)
  3. because of certain medikation (Is not done in NORIP (yet) . Is used in the Skåne study)
  4. because of certain condition: e.g. CK values from persons with extreme physical activity within the last week. This has been done in Norip.

Original criteria for exclusion of individuals:

Plasma- or serum-Glucose over 11.0 mmol/L

Other analytical results that clearly point to a disease

At present (10.08.2002) the exclusions rules for individuals are:

  1. Glucose concentration > 7.00 mmol/l in thawed serum from individuals, who had fasted more than 8 h. If results from fresh or thawed plasma are available, these too should be > 7.00 mmol/l.
  2. Glucose concentration > 11.00 mmol/l in thawed serum. If results from fresh or thawed plasma are available, these too should be > 11.00 mmol/l.
  3. 5s3s *: Results on thawed serum exceeding median (Norip) + 5s (Malmø/Odense) for one component and median (Norip)+ 3 s (Malmø/Odense) for another component. If other materials have been analyzed the rule should be fulfilled for the two considered components in at least one of the additional materials.
  4. 4s4s*: Results on thawed serum exceeding median (Norip) + 4s (Malmø/Odense) for one component and median (Norip)+ 4 s (Malmø/Odense) for another component. If other materials have been analyzed the rule should be fulfilled for the two considered components in at least one of the additional materials.

* The 5s3s and 4s4s rules was not be applied on low values of ALT, AST, CK, GT, ALP, LD , Creatinine, Carbamid(Urea), Triglycerides and/or Bilirubin

Limits used:

Limits used have yellow background (limits with grey background have no clinical interest)

Limits for both gender or men if separate limits for women

Women

Component

CAL target

-5s

-3s

median

+3s

+5s

-5s

-3s

median

+3s

+5s

Na

137.60

131.81

135.55

141.37

147.43

151.62

Ca

2.27

1.94

2.09

2.34

2.62

2.83

Mg

0.81

0.58

0.67

0.84

1.05

1.21

P inorg

1.03

0.50

0.69

1.13

1.85

2.58

Uric acid

285.00

131.83

190.09

329.14

569.92

821.79

79.32

123.90

241.89

472.24

737.66

Cholesterol

4.94

1.83

2.78

5.20

9.73

14.78

Trigly

1.31

0.10

0.26

1.00

3.88

9.58

Bilirubin

8.50

1.39

3.04

9.80

31.57

68.86

ALP

141.50

32.80

58.11

137.04

323.21

572.66

Amylase

192.80

35.61

70.15

193.96

536.28

1056.43

AST

23.70

6.73

11.32

24.69

53.86

90.60

5.69

9.56

20.79

45.22

75.90

K

3.70

2.99

3.38

4.06

4.88

5.51

Alt

17.80

2.14

5.47

22.40

91.76

234.91

1.98

4.65

16.70

59.93

140.50

CK

118.80

6.96

21.81

120.96

670.78

2101.57

6.36

17.59

81.00

372.95

1032.19

LD

264.00

134.01

187.16

308.88

509.76

711.91

Fe

20.23

3.31

6.53

18.10

50.21

99.10

TIBC

63.20

29.06

39.07

60.90

94.95

127.65

GT

35.90

1.98

5.52

25.81

120.63

337.22

1.58

4.20

18.21

78.94

209.92

HDL

1.33

0.44

0.69

1.33

2.58

4.01

0.55

0.85

1.64

3.17

4.93

Creatinin

69.60

43.41

54.75

77.54

109.81

138.49

35.65

45.23

64.64

92.37

117.19

Urea

4.94

1.78

2.79

5.50

10.83

17.02

1.32

2.17

4.60

9.74

16.06

Protein

67.10

52.41

58.74

69.70

82.70

92.68

Albumin

40.80

30.77

35.05

42.59

51.76

58.95

29.54

33.71

41.09

50.08

57.15

Glucose

4.49

2.67

3.41

4.90

7.04

8.97

 

28 individuals were excluded according to these rules.

14 exceeded the glucose limits.

Other characteristics of the 28:

5 had chronic disease (known 3 diabetes, 1 prostatic disease, 1 hypertension)

11 had chronic disease and /or other medicine than P-pills or estrogens.

At least 2 took prescribed medicine other than P-pills or estrogens (should not have been included)

 

Further exclusions?

Diseases and medications should probably be considered further:

 

Chronic disease and other medications than estrogens/P pills

    Chronic

disease

    
    No (including not answered) Yes  
Other medication No (including not answered) 2410 92 2502
during last week Yes 461 70 531
    2871 162 3033

 

Note: "other medication" should not include prescribed drugs if the inclusion rules have been followed. In fact most of above 531 persons who have answered yes to "other medication" only took medicine, which can be obtained without prescription.

However some took medicine , which in Denmark only can be received according to prescription. These persons should in fact be excluded, but this is not yet done.

 

Sampling conditions:

More than 50% of the individuals should have the samples taken in the fasting state between 7.00 and 10.00 in the morning. The individual should have been out of bed for some time and should have been sitting for a minimum of 15 minutes before bloodsampling in the sitting position from a cubital vein with a minimum use of tourniquet.

Hours between last meal and time of sampling

Hours <3 4 - 8 >8
Number of individuals 343 161 2327

 

 

 

Description of the 3035 individuals in the original sample group before exclusions

    Male Female Not answered
Gender   47 % 53 % 0 %
         
    Yes No Not Answered
Nordic origin   96 % 4 % 0 %
Heredity for diabetes   12 % 85 % 3 %
Chronic disease   5 % 95 % 0 %
Estrogens or P-pills (only women) 17 % 82 % 0 %
Other medication   17 % 79 % 4 %
Physical activity   14 % 86 % 0 %
Blood donations   16 % 76 % 8 %
Tobacco (units/day) 0 1-5 >5 Not answered
  83 % 6 % 10 % 2 %
Alcohol (units/week) 0 1-21 >21 Not answered
  45 % 53 % 0 % 1 %