Biochemical values in persons older than 82 years of age: report from a population-based study of twins.

According to international standards, reference values for biochemical tests should be obtained in disease-free subjects and for therapies that may influence measurement values. For elderly persons, especially the very old, such a requirement is difficult to meet, since few of these individuals are free of ongoing or former diseases. The present study of a population-based Swedish twin sample comprises 535 individuals (186 males, 349 females) who were at least 82 years of age at blood sampling. Survival over a 6-year period is used as a reference of overall health. Baseline test values for subjects surviving 6 years are compared with results for persons who died in the follow-up period. Results, including mean and median values, standard deviations and ranges, were given for both genders in the total sample. Cases outside the 5th and 95th percentiles were then excluded, as were those who died during the follow-up period. In a third step, cases with disorders and therapies known to influence measurement values were also excluded. The risk of dying during the observation period was calculated across measurements from the lowest and highest 10th and 20th percentiles. The specific impact of proximity to death on the biochemical values, in addition to age effects, was analysed by comparing co-twins discordant for survival over 7 years. Increased mortality was indicated for subjects of both genders with high serum levels of urea, urate, gamma-GT, free thyroxin and plasma homocysteine. In females, low serum values for albumin and total cholesterol were associated with increased mortality. A lower cholesterol level was found 4 years before death, while a lower HDL-cholesterol level was associated with an increased risk of death across the entire 7-year period.

Association of biochemical values with morbidity in the elderly: a population-based Swedish study of persons aged 82 or more years.

BACKGROUND: Various inter-dependent factors influence serum biochemical values. In the elderly, the impact of these factors may differ compared with younger age groups and therefore population-based studies among older people are needed. The specific morbidity in old age, including also various types of drug therapy, should be observed. METHODS: Various biochemical tests in 349 females and 186 males over 81 years of age were carried out and the associations of biochemical values with morbidity, drug therapy, anthropometry and gender were estimated. RESULTS: Biochemical serum values deviate in various diseases, characterized by increased frequency in the elderly, i.e. congestive heart failure, osteoporosis, hip fractures, depression and dementia. All of these diseases present a tendency to increased homocysteine, usually combined with low folate. Cases with intact cognitive function throughout the six years after sampling are characterized by low homocysteine, which is the opposite of what is found in dementia. Furthermore, congestive heart failure is associated with impaired creatinine clearance and increased urea and urate, and osteoporosis and hip fractures are characterized by low albumin and cholesterol. Increased values for urate and impaired creatinine clearance are found in coronary diseases. In gout, multiple biochemical changes take place. For cases with a history of diabetes, arterial hypertension, peptic ulcer and malignancy, few changes are found compared with the values of the total sample. Furosemide therapy is associated with the same pattern as congestive heart failure, and laxative treatment is characterized by low folate and high homocysteine values.

[Wide variations among hospitals in use of laboratory tests. Information and education to increase cost-effectiveness]. / Stora variationer i sjukhusens användning av laboratorieanalyser. Information och utbildning för ökad kostnadseffektivitet.

Hospitals in Sweden differ greatly in their use of laboratory tests. These differences seem to be due to traditions and regional differences. The cost of a single laboratory test is often low, but since many tests are used in great numbers, the consequences of false or misleading results can be very costly. Recently, several intervention studies have been carried out in Sweden with the aim of optimizing clinical chemistry testing routines in primary care. These studies show that it is possible to reduce the cost to primary care by SEK 100 million per year while increasing clinical utility. SEK 100 million is approximately 10% of the total cost of clinical chemistry testing in primary care. It should also be possible to reduce this cost in secondary and tertiary care. Hospitals order more tests than primary care, and thus the potential savings are larger. We have studied ordering routines at eleven Swedish hospitals. Comparisons were made in the form of ratios between related laboratory tests, in order to reduce the effects of differences of scale between the laboratories that were studied. The large variation between hospitals indicates that an ongoing discussion between clinicians and laboratories could reduce costs. We have used the figures from this comparison and calculated the potential savings for seven frequently used tests. The potential yearly savings in Sweden for these tests alone is approximately SEK 150 million. We estimate that this is just half of the amount that could be saved if all tests were included.

Reminders of drug effects on laboratory test results.

Drug effects on laboratory test results are difficult to take into account without an online decision support system. In this study, drug effects on hormone test results were coded using a drug-laboratory effect (DLE) code. The criteria that trigger the reminders were defined. To issue reminders, it was necessary to write a computer program linking the DLE knowledge base with databases containing individual patient medication and laboratory test results. During the first 10 months, 11% of the results from hormone samples were accompanied by one or more DLE reminders. The most common drugs to trigger reminders were glucocorticoids, furosemide, and metoclopramide. Physicians facing the reminders completed a questionnaire on the usefulness of the reminders. All respondents considered them useful. In addition, DLE reminders had caused 74% of respondents to refrain from additional, usually performed examinations. In conclusion, drug effects on laboratory tests should always be considered when interpreting laboratory results. An online reminder system is useful in displaying potential drug effects alongside test results.

Large differences in laboratory utilisation between hospitals in Sweden.

There are large differences in the use of laboratory tests between hospitals in Sweden. These differences are not only due to differences between the patients treated but also to differences in practice. Use of laboratory test seems to reflect local traditions to a large extent. These large variations in practice are not compatible with the objective of providing care on equal terms and reduce the cost-effectiveness of clinical chemistry. Recently, several intervention studies have been performed in Sweden with the aim to optimise the use of clinical chemistry tests in primary care. The results show that it is possible to reduce the cost in primary care by SEK 100 million per year while increasing the clinical usefulness. This constitutes approximately 10% of the total cost for clinical chemistry tests in primary care. It should also be possible to reduce the cost for clinical chemistry tests in secondary and tertiary care. Hospitals order more tests than primary care and the potential savings are thus greater. We have studied the ordering habits for eleven Swedish hospitals. The comparison was made in the form of ratios between related laboratory tests to reduce the effects of differences in size between the studied laboratories. The large variation between hospitals indicates that a continuous discussion between the clinicians and the laboratories could reduce the cost. We have used the figures from the comparison and calculated the potential savings for seven frequently used tests. The potential yearly saving in Sweden for these tests is approximately SEK 150 million.

Towards common reference intervals in clinical chemistry. An attempt at harmonization between three hospital laboratories in Skåne, Sweden.

The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristianstad, was used to establish new reference intervals in clinical chemistry at the laboratories of the Central Hospital in Kristianstad, the University Hospital in Lund and the University Hospital in Mälmo. Three-hundred and fifty nine subjects, male and female, aged 20-80+ years, were invited to participate in the study, with a participation rate of 70%. Up to 70 analyses were performed on each subject, general clinical chemistry parameters in all three laboratories, specialized analyses where available. Separate a priori exclusion criteria were defined for each test. In addition, the test pattern of each individual was evaluated for signs of preclinical disease. Twelve cases of preclinical disease were discovered and clinically confirmed. Details on all test methods are presented along with information concerning instruments used, calibration procedures, methods of calculation and obtained reference intervals. Although the methods were in general calibrated against acknowledged reference materials, in some instances differences were found that made common reference intervals across all laboratories impossible. Problems relating to the practical use of international recommendations and the establishment of reliable reference intervals are discussed.

Effects of an education programme to change clinical laboratory testing habits in primary care.

OBJECTIVE: The aim of this study was to investigate the use of clinical laboratory tests in primary care and to evaluate if it is possible to improve the cost-effectiveness of laboratory testing by a short-term education programme. Our main goal has been to lower the total costs of care. DESIGN: An education programme that was monitored by laboratory test ratios. SETTING: Primary health care. SUBJECTS: 63 primary care doctors at 19 primary care centres in the county of Uppsala, Sweden. MAIN OUTCOME MEASURES: The effects of the education programme were monitored by laboratory test ratios (e.g. ASAT/ALAT) of individual doctors before and after the education programme. RESULTS: The education programme resulted in significant changes for the majority of the ratios studied. The savings on direct laboratory costs were approximately SEK 400,000 for assays that were recommended to decrease. The increased cost for assays that were recommended to increase was approximately SEK 140,000 but was considered cost-effective. CONCLUSION: It is possible to achieve significant changes in clinical chemistry test ordering habits of primary care doctors with a 2 day education programme. It resulted in cost savings and a better use of clinical chemistry tests in primary care. The effects were sustained for at least 6 months.

Measurement of C-reactive protein and the erythrocyte sedimentation rate in general practice.

OBJECTIVE: To evaluate the NycoCard:::CRP test (Nycomed A/S, Oslo, Norway) in relation to ESR in consecutive patients in general practice. NycoCard:::CRP test was also compared with a reference method for CRP quantitation. DESIGN: C-reactive protein and ESR were simultaneously measured in 607 consecutive patients at four community health centres. SETTING: Four community health centres in southern Sweden. RESULTS: We obtained consistent results in 71% of the cases. In 20% CRP was increased more than ESR, while ESR was increased more than CRP in 9%. CRP was increased in 16% while ESR was below the upper reference limit for age and sex. On the other hand ESR was increased while CRP was below 10 mg/l in five % of the patients. In most of the cases where there was a discrepancy- for example, in infectious diseases-the CRP results were more clear-cut. Using the NycoCard test the CRP concentration can be measured directly in a whole blood sample with the result available within minutes. Comparison of the NycoCard:::CRP test with the reference method for CRP quantitation showed good agreement. CONCLUSION: In clinical situations with suspected inflammatory diseases, the CRP test appears often to yield more useful results than the ESR. The NycoCard:::CRP test is suitable for use in general practice.

[Troponin T in acute myocardial infarction. Diagnosis and prognosis in patients admitted for suspected acute myocardial infarction]. / Troponin T ved akut myokardieinfarkt. Diagnostik og prognostik hos patienter indlagt til observation for akut myokardieinfarkt.

Cardiac troponin T (TnT) is a new serological marker for use as a diagnostic tool for myocardial damage. A blinded prospective multicentre study representing 298 patients who on admission were suspected of acute myocardial infarction (AMI) to the coronary care units of six Scandinavian hospitals was undertaken to assess the diagnostic performance and prognostic efficacy of a new cardiospecific TnT immunoassay. We used a discriminator value of TnT of 0.20 micrograms/l. One hundred and fifty-five patients (52%) had definite AMI, based on WHO criteria (all had peak S-TnT values > or = 0.20 micrograms/l); 127 patients (43%) had ischaemic heart disease (IHD) without AMI; and 16 patients (5%) had non-IHD (all had peak S-TnT values < 0.20 micrograms/l). The 127 IHD-patients without definite AMI could be subdivided into a group of 44 patients with S-TnT peak values > or = 0.20 micrograms/l, and a group of 83 patients with TnT below this level. A follow-up study was able to define the clinical significance of these findings. The cumulative six months probability of suffering cardiac death or AMI was significantly higher in the subgroup with increased TnT values (14% (6/44)) as compared to the other subgroup (4% (3/83)) (Log-rank test, p = 0.025). The probability of cardiac events was 15% for the patients with definite AMI. We conclude that increased troponin T in serum can detect a subgroup of IHD-patients in whom AMI has been ruled out, but who still have a prognosis as serious as that of patients with definite AMI.

Reference intervals and decision limits for plasma lipids and lipoproteins: a practical evaluation of current recommendations.

As part of a longitudinal study--the Kristianstad Survey--we measured plasma cholesterol, HDL- and LDL-cholesterol, triglycerides and lipoprotein (a) in a reference group consisting of 203 men and women aged 20-80, randomly sampled from a well-defined area in the southernmost part of Sweden. The selection of reference individuals and the collection of specimens for assay of the constituents were performed in accordance with current recommendations. The results were subjected to statistical analyses both with and without application of exclusion criteria. Application of the theoretical exclusion criteria resulted in the exclusion of 22% of the participants; however, this procedure had a remarkably weak impact on the results: the mean values and the standard deviations were almost unaltered. The mean (standard deviation) for cholesterol was 5.9 (1.3) mmol l-1, for HDL-C 1.1 (0.3) mmol l-1, and for LDL-C 4.3 (1.2) mmol l-1. Women had higher values than men. Plasma triglycerides were positively skewed; their median and Q3-Q1-values were 1.0 and 0.5 mmol l-1 respectively, men higher than women. There was an increase with age for cholesterol and LDL-C in both sexes and for triglycerides in women. The steepest increase of cholesterol values with age in women coincided with menopause, which have a more clear-cut separation between high and low cholesterol values than did any age limit.

Diagnostic performance and prognostic value of serum troponin T in suspected acute myocardial infarction.

Cardiac troponin T (TnT) is a new serological marker for use as a diagnostic tool for myocardial damage. A blinded prospective multicentre study representing 298 patients suspected of having acute myocardial infarction (AMI), and admitted to the coronary care units of six Scandinavian Hospitals was undertaken to assess the diagnostic performance and prognostic efficacy of a new cardiospecific TnT immunoassay. We used a discriminator TnT value of 0.20 microgram l-1. One hundred and fifty five patients (52%) had definite AMI, based on WHO criteria (all had peak S-TnT values of > or = 0.20 micrograms l-1); 127 patients (43%) had ischaemic heart disease (IHD) without AMI; and 16 patients (5%) had non-IHD (all had peak S-TnT values of < 0.20 microgram l-1). The 127 IHD-patients without definite AMI could be subdivided into a group of 44 patients with S-TnT peak values of > or = 0.20 microgram l-1, and a group of 83 patients with TnT below this level. An equal identification of these patients among the centres was seen (mean +/- SD 35 +/- 13%; range 20-55%). A follow-up study was able to define the clinical significance of these findings. The cumulative 6 months probability of suffering cardiac death or AMI was significantly higher in the subgroup with increased TnT values (14% (6/44)) as compared to the other subgroup (4% (3/83)) (Log-rank test, p = 0.025). The probability of cardiac events was 15% for the patients with definite AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased CKMB (mass concentration) in patients without traditional evidence of acute myocardial infarction. A risk indicator of coronary death.

A study of 102 patients consecutively admitted to a coronary care unit (CCU) investigated the clinical usefulness of three different immunoenzymometrical CKMB methods: NovoClone CK-MB, ICON QSR CKMB and IMx CK-MB. Blood samples were drawn on admission and then every 6 h for 48 h. The three different methods correlated very well (r = 0.93-0.96). With discrimination levels of 10 micrograms.l-1 for NovoClone CK-MB and 5 micrograms.l-1 for the other two methods, a sensitivity of 1.0 and a still acceptable specificity (> 0.81) were achieved. In the group of patients (n = 53) with suspicion of acute myocardial infarction (AMI) but with no standard criteria for AMI, 14 patients were identified with small but significant increase of serum CKMB (mass concentration) and an increased CKMB (mass concentration)/CK ratio. During a 4 year follow-up nine out of these 14 patients died within 2 years, the majority being coronary deaths, as compared to only two out of the remaining 39 non-AMI patients with suspicion of AMI but with normal CKMB values (chi 2 = 18.47, P < 0.001). The finding of such a high mortality rate among patients with increased CKMB (mass concentration) has an important prognostic value even in patients without standard criteria for AMI.