Paediatric reference intervals - an update. / Pediatriske referanseområder ­ en oppdatering.

Children are not small adults, including when it comes to reference intervals. As reference intervals can vary considerably with age, sex and stage of development, it is important to use the correct reference intervals and decision limits in order to ensure optimal diagnostics. Norway's national user manual in clinical chemistry has now been updated to include paediatric reference intervals.

Readmission and mortality one year after acute hospitalization in older patients with explained and unexplained anemia - a prospective observational cohort study.

BACKGROUND: Few studies have examined whether specific subtypes of anemia in older persons are more related to adverse outcomes such as hospital readmissions and death after acute hospitalization and post-acute care. METHODS: An observational prospective cohort study was conducted between 2011 and 2014. A total of 884 community-dwelling patients, ≥70 years of age were transferred from acute medical and orthopaedic hospital departments to a skilled nursing home where they were examined by comprehensive geriatric assessment and had laboratory tests taken for the investigation of anemia. They were divided into three major groups and compared; 1) no anemia (reference group), 2) explained anemia (renal insufficiency, iron deficiency, vitaminB12/folate deficiency or multifactorial anemia) and 3) unexplained anemia. The groups were compared, and association of anemia with hospital readmission and death was estimated by logistic regression analyses. RESULTS: Compared to the patients with unexplained anemia (n=135), patients with explained anemia (n=275) had more often died (22 % vs. 14 %, p=0.05) and had more frequenlty been readmitted to hospital (39 % vs. 27 %, p=0.03). Compared to the patients without anemia (n=474), the patients with explained anemia had increased odds of hospital readmissions (OR = 1.54 (95 % CI: 1.05-2.25), p=0.03), while patients with unexplained anemia, (n=135), had neither increased odds of hospital readmissions, (OR=0.83, 95 % CI: 0.51-1.34, p=0.44) nor death (OR = 0.74, 95 % CI: 0.41-1.31, p=0.30), in adjusted regression analysis. CONCLUSION: Since no increased risk of hospital readmissions or death was seen in older patients with unexplained anemia in the first year after acute hospitalization, no further invasive investigations might be necessary to investigate the cause of anemia in these patients. A close clinical follow up might be the best way to care for older patients with a mild and unexplained anemia.

Serum vitamin B12 concentrations within reference values do not exclude functional vitamin B12 deficiency in PKU patients of various ages.

UNLABELLED: Homocysteine (Hcy) and in particular methylmalonic acid (MMA) are considered reliable parameters for vitamin B(12) status in healthy individuals. Phenylketonuria (PKU) patients are at risk for functional vitamin B(12) deficiency based on their diet. OBJECTIVE: The aim of this study was to investigate the prevalence of functional vitamin B(12) deficiency in continuously treated PKU patients and the association of parameters of vitamin B(12) and metabolic control. METHODS: In 75 continuously treated PKU patients of 1-37 years of age, serum vitamin B(12) concentrations, plasma Hcy, MMA, and phenylalanine concentrations were studied. RESULTS: Eight patients had vitamin B(12) concentrations below normal. Out of these eight patients, two had elevated MMA and/or Hcy concentrations. Ten other patients with normal vitamin B(12) concentrations had elevated concentrations of MMA and/or Hcy. CONCLUSIONS: A vitamin B(12) concentration within the reference range does not automatically imply a sufficient vitamin B(12) status. We recommend measuring serum MMA, or alternatively plasma Hcy, yearly in all PKU patients to diagnose functional vitamin B(12) deficiency.

No association between subnormal serum vitamin B12 and anemia in older nursing home patients.

PURPOSE: Since evidence of an association between vitamin B12 (B12) deficiency and anemia in older people is limited and inconclusive, we wanted to investigate this association in old, frail nursing home patients. METHODS: The study includes patients admitted to short-term, post-acute care (n = 765) and residents in long-term care (LTC) (n = 1665), in the municipality of Bergen. Anemia was defined according to the WHO criteria: Hb < 13 g/dL in men and < 12 g/dL in women, and as Hb < 11 g/dL, in both sex (moderate/severe anemia). The presence of anemia was analyzed in patients with subnormal (< 250 pmol/L), normal (250-650 pmol/L) and high (> 650 pmol/L) B12, and the association between anemia and clinical parameters, and including B12, was analyzed using logistic regression models. The use of B12 supplementation was investigated in the LTC patients. RESULTS: Mean age of the 2430 patients was 86 ± 7 years. WHO-defined anemia was seen in 1023 (42%), and moderate/severe anemia in 384 (16%) of the patients. In multiple logistic regression analyses, we found no statistically significant associations of subnormal B12 with WHO-defined anemia or moderate/severe anemia. Renal insufficiency, iron deficiency and CRP > 10 mg/L were significantly associated with both types of anemia, (p < 0.001). Among the LTC residents, 405 (24%) received B12 supplements, 112 (7%) of them had elevated B12 > 650 pmol/L. CONCLUSION: In older nursing home patients, no association was observed between subnormal B12 and anemia. Older patients in Western societies with mild/moderate anemia should not be treated with B12 supplements without further investigation.

[More adequate use of laboratory services--economical aspects]. / Riktigere bruk av laboratorietjenester--økonomiske aspekter.

BACKGROUND: There has been a substantial increase in reimbursement for outpatient laboratory services in recent years. This article gives an overview of the use of such laboratory services and discusses measures for improved efficiency. MATERIAL AND METHODS: We have analysed reimbursement to the specialist health care for the period 2002-04. RESULTS: In the period 2002-04 the reimbursement to public laboratories increased by 42%. There has been a substantial growth in all reimbursements groups, especially for "General analysis for molecular biological methods" (236%). Reimbursement to private laboratories have increased by 24%, similar to the increase in general clinical chemistry. There has been a trend towards using the expensive reimbursement groups more often, especially for public laboratories. There is substantial variation in the use of laboratory services between the health regions. DISCUSSION: Our results indicate that the growth and variation in the use of laboratory services cannot be explained by deteriorated health or more illness in the population. The variation indicates that the use of laboratory services is not optimal. Establishment of a national laboratory system within specialized health care may contribute to a more knowledge-based use of laboratory services.

[Appropriate use of laboratory tests--medical aspects]. / Riktigere bruk av laboratorietjenester--medisinske aspekter.

BACKGROUND: There has been a large increase in the use and costs of laboratory tests during recent years. Several reports have indicated excessive and inappropriate use. The purpose of this study was to assess the use of public laboratory services within clinical chemistry in two Norwegian health regions. MATERIAL AND METHODS: Production statistics for 2004 were obtained through a questionnaire sent to all public clinical chemistry hospital laboratories in northern and western Norway. Additional detailed production statistics were obtained from Haukeland University Hospital for 2002-04. RESULTS: We observed differences in the absolute frequency of requested tests and a marked variation in relative ratios (ratio between related tests) between the laboratories in northern and western Norway. Data from Haukeland University Hospital showed a mean increase of 12% (range: -24-54%) in the number of ordered tests between 2002-04. INTERPRETATION: There are no known differences in morbidity between the northern and western health regions that can explain the observed variations in the use of laboratory tests. Our observations indicate a need for a thorough investigation of current utilisation of laboratory tests. Initiatives should be taken on a national basis to improve appropriate use.

Mid-trimester amniotic fluid methionine concentrations: a predictor of birth weight and length.

The association between body size at birth and risk of later cardiovascular disease is thought to be a consequence of metabolic changes that accompany slow growth in utero. The metabolism of methionine and homocysteine has been investigated in relation to cardiovascular risk and has also been assigned an important role in organogenesis and normal fetal growth. We determined concentrations of cobalamin, folate, methionine, cysteine, cystathionine, and the marker of B-vitamin function, homocysteine, in 625 samples of amniotic fluid obtained in the second trimester from normal pregnancies. Both vitamins and metabolites varied according to gestational age. The most noticeable observation was that methionine in amniotic fluid during gestational weeks 13 to 17 strongly predicted final birth weight and length. Metabolism of methionine may be a critical factor affecting fetal growth.

Hyperhomocysteinemia and B-vitamin deficiencies in infants and children.

Measurement of total homocysteine (tHcy) in healthy and diseased children has documented the utility of this marker in pediatric research and diagnostics. This article focuses on novel data obtained in infants, children and adolescents, with emphasis on cobalamin status in infants. In children, determinants of plasma tHcy are similar to those established in adults, and include age, gender, nutrition, B-vitamin status, and some drugs interfering with B-vitamin function. In infants (age < 1 year), tHcy is moderately elevated and related to serum cobalamin, whereas in older children and throughout childhood, plasma tHcy is low (about 60% of adult levels), and folate status becomes a strong tHcy determinant. As in adults, hyperhomocysteinemia in childhood is a risk factor for stroke, and folate-responsive hyperhomocysteinemia has been detected in children with renal failure. tHcy seems to be a sensitive indicator of folate deficiency in children on a poor diet, in HIV-infected children, and in children treated with anti-folate drugs. In children at increased risk of cobalamin deficiency, which includes children born to vegetarian mothers or children in developing countries on a poor diet, tHcy and methylmalonic acid are responsive indicators of a deficiency state. In newborns and infants born to mothers with an adequate nutrition, there are consistent observations of low cobalamin, elevated tHcy and methylmalonic acid, and reduction of both metabolites by cobalamin supplementation. These data have raised the question whether cobalamin deficiency may be widespread and undetected in babies born to non-vegetarian women on a Westernized diet.

Cobalamin status and its biochemical markers methylmalonic acid and homocysteine in different age groups from 4 days to 19 years.

BACKGROUND: Recent data indicate that cobalamin and folate status, including the metabolic markers methylmalonic acid (MMA) and total homocysteine (tHcy), undergo marked changes during childhood, particularly during the first year. METHODS: Serum cobalamin, serum and whole-blood folate, and plasma MMA and tHcy were determined in a cross-sectional study of 700 children, ages 4 days to 19 years. RESULTS: During the first 6 months, serum cobalamin was lower than and plasma MMA, tHcy, and serum folate were higher than the concentrations detected in the other age groups. In infants 6 weeks to 6 months of age, median MMA and tHcy concentrations were >0.78 and >75 micro mol/L, respectively. In older children (>6 months), serum cobalamin peaked at 3-7 years and then decreased, median plasma MMA remained low (<0.26 micro mol/L), median plasma tHcy was low (<6 micro mol/L) and increased from the age of 7 years on, and serum folate gradually decreased. Plasma MMA was inversely associated with cobalamin (r = -0.4) in both age groups, but across the whole range of cobalamin concentrations, MMA was markedly higher in infants (< or =6 months) than in older children. Plasma tHcy showed a strong negative correlation to cobalamin (r = -0.52) but not to serum folate in infants < or =6 months. In older children, tHcy showed the expected association with both cobalamin (r = -0.48) and folate (r = -0.51). CONCLUSIONS: In infants 6 weeks to 6 months, concentrations of the metabolic markers MMA and tHcy were higher than in the other age groups and strongly correlated to cobalamin, whereas in older children, both makers showed correlations to cobalamin and folate concentrations documented in adults. Whether this metabolic profile in infants is explained by impaired cobalamin status, which in turn may have long-term effects on psychomotor development, remains to be addressed in intervention studies.