A Head-to-head Comparison of Prostate Cancer Diagnostic Strategies Using the Stockholm3 Test, Magnetic Resonance Imaging, and Swedish National Guidelines: Results from a Prospective Population-based Screening Study.

Background: Strategies for early detection of prostate cancer aim to detect clinically significant prostate cancer (csPCa) and avoid detection of insignificant cancers and unnecessary biopsies. Swedish national guidelines (SNGs), years 2019 and 2020, involve prostate-specific antigen (PSA) testing, clinical variables, and magnetic resonance imaging (MRI). The Stockholm3 test and MRI have been suggested to improve selection of men for prostate biopsy. Performance of SNGs compared with the Stockholm3 test or MRI in a screening setting is unclear. Objective: To compare strategies based on previous and current national guidelines, Stockholm3, and MRI to select patients for biopsy in a screening-by-invitation setting. Design setting and participants: All participants underwent PSA test, and men with PSA ≥3 ng/ml underwent Stockholm3 testing and MRI. Men with Stockholm3 ≥11%, Prostate Imaging Reporting and Data System score ≥3 on MRI, or indication according to SNG-2019 or SNG-2020 were referred to biopsy. Outcome measurements and statistical analysis: The primary outcome was the detection of csPCa at prostate biopsy, defined as an International Society of Urological Pathology (ISUP) grade of ≥2. Results and limitations: We invited 8764 men from the general population, 272 of whom had PSA ≥3 ng/ml. The median PSA was 4.1 (interquartile range: 3.4-5.8), and 136 of 270 (50%) who underwent MRI lacked any pathological lesions. In total, 37 csPCa cases were diagnosed. Using SNG-2019, 36 csPCa cases with a high biopsy rate (179 of 272) were detected and 49 were diagnosed with ISUP 1 cancers. The Stockholm3 strategy diagnosed 32 csPCa cases, with 89 biopsied and 27 ISUP 1 cancers. SNG-2020 detected 32 csPCa and 33 ISUP 1 cancer patients, with 99 men biopsied, and the MRI strategy detected 30 csPCa and 35 ISUP 1 cancer cases by biopsying 123 men. The latter two strategies generated more MRI scans than the Stockholm3 strategy (n = 270 vs 33). Conclusions: Previous guidelines provide high detection of significant cancer but at high biopsy rates and detection of insignificant cancer. The Stockholm3 test may improve diagnostic precision compared with the current guidelines or using only MRI. Patient summary: The Stockholm3 test facilitates detection of significant cancer, and reduces the number of biopsies and detection of insignificant cancer.

Alkaline phosphatase in healthy children: reference intervals and prevalence of elevated levels.

BACKGROUND: Transient hyperphosphatasemia (TH) is an often unnoticed benign entity, primarily affecting children below 5 years of age. However, the prevalence among healthy children is unknown. We used data from a Swedish pediatric reference interval project to estimate the prevalence of high alkaline phosphatase (ALP) among healthy children and to calculate pediatric reference intervals. METHODS: Blood was collected from 699 subjectively healthy children aged 6 months to 18 years. After exclusion of subjects with high ALP, age- and gender-specific reference intervals were calculated. RESULTS: Six children had ALP levels >16.7 µkat/l (>1,000 U/l), including 4 females and 2 males aged 7-22 months. The prevalence in the age group from 6 months to 2 years was 6.2% (6/97). None of the older children had levels of ALP >16.7 µkat/l. The study did not include the follow-up of these apparently healthy children. Consequently, conditions others than TH explaining the elevated ALP could not be excluded. However, general chemistry analyses, such as liver enzymes, calcium, intact PTH and vitamin D, were essentially normal in these children. CONCLUSIONS: The prevalence of high ALP among subjectively healthy children was approximately 2.4% below 5 years of age and 6.2% below 2 years. Reference intervals vary with age and gender.

Estimating reliable paediatric reference intervals in clinical chemistry and haematology.

UNLABELLED: Very few high-quality studies on paediatric reference intervals for general clinical chemistry and haematology analytes have been performed. Three recent prospective community-based projects utilising blood samples from healthy children in Sweden, Denmark and Canada have substantially improved the situation. CONCLUSION: The present review summarises current reference interval studies for common clinical chemistry and haematology analyses.

Population-based pediatric reference intervals for HbA1c, bilirubin, albumin, CRP, myoglobin and serum enzymes.

BACKGROUND: Many previous studies on reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. METHODS: This study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy. A questionnaire on diseases and medications was filled out by parents and by the older children. RESULTS: Alanine aminotransferase (ALT), albumin, aspartate aminotransferase (AST), bilirubin, conjugated bilirubin, C-reactive protein (CRP), creatine kinase (CK), Gamma-glutamyltransferase (GGT), HbA1c (mono S and IFCC calibrations), lactate dehydrogenase (LD), myoglobin and panceratic amylase were analyzed on Abbott Architect ci8200, and for HbA1c on Tosoh G7 and a mono S-system. Age- and gender-related 2.5th and 97.5th percentiles were estimated. For some analytes the differences to comparable studies were substantial. CONCLUSION: The study gives age- and gender-specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results emphasize the importance to evaluate pediatric reference intervals in different populations and ethnic groups including only healthy subjects.

Population-based pediatric reference intervals for hematology, iron and transferrin.

Reference intervals are crucial decision-making tools aiding clinicians in differentiating between healthy and diseased populations. However, for children such values often are lacking or incomplete. Blood samples were obtained from 689 healthy children, aged 6 months to 18 years, recruited in day care centers and schools. Hematology and anemia analytes were measured on the Siemens Advia 2120 and Abbott Architect ci8200 platforms (hemoglobin, erythrocyte volume fraction [EVF], erythrocytes, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], reticulocytes, leukocytes, lymphocytes, monocytes, neutrophils, eosinophils, basophils, platelets, iron, transferrin, transferrin saturation). Age- and gender-specific pediatric reference intervals were defined by calculating 2.5th and 97.5th percentiles. The data generated is primarily applicable to a Caucasian population, but could be used by any laboratory if verified for the local patient population.

Reference intervals on the Abbot Architect for serum thyroid hormones, lipids and prolactin in healthy children in a population-based study.

Pediatric reference intervals for thyroid hormones, prolactin and lipids are of high clinical importance as deviations might indicate diseases with serious consequences. In general, previous reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. The study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy and a questionnaire on diseases and medications was filled out by parents and by the older children. TSH, free T4, free T3, total cholesterol, LDL, HDL, triglycerides and prolactin were analyzed on Abbott Architect ci8200. Age- and gender-related 2.5 and 97.5 percentiles were estimated. The thyroid hormone levels were similar to previous data for the Abbott Architect platform, but exhibited differences from studies performed with other methods. Prolactin displayed wide reference ranges, but relatively small age-related changes, and a marginal difference between sexes during adolescence. Reference intervals for lipids in the different age groups are known to vary geographically. Levels of LDL and total cholesterol were higher than those reported for children in Canada, but lower than those reported for children in China. The study gives age- and gender- specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results presented here differ from previously recommended reference intervals. In many earlier studies, retrospective hospital-based reference intervals, which may include various sub-groups have been presented. By non-hospital studies it is possible to avoid some of these biases.

Population-based pediatric reference intervals for general clinical chemistry analytes on the Abbott Architect ci8200 instrument.

BACKGROUND: Reference intervals are crucial decision-making tools aiding clinicians in differentiating between healthy and diseased populations. However, for children such values often are lacking or incomplete. METHODS: Blood samples were obtained from 692 healthy children, aged 6 months to 18 years, recruited in daycare centers and schools. Twelve common general clinical chemistry analytes were measured on the Abbott Architect ci8200 platform; sodium, potassium, chloride, calcium, albumin-adjusted calcium, phosphate, magnesium, creatinine (Jaffe and enzymatic), cystatin C, urea and uric acid. RESULTS: Age- and gender specific pediatric reference intervals were defined by calculating the 2.5th and 97.5th percentiles. CONCLUSIONS: The data generated is primarily applicable to a Caucasian population when using the Abbott Architect platform, but could be used by any laboratory if validated for the local patient population.