Reference values of mechanical and thermal pain tests in a pain-free population

Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain-free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.

Heritability, determinants and reference values of renal length: a family-based population study

OBJECTIVES: In this population-based study, reference values were generated for renal length, and the heritability and factors associated with kidney length were assessed. METHODS: Anthropometric parameters and renal ultrasound measurements were assessed in randomly selected nuclear families of European ancestry (Switzerland). The adjusted narrow sense heritability of kidney size parameters was estimated by maximum likelihood assuming multivariate normality after power transformation. Gender-specific reference centiles were generated for renal length according to body height in the subset of non-diabetic non-obese participants with normal renal function. RESULTS: We included 374 men and 419 women (mean ± SD, age 47 ± 18 and 48 ± 17 years, BMI 26.2 ± 4 and 24.5 ± 5 kg/m(2), respectively) from 205 families. Renal length was 11.4 ± 0.8 cm in men and 10.7 ± 0.8 cm in women; there was no difference between right and left renal length. Body height, weight and estimated glomerular filtration rate (eGFR) were positively associated with renal length, kidney function negatively, age quadratically, whereas gender and hypertension were not. The adjusted heritability estimates of renal length and volume were 47.3 ± 8.5 % and 45.5 ± 8.8 %, respectively (P < 0.001). CONCLUSION: The significant heritability of renal length and volume highlights the familial aggregation of this trait, independently of age and body size. Population-based references for renal length provide a useful guide for clinicians. KEY POINTS: • Renal length and volume are heritable traits, independent of age and size. • Based on a European population, gender-specific reference values/percentiles are provided for renal length. • Renal length correlates positively with body length and weight. • There was no difference between right and left renal lengths in this study. • This negates general teaching that the left kidney is larger and longer.

Reference Values and Factors Associated With Renal Resistive Index in a Family-Based Population Study

Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population.

BACKGROUND Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. The current reference values for 24-hour urinary creatinine excretion rely on observations performed in the 1960s and 1970s in relatively small and mostly selected groups, and may thus poorly fit to the present-day general European population. The aim of this study was to establish and validate anthropometry-based age- and sex-specific reference values of the 24-hour urinary creatinine excretion on adult populations with preserved renal function. METHODS We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2) and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). Based on current reference values (177 to 221 μmol/kg/24 hours in men and 133 to 177 μmol/kg/24 hours in women), 56% of the urinary collections in the whole population and 67% in people >60 years old would have been considered as inaccurate. A linear regression model with sex, BMI and age as predictor variables was found to provide the best prediction of the observed values and showed a good fit when applied to the validation population. CONCLUSIONS We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

What Are the Radiographic Reference Values for Acetabular Under- and Overcoverage?

Background Both acetabular undercoverage (hip dysplasia) and overcoverage (pincer-type femoroacetabular impingement) can result in hip osteoarthritis. In contrast to undercoverage, there is a lack of information on radiographic reference values for excessive acetabular coverage. Questions/purposes (1) How do common radiographic hip parameters differ in hips with a deficient or an excessive acetabulum in relation to a control group; and (2) what are the reference values determined from these data for acetabular under- and overcoverage? Methods We retrospectively compared 11 radiographic parameters describing the radiographic acetabular anatomy among hip dysplasia (26 hips undergoing periacetabular osteotomy), control hips (21 hips, requiring no rim trimming during surgical hip dislocation), hips with overcoverage (14 hips, requiring rim trimming during surgical hip dislocation), and hips with severe overcoverage (25 hips, defined as having acetabular protrusio). The hips were selected from a patient cohort of a total of 593 hips. Radiographic parameters were assessed with computerized methods on anteroposterior pelvic radiographs and corrected for neutral pelvic orientation with the help of a true lateral radiograph. Results All parameters except the crossover sign differed among the four study groups. From dysplasia through control and overcoverage, the lateral center-edge angle, acetabular arc, and anteroposterior/craniocaudal coverage increased. In contrast, the medial center-edge angle, extrusion/acetabular index, Sharp angle, and prevalence of the posterior wall sign decreased. The following reference values were found: lateral center-edge angle 23° to 33°, medial center-edge angle 35° to 44°, acetabular arc 61° to 65°, extrusion index 17% to 27%, acetabular index 3° to 13°, Sharp angle 38° to 42°, negative crossover sign, positive posterior wall sign, anterior femoral head coverage 15% to 26%, posterior femoral head coverage 36% to 47%, and craniocaudal coverage 70% to 83%. Conclusions These acetabular reference values define excessive and deficient coverage. They may be used for radiographic evaluation of symptomatic hips, may offer possible predictors for surgical outcomes, and serve to guide clinical decision-making.

Reference values for digital X-ray radiogrammetry parameters in children and adolescents in comparison to estimates in patients with distal radius fractures.

The first objective of this study was to determine normative digital X-ray radiogrammetry (DXR) values, based on original digital images, in a pediatric population (aged 6-18 years). The second aim was to compare these reference data with patients suffering from distal radius fractures, whereas both cohorts originated from the same geographical region and were evaluated using the same technical parameters as well as inclusion and exclusion criteria. DXR-BMD and DXR-MCI of the metacarpal bones II-IV were assessed on standardized digital hand radiographs, without printing or scanning procedures. DXR parameters were estimated separately by gender and among six age groups; values in the fracture group were compared to age- and gender-matched normative data using Student's t tests and Z scores. In the reference cohort (150 boys, 138 girls), gender differences were found in bone mineral density (DXR-BMD), with higher values for girls from 11 to 14 years and for boys from 15 to 18 years (p < 0.05). Girls had higher normative metacarpal index (DXR-MCI) values than boys, with significant differences at 11-14 years (p < 0.05). In the case-control investigation, the fracture group (95 boys, 69 girls) presented lower DXR-BMD at 15-18 years in boys and 13-16 years in girls vs. the reference cohort (p < 0.05); DXR-MCI was lower at 11-18 years in boys and 11-16 years in girls (p < 0.05). Mean Z scores in the fracture group for DXR-BMD were -0.42 (boys) and -0.46 (girls), and for DXR-MCI were -0.51 (boys) and -0.53 (girls). These findings indicate that the fully digital DXR technique can be accurately applied in pediatric populations ≥ 6 years of age. The lower DXR-BMD and DXR-MCI values in the fracture group suggest promising early identification of individuals with increased fracture risk, without the need for additional radiation exposure, enabling the initiation of prevention strategies to possibly reduce the incidence of osteoporosis later in life.

Reference values for whole body and cerebral multi-frequency bio-impedance data in neonates less than 12 h postpartum

Multiple frequency bio-electrical impedance analysis (MFBIA) may be useful for monitoring fluid balance in newborn infants or to provide early prediction of the outcome following perinatal asphyxia. A reference range of data is needed for identification of babies with abnormal impedance values. This was a cross-sectional observational study in 84 term and near-term healthy neonates less than 12 h postpartum. Whole body and cerebral MFBIA measurements were performed at the bedside in the post-natal ward. Gestational age, post-natal age, gender, birthweight, head circumference and foot length measures were recorded. Reference values for impedance at the characteristic frequency (Z(C)) and resistance at zero frequency (R-0) are reported for whole body and cerebral impedance. Significant correlations (p < 0.05) were observed between whole body impedance and birthweight, footlength and head circumference. Females had a significantly higher whole body R0 than males. Cerebral impedance did not correlate significantly with any of the demographic measures and therewere no gender differences observed for cerebral impedance. The reference range for whole body multi-frequency bio-impedance values in term and near-term infants within the first 12 h postpartum can be calculated from the footlength (FL) using the following equations: Z(C) = (942.9 - 4.818* FL) +/- 124.6 Omega; R-0 = (1042 - 4.520(*)FL) +/- 135.5 Omega. For cerebral impedance the reference range is 29.5-48.7 Omega for Z(C) and 33.7-58.0 Omega for R-0.

Outcome of the Public Consultation on the Draft Opinion of the Scientific Panel on Dietetic Products, Nutrition, and Allergies (NDA) on Dietary Reference Values for Fats, Including Saturated Fatty Acids, Polyunsaturated Fatty Acids, Monounsaturated Fatty Acids, Trans Fatty Acids, and Cholesterol

On 2 July 2009, the EFSA Panel on Dietetic products, Nutrition and Allergies (NDA) endorsed a draft Opinion on Dietary Reference Values for fats to be released for public consultation. This Scientific Report summarises the comments received through the public consultation and outlines how these were taken into account in the final opinion. EFSA had received contributions from 40 interested parties (individuals, non-governmental organisations, industry organisations, academia and national assessment bodies). The main comments which were received during the public consultation related to: the availability of more recent data, the nomenclature used, the use of a non-European food composition data base, the impact of genetic factors in modulating the absorption, metabolism and health effects of different fatty acids, the definition of “nutritionally adequate diet”, the use of Dietary Reference Values in the labelling of foods, the translation of advice into food-based dietary guidelines, nutrient goals and recommendations, certain risk management issues, and to Dietary Reference Values of fats, individual fatty acids, and cholesterol. All the public comments received that related to the remit of EFSA were assessed and the Opinion on Dietary Reference Values for fats has been revised taking relevant comments into consideration.

Communication of scientific uncertainty: International case studies on the development of folate and vitamin D Dietary Reference Values

Objective Transparent evidence-based decision making has been promoted worldwide to engender trust in science and policy making. Yet, little attention has been given to transparency implementation. The degree of transparency (focused on how uncertain evidence was handled) during the development of folate and vitamin D Dietary Reference Values was explored in three a priori defined areas: (i) value request; (ii) evidence evaluation; and (iii) final values. Design Qualitative case studies (semi-structured interviews and desk research). A common protocol was used for data collection, interview thematic analysis and reporting. Results were coordinated via cross-case synthesis. Setting Australia and New Zealand, Netherlands, Nordic countries, Poland, Spain and UK. Subjects Twenty-one interviews were conducted in six case studies. Results Transparency of process was not universally observed across countries or areas of the recommendation setting process. Transparency practices were most commonly seen surrounding the request to develop reference values (e.g. access to risk manager/assessor problem formulation discussions) and evidence evaluation (e.g. disclosure of risk assessor data sourcing/evaluation protocols). Fewer transparency practices were observed to assist with handling uncertainty in the evidence base during the development of quantitative reference values. Conclusions Implementation of transparency policies may be limited by a lack of dedicated resources and best practice procedures, particularly to assist with the latter stages of reference value development. Challenges remain regarding the best practice for transparently communicating the influence of uncertain evidence on the final reference values. Resolving this issue may assist the evolution of nutrition risk assessment and better inform the recommendation setting process.

Centile curves and reference values for height, body mass, body mass index and waist circumference of peruvian children and adolescents

This study aimed to provide height, body mass, BMI and waist circumference (WC) growth centile charts for school-children, aged 4–17 years, from central Peru, and to compare Peruvian data with North-American and Argentinean references. The sample consisted of 8753 children and adolescents (4130 boys and 4623 girls) aged 4 to 17 years, from four Peruvian cities: Barranco, La Merced, San Ramón and Junín. Height, body mass and WC were measured according to standardized techniques. Centile curves for height, body mass, BMI and WC were obtained separately for boys and girls using the LMS method. Student t-tests were used to compare mean values. Overall boys have higher median heights than girls, and the 50th percentile for body mass increases curvilinearly from 4 years of age onwards. In boys, the BMI and WC 50th percentiles increase linearly and in girls, the increase presents a curvilinear pattern. Peruvian children are shorter, lighter and have higher BMI than their counterparts in the U.S. and Argentina; in contrast, age and sex-specific WC values are lower. Height, body mass and WC of Peruvian children increased with age and variability was higher at older ages. The growth patterns for height, body mass, BMI and WC among Peruvian children were similar to those observed in North-American and Argentinean peers.

Establishing reference values for central blood pressure and its amplification in a general healthy population and according to cardiovascular risk factors

AIMS: Estimated central systolic blood pressure (cSBP) and amplification (Brachial SBP-cSBP) are non-invasive measures potentially prognostic of cardiovascular (CV) disease. No worldwide, multiple-device reference values are available. We aimed to establish reference values for a worldwide general population standardizing between the different available methods of measurement. How these values were significantly altered by cardiovascular risk factors (CVRFs) was then investigated. METHODS AND RESULTS: Existing data from population surveys and clinical trials were combined, whether published or not. Reference values of cSBP and amplification were calculated as percentiles for 'Normal' (no CVRFs) and 'Reference' (any CVRFs) populations. We included 45,436 subjects out of 82,930 that were gathered from 77 studies of 53 centres. Included subjects were apparently healthy, not treated for hypertension or dyslipidaemia, and free from overt CV disease and diabetes. Values of cSBP and amplification were stratified by brachial blood pressure categories and age decade in turn, both being stratified by sex. Amplification decreased with age and more so in males than in females. Sex was the most powerful factor associated with amplification with 6.6 mmHg (5.8-7.4) higher amplification in males than in females. Amplification was marginally but significantly influenced by CVRFs, with smoking and dyslipidaemia decreasing amplification, but increased with increasing levels of blood glucose. CONCLUSION: Typical values of cSBP and amplification in a healthy population and a population free of traditional CVRFs are now available according to age, sex, and brachial BP, providing values included from different devices with a wide geographical representation. Amplification is significantly influenced by CVRFs, but differently in men and women.

Centile curves and reference values for height, body mass, body mass index and waist circumference of peruvian children and adolescents

This study aimed to provide height, body mass, BMI and waist circumference (WC) growth centile charts for school-children, aged 4–17 years, from central Peru, and to compare Peruvian data with North-American and Argentinean references. The sample consisted of 8753 children and adolescents (4130 boys and 4623 girls) aged 4 to 17 years, from four Peruvian cities: Barranco, La Merced, San Ramón and Junín. Height, body mass and WC were measured according to standardized techniques. Centile curves for height, body mass, BMI and WC were obtained separately for boys and girls using the LMS method. Student t-tests were used to compare mean values. Overall boys have higher median heights than girls, and the 50th percentile for body mass increases curvilinearly from 4 years of age onwards. In boys, the BMI and WC 50th percentiles increase linearly and in girls, the increase presents a curvilinear pattern. Peruvian children are shorter, lighter and have higher BMI than their counterparts in the U.S. and Argentina; in contrast, age and sex-specific WC values are lower. Height, body mass and WC of Peruvian children increased with age and variability was higher at older ages. The growth patterns for height, body mass, BMI and WC among Peruvian children were similar to those observed in North-American and Argentinean peers.