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Responding to the expansion of scientific knowledge about the roles of nutrients in human health, the Institute of Medicine has developed a new approach to establish Recommended Dietary Allowances (RDAs) and other nutrient reference values. The new title for these values Dietary Reference Intakes (DRIs), is the inclusive name being given to this new approach. These are quantitative estimates of nutrient intakes applicable to healthy individuals in the United States and Canada. This new book is part of a series of books presenting dietary reference values for the intakes of nutrients. It establishes recommendations for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. This book presents new approaches and findings which include the following: The establishment of Estimated Energy Requirements at four levels of energy expenditure Recommendations for levels of physical activity to decrease risk of chronic disease The establishment of RDAs for dietary carbohydrate and protein The development of the definitions of Dietary Fiber, Functional Fiber, and Total Fiber The establishment of Adequate Intakes (AI) for Total Fiber The establishment of AIs for linolenic and a-linolenic acids Acceptable Macronutrient Distribution Ranges as a percent of energy intake for fat, carbohydrate, linolenic and a-linolenic acids, and protein Research recommendations for information needed to advance understanding of macronutrient requirements and the adverse effects associated with intake of higher amounts Also detailed are recommendations for both physical activity and energy expenditure to maintain health and decrease the risk of disease.

PurposeSerum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members’ hospitals and laboratories, presenting an urgent need for standardization.MethodsWe gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide.ResultsSerum magnesium levels designating “hypomagnesemia” differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from “normal” populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used “normal” ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD.ConclusionsWidely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

Basic Skills in Interpreting Laboratory Data continues to be the most popular teaching text on laboratory data for pharmacy students as well as the go-to reference for pharmacists in therapeutic practice. Now in its seventh edition, Basic Skills has been expanded and updated to cover new drugs, research, and therapeutic approaches.

Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate The Dietary Reference Intakes (DRIs) are quantitative estimates of nutrient intakes to be used for planning and assessing diets for healthy people. This new report, the sixth in a series of reports presenting dietary reference values for the intakes of nutrients by Americans and Canadians, establishes nutrient recommendations on water, potassium, and salt for health maintenance and the reduction of chronic disease risk. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate discusses in detail the role of water, potassium, salt, chloride, and sulfate in human physiology and health. The major findings in this book include the establishment of Adequate Intakes for total water (drinking water, beverages, and food), potassium, sodium, and chloride and the establishment of Tolerable Upper Intake levels for sodium and chloride. The book makes research recommendations for information needed to advance the understanding of human requirements for water and electrolytes, as well as adverse effects associated with the intake of excessive amounts of water, sodium, chloride, potassium, and sulfate. This book will be an invaluable reference for nutritionists, nutrition researchers, and food manufacturers.

Ob jectives The European Society of Radiology identified 10 common indications for computed tomography (CT) as part of the European Study on Clinical Diagnostic Reference Levels (DRLs, EUCLID), to help standardize radiation doses. The objective of this study is to generate DRLs and median doses for these indications using data from the UCSF CT International Dose Registry. Methods Standardized data on 3.7 million CTs in adults were collected between 2016 and 2019 from 161 institutions across seven countries (United States of America (US), Switzerland, Netherlands, Germany, UK, Israel, Japan). DRLs (75th percentile) and median doses for volumetric CT-dose index (CTDI vol ) and dose-length product (DLP) were assessed for each EUCLID category (chronic sinusitis, stroke, cervical spine trauma, coronary calcium scoring, lung cancer, pulmonary embolism, coronary CT angiography, hepatocellular carcinoma (HCC), colic/abdominal pain, appendicitis), and US radiation doses were compared with European. Results The number of CT scans within EUCLID categories ranged from 8,933 (HCC) to over 1.2 million (stroke). There was greater variation in dose between categories than within categories ( p  < .001), and doses were significantly different between categories within anatomic areas. DRLs and median doses were assessed for all categories. DRLs were higher in the US for 9 of the 10 indications (except chronic sinusitis) than in Europe but with a significantly higher sample size in the US. Conclusions DRLs for CTDI vol and DLP for EUCLID clinical indications from diverse organizations were established and can contribute to dose optimization. These values were usually significantly higher in the US than in Europe. Key Points • Registry data were used to create benchmarks for 10 common indications for CT identified by the European Society of Radiology. • Observed US radiation doses were higher than European for 9 of 10 indications (except chronic sinusitis). • The presented diagnostic reference levels and median doses highlight potentially unnecessary variation in radiation dose.

Background The measurement of handgrip strength (HGS) has prognostic value with respect to all‐cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high‐income countries. There is a paucity of information on normative HGS values in non‐Caucasian populations from low‐ or middle‐income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. Methods HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35‐70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Results HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25th–75th percentile) 50 kg (43–56 kg) in men <40 years from Europe/North America to 18 kg (14–20 kg) in women >60 years from South East Asia. Reference ranges by ethnicity and body‐mass index are also reported. Conclusions Individual HGS measurements should be interpreted using region/ethnic‐specific reference ranges.

Gait disorders, a highly prevalent condition in older adults, are associated with several adverse health consequences. Gait analysis allows qualitative and quantitative assessments of gait that improves the understanding of mechanisms of gait disorders and the choice of interventions. This manuscript aims (1) to give consensus guidance for clinical and spatiotemporal gait analysis based on the recorded footfalls in older adults aged 65 years and over, and (2) to provide reference values for spatiotemporal gait parameters based on the recorded footfalls in healthy older adults free of cognitive impairment and multi-morbidities. International experts working in a network of two different consortiums (i.e., Biomathics and Canadian Gait Consortium) participated in this initiative. First, they identified items of standardized information following the usual procedure of formulation of consensus findings. Second, they merged databases including spatiotemporal gait assessments with GAITRite® system and clinical information from the \"Gait, cOgnitiOn & Decline\" (GOOD) initiative and the Generation 100 (Gen 100) study. Only healthy-free of cognitive impairment and multi-morbidities (i.e., ≤ 3 therapeutics taken daily)-participants aged 65 and older were selected. Age, sex, body mass index, mean values, and coefficients of variation (CoV) of gait parameters were used for the analyses. Standardized systematic assessment of three categories of items, which were demographics and clinical information, and gait characteristics (clinical and spatiotemporal gait analysis based on the recorded footfalls), were selected for the proposed guidelines. Two complementary sets of items were distinguished: a minimal data set and a full data set. In addition, a total of 954 participants (mean age 72.8 ± 4.8 years, 45.8% women) were recruited to establish the reference values. Performance of spatiotemporal gait parameters based on the recorded footfalls declined with increasing age (mean values and CoV) and demonstrated sex differences (mean values). Based on an international multicenter collaboration, we propose consensus guidelines for gait assessment and spatiotemporal gait analysis based on the recorded footfalls, and reference values for healthy older adults.

RationaleWhile one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges.ObjectivesHere, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders.MethodsThe relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated.ResultsFifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120–270 ng/ml and 180–380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders.ConclusionsHigh interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers.

Abstract Objectives The Hoffmann method is a procedure for reference interval estimation using routine clinical results. Many authors incorrectly prepare Hoffmann plots on a linear rather than normal probability scale. We explore the consequences. Methods This was investigated algebraically, by random number simulations (45 simulations, n = 100,000 each) and using clinical data sets. Strategies compared were: Hoffmann’s method as originally and incorrectly implemented, Bhattacharya’s method, and maximum likelihood (ML). All R source code and data sets are provided. Results As the proportion of healthy individuals approaches 1, the incorrect approach generates reference interval estimates of approximately μH ± 1.19 σH delineating the central 77% of the healthy subpopulation, not the central 95%. Inappropriately narrow reference interval estimates were seen on random simulations and clinical data sets. ML methods performed best. Conclusions The erroneous variant Hoffmann method should not be used. ML methods outperform others and are not restricted by Gaussian assumptions.

The water content in milk powder must be controlled to ensure its stability. The analytical methods used for its determination can be verified through proficiency testing (PT). This study evaluated the reference values, their uncertainty, and the implications for nine PT rounds on moisture determination in milk powder conducted between 2017 and 2021 by a Chilean PT provider. An independent laboratory assigned the reference values, considering the analysis session as a source of uncertainty. Results showed that in 77.8% of the rounds, uncertainty did not meet the ISO 13528:2022 criterion, requiring the use of z′-score, which increased the risk of erroneous evaluations in 5.8% of cases, particularly near threshold values (z′ ≈ 2.0 or 3.0). The robust standard deviation from participants’ results exceeded 0.14 g water/100 g milk powder in 63.0% of PT items, suggesting that future evaluations should consider modifying the standard deviation for proficiency assessment. Reference values were found to be compatible with participants’ consensus values, though their use affected 19.3% of performance classifications, reinforcing the need for independent reference values in PT schemes with a small number of laboratories. These findings highlight the importance of evaluating the dispersion trends in proficiency assessment and adapting standard deviation criteria for more accurate performance evaluation.