Adjusted Body Weight Research Articles

Carboplatin dosing in obese patients.

The study aimed to: 1) Describe the carboplatin dosing criteria in obese patients in routine clinical practicein a general university hospital. 2) Evaluate toxicity based on the dosing criterion used. 3) Assess effectiveness in major diagnoses according to the dosing criterion employed. An observational, retrospective, descriptive study, including all obese patients (BMI ≥ 30 kg/m2) who started carboplatin treatment between 1st January 2012 and 31st January 2015. Data on patient characteristics, disease and treatment were collected. As a result variables were collected: carboplatin dosing methods, dosage criteria, alternative dosing approaches, treatment delays, dose reductions, relative dose intensity, adverse reactions and severity (CTCAE v. 4.0) as well as overall survival and progressive free survival for major diagnoses. 1) Carboplatin dosing at the centre used Calvert's formula for calculating AUC and Cockcroft-Gault's formula for estimating glomerular filtration rate. 2) Cockcroft-Gault's formula employed actual body weight and ideal adjusted body weight in similar proportions. 3) The ideal adjusted body weight was more commonly used in patients with higher obesity and diabetes. 4) In the general population, the developmental trend of toxicity during treatment was greater in the group dosed by actual body weight, reaching significant differences in thrombopenia, neutropenia, GOT elevation, hyporexia and myalgias. 5) Major diagnoses in the present study were ovarian cancer and non-small cell lung cancer. The effectiveness in terms of overall survival and progression-free survival, comparing the groups dosed by actual body weight and ideal adjusted body weight within each pathology did not show statistically significant differences.

Factors associated with major adverse cardiovascular events among Arabs and Jews in Israel: a population-based cohort study

Abstract Introduction Arabs in Israel are at higher risk of cardiovascular mortality; however, there are no data on factors associated with disparities in major adverse cardiovascular events (MACE) incidence among Arabs and Jews. Purpose To study factors associated with MACE incidence among Arabs and Jews in Israel. Materials and Methods This is a cohort study carried out in urban localities of Hadera District in Israel. The study sample included 1,100 participants, stratified in equal numbers by ethnicity (Arab and Jewish), sex, and five 10-year age group (mean age: 51 years, range: 26-77). Data collected via in-person interviews conducted between 2001-2006 included socio-demographic characteristics and health-related behaviors (smoking, physical activity, and diet). Data on baseline diabetes, hypertension, dyslipidemia, and cardiovascular disease were collected from interviews and participants' health records. Information on MACE occurring during follow-up was determined based on hospital discharge diagnoses, recorded in the Israel Ministry of Health hospital admission database. MACE was defined as an acute coronary, cerebrovascular or peripheral artery event, or invasive procedure for its treatment. Factors associated with the time to first MACE were tested in Cox proportional hazards models. Sensitivity analysis included death from any cause as a competing risk, using Fine and Gray’s model. Results During a median follow-up period of 20 years, there were 221 first MACE during follow-up; 91 among Jewish participants and 130 among Arab participants, hazard ratio (HR) Arab vs. Jewish: 1.59; 95% confidence interval (CI) 1.22, 2.09, adjusted for age and sex. Arab ethnicity was no longer significantly associated with MACE, following further adjustment for years of education; HR: 1.32; 95%CI 0.95, 1.84. The HR (95%CI) associated with ethnicity after additional adjustment for health-related behaviors, body weight and baseline chronic morbidity was 1.02 (95%CI: 0.73, 1.42). A subgroup analysis among 950 participants, who did not have a baseline diagnosis of cardiovascular disease, produced similar results. These participants experience 147 first MACE during follow-up. The age and sex-adjusted HR (95%CI) associated with Arab ethnicity was 1.72 (1.23, 2.40), compared to 1.08 (0.72, 1.64) in a fully adjusted model. Competing risk analysis did not materially change these results. Conclusions Arabs in Israel are at higher risk for MACE. Lower socioeconomic position and higher prevalence of unhealthy lifestyle and cardiovascular risk factors may explain the excess risk of MACE among Arabs. Improving cardiovascular health among Arabs should consider social determinants of health and cultural aspects.

Demographic Risk Factors Vary in the Invasion Front of Chronic Wasting Disease in West Virginia, USA.

After detecting chronic wasting disease (CWD) in white-tailed deer (Odocoileus virginianus) in Hampshire County, West Virginia, USA, in 2005, we investigated the change of CWD apparent prevalence and potential factors influencing infection risk during the invasion front. Over eight sampling years (2006-2012 and 2017) during a 12-yr period within a 101-km2-area monitoring zone, we sampled and tested a total of 853 deer for CWD by ELISA and immunohistochemistry. Bayesian logistic regression of risk factors included collection year, age class, sex, and adjusted body weight (weight after accounting for sex, age, kidney fat index, and number of fetuses). In the whole-herd model (n=634), collection year, age, and adjusted body weight were associated with increased odds of CWD, whereas an age-weight interaction had a negative relationship. We found that males drove the positive associations with age and adjusted body weight, whereas females were responsible for the negative interaction effect. These findings suggest potential behavioral and physiological mechanisms related to sex that may influence CWD exposure. Older males exhibited higher CWD prevalence, aligning with previous studies. Notably, the novel finding of adjusted body weight as a risk factor in males warrants further investigation, and this study highlights the need for future research on social behavior and its role in CWD transmission within white-tailed deer populations.

Influence of Obesity on the Efficacy and Toxicity of Patients Undergoing Autologous Hematopoietic Cell Transplantation for Lymphoma

Hematopoietic cell transplantation requires higher doses of chemotherapy, and practices of adjusting the weight because of concerns of organ toxicity are common. This retrospective analysis of 239 adult recipients of autologous hematopoietic cell transplantation for lymphoma assessed the effect of obesity on transplantation outcomes. BackgroundPrior data evaluating the impact of obesity in autologous hematopoietic cell transplantation (AHCT) for lymphomas have provided differing results when assessing overall (OS) and progression-free survival (PFS). Impact on survival outcomes have been described, but direct comparison of discrete toxicities is lacking. Patients and methods: We retrospectively compared outcomes with patients divided between 3 groups: nonobese patients (n = 129), obese patients dosed on adjusted body weight (AdjBW) (n = 32), and obese patients dosed on total body weight (TBW) (n = 78). ResultsIn multivariate analysis of OS with the nonobese group as the comparator, outcomes trended worse in obese patients dosed on AdjBW (HR 1.22, 95% CI 0.52-2.85) but were improved in obese patients dosed on TBW (HR 0.19, 95% CI 0.04-0.85, P = .012). PFS of obese patients dosed on AdjBW vs. the nonobese group was comparable (HR 1.19, 95% CI 0.63-2.24), but improved in obese patients dosed on TBW (HR 0.45, 95% CI 0.23-0.89, P = .021). Notably, no differences were noted between groups in gastrointestinal, infectious, renal, or hepatic toxicities. ConclusionIn summary, our data suggest that recipients of AHCT for lymphoma should be dosed on TBW to maximize curative outcomes with no apparent increase in toxicities.

The pharmacokinetics of ganciclovir during prolonged intermittent kidney replacement therapy in a cardiac transplant recipient.

Ganciclovir, a guanine analogue, is used intravenously (IV) first-line for the prophylaxis and treatment of cytomegalovirus (CMV) infection in solid organ transplant recipients. The pharmacokinetics (PK) of ganciclovir are highly variable, with myelosuppression occurring at high concentrations. Ganciclovir is primarily renally excreted as the parent compound, and clearance is significantly reduced in renal impairment. Acute kidney injury (AKI) is a common post-operative complication of cardiac transplantation, reducing the clearance of ganciclovir. In the intensive care unit (ICU), AKI is often managed by kidney replacement therapy (KRT). One form of KRT, prolonged intermittent kidney replacement therapy (PIKRT) is increasingly used for cost and flexibility advantages. Ganciclovir dosing recommendations are available for varying degrees of renal impairment and KRT, except for PIKRT. In this case of cardiac transplantation, complicated by anuric AKI, a ganciclovir dose of 2.0-2.5 mg/kg of adjusted body weight given after each PIKRT session was demonstrated to achieve PK targets.

Correlation between Body Composition and Bone Mineral Density Differs by Sex and Skeletal Site in Overweight and Obese Chinese Subjects

Previous studies have yielded inconsistent results regarding the relationship between obesity and bone mineral density (BMD). The aim of this study was to determine the influence of body composition on BMD and the serum sclerostin level in overweight and obese adults. The study had a cross-sectional design and included 90 men and 118 women with a body mass index ≥25. Fat mass, lean mass, and spinal and pelvic BMD were measured using dual-emission X-ray absorptiometry. Subcutaneous fat, visceral fat, and lean mass were measured between L2 and L3 by 16-slice spiral computed tomography. The serum sclerostin level was determined by enzyme-linked immunosorbent assay. Pearson analysis showed that fat mass and appendicular lean mass were positively correlated with spinal BMD in both sexes. A positive association of both fat mass and lean mass with pelvic BMD, which was stronger in women, was also found. Partial correlation analysis showed the positive association between fat mass and BMD was significantly attenuated but the positive association between lean mass and pelvic BMD remained after adjustment for age and body weight. A negative correlation was observed between visceral fat and spinal and pelvic BMD only in women, and the positive association between lean mass with pelvic BMD was more obvious in women than in men, indicating body composition seemed to have a greater impact on the BMD in women. The serum sclerostin level was positively associated with BMD but not with body composition. These findings suggest that the correlation between body composition and BMD is influenced by sex and skeletal site.

Ammonia and urea metabolism in acute liver failure: A multicentre cohort study.

Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied. Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight. Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (p < .009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); p = .004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (R2 of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (p = .024) or lower (p < .001) urea was independently associated with lower explanted liver weight. Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.

Comparison of Weight-Based Valproic Acid Dosing in Treatment of Mental Illness Among Obese and Nonobese Patients.

A weight-based dosing approach of 20-30 mg/kg per day of valproic acid (VPA) has been shown to achieve rapid attainment of mood symptom control. Due to interindividual pharmacokinetic variability, therapeutic drug monitoring may be a useful tool to avoid VPA toxicity. Limited research exists on the impact of patient body weight on VPA pharmacokinetic profiles. This analysis aims to explore the correlation between steady-state serum levels of VPA and weight-based dosing strategies, including total body weight (TBW), ideal body weight (IBW), and adjusted body weight (AdjBW), between obese and nonobese patients. This single-center, retrospective, observational cohort analysis evaluated weight-based dosing of VPA in obese and nonobese patients admitted to inpatient psychiatry at a large academic medical center between July 1, 2017, and July 1, 2022. This analysis included 93 obese and 93 nonobese patients. No significant difference in median VPA serum concentrations was observed between groups ( P = 0.82). However, the obese group received a lower median weight-based dose (15.6 mg/kg) compared with the nonobese group (19.5 mg/kg, P < 0.001). A stronger correlation was found between VPA dose and therapeutic serum levels in the obese group compared with the nonobese group regardless of weight-based dosing strategy. Dosing with AdjBW in obese patients most closely approximated dosing with TBW in nonobese patients. In obese patients, our analysis suggests dosing VPA using AdjBW may be considered as the preferred dosing strategy over IBW or TBW to minimize toxicity risk. Further research is needed with larger sample sizes and diverse patient populations to confirm these findings.

Fat-Free Mass Derived From Bioimpedance Spectroscopy and Computed Tomography are in Good Agreement in Patients With Chronic Kidney Disease

Malnutrition is highly prevalent in patients with kidney failure. Since body weight does not reflect body composition, other methods are needed to determine muscle mass, often estimated by fat-free mass (FFM). Bioimpedance spectroscopy (BIS) is frequently used for monitoring body composition in patients with kidney failure. Unfortunately, BIS-derived lean tissue mass (LTMBIS) is not suitable for comparison with FFM cutoff values for the diagnosis of malnutrition, or for calculating dietary protein requirements. Hypothetically, FFM could be derived from BIS (FFMBIS). This study aims to compare FFMBIS and LTMBIS with computed tomography (CT) derived FFM (FFMCT). Secondarily, we aimed to explore the impact of different methods on calculated protein requirements. CT scans of 60 patients with kidney failure stages 4-5 were analyzed at the L3 level for muscle cross-sectional area, which was converted to FFMCT. Spearman rank correlation coefficient and 95% limits of agreement were calculated to compare FFMBIS and LTMBIS with FFMCT. Protein requirements were determined based on FFMCT, FFMBIS, and adjusted body weight. Deviations over 10% were considered clinically relevant. FFMCT correlated most strongly with FFMBIS (r=0.78, P<.001), in males (r=0.72, P<.001) and in females (r=0.60, P<.001). A mean difference of -0.54kg was found between FFMBIS and FFMCT (limits of agreement: -14.88 to 13.7kg, P=.544). Between LTMBIS and FFMCT a mean difference of -12.2kg was apparent (limits of agreement: -28.7 to 4.2kg, P<.001). Using FFMCT as a reference, FFMBIS best predicted protein requirements. The mean difference between protein requirements according to FFMBIS and FFMCT was -0.7±9.9g in males and -0.9±10.9g in females. FFMBIS correlates well with FFMCT at a group level, but shows large variation within individuals. As expected, large clinically relevant differences were observed in calculated protein requirements.

Optimal Weight-based Dosing of Intravenous Immunoglobulin (IVIG) among Overweight and Obese Patients

Background: Intravenous immunoglobulin (IVIG), as an expensive medication under a national shortage, has been widely used for the treatment of several autoimmune diseases and immunodeficiency syndromes. Although conducting studies on therapeutic indications of IVIG has increased significantly, a limited number of researches have investigated individualized dosing in terms of the drug, disease state, and some patient-specific factors like obesity. Objective: The objective of the review was to describe the impact of various weight-based dosing regimens on the pharmacokinetics parameters, efficacy, safety, and cost of IVIG and to choose the best dosing approach for obese patients. Methods and Results: Thirteen of the total 128 manuscripts collected, reviewed, and analyzed were found from Scopus, PubMed, and Google scholar. Discussion: The evidence suggests that obesity may have an impact on IVIG pharmacokinetics, safety, and efficacy. Conclusion: The logical approach is to initial the dose based on the ideal or adjusted body weight and then modify the maintenance dose according to the patient's clinical response.

The impact of sugammadex dosing and administration practices on potential cost savings for pharmacy departments.

Neuromuscular blocking agents (NMBAs) are commonly used during surgery, and restoring neuromuscular function at the end of surgery is vital in preventing complications of residual paralysis. Recent guidelines from the American Society of Anesthesiology recommend using sugammadex over neostigmine; however, sugammadex is significantly more expensive than neostigmine and may increase drug expenditure for pharmacy departments. This review summarizes evidence evaluating sugammadex dose adjustments and the potential of these dose adjustments to lead to cost savings for pharmacy departments. We found evidence suggesting that the manufacturer-recommended sugammadex dose may not be needed in many patients and that dosing based on an adjusted body weight or based on depth of neuromuscular blockade may lead to lower sugammadex usage. Combining sugammadex with neostigmine could also decrease the dose of sugammadex required. We have highlighted the importance of objective neuromuscular monitoring to guide sugammadex dosing and evaluation for residual neuromuscular blockade. Cost savings for pharmacy departments may be realized by these alternative dosing strategies and/or vial-splitting practices. Implementing practices related to sugammadex vial splitting and dose adjustment based on body weight and depth of neuromuscular blockade shows potential benefits in terms of sugammadex cost savings.

Pharmacokinetics of propofol in severely obese surgical patients.

Existing PK models of propofol include sparse data from very obese patients. The aim of this study was to develop a PK model based on standardised surgical conditions and spanning from normal-weight up to, and including, a high number of very obese patients. Adult patients scheduled for laparoscopic cholecystectomy or bariatric surgery were studied. Anaesthesia was induced with propofol 2 mg/kg adjusted body weight over 2 min followed by 6 mg/kg/h adjusted body weight over 30 min. For the remainder of the operation anaesthesia was maintained with sevoflurane. Remifentanil was dosed according to clinical need. Eight arterial samples were drawn in a randomised block sampling regimen over a span of 24 h. Time-concentration data were analysed by population PK modelling using non-linear mixed-effects modelling. Four hundred and seventy four serum propofol concentrations were collected from 69 patients aged 19-60 years with a BMI 21.6-67.3 kg/m2. Twenty one patients had a BMI above 50 kg/m2. A 3-compartment PK model was produced wherein three different body weight descriptors and sex were included as covariates in the final model. Total body weight was found to be a covariate for clearance and Q3; lean body weight for V1, V2 and Q2; predicted normal weight for V3 and sex for V1. The fixed allometric exponent of 0.75 applied to all clearance parameters improved the performance of the model. Accuracy and precision were 1.4% and 21.7% respectively in post-hoc performance evaluation. We have developed a new PK model of propofol that is suitable for all adult weight classes. Specifically, it is based on data from an unprecedented number of individuals with very high BMI.

Loss of maternal calcitriol reversibly alters early offspring growth and skeletal development in mice.

Ablation of Cyp27b1 eliminates calcitriol but does not disturb fetal mineral homeostasis or skeletal development. However, independent of fetal genotypes, maternal loss of Cyp27b1 altered fetal mineral and hormonal levels compared to offspring of WT dams. We hypothesized that these maternal influences would alter postnatal skeletal development. Cyp27b1 null and WT females were mated to bear only Cyp27b1+/- offspring. Forty-eight hours after birth, pups were cross-fostered to dams of the same or opposite genotype that bore them. Maternal and offspring samples were collected on days 21 (weaning) and 42. Offspring measurements included minerals and hormones, BMC by DXA, ash weight and mineral content, gene expression, 3-point bending tests, and microCT. Maternal lactational behavior was evaluated. Milk was analyzed for nutritional content. At day 21, offspring fostered by nulls, independent of birth dam, had ~20% lower weight, BMC, ash weight, and ash calcium than pups fostered by WT dams. Adjustment for body weight accounted for the lower BMC but not the lower ash weight and ash calcium. Hormones and serum/urine minerals did not differ across offspring groups. Offspring fostered by nulls had shorter femurs and lower cortical thickness, mean polar moment of inertia, cortical area, trabecular bone volume, and trabecular number. Dam lactational behaviors and milk nutritional content did not differ between groups. At day 42, body weight, ash weight, lengths, BMC, and tibial bone strength were no longer different between pups fostered by null vs WT dams. In summary, pups fostered by Cyp27b1 nulls, regardless of birth dam, have proportionately smaller skeletons at 21d, impaired microstructure, but normal mineral homeostasis. The skeletal effects are largely recovered by day 42 (3 wk after weaning). In conclusion, maternal loss of calcitriol impairs early postnatal cortical bone growth and trabecular bone mass, but affected offspring catch up after weaning.

Comparison of the Efficacy of Anti-Obesity Medications in Real-World Practice.

Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the efficacy of AOMs has been reported, there have been no direct comparisons of these drugs. Therefore, in the present study, we aimed to compare the efficacy of all the AOMs available in Korea in a real-world setting. The body weight and composition of 205 adults treated with phentermine, phentermine/topiramate, liraglutide, naltrexone/bupropion, lorcaserin, or orlistat for at least 6 months were analyzed at 2 month intervals. The prevalence of the achievement of a ≥5% weight loss and the changes in body composition were compared between participants using each AOM at each visit. A total of 132 (64.4%) participants achieved ≥5% weight loss within 6 months (prevalence of ≥5% weight loss after 6 months: phentermine, 87.2%; phentermine/topiramate, 67.7%; liraglutide, 58.1%; naltrexone/bupropion, 35.3%; lorcaserin, 75%; orlistat, 50%). At each visit, after adjustment for age, sex, and baseline body weight, phentermine use was associated with a significantly higher prevalence of ≥5% weight loss than the use of the other AOMs, except for liraglutide. There were significant differences in the body weight, body mass index and body fat mass among the AOM groups by visit (P for interaction <0.05), but not in their waist circumference, skeletal muscle mass, percentage body fat, or visceral fat area. All the AOMs were effective at inducing and maintaining weight loss, in the absence of significant changes in muscle mass, over a 6 month period, and the short-term use of phentermine and the long-term use of phentermine/topiramate or liraglutide would be practical choices for the treatment of obesity. However, further, large-scale studies are necessary to confirm these findings.

2027 Protein consumption and determinants in community dwelling older adults: National Diet and Nutrition Survey (NDNS) years 9-11

Abstract Introduction Reference nutrient intake for protein amongst the general population is 0.75 grammes of protein per kilogram of body weight per day (g/kg BW/d). Expert groups recommend healthy adults over 65years have 1.0-1.2g/kg BW/d to support good health and maintain functionality (Deutz, Bauer and Barrazoni, Clinical Nutrition, 33(6):929-36). A recent paper suggested age specific recommendations of 1.2g/kg BW/d (Dorrington, Fallaize and Hobbs, Journal of Nutrition, 150(9):2245-2256). This study aimed to quantify percentage of community dwelling older adults meeting recommendations for protein intake and explore factors associated with low consumption. Methods The study population comprised &amp;gt;65s completing the NDNS survey years 9-11 (2016-2019). Dietary intake was recorded in food diaries. Protein consumption was calculated as grammes per kilogram adjusted body weight per day (g/kg aBW/d). Adjustment made for body mass index (BMI) below 22kg/m2 and above 27kg/m2. Percentage of participants meeting protein recommendations for 0.75, 1.0 and 1.2g/kg BW/d was calculated. Chi-squared test for independence was utilised to determine association between social, health and lifestyle factors and low protein intake. Results Data from 385 participants were included; 43% male, 98% white. Mean protein intake was 0.98g/kg aBW/d (SD ±0.25). Prevalence of protein intake below 0.75g/kg aBW/d was 16.4% (n=63), below 1.0g/kg aBW/d was 52.2% (n=201) and below 1.2g/kg aBW/d 82.1% (n=316). Current and ex-regular smoking was associated with protein intake &amp;lt;1g/kg aBW/d (p=0.01). No other analysis reached statistical significance although prevalence of low protein intake was higher in those without their own teeth (p=0.08), use of dentures (p=0.14) and BMI of 27-30kg/m2 (p=0.09). Conclusion A large percentage of older adults are below expert recommendations for protein intake. There is a need for clarity over recommendations so that a clear public message can be given to optimise health and function in ageing. Factors influencing poor protein intake require further examination.

EQUATIONS FOR BODY WEIGHT ADJUSTMENTS IN BLACK BELLY EWE LAMBS

&lt;p&gt;&lt;strong&gt;Background. &lt;/strong&gt;As body weight (BW) is rarely determined on fasted animals in most production systems, the need to develop accurate mathematical models for adjusting BW has been identified. &lt;strong&gt;Objective.&lt;/strong&gt; To evaluate models for estimating shrunk body weight (SBW) and empty body weight (EBW) in Black Belly growing ewe lambs raised in tropical conditions. &lt;strong&gt;Methodology.&lt;/strong&gt; Data of sixty Black Belly ewe lambs, between four to eight months of age with a mean BW of 26.55± 3.92 kg (± SD) were used. The SBW was estimated based on the BW without fasting (fed) and the EBW based on SBW through three models: 1. Linear; 2.-Linear without intercept and 3.- Exponential. The predictive capacity of the models was evaluated by cross-validation. &lt;strong&gt;Results. &lt;/strong&gt;The correlation coefficients between BW and SBW and SB and EBW were high (r = 0.94; &amp;lt;0.0001). The coefficients of determination (r&lt;sup&gt;2&lt;/sup&gt;) for the equations between BW and SBW were 0.89 (P&amp;lt;0.001); and 0.86 (P&amp;lt;0.001) for the relationship between SBW and EBW. Based on the AIC (26.81) Eq. 2 described the relationship between BW and SBW better than Eq. 1, (AIC = 28.44) and Eq. 3 (AIC =28.35). The final model to estimate SBW as a function of BW was: SBW (kg): 0.96 (±0.001***) × BW. With respect to the SBW and EBW ratio, Equation 5, was better than the linear Eq. 4, (AIC = 33.01) and Eq. 6 (AIC = 33.35). The following model was: EBW (kg): 0.81 (± 0.06***) × SBW. The cross-validation of the equation of the relationship between BW and SBW showed that Eq. 1 had a higher r2 (0.87), and lower RMSEP and MAE than Eq. 2 and Eq. 3. Also, the equation of the relationship between SBW and EBW the cross-validation revealed that Eqs. 4 and 6 had the higher &lt;sup&gt;r2&lt;/sup&gt; (0.82), and lower RMSEP and MAE and tended to be more accurate than Eq. 5. &lt;strong&gt;Implications. &lt;/strong&gt;The results obtained in present study contributes to the development of mathematical models for more accurate body weight adjustments in tropical sheep. &lt;strong&gt;Conclusion. &lt;/strong&gt;The equations developed and evaluated in the present study revealed that the linear relationship between BW and SBW, and the linear and exponential relationship between SBW and EBW can be used to body weight adjustments in growing Black Belly ewe lambs. It's worth noting that this confirms that the SBW can be calculated using an adjustment factor of 0.96 FBW.&lt;/p&gt;

Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype.

Tacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the de novo kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression. Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the de novo setting. To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype. Single-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion. Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (6 d vs 13.5 d vs 4.5 d; P = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (16 mg vs 16 mg vs 12 mg; P = 0.010) (0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg; P = 0.018). CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers (7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL; P = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients. Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

Distribution of water turnover by sex and age as estimated by prediction equation in Japanese adolescents and adults: the 2016 National Health and Nutrition Survey, Japan

BackgroundAlthough water is essential to the maintenance of health and life, standard values for human water requirements are yet to be determined. This study aimed to evaluate the distribution of water turnover (WT) according to sex and age, estimated using a prediction equation, in Japanese adolescents and adults.MethodsThis cross-sectional study used data from the 2016 National Health and Nutrition Survey, Japan. Data were obtained from electronically available aggregated reports in the survey’s official website. Participants aged between 15 and 80 years (10,546 men, 12,355 women) were selected using stratified random sampling. WT was calculated considering lifestyle and environmental factors, and using an equation (coefficient of determination = 0.471) previously developed by the international doubly labelled water (DLW) database group. As data on physical activity levels (PAL) were not collected in the survey, we used two evaluation methods: (1) energy intake assessed by dietary records and (2) total energy expenditure measured by the DLW method reported in previous Japanese studies, divided by basal metabolic rate predicted using the equation. We evaluated the relationship between WT and age using a restricted cubic spline model.ResultsThe average WT for the 15–19, 20–29, 30–39, 40–49, 50–59, 60–69, and ≥ 70 years was 3291, 3151, 3213, 3243, 3205, 3104, and 2790 ml/day, respectively in men, and 2641, 2594, 2741, 2739, 2753, 2707, and 2482 ml/day, respectively in women. In the spline model, WT showed an inverse association with age in men older than 50 years, whereas women showed a reverse U-shaped relationship between WT and age (p for non-linearity < 0.001), although results differed with body weight adjustment. Similar results were found for both PAL evaluation methods, and the range of WT per body weight was 45–56 ml/day for both sexes.ConclusionsWe determined the standard values of WT in Japanese population using a prediction equation and national large-scale survey data. These findings may be useful for setting water requirements for dietary guidelines in future.

Association of dietary salt intake with diabetes mellitus in the Japanese general population

Abstract Background/Introduction Excess salt intake, one of the most important modifiable factors in our lifestyle, has been reported to be a risk of cardiovascular morbidity and mortality. Several mechanisms underlying the development of cardiovascular disease after excess salt intake are proposed, among which hypertension has been established. Diabetes mellitus (DM) is also a risk factor of cardiovascular disease and, thus, there may be some association between excess salt intake and DM. Purpose The present study was designed to investigate possible relationship between dietary salt intake and DM in the general population. Methods Dietary salt intake was estimated using a spot urine sample in 16018 subjects (male=9642, 52.0±12.3 year-old) who visited our hospital for a yearly physical checkup from July 2008 to March 2019 (baseline). A cross-sectional analysis for the relationship between salt intake and DM was performed at baseline. Then, subjects without DM (n=14715, male=8651, 51.3±12.3 year-old) were followed up until March 2020 (median 2107 days) with the endpoint being the development of DM. DM was defined as fasting plasma glucose (FPG) ≥126mg/dL, HbA1c≥6.5% or the use of antidiabetic medications. Results A cross-sectional analysis revealed that salt intake in subjects was 8.67±1.98 g/day. Salt intake was significantly higher in subjects with (n=1280) than without DM (9.55±2.17 vs. 8.61±1.94 g/day). Multivariate regression analysis adjusted for age, gender, body weight, systolic blood pressure, pulse rate, serum creatinine, uric acid, FPG, LDL-cholesterol, triglyceride, current smoking and frequent alcohol drink showed that salt intake was associated with the presence of DM (r=0.027, p&amp;lt;0.001). In the follow-up study, 861 subjects developed DM (10.1 per 1000 person-year), with the incidence being more frequent in males than in females (11.7 vs. 7.6 per 1,000 person-year). The incidence of DM was increased across the quartiles of salt intake at baseline (7.5, 7.6, 10.5 and 14.8 per 1000 person-year). In analysis where salt intake at baseline was taken as continuous variables, non-adjusted hazard ratio (HR) (95% confidence interval [CI]) of salt intake for the new onset of DM was 1.146 (1.109-1.184). Multivariate Cox-hazard analysis adjusted for possible risk factors showed that salt intake was a significant predictor for the future development of DM (HR: 1.037, 95%CI: 1.001-1.073), while additional adjustment for baseline body weight disappeared the statistical significance (HR: 0.994, 95%CI: 0.958-1.031). Conclusions Salt intake is associated with the development of DM and excess salt intake may predict future development of DM in the general population. Excess food intake which is usually accompanied by excess salt intake in individuals with increased body weight may be responsible for the development of DM. Maintenance of appropriate body weight as well as restriction of dietary salt may lead to the prevention from developing DM.

PSIX-17 Preliminary Assessment of Preweaning Growth Performance of Dexter and Mashona X Dexter Calves

Abstract Non-traditional cattle breeds are often considered by managers for niche beef production and marketing systems. Some of these alternative breeds are small-framed and thus desired by small-farm operators but have received little research attention because they do not fit traditional commodity beef production systems. Very few of these small breeds also offer heat tolerance. This project was designed to evaluate preweaning performance of straightbred (n = 76) and F1 crossbred calves (n = 81) produced by mature Dexter cows across three years and two Tennessee State University research farms. Spring-born calves were sired by Dexter (n = 7; DD) and Mashona bulls (n = 6; MD) in single-sire, natural service breeding groups following 60-d breeding seasons. Breed of sire was balanced across cow age and farm locations. Calves were weighed within 24-h of birth, at 4 months (125 d of age) of age, and at weaning (227 d of age). Calves were not creep-fed and bull calves were not castrated until after weaning. No cases of dystocia were observed as a result of crossbreeding. Calf performance traits were evaluated using MIXED models of SAS. Fixed effects included sire breed, sex, farm location, and the interaction of sire breed and sex. Random effect terms were production year and sire nested within sire breed. For all the traits evaluated, models were consistent in that the sire breed x calf sex interaction was not significant (P &amp;gt; 0.1), whereas sire breed and calf sex were consistently important (P &amp;lt; 0.01) sources of variation. Bull calves had greater weight and ADG values than heifer calves from birth to weaning. Mean body weight was heavier for MD than DD calves at birth (28.4 ± 0.8 vs. 23.9 ± 0.7 kg), at 4 months of age (120.6 ± 9.7 vs. 96.7 ± 9.6 kg), and at weaning (154 ± 8.6 vs. 124.4 ± 8.6 kg). The MD calves had greater ADG than DD calves from birth to 4 months of age (715.8 ± 36.1 vs. 599.1 ± 36 g/d), from 4 months of age to weaning (334 ± 44.3 vs. 256.8 ± 44 g/d), and from birth to weaning (547 ± 35.7 vs. 447.1 ± 35.7 g/d). Mean 205-d adjusted body weight was heavier for MD than DD (140.2 ± 7.6 vs. 114.7 ± 7.6 kg). Preliminary results indicated that crossbreeding with Mashona bulls significantly increased preweaning growth of calves produced by Dexter cows, while the F1 calves maintained small statute. The spring-born MD F1 calves likely benefited from heat tolerance provided by the Mashona influence and heterosis generated by crossbreeding.