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Objective: To develop and validate a multivariate model for predicting respiratory status in patients with advanced chronic obstructive pulmonary disease (COPD).Design: Prospective, double-blind study of peak flow monitoring.Setting: Albuquerque Veterans Affairs Medical Center.Patients: Male veterans with an irreversible component of airflow obstruction on baseline pulmonary function tests.Measurements: This study was conducted between January 1995 and May 1996. At entry, subjects were instructed in the use of the modified Medical Research Council Dyspnea Scale and a mini-Wright peak flow meter equipped with electronic storage. For the next 6 months, they recorded their dyspnea scores once daily and peak expiratory flow rates twice daily, before and after the use of bronchodilators. Patients were blinded to their peak expiratory flow rates, and medical care was provided in the customary manner. Readings were aggregated into 7-day sampling intervals, and interval means were calculated for dyspnea score and peak expiratory flow rate parameters. Intervals from all subjects were then pooled and randomized to separate groups for model development (training set) and validation (test set). In the training set, logistic regression was used to identify variables that predicted future respiratory status. The dependent variable was the log odds that the subject would attain his highest level of dyspnea in the next 7 days. The final model was used to stratify the test set into "high-risk" and "low-risk" categories. The analysis was repeated for 3-day intervals.Main Results: Of the 40 patients considered eligible for study, 8 declined to participate, 4 could not master the technique of peak flow monitoring, and 6 had no fluctuations in their dyspnea level. The remaining 22 subjects form the basis of this report. Fourteen (64%) of the latter completed the 6-month protocol. Data from the 8 who were dropped or died were included up to the point of withdrawal. For 7-day forecasts, mean dyspnea score and mean daily prebronchodilator peak expiratory flow rate were identified as predictor variables. The adjusted odds ratio (OR) for mean dyspnea score was 2.71 (95% confidence interval [CI] 1.79, 4.12) per unit. For mean prebronchodilator peak expiratory flow rate, it was 1.05 (95% CI 1.01, 1.09) per percentage predicted. For 3-day forecasts, the model was composed of mean dyspnea score and mean daily bronchodilator response. The ORs for these terms were 2.66 (95% CI 2.06, 3.44) per unit and 0.980 (95% CI 0.962, 0.998) per percentage of improvement over baseline, respectively. For a given level of dyspnea, higher pre-bronchodilator peak expiratory flow rate and lower bronchodilator response were poor prognostic findings. When the models were applied to the test sets, "high-risk" intervals were 4 times more likely to be followed by maximal symptoms than "low-risk" intervals.Conclusions: Dyspnea scores and certain peak expiratory flow rate parameters are independent predictors of respiratory status in patients with COPD. However, our results suggest that monitoring is of little benefit except in patients with the most advanced form of this disease, and its contribution to their management is modest at best. [ABSTRACT FROM AUTHOR]

Examines the validity of the Dialysis Outcomes Quality Initiative (DOQI) guidelines in monitoring the normalization of both urea and creatinine clearance in peritoneal dialysis. Differences in the agreement between actual and predicted normalized clearance using the different size indicators.

Abstract Background Racial/ethnic disparities in cardiovascular disease complications have been observed in diabetic patients. We examined the association between race/ethnicity and cardiovascular disease risk factor control in a large cohort of insulin-treated veterans with type 2 diabetes. Methods We conducted a cross-sectional observational study at 3 Veterans Affairs Medical Centers in the American Southwest. Using electronic pharmacy databases, we randomly selected 338 veterans with insulin-treated type 2 diabetes. We collected medical record and patient survey data on diabetes control and management, cardiovascular disease risk factors, comorbidity, demographics, socioeconomic factors, psychological status, and health behaviors. We used analysis of variance and multivariate linear regression to determine the effect of race/ethnicity on glycemic control, insulin treatment intensity, lipid levels, and blood pressure control. Results The study cohort was comprised of 72 (21.3%) Hispanic subjects (H), 35 (10.4%) African Americans (AA), and 226 (67%) non-Hispanic whites (NHW). The mean (SD) hemoglobin A1c differed significantly by race/ethnicity: NHW 7.86 (1.4)%, H 8.16 (1.6)%, AA 8.84 (2.9)%, p = 0.05. The multivariate-adjusted A1c was significantly higher for AA (+0.93%, p = 0.002) compared to NHW. Insulin doses (unit/day) also differed significantly: NHW 70.6 (48.8), H 58.4 (32.6), and AA 53.1 (36.2), p < 0.01. Multivariate-adjusted insulin doses were significantly lower for AA (-17.8 units/day, p = 0.01) and H (-10.5 units/day, p = 0.04) compared to NHW. Decrements in insulin doses were even greater among minority patients with poorly controlled diabetes (A1c ≥ 8%). The disparities in glycemic control and insulin treatment intensity could not be explained by differences in age, body mass index, oral hypoglycemic medications, socioeconomic barriers, attitudes about diabetes care, diabetes knowledge, depression, cognitive dysfunction, or social support. We found no significant racial/ethnic differences in lipid or blood pressure control. Conclusion In our cohort, insulin-treated minority veterans, particularly AA, had poorer glycemic control and received lower doses of insulin than NHW. However, we found no differences for control of other cardiovascular disease risk factors. The diabetes treatment disparity could be due to provider behaviors and/or patient behaviors or preferences. Further research with larger sample sizes and more geographically diverse populations are needed to confirm our findings.

Background: The Extension for Community Healthcare Outcomes (ECHO) model was developed to improve access to care for underserved populations with complex health problems such as hepatitis C virus (HCV) infection. With the use of video-conferencing technology, the ECHO program trains primary care providers to treat complex diseases.Methods: We conducted a prospective cohort study comparing treatment for HCV infection at the University of New Mexico (UNM) HCV clinic with treatment by primary care clinicians at 21 ECHO sites in rural areas and prisons in New Mexico. A total of 407 patients with chronic HCV infection who had received no previous treatment for the infection were enrolled. The primary end point was a sustained virologic response.Results: A total of 57.5% of the patients treated at the UNM HCV clinic (84 of 146 patients) and 58.2% of those treated at ECHO sites (152 of 261 patients) had a sustained viral response (difference in rates between sites, 0.7 percentage points; 95% confidence interval, -9.2 to 10.7; P=0.89). Among patients with HCV genotype 1 infection, the rate of sustained viral response was 45.8% (38 of 83 patients) at the UNM HCV clinic and 49.7% (73 of 147 patients) at ECHO sites (P=0.57). Serious adverse events occurred in 13.7% of the patients at the UNM HCV clinic and in 6.9% of the patients at ECHO sites.Conclusions: The results of this study show that the ECHO model is an effective way to treat HCV infection in underserved communities. Implementation of this model would allow other states and nations to treat a greater number of patients infected with HCV than they are currently able to treat. (Funded by the Agency for Healthcare Research and Quality and others.). [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis (ACD) is an inflammatory skin reaction whose incidence has increased and has been associated with a dietary pattern rich in saturated fats and refined sugars. Considering the increased incidence of ACD and the lack of research about the influence of a short-term high-sugar diet on dermatitis, our aim is to improve understanding of the influence of a high-sugar diet on ACD. We introduced a diet rich in sugar fifteen days before inducing contact dermatitis with oxazolone, in mice, and maintained it until the end of the experiment, which lasted three weeks in total. The dermatitis model increased cholesterol and triglycerides in the liver, and the combination of diet and dermatitis increased weight and worsened liver cholesterol measurements. Furthermore, the high-sugar diet increased the production of IL-6, IFN-γ and TNF-α in the skin, which may be involved in the increase in epithelial skin thickness observed in experimental ACD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Objective: Risk for asthma in the overweight/obese may be mediated by adiponectin and peroxisome proliferator activated receptor pathways and may be reduced by the use of oral drugs impacting these pathways, such as angiotensin converting enzyme inhibitors (ACE-I), thiazolidinediones (TZD), and angiotensin receptor blockers (ARB). Our study objective was to determine whether ACE-I, TZD, and/or ARB use in overweight/obese adults with diabetes mellitus and/or hypertension is associated with a lower risk for incident asthma., Methods: Using an existing cohort of American veterans, we performed a longitudinal data analysis over 15 years. Exposure was defined by the prescription pickup of ACE-I, TZD, and/or ARB for at least 4 weeks. The outcome, time until new-onset of clinician-diagnosed asthma, was studied using survival analysis. The propensity scoring method controlled for treatment selection bias., Results: 2.83 million eligible veterans, including 77,278 with incident asthma, were studied. As compared to those unexposed, the use of ACE-I alone, TZD alone, or their combinations were each associated with decreased risk for incident asthma (hazard ratios of 0.88, 0.74, and 0.20, respectively; p  < 0.001 for all analyses in the fully adjusted statistical models). TZD lowered the risk among racial/ethnic minority subjects more than among White participants ( p  < 0.001). On the other hand, ARB use alone or in combination with TZD was associated with a higher risk for incident asthma., Conclusions: Use of ACE-I and/or TZD was associated with a lower risk for incident asthma in overweight/obese patients with diabetes mellitus and/or hypertension.

Some studies have demonstrated the participation of leptin in magnesium metabolism. On the other hand, there is evidence of the role of magnesium in the leptin intracellular signaling pathway. Therefore, the aim of this study was to investigate the existence of a relationship between serum leptin concentrations and magnesium biomarkers in women with obesity. Case-control study involving 108 women aged between 20 and 50 years, divided into two groups: obese (n = 52) and control (n = 56). Body weight, height and waist circumference, body mass index, dietary magnesium intake, magnesium biomarkers and serum leptin concentrations were measured. Serum leptin concentrations showed a statistically significant difference between groups (p < 0.001). Mean values of magnesium intake were lower than intake recommended, and with no statistically significant difference between two groups (p > 0.05). Women with obesity had lower plasma and erythrocyte magnesium concentrations than control group did (p < 0.001). Magnesium concentrations found in the urine of women with obesity were higher than the control group was, with a statistically significant difference (p < 0.001). There was a correlation between serum leptin and magnesium biomarkers (p < 0.001). Women with obesity show an inadequate magnesium nutritional status characterized by low plasma and erythrocyte concentrations and high concentrations in urine, and they also have high serum leptin concentrations. Thus, it was possible to observe a correlation between hyperleptinemia and magnesium biomarkers, requiring further studies to determine whether the dysfunction of this hormone can influence the compartmentalization of the mineral in obese organisms., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Trypanosoma cruzi, the parasite causing Chagas disease, is a digenetic flagellated protist that infects mammals (including humans) and reduviid insect vectors. Therefore, T. cruzi must colonize different niches in order to complete its life cycle in both hosts. This fact determines the need of adaptations to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. In this regard, it is well known that T. cruzi has a flexible metabolism able to rapidly switch from carbohydrates (mainly glucose) to amino acids (mostly proline) consumption. Also established has been the capability of T. cruzi to use glucose and amino acids to support the differentiation process occurring in the insect, from replicative non-infective epimastigotes to non-replicative infective metacyclic trypomastigotes. However, little is known about the possibilities of using externally available and internally stored fatty acids as resources to survive in nutrient-poor environments, and to sustain metacyclogenesis. In this study, we revisit the metabolic fate of fatty acid breakdown in T. cruzi. Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-14C]-palmitate can be taken up from the medium, leading to CO2 production. Additionally, we show that electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid (TCA) cycle, which can be used to feed anabolic pathways such as the de novo biosynthesis of fatty acids. Finally, we show as well that the inhibition of fatty acids mobilization into the mitochondrion diminishes the survival to severe starvation, and impairs metacyclogenesis., Competing Interests: The authors have declared that no competing interests exist.

Background: Root-knot nematodes (RKN, Meloidogyne spp.) are harmful phytophagous pests of Solanum spp. Some RKN species are becoming worldwide problems because of their virulence to RKN-resistant Solanum species. A new Solanum species carrying broad-spectrum resistance to Meloidogyne spp. is required for the effective management of this pest. Here we sought to determine the host suitability of RKN to Solanum palinacanthum, a wild Solanum species, and to evaluate its potential effectiveness in RKN management., Results: We identified an RKN-resistant Solanum species, S. palinacanthum, by screening Solanum accessions. We tested its spectrum of resistance to common Meloidogyne spp. in Japan. In pot tests inoculated with second-stage juveniles, S. palinacanthum showed poor host suitability for Melidogyne incognita, M. arenaria genotypes A2-J and A2-O, M. javanica and M. hapla, indicating broad-spectrum resistance to RKN. The development of M. incognita within S. palinacanthum roots was significantly poorer than that in susceptible S. melongena and S. lycopersicum at 10 and 21 days after inoculation. Microplot tests confirmed that the number of second-stage juveniles in plots where S. palinacanthum grew and root galling of the root system were significantly lower than those of susceptible S. melongena, suggesting that the resistance could be used to manage RKN under field conditions., Conclusion: S. palinacanthum showed poor host suitability to all Meloidogyne spp. tested in this study, and it thus has the potential to be used as a genetic resource with broad-spectrum RKN resistance, and it could be effective against multiple RKN species in a field. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

Objective: The objective of this study was to compare women with a known diagnosis of interstitial cystitis (IC) to a population that might be at risk for the diagnosis of IC, women with diagnoses of both chronic pelvic pain (CPP) and overactive bladder (OAB)., Methods: We conducted a retrospective study of data from the Veterans Affairs Corporate Data Warehouse. The cohort included all female veterans who had established care with a primary care provider from 1997 to present. International Classification of Diseases, Ninth Revision codes were used to identify women with a diagnosis of IC, CPP, and OAB. Demographic data and comorbidities were compared between groups., Results: A total of 596,815 women were identified. Two thousand three hundred one women (0.4%) were diagnosed with IC; 4459 women (0.7%) were diagnosed with CPP and OAB. At baseline, women with OAB and CPP were more likely to identify as minority (P < 0.001). Anxiety (57.3% vs 49.5%), depression (39.0% vs 46.0%), and posttraumatic stress disorder (29.7 vs 26.4%) were all more common in the CPP and OAB group than in the IC group. In the multivariable model, women with CPP and OAB were more likely to identify as a minority, use tobacco, and carry a diagnosis of anxiety., Conclusions: There were more patients diagnosed with CPP and OAB compared with patients diagnosed with IC in this population of female veterans. Given the high rate of comorbid anxiety and depression in both groups, further study is warranted to determine whether these women are misdiagnosed.

Background: Obesity can lead to a chronic systemic inflammatory state that increases the risk of cancer development. Therefore, this study aimed to evaluate the alterations in tumor non-infiltrated lymphocytes function and melanoma growth in animals maintained on a high-fat diet and/or moderate physical exercise program in a murine model of melanoma., Methods: Female mice were randomly divided into eight groups: 1) normolipidic control (N), 2) normolipidic + melanoma (NM), 3) high-fat control (H), 4) high-fat + melanoma (HM), 5) normolipidic control + physical exercise (NE), 6) normolipidic melanoma + physical exercise (NEM), 7) high-fat control + physical exercise (HE), and 8) high-fat melanoma + physical exercise (HEM). After 8 weeks of diet treatment and/or moderate physical exercise protocol, melanoma was initiated by explanting B16F10 cells into one-half of the animals., Results: Animals fed a high-fat diet presented high-energy consumption (30%) and body weight gain (H and HE vs N and NE, 37%; HM and HEM vs NM and NEM, 73%, respectively), whether or not they carried melanoma explants. Although the tumor growth rate was higher in animals from the HM group than in animals from any other sedentary group, it was reduced by the addition of a physical exercise regimen. We also observed an increase in stimulated peripheral lymphocyte proliferation and a decrease in the T-helper 1 response in the HEM group., Conclusions: The results of the present study support the hypothesis that altering function of tumor non-infiltrated lymphocytes via exercise-related mechanisms can slow melanoma progression, indicating that the incorporation of a regular practice of moderate-intensity exercises can be a potential strategy for current therapeutic regimens in treating advanced melanoma., Competing Interests: Competing interestsThere are no competing interests.

Aims: The present investigation evaluated whether pregnancy followed by lactation exerts long-term impacts on maternal hepatic lipid metabolism., Main Methods: Female mice were subjected to two pregnancies, after which they were either allowed to breastfeed their pups for 21 days (L21) or had their litter removed (L0). Age-matched virgin mice were used as controls (CTL). Three months after the second delivery, serum was collected for lipid profiling, and fragments of liver were used to assess lipid content and to evaluate the key steps of de novo non-esterified fatty acid (NEFA) synthesis, esterification and β-oxidation, very low density lipoprotein (VLDL) assembly and secretion and autophagy., Key Findings: L0 exhibited a significant increase in hepatic TG and reduced apolipoprotein B-100 (ApoB-100) expression. L21 mice had increased ATP citrate lyase (ACLY) activity and reduced acetyl-CoA carboxylase (ACC) phosphorylation but no increased hepatic TG. On the other hand, L21 mice had reduced hepatic sequestosome 1 (SQSTM1/p62) levels. Increased high density lipoprotein (HDL) cholesterol and hepatic apolipoprotein A-1 (ApoA-1) expression were found exclusively in L21., Significance: The present study reveals that long-term hepatic lipid accumulation is induced by the history of pregnancy without lactation. On the other hand, reduced SQSTM1/p62 levels indicate that increased autophagic flux during life may prevent hepatic fat in dams subjected to lactation. Lactation after pregnancy is also obligatory for a long-term increase in maternal HDL. The present data may contribute to the understanding of the mechanisms leading to elevated cardiometabolic risk in women limited to short periods of lactation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Chronic pelvic pain (CPP) affects an estimated 30% of women Veterans. Previous research shows high rates of narcotic abuse in the women Veteran population. Narcotics are not recommended for the treatment of CPP. Understanding how CPP impacts narcotic prescribing in the women Veteran population is critical to addressing the public health crisis of opioid abuse. Our objective was to compare chronic opioid therapy (COT) prescribed 5 yr prior to and following CPP diagnosis and to identify predictors of COT as well as adverse events associated with COT. We choose to look at 10 yr of data because we thought this time period would provide unique insight into the longitudinal associations of CPP and COT and was available in the database., Materials and Methods: Women with non-cancer CPP were included for analyses from the Veteran's Affairs Corporate Database Warehouse. COT was defined as 90 d of opiates/calendar year for each of the 5 yr proceeding and following the diagnosis of CPP. Patient characteristics and potential variables influencing COT were collected. We compared baseline demographics between the women who received COT to the women who did not receive COT to find additional demographic predictors of COT in association with CPP. Multivariable analysis identified predictors of COT in this population of women with CPP. We utilized an interrupted time series analysis to understand the impact of the diagnosis of CPP on COT., Results: A total of 49,601 women met inclusion criteria with an average age of 40.1 ± 11.5 yr; 37.3% self-characterized as being a racial minority and 24% had a history of military sexual trauma. Chronic use increased significantly (p < 0.001) in the 5 yr preceding the diagnosis of CPP from 6.3% (n = 3124) of women at time -5 to 13.6% (n = 6746) at time 0. In the first year following the diagnosis of CPP, 16.8% (n = 8,333) of women with CPP met the criteria for COT (p < 0.001) and 15% (n = 7440) of women with CPP remained in the COT group for the remaining 5 yr following the diagnosis. On average women in the COT group had 250-292 d of opioids/year. When comparing women who received chronic narcotics following the diagnosis of CPP versus those who did not receive chronic narcotics, women who received COT were older, more likely to smoke and more frequently diagnosed with other pain conditions such as back pain, headaches, and fibromyalgia. (All p < 0.001). In the multivariable model, predictors of COT following CPP diagnosis included prior COT (OR = 10.0 (95% CI 9.4, 10.6), a positive history of military sexual trauma, smoking, and other chronic pain conditions., Conclusions: The distinct pattern of prescribing shown in this cohort may mean COT is prescribed for CPP and this prescribing pattern contributes to the adverse events associated with COT. As COT is not recommended for CPP, physicians need more education on the therapies available to help CPP patients.

Objectives: The aims of this study were to describe relationships between women given a diagnosis of nocturnal enuresis (NE) and controls without any urinary complaints and to compare women with NE with those with overactive bladder (OAB). We hypothesized that NE has unique associations with demographics and medical and psychosocial diagnoses., Methods: This is a secondary analysis of a database that included all female veterans who established care with a primary care provider from 1997 to 2015. International Classification of Diseases, Ninth Revision, codes identified women with a diagnosis of NE or OAB. Patient characteristics, medical diagnoses, and psychosocial factors previously described as relating to NE and/or OAB were compared between the 2 distinct comparative groups, with significance set at P < 0.05. Stepwise logistic regression was used to assess all significant findings., Results: A total of 596,815 women were identified; controls totaled 570,049, the group with OAB totaled 26,446 (4.4%), and the group with NE totaled 301 (0.05%).Multivariable analysis compared the group with NE with controls; all measured psychosocial characteristics remained significantly associated with an NE diagnosis (all Ps < 0.05), as well as obstructive sleep apnea history, stroke, self-identification as "minority," smoking, hypertension, and a body mass index higher than those of the general control population (all Ps < 0.05).When the populations with NE and OAB were compared, a diagnosis of posttraumatic stress disorder, an overdose history, depression, military sexual trauma, increasing body mass index, and younger age remained significantly associated with NE (all Ps < 0.05)., Conclusions: The association of NE with psychosocial characteristics and psychiatric illnesses persisted irrespective of the comparison population. Practitioners should investigate the diagnosis of NE in those female veterans with psychosocial issues.

Pathological cardiac hypertrophy leads to derangements in lipid metabolism that may contribute to the development of cardiac dysfunction. Since previous studies, using high saturated fat diets, have yielded inconclusive results, we investigated whether provision of a high-unsaturated fatty acid (HUFA) diet was sufficient to restore impaired lipid metabolism and normalize diastolic dysfunction in the pathologically hypertrophied heart. Male, Wistar rats were subjected to supra-valvar aortic stenosis (SVAS) or sham surgery. After 6 weeks, diastolic dysfunction and pathological hypertrophy was confirmed and both sham and SVAS rats were treated with either normolipidic or HUFA diet. At 18 weeks post-surgery, the HUFA diet failed to normalize decreased E/A ratios or attenuate measures of cardiac hypertrophy in SVAS animals. Enzymatic activity assays and gene expression analysis showed that both normolipidic and HUFA-fed hypertrophied hearts had similar increases in glycolytic enzyme activity and down-regulation of fatty acid oxidation genes. Mass spectrometry analysis revealed depletion of unsaturated fatty acids, primarily linoleate and oleate, within the endogenous lipid pools of normolipidic SVAS hearts. The HUFA diet did not restore linoleate or oleate in the cardiac lipid pools, but did maintain body weight and adipose mass in SVAS animals. Overall, these results suggest that, in addition to decreased fatty acid oxidation, aberrant unsaturated fatty acid metabolism may be a maladaptive signature of the pathologically hypertrophied heart. The HUFA diet is insufficient to reverse metabolic remodeling, diastolic dysfunction, or pathologically hypertrophy, possibly do to preferentially partitioning of unsaturated fatty acids to adipose tissue.

Aim: To investigate whether Brazilian green propolis improves the immune response against recurrent form isolate recurrent vulvovaginal candidiasis (RVVC) caused by Candida albicans by increasing neutrophil oxidative burst., Materials & Methods: We evaluated oxidant species production, oxygen consumption, microbicidal activity and myeloperoxidase activity in neutrophils previously treated with propolis and activated with different isolates of C. albicans (RVVC), vulvovaginal candidiasis, asymptomatic isolates and the reference strain., Results: Propolis significantly increased oxidant species production, oxygen consumption, microbicidal activity and myeloperoxidase activity of neutrophils against different isolates of C. albicans including RVVC isolate that are considered resistant to the microbicidal activity of neutrophils., Conclusion: Brazilian green propolis may increase neutrophil burst oxidative response to RVVC leading to an efficient removal of C. albicans.

Asthma is a chronic inflammatory disease that affects more females than males after puberty, and its symptoms and severity in women change during menstruation and menopause. Recently, evidence has demonstrated that interactions among the microbiota, female sex hormones, and immunity are associated with the development of autoimmune diseases. However, no studies have investigated if therapeutic gut microbiota modulation strategies could affect asthma exacerbation during menstruation and menopause. Here we aimed to examine the preventive effects of a probiotic, Bifidobacterium longum 5 1A , on airway inflammation exacerbation in allergic ovariectomized mice. We first evaluated the gut microbiota composition and diversity in mice 10 days after ovariectomy. Next, we examined whether re-exposure of ovariectomized allergic mice to antigen (ovalbumin) would lead to exacerbation of lung inflammation. Finally, we evaluated the preventive and treatment effect of B. longum 5 1A on lung inflammation and airway hyperresponsiveness. Our results showed that whereas ovariectomy caused no alterations in the gut microbiota composition and diversity in this animal model, 10 days after ovariectomy, preventive use administration of B. longum 5 1A , rather than its use after surgery was capable of attenuate the exacerbated lung inflammation and hyperresponsiveness in ovariectomized allergic mice. This prophylactic effect of B. longum 5 1A involves acetate production, which led to increased fecal acetate levels and, consequently, increased Treg cells in ovariectomized allergic mice.

We investigated the effect of dexamethasone during the last week of pregnancy on glucose and lipid metabolism in male offspring. Twelve-week old offspring were evaluated after fasting for 12-hours (physiological) and 60-hours (prolonged). Physiological fasting resulted in glucose intolerance, decreased glucose clearance after pyruvate load and increased PEPCK expression in rats born to dexamethasone-treated mothers (DEX). Prolonged fasting resulted in increased glucose tolerance and increased glucose clearance after pyruvate load in DEX. These modulations were accompanied by accumulation of hepatic triglycerides (TG). Sixty-hour fasted DEX also showed increased citrate synthase (CS) activity, ATP citrate lyase (ACLY) content, and pyruvate kinase 2 (pkm2), glucose transporter 1 (slc2a1) and lactate dehydrogenase-a (ldha) expressions. Hepatic AKT2 was increased in 60-hour fasted DEX, in parallel with reduced miRNAs targeting the AKT2 gene. Altogether, we show that metabolic programming by prenatal dexamethasone is characterized by an unexpected hepatic TG accumulation during prolonged fasting. The underlying mechanism may depend on increased hepatic glycolytic flux due to increased pkm2 expression and consequent conversion of pyruvate to non-esterified fatty acid synthesis due to increased CS activity and ACLY levels. Upregulation of AKT2 due to reduced miRNAs may serve as a permanent mechanism leading to increased pkm2 expression.

Introduction: Little is known about the impact of MST on chronic pain conditions among female Veterans. The primary objective of this study was to compare the prevalence of chronic pain conditions among U.S. female veterans with a history of military sexual trauma (MST) to those without a history of MST. We anticipated that female Veterans with a history of MST would have higher associations with chronic pain conditions than the female Veterans without a history of MST., Materials and Methods: This was a large-scale, retrospective study using the Veterans' Health Administration Corporate Data Warehouse with institutional approval (15-H175). International Classification of Diseases, 9th Revision codes from the outpatient visits, outpatient problem lists, and inpatient discharge diagnoses were used to identify chronic pain diagnoses. Baseline demographic data including date of birth, self-identified race/ethnicity, and body mass index were obtained. Significant findings in the univariate analysis were then placed into a multivariable logistic regression model to adjust the effect of each predictor for the presence of others. Significance was set at p < 0.01 because of multiple comparisons made., Results: For the entire cohort (516,950 women), 28.9% (149,540) were diagnosed with headaches, 18.3% (94,393) with chronic pelvic pain, 14.4% (74,216) with chronic back pain, 10.5% (54,302) with nonspecific joint pain, 9% (48,509) with fibromyalgia, 6.2% (32,037) with generalized abdominal pain, 4.2% (21,911) with irritable bowel syndrome, and 3.2% (16,309) with dyspareunia. Most women had more than one chronic pain diagnosis. At baseline, women with a history of MST were younger (63.3 ± 15.9 vs. 67.4 ± 17.9 years p < 0.001), heavier (29.5± 6.2 vs. 28.8 ± 6.1 kg/m 2 p < 0.001), smokers (49.3 vs. 38.8% p < 0.001), and more likely to be non-Hispanic white (56.3 vs. 52.3% p < 0.001) than women without a history of MST. Women with a history of MST had more pain diagnoses than those without the history of MST (all p < 0.001). The adjusted odds ratio of women with history of MST presenting with any pain condition compared to a women without a history of MST was 1.26 (95% confidence interval 1.24-1.28). In the multivariable model there remained an association between MST and chronic pain conditions including irritable bowel syndrome, chronic pelvic pain, back pain, chronic joint pain, fibromyalgia, dyspareunia, chronic abdominal pain, and headaches after adjusting for baseline differences in age, body mass index, smoking, and ethnicity. Importantly, drug abuse, and overdose were also associated with MST., Conclusion: A history of MST is associated with chronic pain diagnoses. Weaknesses of this study are those applicable to analyses of any retrospective database study. Specifically, the data are limited by the accuracy of physician coding and reporting. The strength of this study is that it represents a comprehensive, retrospective evaluation of potential sources for chronic pain within the female veteran population. In summary, we found that female veteran survivors of MST face an increased burden of chronic pain, including a broad range of pain conditions independent of the psychological effects of MST., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Obesity associated with a sedentary lifestyle can lead to changes in the immune system balance resulting in the development of inflammatory diseases. The aim of this study was to compare lymphocyte activation mechanisms between overweight children practicing regular circus physical exercises with non-exercised children. The study comprised 60 pubescent children randomly divided into 4 groups: Overweight Children (OWC) (10.67 ± 0.22 years old), Overweight Exercised Children (OWE) (10.00 ± 0.41 years old), Eutrophic Children (EC) (11.00 ± 0.29 years old) and Eutrophic Exercised Children (EE) (10.60 ± 0.29 years old). OWE and EE groups practiced circus activities twice a week, for 4.3 ± 0.5 and 4.4 ± 0.5 months, respectively. Percentage of T regulatory cells (Treg) and the expression of CD95 and CD25 in CD4+ lymphocytes were evaluated by flow cytometry. Lymphocyte proliferation capacity was measured by [14C]-thymidine incorporation and mRNA expression of IL-35, TGF-beta, IL-2 and IL-10 by real-time PCR. Lymphocyte proliferation was higher in OWC and OWE groups compared with the EC (3509 ± 887; 2694 ± 560, and 1768 ± 208 cpm, respectively) and EE (2313 ± 111 cpm) groups. CD95 expression on lymphocytes was augmented in the EC (953.9 ± 101.2) and EE groups (736.7 ± 194.6) compared with the OWC (522.1 ± 125.2) and OWE groups (551.6 ± 144.5). CTLA-4 expression was also lower in the OWC and OWE groups compared with the EC and EE groups. Percentage of Treg, IL-35, and IL-10 mRNA expression were lower in the OWC and OWE groups compared with the EC and EE groups. In conclusion, overweight children present altered immune system balance characterized by elevated lymphocyte proliferation due to a decrease in T regulatory cell percentage. These effects were partially reverted by moderate physical exercise, as demonstrated by decreased lymphocyte proliferation.

Purpose: Mental illness may be a barrier to achieving timely and appropriate cancer screening. We evaluated the association of mental illness with receipt of and adherence to breast, cervical, and colorectal cancer screening among women Veterans., Methods: The study population included all female Veterans ages 50 to 65 who obtained care at the New Mexico VA Health Care System continuously from fiscal years 2004 to 2006 (n = 606). Measures were odds ratios (OR) for receipt of any cancer screening, and adherence to recommended cancer screening frequency, adjusted for age, insurance, service connection, and primary care and women's clinic visits., Results: Overall, 53% of the women had a mental health diagnosis (MHD). Women with an MHD were less likely to adhere to recommended breast cancer screening than women without MHD: unadjusted OR (95% CI): 0.73 (0.54-0.98; p < .05), adjusted OR (aOR) (95% CI) 0.60 (0.44-0.82; p < .01). Women with an MHD were as likely as women without MHD to receive any breast, cervical, and colon cancer screening: Respective aORs (95% CI): 0.79 (0.50-1.25); 1.71 (0.91-3.21); and 0.85 (0.56-1.28)., Conclusion: Women with a mental illness are at risk for not adhering to recommended routine breast cancer screening, and may require more intensive efforts to achieve optimal rates of recommended breast cancer screening., (Published by Elsevier Inc.)

Many of the estimated thirty-two million Americans expected to gain coverage under the Affordable Care Act are likely to have high levels of unmet need because of various chronic illnesses and to live in areas that are already underserved. In New Mexico an innovative new model of health care education and delivery known as Project ECHO (Extension for Community Healthcare Outcomes) provides high-quality primary and specialty care to a comparable population. Using state-of-the-art telehealth technology and case-based learning, Project ECHO enables specialists at the University of New Mexico Health Sciences Center to partner with primary care clinicians in underserved areas to deliver complex specialty care to patients with hepatitis C, asthma, diabetes, HIV/AIDS, pediatric obesity, chronic pain, substance use disorders, rheumatoid arthritis, cardiovascular conditions, and mental illness. As of March 2011, 298 Project ECHO teams across New Mexico have collaborated on more than 10,000 specialty care consultations for hepatitis C and other chronic diseases.

Purpose: The demographic characteristics of veterans with coronary artery disease or diabetes were studied to determine their correlation with achieving a low-density-lipoprotein (LDL) cholesterol concentration of <100 mg/dL., Methods: The New Mexico Veterans Affairs Health Care System's outcomes database was queried for data on patients with coronary artery disease (CAD) or its equivalent (diabetes). All patients treated with statins between 1998 and 2008 were eligible for the study. The database was also queried for patients' race, age, sex, body mass index, and serum LDL cholesterol concentrations. Information regarding statin type, dosage, timing, and regimen adjustment was collected and analyzed., Results: A total of 5191 patients were included in analyses. Of these, 3629 reached the LDL cholesterol goal of <100 mg/dL. The mean ± S.D. baseline LDL cholesterol value of patients who met goal was lower than that of those who did not (p < 0.001). The probability of attaining the LDL cholesterol goal increased with age but tapered off as patients reached their 70s and 80s (p < 0.001). Women were less likely to reach the goal LDL cholesterol level (p < 0.001). Use of a statin before CAD diagnosis was associated with a higher rate of goal LDL cholesterol attainment (p = 0.03) than if no statin was used. Regimen adjustments were inversely associated with achieving goal LDL cholesterol (p < 0.001)., Conclusion: Lower LDL cholesterol level before treatment, older age, male sex, statin use before CAD diagnosis, the last statin medication used by a patient before the end of the study, higher dosages of simvastatin or lovastatin, and a lower number of medication adjustments were associated with achieving an LDL cholesterol concentration of <100 mg/dL.

The Extension for Community Healthcare Outcomes (ECHO) Model was developed by the University of New Mexico Health Sciences Center as a platform to deliver complex specialty medical care to underserved populations through an innovative educational model of team-based interdisciplinary development. Using state-of-the-art telehealth technology, best practice protocols, and case-based learning, ECHO trains and supports primary care providers to develop knowledge and self-efficacy on a variety of diseases. As a result, they can deliver best practice care for complex health conditions in communities where specialty care is unavailable. ECHO was first developed for the management of hepatitis C virus (HCV), optimal management of which requires consultation with multidisciplinary experts in medical specialties, mental health, and substance abuse. Few practitioners, particularly in rural and underserved areas, have the knowledge to manage its emerging treatment options, side effects, drug toxicities, and treatment-induced depression. In addition, data were obtained from observation of ECHO weekly clinics and database of ECHO clinic participation and patient presentations by clinical provider. Evaluation of the ECHO program incorporates an annual survey integrated into the ECHO annual meeting and routine surveys of community providers about workplace learning, personal and professional experiences, systems and environmental factors associated with professional practice, self-efficacy, facilitators, and barriers to ECHO. The initial survey data show a significant improvement in provider knowledge, self-efficacy, and professional satisfaction through participation in ECHO HCV clinics. Clinicians reported a moderate to major benefit from participation. We conclude that ECHO expands access to best practice care for underserved populations, builds communities of practice to enhance professional development and satisfaction of primary care clinicians, and expands sustainable capacity for care by building local centers of excellence.

Background & Aims: As the economic burden of gastroesophageal reflux disease (GERD) is largely weighted to maintenance as opposed to initial therapy, switching from more potent to less expensive medication once symptoms are alleviated (step-down therapy) may prove to be most cost-effective. This study aimed to prospectively evaluate the feasibility of step-down therapy in a cohort of patients with symptoms of uncomplicated GERD., Methods: Patients whose GERD symptoms were alleviated by proton pump inhibitors (PPIs) were recruited from outpatient general medicine clinics. After baseline demographic and quality of life information were obtained, PPIs were withdrawn from subjects in a stepwise fashion. Primary outcome was recurrence of symptoms during follow-up that required reinstitution of PPIs. Secondary outcomes included changes in quality of life and overall cost of management. Predictors of nonresponse to step-down were assessed., Results: Seventy-one of 73 enrolled subjects completed the study. Forty-one of 71 (58%) were asymptomatic off PPI therapy after 1 year of follow-up. Twenty-four of 71 (34%) required histamine 2-receptor antagonists, 5/71 (7%) prokinetic agents, 1/71 (1%) both, and 11/71 (15%) remained asymptomatic without medication. Quality of life did not significantly change, whereas management costs decreased by 37%. Multivariable analysis revealed younger age and a dominant symptom of heartburn to predict PPI requirement., Conclusions: Step-down therapy is successful in the majority of patients and can decrease costs without adversely affecting quality of life.

We investigated the hypothesis that the rate of loss of creatinine excretion with age in peritoneal dialysis (PD) patients differs from the rate predicted from the Cockroft-Gault formula (Cr(Pred)) by analyzing creatinine excretion data obtained from clearance studies of 925 patients on continuous ambulatory PD therapy with an age range of 12 to 91 years. Measured creatinine generation (Cr(Meas)) is the sum of creatinine excretion in urine plus dialysate (Cr(Excr)) plus an estimated metabolic degradation of creatinine. The effect of age on Cr(Excr) and the differences Cr(Excr) - Cr(Pred) and Cr(Meas) - Cr(Pred) were analyzed by linear regression. In 373 women, Cr(Excr) = W(16.9360 - 0.084A), r = -0.342, P < 0.001 (where W is weight in kilograms and A is age in years). The regression slope was one half of the slope in the Cockroft-Gault formula. Cr(Excr) - Cr(Pred) = -413.91 + 4.78A, r = 0.300, P < 0.001. Cr(Meas) - Cr(Pred) = -176.36 + 4.37A, r = 0.278, P < 0.001. In 552 men, Cr(Excr) = W(21.079 - 0.108A), r = -0.338, P < 0.001. The regression slope was approximately one half of the slope in the Cockroft-Gault formula. Cr(Excr) - Cr(Pred) = -493.25 + 6.28A, r = 0.267, P < 0.001. Cr(Meas) - Cr(Pred) = -66.41 + 3.63A, r = 0.143, P = 0.001. The rate of loss of creatinine excretion with age is one half of the rate predicted by the Cockroft-Gault formula in both women and men on PD therapy. Therefore, the difference between excretion (or measured generation) of creatinine and creatinine generation predicted by the Cockroft-Gault formula is not constant, but increases with age. The Cockroft-Gault formula systematically overestimates the effect of age on creatinine excretion in PD patients and is not suitable for predicting creatinine excretion in these subjects.

Lean body mass computed from creatinine kinetics (LBM) is an index of somatic nutrition and correlates with other nutrition indices in CAPD. However, LBM exceeding 90% of body weight (LBM/W > or = 0.9) may be an index of non-compliance, rather than nutrition. To test this hypothesis, we analyzed fluid and solute excretion in 40 CAPD patients with LBM/W > or = 0.9 (group A). The comparison group (group B) consisted of 885 CAPD patients with LBM/W < 0.9. Group A was younger (38.3+/-14.8 vs 54.7+/-14.7 yr) and had a lower percent of women (23.5% vs 41.1%) and diabetic subjects (17.5% vs 42.6%) than group B (at P < or = 0.019). Group A also had lower body mass index (22.7+/-2.7 vs 25.8+/-5.1 kg/m2, P <0.001) and serum albumin (33.0+/-6.7 vs 35.2+/-5.5 g/L, P = 0.014). Despite similar prescribed daily fill volumes (group A 8.3+/-2.4, group B 8.5+/-2.2 L/24 h) and similar D/P urea and creatinine values, group A had higher daily drain volume (11.0+/-3.6 vs 9.6+/-2.1 L/24 h, P < 0.001). Renal clearances were similar, while peritoneal and total clearances were apparently higher in group A. Creatinine excretion was higher in group A (27.4+/-5.1 vs 13.6+/-4.1 mg/kg x 24 h, P < 0.001), with a large part of the excess creatinine excretion in group A being accounted for by peritoneal excretion. The combination of an apparently high daily ultrafiltration volume (2.7 L/24 h on the average), unrealistically high creatinine excretion rate, and relatively poor nutrition (low body mass index and serum albumin) in group A is consistent with non-compliance. We suggest that the finding of LBM/W > or = 0.9 during a clearance study in CAPD should trigger an investigation for non-compliance.

We analyzed the effect of diabetes on the decline of residual renal function during the course of CAPD in a cross-sectional study including 105 diabetic subjects (41 women) who had 207 clearance studies and 125 non-diabetic subjects (50 women, 265 clearance studies). CAPD duration was 11.5+/-10.5 months in the diabetic group (DG) and 16.8+/-18.6 months in the non-diabetic group (NDG, P < 0.001). The DG had lower urine volume than the NDG (0.52+/-0.46 vs 0.61+/-0.50 L/24-h, P < 0.05), while urine-to-plasma concentration ratio was higher in the DG for creatinine (13.5+/-9.4 vs 11.5+/-11.0, P <0.05) and did not differ for urea. Weekly renal Kt/V urea (DG 0.51+/-0.57, NDG 0.53+/-0.49) and Ccr (DG 31.0+/-28.7 NDG 29.3+/-26.5 L/1.73 m2) did not differ. The slopes of the regressions of CAPD duration on renal clearances did not differ. These regressions allowed estimates of the time, from the onset of CAPD, at which renal clearances become negligible. These estimates differed for both urea clearance (DG 35.3, NDG 50.5 months) and creatinine clearance (DG 43.2, NDG 57.6 months). The slope of the regression of renal urea clearance on renal creatinine clearance was steeper in the DG, suggesting a higher renal creatinine clearance in the DG than in the NDG when renal urea clearance is the same in the two groups. Subtle differences in the rate of decline of renal function can be detected between diabetic and non-diabetic subjects on CAPD by detailed statistical analysis. These findings are supportive of the studies which have identified diabetes mellitus as a predictor of loss of residual renal function during the course of CAPD. In addition, the relationship between the renal urea and creatinine clearances differs between diabetic and nondiabetic subjects on CAPD. Therefore, the dose of CAPD required for adequate total clearances may differ between diabetic and non-diabetic subjects.

Peritoneal dialysis (PD) patients are classified as underweight, normal weight, or obese by height/weight indices including body mass index (BMI) and the body weight/desired weight (W/DW) ratio. We compared these classifications of degree of obesity in 378 women and 555 men on PD. We used these cut-off values: for underweight, BMI < or = 18.5 and W/DW < or = 0.9; for obesity, BMI > or = 30.0 and W/DW > or = 1.2. The W/DW values were calculated assuming first a small frame, then a medium frame, and finally a large frame for all subjects. Regardless of sex or skeletal frame, BMI correlated highly with W/DW (r value between 0.98 and 0.99); however, the range of BMI values corresponding by linear regression to the normal range of W/DW (0.9-1.2) was narrower than the range of "normal" BMI (18.5-30.0). Consequently, regardless of sex or skeletal frame, smaller fractions of the patient population were classified as underweight or obese by BMI standards than by W/DW standards. The degree of agreement of the classifications of subjects as underweight, normal weight, or obese by BMI and W/DW was evaluated by Cohen's kappa ratio. The kappa ratio varied between 0.47 and 0.58, indicating a reasonable--but not high--degree of agreement beyond chance. The highest kappa ratios were obtained assuming a medium skeletal frame for both women and men. Substantial discrepancies are observed in the classification of PD patients as underweight, normal weight, or obese by BMI and W/DW. Further research is needed to identify the height/weight index that has the strongest association both with clinical outcomes and with other, more precise measurements of body fat content.

Objective: To analyze the effect of age on nutrition indices in subjects on the same continuous ambulatory peritoneal dialysis (CAPD) schedule., Methods: We analyzed 613 sets of clearance values and nutrition indices in 302 CAPD patients. Small solute clearances included urea clearance (Kt/Vurea) and creatinine clearance (Ccr). Nutrition indices included body mass index (BMI), serum albumin, urea and creatinine, 24-h urea nitrogen and creatinine excretion in urine plus dialysate, protein nitrogen appearance (PNA), PNA normalized by standard weight (nPNA), lean body mass (LBM) computed by creatinine kinetics, and LBM/Weight. CAPD subjects were classified in 4 age quartiles (Q): Group Q1, age 33.7 +/- 7.6 years, N = 149; group Q2, age 49.5 +/- 3.8 years, N = 158; group Q3, age 61.5 +/- 2.6 years, N = 154; and group Q4, age 72.1 +/- 5.4 years, N = 152. Group comparison was done by one-way ANOVA or chi-square. Predictors of low nutritional parameters were identified by logistic regression. Selected variables were compared by linear regression., Results: Mean Kt/Vurea and Ccr were above the current adequacy standards and did not differ between the age quartiles. In contrast, older quartiles had, in general, lower nutrition indices than younger quartiles. However, the youngest quartile had the lowest BMI. By logistic regression, young age was a predictor of low BMI, while advanced age was a predictor of low creatinine and urea nitrogen excretion, low nPNA, and low LBM/Weight. The regressions of nPNA on Kt/Vurea differed between the age quartiles. By these regressions, the youngest quartile had higher nPNA values for the same Kt/Vurea than the oldest quartile in the clinically relevant range of Kt/Vurea and nPNA values., Conclusions: Nutrition indices are worse in older than in younger CAPD patients with the same small solute clearances. Nutrition of CAPD patients is adversely affected by age and requires special attention in the older age group.

Objective: To compare body water (V) estimates from the Chertow formula (Vc), which was derived in an end-stage renal disease population, to V estimates from the Watson formulas (Vw) in continuous ambulatory peritoneal dialysis (CAPD) patients. To identify CAPD patients in whom Vc is preferred to Vw for clearance studies., Design: Retrospective analysis of clearance studies., Setting: Dialysis units of four academic medical centers., Participants: 302 subjects on CAPD., Intervention: 613 clearance studies by standard methods., Main Outcome Measures: Comparisons between Vc and Vw, and between urea clearance normalized by Vc [(KtVc)ur] and Vw [(Kt/Vw)ur]., Results: Vc exceeded Vw by 3.5 +/- 1.6 L (p < 0.001), or 9.6% on average. This degree of overestimation of Vw is in the range of body water estimates found in CAPD subjects with severe volume overload (> 5% of body weight) in previous studies. Total (Kt/Nw)ur exceeded total (Kt/Vc)ur by 8.6%. By linear regression, Vc = -0.589 + (1.112 x Vw), r = 0.983. Vw exceeded Vc in only 12 studies. Young age, short height, low body weight, and low prevalence of diabetes characterized the studies with Vw > Vc. Total (Kt/Vw)ur was adequate (> or = 2.0 weekly) in 276 studies. Among these, 74 studies had inadequate total (Kt/Vc)ur (< 2.0 weekly). By logistic regression, the predictors of inadequate (Kt/Vc)ur, when (Kt/Vw)ur was adequate, included the presence of diabetes, great height, and long duration of CAPD., Conclusions: Vc provides estimates of body water exceeding those provided by Vw in a great majority of CAPD patients. Consequently, approximately 25% of the clearance studies that are adequate when Vw is used as the normalizing parameter may be inadequate when Vc is used. Vc may provide a more appropriate estimate of body water than Vw in CAPD patients with volume overload.

In peritoneal dialysis (PD), small solute clearances are normalized by body water (V) and body surface area (BSA). The purpose of this study was to identify if V or BSA produced stronger associations between body size and normalized clearances. We studied the relationship between four size indicators (V, BSA, height, and weight) and either peritoneal urea clearance normalized to V (Kt/V(ur)) and BSA (C(ur)) or creatinine clearance normalized to V (Kt/V(cr)) and BSA (C(cr)). A total of 613 clearance studies were performed in subjects on continuous ambulatory peritoneal dialysis (CAPD) with four daily exchanges and a 2 L fill volume. As size increased, the normalized peritoneal clearances decreased in a nonlinear fashion (regression: y = b0 + b1x(-1), where x is a size indicator and y is a normalized clearance). Significant (p < 0.001) negative correlations were found between each normalized clearance and each size indicator. However, in each case, the correlation was higher when V, rather than BSA, was used. For example, BSA correlated more closely with K/V(ur)(-0.660) than C(ur)(-0.556), and also with Kt/V(cr)(-0.579) than C(cr)(-0.446). Normalized clearances are smaller in large subjects on CAPD because one mathematic determinant of the clearance, the drain volume (Dv) normalized by V (Dv/V) or BSA (DV/BSA), decreases as size increases. The relationship between Dv/V or Dv/BSA and the size indicators was studied by the same nonlinear regression model. The correlations of the size indicators with Dv/V were also consistently higher than the corresponding correlations with Dv/BSA. In subjects who were on the same PD schedule, the dependence of clearances on size was consistently higher when V, rather than BSA, was the normalizing parameter. Because prescription of the dose of PD is based on body size, there is a practical advantage by using V as the sole normalizing parameter for both urea and creatinine clearance.

Unlabelled: "Weight-height" indices including percent of ideal weight (%IW) and body mass index (BMI) are used to estimate degree of obesity in populations and are predictors of survival in dialysis patients. Amputation affects the relationship between weight and height independently of the degree of obesity. Corrections of both %IW and BMI for amputation have been published, but a National (U.S.) computer nutrition program used in the authors' institution uses only the correction for %IW. This study had two parts: (1) To test whether the weight-height cut-off values for weight deficit (%IW 90%, BMI 20 kg/m2) and obesity (%IW 120%, BMI 30 kg/m2) are compatible, we performed linear regression of BMI on %IW in peritoneal dialysis (PD) patients without amputations. In 349 men, BMI = 0.834 + 0.226 (%IW), r = 0.979. From this regression, the 95% confidence interval (CI) of BMI is 19.2-23.1 kg/m2 if %IW is 90%, and 26.1-29.9 kg/m2 if %IW is 120%. In 260 women, BMI = 2.194 + 0.184 (%IW), r = 0.974. From this regression, the 95% CI of BMI is 15.7-21.8 kg/m2 if %IW is 90%, and 21.3-27.3 kg/m2 if %IW is 120%. (2) To identify the direction and magnitude of the error of uncorrected BMI (BMIu) in dialysis patients with amputations, we analyzed weight-height indices in two groups of men by the computer nutrition program, which corrects %IW, but not BMI for amputation, and by the corrected BMI (BMIc) formula. In group A (amputation without height loss, n = 11), %IW = 110.2% +/- 16.9%, BMIu = 23.6 +/- 2.7 kg/m2, BMIc = 26.4 +/- 3.8 kg/m2 (p < 0.001, BMIc vs BMIu), and 5 of the 11 BMIu values fell below the 95% confidence band of the regression of BMI on %IW in patients without amputations. In group B (amputation with loss of height, n = 6), %IW = 92.7% +/- 19.9%, BMIu = 33.9 +/- 10.7 kg/m2, BMIc = 22.1 +/- 4.4 kg/m2 (p < 0.005, BMIc vs BMIu), and 5 of the 6 BMIu values fell above the 95% confidence band of the regression of BMI on %IW in patients without amputations., Conclusions: (1) The weight deficit cut-offs for %IW and BMI are compatible in non amputated men and women. (2) The obesity cut-offs for %IW and BMI are compatible in non amputated men, but not in non amputated women. (3) Amputation without height loss decreases BMIu, while amputation with height loss increases, in general, BMIu. (4) BMI should be corrected in PD patients with amputations.

The normalized peritoneal clearances of small solutes depend on the ratio of their concentration in dialysate and plasma (D/P) and the drain volume (Dv) corrected for some measure of body size such as body water (V) or body surface area (BSA). The clearance formulas (D/P) x (Dv/V) and (D/ P) x (Dv/BSA) can be used to examine why large individuals tend to be underdialyzed. Large people have low normalized drain volumes (Dv/V, Dv/BSA). It is not known whether size affects the D/P ratios. The purpose of this study was to examine the relationship between normalized peritoneal clearances (Kt/Vurea, CCr per 1.73 m2 BSA) and four size indicators (weight, height, V, BSA) in 301 patients on continuous ambulatory peritoneal dialysis (four daily exchanges with 2-L exchange volume) who underwent 613 clearance studies. Highly significant (P < 0.001) nonlinear relationships were found between Kt/Vurea and weight (r2 = 0.371), height (r2 = 0.289), BSA (r2 = 0.436), and V (r2 = 0.527); and between CCr and weight (r2 = 0.178), height (r2 = 0.115), BSA (r2 = 0.199), and V (r2 = 0.151). There were also significant negative correlations between the normalized drain volumes (Dv/V and Dv/BSA) and all four indicators of body size. Raw (not normalized) peritoneal clearances and drain volumes correlated positively with size. However, D/P(urea) or D/P(creatinine) did not vary with any size indicator except for a weak association between D/P(creatinine) and V (r = 0.089, P = 0.028). This association was not confirmed when V was used to stratify subjects into quartiles, and group differences for D/P(creatinine were tested by one-way ANOVA. This study shows that the exclusive cause of the low normalized peritoneal clearances in large subjects on continuous ambulatory peritoneal dialysis is a low normalized drain volume. No evidence was found to indicate that body size influences the D/P ratio of small solutes. The portion of the variance in normalized clearance explained by size varies by size indicator and solute (urea versus creatinine).

Objective: To compare raw (not normalized) and normalized urea and creatinine clearances between women and men on continuous ambulatory peritoneal dialysis (CAPD). To study whether potential gender differences are due to the normalization process., Design: Retrospective analysis of clearance studies., Setting: Dialysis units of four academic medical centers., Participants: The study included 302 subjects (135 women and 167 men) on CAPD with four daily exchanges and a 2-L exchange volume., Intervention: Measurement of urea and creatinine clearances (261 in women, 352 in men) by standard methods. Body water (the volume of distribution, V, for both urea and creatinine) was estimated by the Watson anthropometric formulas., Main Outcome Measures: Comparison of raw and normalized clearances between women and men. Urea clearance was normalized by V (Kt/Vur), while creatinine clearances was normalized by both V (Kt/Vcr) and body surface area (BSA) (Ccr)., Results: Mean values of weekly total (peritoneal plus renal) raw clearances were higher in men (urea clearance: women 67.1 L, men 77.4 L; Ccr: women 61.7 L, men 78.3 L). Raw renal clearances were higher in men, while raw peritoneal clearances were comparable. Mean weekly total Kt/Vur was higher in women (2.19 vs 1.94 in men), mean weekly total Kt/Vcr did not differ between the genders (women 2.01, men 1.95), while mean weekly Ccr was higher in men (73.0 vs 64.7 L/1.73 m2 in women). When clearances differed, the differences were significant at p < 0.001. Men had greater height and weight, while women had greater body mass index. On the average, V in men exceeded V in women by 31%, while BSA in men exceeded BSA in women by only 12%., Conclusions: Normalization of clearances by V creates relatively higher clearance values in women, while normalization by BSA creates relatively higher clearance values in men. Thus the normalization process may create artificial differences in the normalized clearances between genders.

Normalized clearances for urea and creatinine were compared between 121 diabetic subjects (256 clearances) and 181 nondiabetic subjects (357 clearances) on continuous ambulatory peritoneal dialysis (CAPD) with four 2-L exchanges daily. Urea clearance was normalized by VWatson (Kt/Vur), while creatinine clearance was normalized by both VWatson (Kt/Vcr) and body surface area (Ccr). Height, weight, body water (V), and body surface area did not differ between the diabetic and the nondiabetic groups. Also, renal Kt/Vur, renal Kt/Vcr, renal Ccr, and peritoneal Kt/Vur did not differ between the groups. Weekly peritoneal Kt/Vcr (diabetic group 1.36 +/- 0.38, nondiabetic group 1.31 +/- 0.31, p = 0.048) and weekly peritoneal Ccr (diabetic group 47.6 +/- 11.0 L/1.73 m2, nondiabetic group 45.4 +/- 9.2 L/1.73 m2, p = 0.012) were both higher in diabetic subjects. The percentage of high/high-average transporters was higher in the diabetic group (64.9% vs 48.6% in nondiabetic group, p = 0.006). The following total (peritoneal + renal) weekly clearances were obtained: Kt/Vur, diabetic group 2.07 +/- 0.63, nondiabetic group 2.02 +/- 0.56, NS; Kt/Vcr, diabetic group 2.06 +/- 0.78, nondiabetic group 1.92 +/- 0.74, p = 0.026; Ccr, diabetic group 72.7 +/- 28.5 L/1.73 m2, nondiabetic group 67.2 +/- 26.4 L/1.73 m2, p = 0.013. Normalized total creatinine clearances are higher in diabetic subjects than nondiabetic subjects on the same CAPD schedule and with the same renal clearances of urea and creatinine and the same total Kt/Vur, because peritoneal creatinine clearances are higher in the diabetic subjects. This finding is caused by higher peritoneal transport in the diabetic subjects and is not an artifact caused by the normalization process.

Whether salt or water intake is the primary cause of interdialytic weight gain (deltaW) has important implication for the design of measures to prevent large deltaW. In 17 hemodialysis patients dialyzed against a bath containing 140 mmol/L of sodium, monthly predialysis serum sodium was compared with post dialysis serum sodium. A decrease in serum sodium in the interdialytic period would indicate that primary water consumption accounts for at least part of the deltaW. Interdialytic sodium intake, isotonic fluid gain (deltaW(isotonic)) and net pure water gain (deltaWH2O) were calculated by balance formulae. Serum sodium concentration was corrected in diabetic subjects to the value corresponding to euglycemia (100 mg/dl). Estimated interdialytic sodium intake was compared with the prescribed sodium intake and, in seven subjects, to sodium intake estimated from dietary records. Results for nondiabetic subjects (N = 9): [Na]post 139.3 +/- 1.9 mmol/L, [Na]pre 140.1 +/- 2.1 mmol/L (NS), deltaW 1.15 +/- 0.55 L/24 hr, deltaW(isotonic) 1.33 +/- 0.57 L/24 hr, deltaWH2O -0.20 +/- 0.58 L/24 hr, estimated sodium intake 206 +/- 75 mmol/24 hr, prescribed sodium intake 121 +/- 29 mmol/24 hr (p = 0.028). Results for diabetic subjects (N = 7): [Na]post 140.1 +/- 2.5 mmol/L, [Na]pre 137.7 +/- 3.1 mmol/L (p < 0.01), deltaW 1.26 +/- 0.38 L/24 hr, deltaW(isotonic) 0.59 +/- 0.63 L/24 hr, deltaWH2O 0.66 +/- 0.39 L/24 hr, estimated sodium intake 160 +/- 81 mmol/24 hr, prescribed sodium intake 124 +/- 30 mmol/24 hr (NS), glycosylated hemoglobin 9.7 +/- 2.8% (normal, 4.1-5.7%). In seven subjects, estimates of sodium intake from balance formulae (233 +/- 113 mmol/24 hr) were not different from estimates from dietary records (212 +/- 87 mmol/24 hr). Sodium intake accounted for all the interdialytic weight gain in nondiabetic subjects. In diabetic patients, only approximately half of the interdialytic weight gain was accounted for by sodium intake. The other half was due to pure water gain, probably caused by hyperglycemia.

The authors developed formulae calculating the daily drain volume (DV) required for a target normalized peritoneal clearance of urea (Kt/V(ur)) or creatinine (Ccr, Kt/Vcr) in peritoneal dialysis (PD). DV depends on the target clearance, the peritoneal solute transport type, and the size of the person as expressed by body surface area (BSA) or body water (V). To illustrate the formulae, we constructed nomograms for the following weekly target clearances: Ccr = 60 L/1.73 m2, Kt/V(ur) = 2.0, Kt/Vcr = 1.8 (the value corresponding to a Ccr of 60 L/1.73 m2 in a linear regression of the two parameters in 476 clearance studies in continuous ambulatory PD [CAPD] patients). The PD schedules studied included CAPD, continuous cycling PD (CCPD) with one 2 L daytime dwell, and a combination of daytime CAPD and nighttime automated PD (APD) with 2 hr dwell times. Peritoneal transport was characterized as low, low-average, high-average, or high by the dialysate-to-plasma (D/P) creatinine concentration ratio in a peritoneal equilibration test (PET). The D/P value entered for each transport type was the appropriate 95% lower confidence limit of the mean D/P in actual studies (2 hr and 4 hr D/P from 102 PET studies and 5.5 hr D/P from 476 clearance studies in CAPD patients). For high transport, the required DV values were similar in all three PD schedules studied. For low transport, the required DV was much larger, comparatively, for CCPD and CAPD-APD than for CAPD. Furthermore, the DV values required for a weekly Kt/V(ur) of 2.0 were comparatively less than the DV values required for a weekly Kt/Vcr of 1.8 (Ccr of 60 L/1.73 M2). Calculation of the DV required for different PD schedules, a target peritoneal clearance, and the patients's size is feasible when the patient's peritoneal transport characteristics are known. This calculation also allows the selection of the least costly PD schedule. Current target values for urea and creatinine clearance are incompatible in anuric PD patients.