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OBJECTIVE: To identify clinical factors that affect hypoglycemia perception in type 2 diabetes. METHODS: Prospective observational study of 344 insulin-treated subjects randomly selected from pharmacy records at three large medical centers. At entry, subjects underwent an extensive psychological evaluation and then monitored their blood glucoses in their usual fashion for up to 52 weeks using a glucose meter capable of storing 1000 readings. For blood glucoses

Objective: To examine the effect of intensified self-monitored blood glucose (SMBG) testing on glycemic control.Research Design and Methods: Subjects with stable, insulin-treated type 2 diabetes performed SMBG using an electronic blood glucose meter before all meals and at bedtime for 8 weeks. Baseline data were collected on demographics, clinical characteristics, diet, and exercise. HbA(1c) was measured at baseline, at 4 weeks, and at 8 weeks. After the intensified monitoring period, subjects resumed their usual monitoring. HbA(1c) was then measured at 24, 37, and 52 weeks. Multivariate linear regression was used to determine the effect of monitoring on glycemic control.Results: A total of 201 subjects completed the monitoring period. The baseline HbA(1c) (8.10 +/- 1.67%) decreased during the monitoring period by 0.30 +/- 0.68% (P < 0.001) at 4 weeks and by 0.36 +/- 0.88% (P < 0.001) at 8 weeks. Although entry HbA(1c) and compliance independently predicted the week 8 HbA(1c) (r = 0.862, P < 0.001), standardized regression analysis found that compliance with the SMBG protocol influenced the week 8 HbA(1c) more than age, sex, BMI, exercise level, carbohydrate consumption, or treatment intensity at baseline. However, SMBG benefited only subjects whose testing compliance exceeded 75% or with an entry HbA(1c) >8.0%. Decreases in HbA(1c) (-0.31 +/- 1.17%, P = 0.001) persisted in the 159 subjects followed for 52 weeks.Conclusions: Intensified blood glucose monitoring improved glycemic control in a large cohort of stable, insulin-treated veterans with type 2 diabetes. SMBG provided a strong stimulus for improved self-care resulting in clinically important and sustained reductions in HbA(1c). [ABSTRACT FROM AUTHOR]

Objective: To evaluate once- and twice-daily self-monitored blood glucose testing strategies in assessing glycemic control and detecting hypoglycemia or hyperglycemia in patients with stable insulin-treated type 2 diabetes.Research Design and Methods: Subjects with stable insulin-treated type 2 diabetes monitored blood glucose four times daily (prebreakfast, prelunch, predinner, and bedtime) for 8 weeks. We correlated mean blood glucose values with HbA(1c) measured after 8 weeks and determined the number of hypoglycemic (< or =3.33 mmol/l) and hyperglycemic (> or =22.20 mmol/l) readings captured at the various testing times.Results: A total of 150 subjects completed the monitoring period; their average age was 67 years, 90% were men, and the mean HbA(1c) at baseline was 8.0 +/- 1.8%. The overall correlation of glucose testing and HbA(1c) was 0.79 (P < 0.0001). Mean blood glucose values for each of the four once-daily testing strategies were significantly correlated with HbA(1c) (r = 0.65-0.70, P < 0.0001), as were mean blood glucose values for each of the six twice-daily testing strategies (r = 0.73-0.75, P < 0.0001). The prebreakfast/prelunch measurements captured the largest proportion (63.6%) of the hypoglycemic readings, the predinner/bedtime measurements captured the largest proportion (66.2%) of hyperglycemic readings, and the prelunch/predinner measurements captured the largest proportion (57.7%) of all out-of-range readings.Conclusions: Twice-daily testing strategies, particularly prelunch/predinner, effectively assess glycemic control and capture a substantial proportion of out-of-range readings. However, personal testing strategies will vary depending on an individual's risk for hypoglycemia and hyperglycemia. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections., Design, Setting and Participants: The US Department of Veterans Affairs has 130 medical centres. We created multivariate models from these data-339 772 patients with COVID-19-as of 30 September 2021., Outcome Measures: The primary outcome for all models was death within 60 days of the diagnosis. Logistic regression was used to derive adjusted ORs for vaccination and infection with Delta versus earlier variants. Models were adjusted for confounding factors, including demographics, comorbidity indices and novel parameters representing prior diagnoses, vital signs/baseline laboratory tests and outpatient treatments. Patients with a Delta infection were divided into eight cohorts based on the time from vaccination to diagnosis. A common model was used to estimate the odds of death associated with vaccination for each cohort relative to that of unvaccinated patients., Results: 9.1% of subjects were vaccinated. 21.5% had the Delta variant. 18 120 patients (5.33%) died within 60 days of their diagnoses. The adjusted OR for a Delta infection was 1.87±0.05, which corresponds to a relative risk (RR) of 1.78. The overall adjusted OR for prior vaccination was 0.280±0.011 corresponding to an RR of 0.291. Raw CFR rose steadily after 10-14 weeks. The OR for vaccination remained stable for 10-34 weeks., Conclusions: Our CFR model controls for the severity of confounding factors and priority of vaccination, rather than solely using the presence of comorbidities. Our results confirm that Delta was more lethal than earlier variants and that vaccination is an effective means of preventing death. After adjusting for major selection biases, we found no evidence that the benefits of vaccination on CFR declined over 34 weeks. We suggest that this model can be used to evaluate vaccines designed for emerging variants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Many mathematical models have been proposed to predict death following the Coronavirus Disease 2019 (COVID-19); all started with comorbidity subsets for this still-little understood disease. Thus, we derived a novel predicted probability of death model (PDeathDx) upon all diagnostic codes documented in the Department of Veterans Affairs. We present the conceptual underpinnings and analytic approach in estimating the independent contribution of pre-existing conditions. This is the largest study to-date following patients with COVID-19 to predict mortality. Cases were identified with at least one positive nucleic acid amplification test. Starting in 1997, we use diagnoses from the first time a patient sought care until 14 days before a positive nucleic acid amplification test. We demonstrate the clear advantage of using an unrestricted set of pre-existing conditions to model COVID-19 mortality, as models using conventional comorbidity indices often assign little weight or usually do not include some of the highest risk conditions; the same is true of conditions associated with COVID-19 severity. Our findings suggest that it is risky to pick comorbidities for analysis without a systematic review of all those experienced by the cohort. Unlike conventional approaches, our comprehensive methodology provides the flexibility that has been advocated for comorbidity indices since 1993; such an approach can be readily adapted for other diseases and outcomes. With our comorbidity risk adjustment approach outperforming conventional indices for predicting COVID-19 mortality, it shows promise for predicting outcomes for other conditions of interest., (Published by Oxford University Press 2022.)

Background: Diabetes affects 30.3 million people in the USA. Among these people, a major risk factor for microvascular complications is having a glycated haemoglobin (HbA1c) value of ≥75 mmol/mol; therefore, it would be helpful to identify patients who will obtain future HbA1c values of <75 mmol/mol., Objectives: To develop and validate two prediction rules among patients with diabetes having a baseline HbA1c value of ≥75 mmol/mol: (1) HbA1c measurement ever <75 mmol/mol and (2) final HbA1c measurement of <75 mmol/mol., Methods: Retrospective cohort study using a registry extracting data from the Department of Veterans Affairs's (VA's) electronic health records system. Baseline was 1 Jul 2013-30 June 2014; patients were followed up until 31 July 2016., Results: Our population consisted of 145 659 patients. Across models, predictors were age, sex, minority status, baseline HbA1c value, time, HbA1c≥75 mmol/mol, receiving insulin treatment and consecutive number of HbA1c values of 75 mmol/mol. The overall likelihood of a patient ever having an HbA1c<75 mmol/mol was 73.65%; with the rule, predicted probabilities were 38.94%, 50.75% and 78.88%. The overall likelihood of patients having a final HbA1c measurement of <75 mmol/mol was 55.35%; the rule provided predicted probabilities of 29.93%, 50.17% and 68.58%., Conclusions: Within each rule, there were similar observed and predicted tertile probabilities; maintaining HbA1c values of <75 mmol/mol resulted in probability shifts in the majority of patients. We recommend psychosocial screening for 15% of patients for whom there is less than one-third chance of maintaining HbA1c<75 mmol/mol. We plan to conduct additional research to see whether this approach helps., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Dialysis-associated hyperglycemia (DAH), is associated with a distinct fluid and electrolyte pathophysiology. The purpose of this report was to review the pathophysiology and provide treatment guidelines for DAH., Methods: Review of published reports on DAH. Synthesis of guidelines based on these reports., Results: The following fluid and solute abnormalities have been identified in DAH: (a) hypoglycemia: this is a frequent complication of insulin treatment and its prevention requires special attention. (b) Elevated serum tonicity. The degree of hypertonicity in DAH is lower than in similar levels of hyperglycemia in patients with preserved renal function. Typically, correction of hyperglycemia with insulin corrects the hypertonicity of DAH. (c) Extracellular volume abnormalities ranging from pulmonary edema associated with osmotic fluid shift from the intracellular into the extracellular compartment as a consequence of gain in extracellular solute (glucose) to hypovolemia from osmotic diuresis in patients with residual renal function or from fluid losses through extrarenal routes. Correction of DAH by insulin infusion reverses the osmotic fluid transfer between the intracellular and extracellular compartments and corrects the pulmonary edema, but can worsen the manifestations of hypovolemia, which require saline infusion. (d) A variety of acid-base disorders including ketoacidosis correctable with insulin infusion and no other interventions. (e) Hyperkalemia, which is frequent in DAH and is more severe when ketoacidosis is also present. Insulin infusion corrects the hyperkalemia. Extreme hyperkalemia at presentation or hypokalemia developing during insulin infusion require additional measures., Conclusions: In DAH, insulin infusion is the primary management strategy and corrects the fluid and electrolyte abnormalities. Patients treated for DAH should be monitored for the development of hypoglycemia or fluid and electrolyte abnormalities that may require additional treatments.

Osmotic diuresis results from urine loss of large amounts of solutes distributed either in total body water or in the extracellular compartment. Replacement solutions should reflect the volume and monovalent cation (sodium and potassium) content of the fluid lost. Whereas the volume of the solutions used to replace losses that occurred prior to the diagnosis of osmotic diuresis is guided by the clinical picture, the composition of these solutions is predicated on serum sodium concentration and urinary sodium and potassium concentrations at presentation. Water loss is relatively greater than the loss of sodium plus potassium leading to hypernatremia which is seen routinely when the solute responsible for osmotic diuresis (e.g., urea) is distributed in body water. Solutes distributed in the extracellular compartment (e.g., glucose or mannitol) cause, in addition to osmotic diuresis, fluid transfer from the intracellular into the extracellular compartment with concomitant dilution of serum sodium. Serum sodium concentration corrected to euglycemia should be substituted for actual serum sodium concentration when calculating the composition of the replacement solutions in hyperglycemic patients. While the patient is monitored during treatment, the calculation of the volume and composition of the replacement solutions for losses of water, sodium and potassium from ongoing osmotic diuresis should be based directly on measurements of urine volume and urine sodium and potassium concentrations and not by means of any predictive formulas. Monitoring of clinical status, serum sodium, potassium, glucose, other relevant laboratory values, urine volume, and urine sodium and potassium concentrations during treatment of severe osmotic diuresis is of critical importance.

The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance., Competing Interests: Conflict-of-interest statement: Dominic SC Raj is supported by RO1 DK073665-01A1, 1U01DK099914-01 and IU01DK09924-01 from the National Institutes of Health. Joseph I Shapiro is supported by HL105649, HL071556 and HL109015 from the National Institutes of Health. The other authors declare no conflicts of interest.

Aim: To test whether muscle mass evaluated by creatinine excretion (EX Cr ) is maintained in patients with end-stage kidney disease (ESKD) treated by peritoneal dialysis (PD), we evaluated repeated measurements of EX Cr in a PD population., Methods: One hundred and sixty-six PD patients (94 male, 72 female) receiving the same PD dose for the duration of the study (up to approximately 2.5 years) had repeated determinations of total (in urine plus spent dialysate) 24-h EX Cr (EX Cr T) to assess the adequacy of PD by creatinine clearance. All 166 patients had two EX Cr T determinations, 84 of the 166 patients had three EX Cr T determinations and 44 of the 166 patients had four EX Cr T measurements. EX Cr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times., Results: In patients who were studied twice, with the first and second EX Cr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD, respectively, EX Cr T did not differ between the first and second study. In patients studied three times and whose final assessment occurred 24.7 ± 16.3 mo after initiating PD, EX Cr T did not differ between the first and second study, but was significantly lower in the third study compared to the first study. In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD, EX Cr T did not differ between any of the studies. The average EX Cr T value did not change significantly, with the exception of the third study in the patients studied thrice. However, repeated determinations of EX Cr T in individuals showed substantial variability, with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more., Conclusion: The average value of EX Cr T remains relatively constant for up to 2.5 years of follow-up in PD patients who adhere to the same PD schedule. However, repeated individual EX Cr T values vary considerably in a large proportion of the patients. Further studies are needed to evaluate the clinical significance of varying EX Cr T values and the stability of EX Cr T beyond 2.5 years of PD follow-up., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose.

Aim: To identify patients with end-stage renal disease treated by peritoneal dialysis (PD) who had zero body fat (BF) as determined by analysis of body composition using anthropometric formulas estimating body water (V) and to compare nutritional parameters between these patients and PD patients whose BF was above zero., Methods: Body weight (W) consists of fat-free mass (FFM) and BF. Anthropometric formulas for calculating V allow the calculation of FFM as V/0.73, where 0.73 is the water fraction of FFM at normal hydration. Wasting from loss of BF has adverse survival outcomes in PD. Advanced wasting was defined as zero BF when V/0.73 is equal to or exceeds W. This study, which analyzed 439 PD patients at their first clearance study, used the Watson formulas estimating V to identify patients with V Watson /0.73 ≥ W and compared their nutritional indices with those of PD patients with V Watson /0.73 < W., Results: The study identified at the first clearance study two male patients with V Watson /0.73 ≥ W among 439 patients on PD. Compared to 260 other male patients on PD, the two subjects with advanced wasting had exceptionally low body mass index and serum albumin concentration. The first of the two subjects also had very low values for serum creatinine concentration and total (in urine and spent peritoneal dialysate) creatinine excretion rate while the second subject had an elevated serum creatinine concentration and high creatinine excretion rate due, most probably, to non-compliance with the PD prescription., Conclusion: Advanced wasting (zero BF) in PD patients, identified by the anthropometric formulas that estimate V, while rare, is associated with indices of poor somatic and visceral nutrition., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose.

Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypovolemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium deficit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the first component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fluid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtained by the corrected sodium concentration, which represents a calculated value of the serum sodium concentration that would result from reduction of the serum glucose concentration to a normal level., Competing Interests: Conflict-of-interest statement: Helbert Rondon-Berrios is a member of the advisory board of Astute Medical Inc. The rest of the authors declare no conflict of interest.

Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted by these formulas and observed in animals infused with hypertonic solutions clearly demonstrated that hypertonicity creates new intracellular solutes causing rises in serum osmolality higher than those predicted by the formulas. The mechanisms and types of intracellular solutes generated by hypertonicity and the effects of the solutes have been studied extensively in recent times. The solutes accumulated intracellularly in hypertonic states have potentially major adverse effects on the outcomes of treatment of these states. When hypertonicity was produced by the infusion of hypertonic sodium chloride solutions, the predicted and observed changes in serum sodium concentration were equal. This finding justifies the use of the predictive formulas in the management of hypernatremic states.

Respiratory failure complicating the course of diabetic ketoacidosis (DKA) is a source of increased morbidity and mortality. Detection of respiratory failure in DKA requires focused clinical monitoring, careful interpretation of arterial blood gases, and investigation for conditions that can affect adversely the respiration. Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment. These conditions include deficits of potassium, magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema. Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system, pre-existing respiratory or neuromuscular disease and miscellaneous other conditions. Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA.

Although disturbances of serum tonicity (effective osmolality) may have dire consequences, only surrogate indices of tonicity are available in practice. This report identifies the appropriate index for expressing clinical states of dystonicity. Serum sodium concentration ([Na]S) and osmolality ([Osm]S) may be incongruent. When the tonicity state shown by [Osm]S is higher than [Na]S and the difference between the 2 indices is caused by an excess of solute that distributes in total body water, tonicity is described by [Na]S. When this difference results from a gain of solute with extracellular distribution like mannitol or a decrease in serum water content, causing a falsely low measurement of [Na]S, [Osm]S accurately reflects tonicity. Two indices of tonicity are applicable during hyperglycemia: the tonicity formula (2 ·[Na]S + [Glucose]S/18) and the corrected [Na]S ([Na]S corrected to a normal [Glucose]S using an empirically derived coefficient). Clinicians should understand the uses and limitations of the tonicity indices.

Aim: To quantify the incidence of non-severe hypoglycaemic events among veterans with Type 2 diabetes and its association with primary care provider prescribing behaviour., Methods: This was a prospective observational study involving 30 primary care providers and patients enrolled with these primary care providers, identified from computerized pharmacy records. Two sampling frames were created consisting of (1) patients not treated with insulin and receiving sulfonylurea treatment (with or without other oral hypoglycaemic agents) and (2) patients treated with insulin (with or without sulfonylureas or other oral hypoglycaemic agents). Patients recorded the frequency, proximal cause of, and response to each hypoglycaemic event over a 12-week period and made three visits to a research coordinator over 24 weeks. Data were provided to the primary care provider before their next visit and charts were reviewed for medication changes., Results: A total of 265 patients were enrolled in study. During the 12 weeks of structured self-monitoring of blood glucose, patients recorded a mean (sd) of 6.9 (10.3) hypoglycaemic events. Duration of diabetes increased monotonically with increasing category of hypoglycaemic event (P < 0.001). Among insulin users, an increased frequency of hypoglycaemic events was associated with a decreased likelihood of dose intensification by primary care providers (relative risk 0.86 per event; P = 0.02) but no significant increase in tendency for dose reduction (relative risk 1.04 per event; P = 0.06). Increased frequency of hypoglycaemic events was associated with an increased likelihood of dose reduction (relative risk 1.12 per event; P = 0.03) in the sulfonylurea treatment group., Conclusions: Non-severe hypoglycaemia is common among veterans with Type 2 diabetes receiving insulin or sulfonylureas and influences the prescribing behaviour of primary care providers., (Published 2014. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. Inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution after saline infusion. In this setting, desmopressin infusion helps prevent overcorrection of the hyponatremia. Monitoring of the changes in serum sodium concentration as a guide to treatment changes is imperative regardless of the initial treatment of severe hyponatremia.

Aims: To compare angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) for end-stage renal disease (ESRD) development and all-cause mortality in veterans with macroalbuminuria and with newly documented type 2 diabetes., Methods: A retrospective cohort study utilizing data from the national Department of Veterans Affairs (VA) databases. The study followed 5166 subjects without a history of use of ACEIs or ARBs. To control for differences in baseline characteristics between groups, comparisons of subjects ACEIs and ARBs were made by incorporating propensity scores analysis into multivariate logistic regression. This resulted in adjusted odds ratios and 95% confidence intervals for ESRD development and all-cause mortality., Results: The sample was followed up to five years with a mean follow-up of three years. Subjects taking ACEIs has lower odds of ESRD development (OR, 0.33 [95% CI, 0.13-0.82]) and all-cause mortality (OR, 0.10 [95% CI, 0.04-0.21]) than ARBs., Conclusions: This study shows that ACEIs are associated with lower ESRD development and all-cause mortality than ARBs. This may have implications for guidelines which currently suggest that these two therapeutic classes provide similar benefits in people with newly diagnosed type 2 diabetes and macroalbuminuria., (Published by Elsevier Ireland Ltd.)

Background: The purpose of this study was to determine whether number of hospital admissions per patient per year (n/[pt-yr]) and hospital days per patient per year (d/[pt-yr]) differ between elderly and younger patients on chronic hemodialysis (HD)., Patients and Methods: In a retrospective cohort analysis of incident HD patients in one dialysis unit over 15 years, we compared 166 HD patients older than 70 years (77.1 ± 4.7 yrs) at the onset of HD (group A) and 216 patients younger than 70 years both at onset (57.1 ± 7.6 yrs) and at the end of the HD period (group B). Eighty (48.2%) of group A and 141 (65.3%) patients of group B had diabetes mellitus., Results: No differences were noted in the overall hospitalization rate, presented as mean, {95% Confidence interval} (group A 2.40 {2.04-2.75}, group B 2.03 {1.89-2.16} n[pt-yr]) and days/[pt-year] (group A 33.6 {25.3-41.8}, group B 24.1 {18.9-29.23}). Group A had higher number of hospitalization days (P = 0.012) for surgery or trauma and higher rate (P = 0.045) and days (P = 0.041) of hospitalization for miscellaneous causes, primarily pulmonary disease, or malignancy. Among diabetic patients, group A had only a greater number of hospital days for cardiac disease (P = 0.050). Among patients without diabetes, group A had a higher number for hospital days for surgery or trauma (P = 0.027). All other univariate comparisons were not significant. Multiple linear regression identified comorbidity, quantified by the Charlson index, Caucasian race and poor compliance with the HD schedule as predictors of admission rate and days per year for vascular access issues and comorbidity, poor compliance, and advanced age at onset of HD as predictors of admission for causes other than vascular access related., Conclusion: Hospitalizations, which affect quality of life, differ little between elderly and younger patients on HD. Therefore, hospitalizations do not constitute an argument for restricting access to HD to elderly patients.

Hospitalization rate is high in patients on chronic hemodialysis (HD). We investigated whether initiation of HD changes the rate and length of hospitalization. We analyzed hospitalizations in HD patients in one hospital over 15 years. We compared annual rate and length of hospitalizations, both presented as mean (95% confidence interval [CI]) between the pre-HD and HD period. Three hundred ninety-two patients, 98% men, 59% diabetic, and 66.3 ± 11.2 years old at the onset of HD, had 1016 hospitalizations in the pre-HD period (60.0 ± 42.9 months) and 1627 hospitalizations in the HD period (32.5 ± 25.9 months). Higher values were found in the HD than the pre-HD period for rate, (pre-HD 0.557 [95% CI 0.473-0.611], HD 2.198 [95% CI 1.997-2.399] admissions/[patient-year], P<0.001) and length (pre-HD 4.63 [95% CI 3.71-5.55], HD 28.07 [95% CI 23.55-32.59] days/patient-year], P<0.001) of hospitalizations for all causes, cardiac disease, infections, vascular access, peripheral vascular disease, metabolic disturbances, gastrointestinal diseases, and miscellaneous conditions, mainly respiratory illness and malignancy. Similar differences were found when we compared the year before and the year after the start of HD. Diabetics had higher all cause rate and length of hospitalizations than non-diabetics in the pre-HD and HD periods. The rate and length of hospitalizations was higher in the HD than the pre-HD period for both HD-specific conditions and conditions encountered in both HD and general populations. Study of factors specific to HD that may affect these conditions should constitute the first step toward improving the morbidity of patients on HD., (© 2011 The Authors. Hemodialysis International © 2011 International Society for Hemodialysis.)

The main difference between dialysis-associated hyperglycemia (DH) and diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH) occurring in patients with preserved renal function is the absence of osmotic diuresis in DH, which eliminates the need for large fluid and solute (including potassium) replacement. We analyzed published reports of serum potassium (K(+)) abnormalities and their treatment in DH. Hyperkalemia was often present at presentation of DH with higher frequency and severity than in hyperglycemic syndromes in patients with preserved renal function. The frequency and severity of hyperkalemia were higher in DH episodes with DKA than those with NKH in both hemodialysis and peritoneal dialysis. For DKA, the frequency and severity of hyperkalemia were similar in hemodialysis and peritoneal dialysis. For NKH, hyperkalemia was more severe and frequent in hemodialysis than in peritoneal dialysis. Insulin infusion corrected the hyperkalemia of DH in most cases. Additional measures for the management of hyperkalemia or modest potassium infusions for hypokalemia were needed in a few DH episodes. The predictors of the decrease in serum K(+) during treatment of DH with insulin included the starting serum K(+) level, the decreases in serum values of glucose concentration and tonicity, and the increase in serum total carbon dioxide level. DH represents a risk factor for hyperkalemia. Insulin infusion is the only treatment for hyperkalemia usually required.

Objective: To determine whether mailing guaiac-based fecal occult blood tests (gFOBTs) directly to patients who are due for colorectal cancer screening would achieve higher screening uptake than using visit-based screening., Study Design: Comparative effectiveness analysis., Methods: We used an electronic medical record to identify 7053 New Mexico Veterans Affairs Health Care System patients aged 50 to 80 years who were due for screening in 2008. We invited 3869 randomly selected patients to participate in a randomized controlled trial comparing adherence with different fecal blood tests; 202 intervention patients were assigned to receive mailed gFOBTs. We identified the following 3 control groups who could receive only visit-based colorectal cancer screening: 3184 individuals who were not invited for the randomized controlled trial (control group 1), 2525 individuals who did not respond to invitations to participate in the randomized controlled trial (control group 2), and 255 individuals who could not be contacted (control group 3). We measured gFOBT screening within 3 months after enrollment in the intervention group, as well as gFOBT or colonoscopy screening within 6 months of identification as a control subject. We compared screening across groups using multivariate logistic regression analysis to adjust for sex, race/ethnicity, clinic site, previous gFOBT, and comorbidities., Results: Colorectal screening occurred less often in each of the control groups (in 18.6% of control group 1, in 14.3% of control group 2, and in 18.8% of control group 3) than among patients mailed a gFOBT (48.5%). Adjusted odds ratios for screening among the control groups were all less than in the intervention group (adjusted odds ratios, 0.25, 0.19, and 0.23, respectively; all, P <.001)., Conclusion: Using an electronic medical record to identify screening-eligible patients and mailing them gFOBT cards achieved higher colorectal screening uptake than performing visit-based screening.

The absence of significant losses of potassium in the urine makes dialysis-associated hyperglycemia (DH) a model for the study of the internal potassium balance. Studies of DH have revealed that hyperkalemia is frequent at presentation, insulin infusion is usually the only treatment required, and the magnitude of the decrease in serum potassium concentration (K(+)) during treatment of DH with insulin depends on the starting serum K(+) level, the decreases in serum glucose concentration and tonicity, and the increase in serum total carbon dioxide level. We present an analysis of these findings based on previously studied actions of insulin. Calculations of transcellular potassium shifts based on the combined effects of insulin-the increase in the electrical potential differences (hyperpolarization) of the cell membranes and the correction of the hyperglycemic intracellular dehydration through decrease in serum glucose concentration-produced quantitative predictions of the decrease in serum K(+) similar to the reported changes in serum K(+) during treatment of DH with insulin. The lessons from analyzing serum K(+) changes during treatment of DH with insulin are applicable to other conditions where internal potassium balance is called upon to protect serum K(+), such as the postprandial state. The main questions related to internal potassium balance in DH that await clarification include the structure and function of cell membrane potassium channels, the effect of insulin on these channels, and the mechanisms of feedforward potassium regulation.

Mortality from various causes is higher in patients on chronic hemodialysis (HD) than in the general population. There is evidence suggesting that some of the deaths in HD patients are preventable. To identify potentially preventable causes of death, we analyzed deaths that occurred in HD patients during hospitalization over a period of 15 years. We performed a retrospective cohort analysis of 410 patients on HD for at least 6 months between 1995 and 2009 (included), who had all their hospitalizations in the same hospital. The patients were classified into 3 groups: Those who died during hospitalization (group A, n=120), those who died away from the hospital (group B, n=135), and those who were alive at the end of the observation period (group C, n=155). Continuous variables were compared between groups by the Kruskall-Wallis statistic. Logistic regression was used to identify predictors of dying during the observation period and predictors of death in the hospital. For the whole HD group of 410 patients, only 9 (2.2%) were women. 59% of the patients had diabetes mellitus. Age at the onset of HD was 65.8 ± 11.5 years and the duration of HD was 34.4 ± 27.9 months. Group A patients had a higher annual rate and duration of hospitalization and a higher Charlson comorbidity index than either of the other 2 groups, and, in comparison with patients in group C, were older at the end of observation and had a shorter duration of HD. Cardiac disease (19.2%), vascular access complications (18.3%), peripheral vascular disease (16.7%), infections (15.8%), trauma (11.7%), central nervous system disease (7.5%), respiratory failure (4.2%), malignancy (3.3%), and gastrointestinal disease (3.3%) were the causes of the last hospitalization in group A. Compared with the patients who died during hospitalization without discontinuing HD, group A patients who discontinued HD had a longer duration of their last hospitalization (52.7 ± 77.7 vs. 14.3 ± 23.8 days, P<0.001). Discontinuation of HD occurred in 80% of the hospitalizations for respiratory failure, 75% of the hospitalizations for malignancy, 57% of the hospitalizations for trauma, and 56% of the hospitalizations for central nervous system disease. Logistic regression identified a high Charlson index, advanced age, and short duration of HD as predictors of death, and an absence of diabetes, high Charlson index, prolonged annual duration of hospitalization, and short distance of the patient's domicile from the dialysis unit as predictors of death in the hospital. A substantial number of hospitalizations leading to the death of HD patients are caused by potentially preventable conditions, including vascular access complications, peripheral vascular disease, and trauma. Implementation of measures preventing these hospitalizations is a worthwhile undertaking., (© 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.)

Objective: To report a case of idiosyncratic hepatotoxicity associated with metformin in the treatment of type 2 diabetes with nonalcoholic fatty liver disease (NAFLD)., Case Summary: A 61-year-old obese man presented with jaundice, nausea, fatigue, and an unintentional weight loss 2 weeks following initiation of metformin. Laboratory findings revealed aminotransferase values 10-15 times the upper limit of normal. Potential causative agents, including metformin, simvastatin, and Niaspan (extended-release niacin), were discontinued. Two months later, the patient's signs and symptoms had resolved and aminotransferase values returned to normal. An objective causality assessment revealed that the adverse reaction was probably associated with metformin., Discussion: Since numerous medications and disease states can cause abnormalities in liver enzymes, it is important for providers to be able to distinguish the cause(s) and take appropriate actions. This can take a great deal of time and effort in patients with multiple medications and comorbidities. In this patient's case, viral hepatitis, worsening NAFLD, and the concomitant drugs were highly suspected. As hydroxymethylglutaryl coenzyme A reductase inhibitors offer substantial cardiovascular benefits and as metformin is a first-line agent in helping to lower blood glucose concentrations and to normalize the metabolic profile in type 2 diabetes, reintroduction of metformin and simvastatin would likely be beneficial., Conclusions: This is a case report of metformin-induced hepatotoxicity. As the prevalence of type 2 diabetes and subsequent metabolic effects increases in the US, metformin use will likewise increase. As potential for increased idiosyncratic hepatotoxicity associated with metformin use is likely to occur, clinicians should be vigilant.

Objective: To explore the hypothesis that CD36, a scavenger receptor and fatty acid translocase, is upregulated in peripheral blood mononuclear cells (PBMCs) among patients with type 2 diabetes and is a biomarker of PBMC activation and inflammation., Research Design and Methods: We used a cross-sectional observational design to study a multi-racial/ethnic population sample consisting of Caucasians, Hispanics, and Native Americans with type 2 diabetes (n = 33) and nondiabetic control subjects (n = 27). PBMC CD36 mRNA/protein and plasma high sensitivity (hs) C-reactive protein (hsCRP), hs-interleukin-6 (hsIL-6), and adiponectin were measured., Results: Unadjusted PBMC CD36 mRNA and protein were 1.56- and 1.63-fold higher, respectively, among type 2 diabetic subjects versus control subjects. PBMC CD36 protein was directly associated with CD36 mRNA, plasma hsCRP, and hsIL-6 and inversely associated with plasma adiponectin in both groups., Conclusions: Increased CD36 expression is a biomarker of PBMC activation and inflammation and may become a useful tool in cardiovascular disease risk stratification.

Objectives: Determine whether colorectal cancer screening adherence is greater with fecal immunochemical tests (FIT) or guaiac-based fecal occult blood tests (gFOBT)., Methods: We used electronic health records to identify 3869 New Mexico Veterans Affairs Health Care System primary care patients due for screening in 2008 for whom fecal blood testing was appropriate. We invited randomly selected patients by mail to participate in a study comparing FIT and gFOBT. We randomly allocated 404 subjects to receive FIT (n=202) or gFOBT (n=202) by mail. We determined the proportion of subjects completing testing within 90days of agreeing to participate in the study. We also used multivariate logistic regression to evaluate screening completion, adjusting for age, gender, race/ethnicity, clinic site, previous gFOBT testing, and co-morbidity., Results: Screening adherence was higher with FIT than gFOBT (61.4% vs. 50.5%, P=0.03). The adjusted odds ratio for completing FIT vs. gFOBT was 1.56, 95% CI 1.04, 2.32., Conclusion: In a clinic setting of patients who were due for colorectal cancer screening, adherence was significantly higher with FIT than gFOBT., (Published by Elsevier Inc.)

Objective: We identified factors that account for differences between lean body mass computed from creatinine kinetics (LBM(cr)) and from either body water (LBM(V)) or body mass index (LBM(BMI)) in patients on continuous peritoneal dialysis (CPD)., Design: We compared the LBM(cr) and LBM(V) or LBM(BMI) in hypothetical subjects and actual CPD patients., Patients: We studied 439 CPD patients in Albuquerque, Pittsburgh, and Toronto, with 925 clearance studies., Intervention: Creatinine production was estimated using formulas derived in CPD patients. Body water (V) was estimated from anthropometric formulas. We calculated LBM(BMI) from a formula that estimates body composition based on body mass index. In hypothetical subjects, LBM values were calculated by varying the determinants of body composition (gender, diabetic status, age, weight, and height) one at a time, while the other determinants were kept constant. In actual CPD patients, multiple linear regression and logistic regression were used to identify factors associated with differences in the estimates of LBM (LBM(cr)LBM(V). The differences in determinants of body composition between groups with high versus low LBM(cr) were similar in hypothetical and actual CPD patients. Multivariate analysis in actual CPD patients identified serum creatinine, height, age, gender, weight, and body mass index as predictors of the differences LBM(V)-LBM(cr) and LBM(BMI)-LBM(cr)., Conclusions: Overhydration is not the sole factor accounting for the differences between LBM(cr) and either LBM(V) or LBM(BMI) in CPD patients. These differences also stem from the coefficients assigned to major determinants of body composition by the formulas estimating LBM., (Published by Elsevier Inc.)

Background: The value of self-monitoring blood glucose (SMBG) in type 2 diabetes is controversial., Objective: To determine SMBG testing rates are positively associated with glycemic control in veterans on oral hypoglycemic agents (OHA)., Design: Observational database study., Subjects: Southwestern Healthcare Network veterans taking OHA in 2002 and followed through the end of 2004., Measurements: OHA and glucose test strip (GTS) prescriptions were derived from pharmacy files. Subjects were categorized into five groups according to their end-of-study treatment status: group 1 (no medication changes), group 2 (increased doses of initial OHA), group 3 (started new OHA), group 4 (both OHA interventions), and group 5 (initiated insulin). We then used multiple linear regression analyses to examine the relationship between the SMBG testing rate and hemoglobin A1c (HbA1c) within each group., Results: We evaluated 5,862 patients with a mean follow-up duration of 798 +/- 94 days. Overall, 44.2% received GTS. Ultimately, 47% of subjects ended up in group 1, 21% in group 2, 9% in group 3, 8% in group 4, and 16% in group 5. A univariate analysis showed no association between the SMBG testing rate and HbA1c. However, after stratifying by group and adjusting for initial OHA dose, we found that more frequent testing was associated with a significantly lower HbA1c in groups 1, 4, and 5. The effect ranged from -0.22% to -0.94% for every ten GTS/week., Conclusions: Higher SMBG testing rates were associated with lower HbA1c, but only when stratifying the analyses to control for treatment intensification.

It is not established whether hospitalizations are more frequent or longer in patients on peritoneal dialysis (PD) or chronic in-center hemodialysis (HD). Comorbidity is a major factor affecting the comparison of hospitalizations. To account for comorbidity, we compared hospitalizations between the PD and HD periods in 16 patients, 8 of whom were treated by PD first (group A), and 8, by HD first (group B). In group A, causes of renal failure were diabetes (n = 3), primary renal disease (n = 2), systemic disease (n = 2), and hereditary nephropathy (n = 1). Age at onset of PD was 53 +/- 11 years; duration of PD, 31 +/- 17 months; and duration of HD, 40 +/- 33 months. This group had 52 hospitalizations in the PD period and 80 hospitalizations in the HD period. Hospitalization rate (n/ patient-year) was 2.5 +/- 2.0 during PD and 3.0 +/- 3.0 during HD (nonsignificant), and duration of hospitalization (days/patient-year) was 19.6 +/- 15.5 during PD and 21.9 +/- 17.7 during HD (nonsignificant). The three most common causes of hospitalization were peritonitis (27%), other infections (21%), and cardiovascular disease (14%) in the PD period, and HD access problems (35%), infections (16%), and cardiovascular disease (12%) in the HD period. In group B, causes of renal failure were diabetes (n = 4), primary renal disease (n = 3), and hypertension (n = 1). Age at onset of HD was 56 +/- 10 years; duration of HD, 41 +/- 19 months; and duration of PD, 60 +/- 24 months. This group had 82 hospitalizations in the HD period and 76 hospitalizations in the PD period. Hospitalization rate was 3.0 +/- 2.4 during HD and 1.9 +/- 2.8 during PD (nonsignificant), and duration of hospitalization was 17.3 +/- 25.1 during HD and 12.7 +/- 21.3 during PD (nonsignificant). The three most common causes of hospitalization were HD access problems (40%), cardiovascular disease (19%), and infections (12%) in the HD period, and other infections (36%), cardiovascular disease (19%), and peritonitis (21%) in the PD period. In patients changing dialysis modalities, rate and duration of hospitalizations did not vary between HD and PD. The causes of hospitalization were similar in the HD and PD periods regardless of which modality was applied first.

Background: A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes., Methods and Results: The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of approximately 11 million individuals treated through various health care delivery models. Each site's rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators., Conclusions: The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases.

The mechanisms of fluid and solute abnormalities that should be considered in any patient with severe hyperglycemia include changes in the total amount of extracellular solute, osmotic diuresis, intake of water driven by thirst, and influences from associated conditions. The absence of osmotic diuresis distinguishes dialysis-associated hyperglycemia (DH) from hyperglycemia with preserved renal function (HPRF). Mainly because of this absence, comparable degrees of hyperglycemia tend to produce less hypertonicity and less severe intracellular volume contraction in DH than in HPRF, while extracellular volume is expanded in DH but contracted in HPRF. Ketoacidosis can develop in both DH and HPRF. Among DH patients, hyperkalemia appears to be more frequent when ketoacidosis is present than when nonketotic hyperglycemia is present. Among HPRF patients, the frequency of hyperkalemia appears to be similar whether ketoacidosis or nonketotic hyperglycemia is present. Usually patients with severe DH have no symptoms or may exhibit a thirst. Infrequent clinical manifestations of DH include coma and seizures from hypertonicity or ketoacidosis and pulmonary edema from extracellular expansion. Insulin infusion is usually the only treatment required to correct the biochemical abnormalities and reverse the clinical manifestations of DH. Monitoring of the clinical manifestations and biochemical parameters during treatment of DH with insulin is needed to determine whether additional measures, such as administration of saline, free water, or potassium salts, as well as emergency hemodialysis (HD) are needed. Emergency HD carries the risk of excessively rapid decline in tonicity; its benefits in the treatment of DH have not been established.

In addition to the maintenance of normal extracellular electrolyte composition, the prescription of continuous peritoneal dialysis (CPD) should address four other specific issues: (i) prevention of uremia by achievement of adequate clearance of azotemic substances, (ii) prevention of progressive expansion of the extracellular volume by adequate peritoneal ultrafiltration, (iii) prevention of loss of residual renal function, and (iv) prevention of deterioration of the peritoneal membrane structure and function. Urea clearance, in the form of Kt/V(Urea), is the index of removal of azotemic substances proposed by current guidelines. The target total (renal plus peritoneal) Kt/V(Urea) is >or=1.7 weekly. To provide the desired peritoneal Kt/V(Urea) (K(p)t/V(Urea)), the prescription of peritoneal dialysis must provide a daily drain volume (Dv) defined by the clearance equations as Dv = V x (K(p)t/V(Urea))/(D/P(Urea)), where V is body water obtained from published anthropometric formulas, K(p)t/V(Urea) = (1.7 - renal Kt/V(Urea))/7 and D/P(Urea) is the dialysate-to-plasma urea concentration ratio at the dwell time prescribed. Computer programs obtain the relevant D/P(Urea) values from formal studies of peritoneal transport. In the absence of these studies (for example, at initiation of CPD), D/P(Urea) values can be obtained from published studies with similar dwell times. Body size, indicated by V, is the major determinant of the K(p)t/V(Urea) limit provided by a given CPD schedule. Other obstacles to achievement of adequate urea clearance are created by poor patient compliance, inaccuracies of the anthropometric formulas estimating V, and mechanical complications of CPD that lead to retention of dialysate in the body. The main requirements for the prescription of adequate ultrafiltration are knowledge of the individual peritoneal transport characteristics, monitoring of urinary volume, and restriction of dietary sodium intake. Excessive dietary sodium intake is the major cause of extracellular volume expansion in CPD. Ideally, sodium intake should be kept at the level of total (peritoneal plus renal) sodium removal. Preventing the loss of residual renal function involves avoidance of nephrotoxic influences in the form of medications, radiocontrast agents, urinary obstruction and infection, and possibly other influences, such an elevated calcium-phosphorus product and anemia. Use of the lowest dialysate dextrose concentration that will allow adequate ultrafiltration is currently the most widespread practical measure of prevention of peritoneal membrane deterioration. Formulation of biocompatible dialysate is a major ongoing research effort and may greatly enhance the success of CPD in the future.

The field of ethics in medical research has seen important developments in the last three decades, but it also faces great challenges in the new century. The purposes of this report are to examine the current status of ethics of medical research involving human subjects and the nature of the ethical challenges facing this research, to identify the weakness of the current system of safeguards for ethical research, and to stress the importance of the ethical character of the researcher, which is the safeguard that has the greatest potential for protecting the research subjects. Researchers appreciate the risks of human medical research that create ethical dilemmas and the need for an ethical compromise in order to proceed with the research. The main elements of the compromise, formulated primarily from experiences in the Second World War, include: (1) the dominant position of the ethical principle of autonomy; (2) the demand for a signed informed consent; (3) the likelihood of improving health with the research protocol, which must be approved by a duly appointed supervising committee; and (4) an acceptable risk/benefit ratio. The main weakness of this set of safeguards is the difficulty with obtaining a truly informed consent. The new challenges to ethical medical research stem from certain types of research, such as genetic and stem cell research, and from the increasing involvement of the industry in planning and funding the research studies. Developing medical researchers with an ethical character and knowledge about ethics in medicine may be the most effective safeguard in protecting participants of medical research experiments.

Reports of dialysis-associated hyperglycemia (DH) were compared to reports of diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH) in patients with preserved renal function. Average serum values in DH (491 observations), DKA (1036 observations), and NKH (403 observations) were as follows, respectively: glucose, 772, 649, and 961 mg/dl; sodium, 127, 134, and 149, mmol/l; and tonicity, 298, 304, and 355 mOsm/kg. Assuming that euglycemic (serum glucose, 90 mg/dl) values were the same (sodium, 140 mmol/l; tonicity, 285 mOsm/kg) for all three states, the hyperglycemic rise in the average serum tonicity value per 100-mg/dl rise in serum glucose concentration was 1.9 mOsm/kg in DH, 3.5 mOsm/kg in DKA, and 8.1 mOsm/kg in NKH. Neurological manifestations in DH patients were caused by coexisting conditions (ketoacidosis, sepsis, and neurological disease) in most instances, and by severe hypertonicity (>320 mOsm/kg), with clearing after insulin administration, in a few instances. In 148 episodes of DH corrected with insulin only, the mean increase in serum sodium per 100-mg/dl decrease in serum glucose (Delta[Na]/Delta[Glu]) was -1.61 mmol/l. In agreement with theoretical predictions, Delta[Na]/Delta[Glu] was numerically smaller in patients with edema than in those with euvolemia. The average hyperglycemic increase in extracellular volume, calculated from changes in serum sodium concentration during correction of DH using insulin alone, was 0.013 l/l per 100-mg/dl increase in serum glucose concentration. A small number of DH patients presented with pulmonary edema rectified by insulin alone. DH causes modest hypertonicity, with few patients having neurological manifestations caused usually by other coexisting conditions. In contrast to DKA or NKH, which usually presents with hypovolemia, DH causes hypervolemia manifested occasionally by pulmonary edema. Insulin is adequate treatment for DH.

Hyperglycemic syndromes cause disturbances in the tonicity of body fluids, the distribution of body water between major body fluid compartments, and the external balance of body solute and water. The unique feature of dialysis-associated hyperglycemia (DH) is that, during its development, it can cause changes exclusively in the internal balance of body solute (hypertonicity) and fluids (intracellular volume contraction and extracellular volume expansion) without affecting the external balance of water or solute. This makes DH the proper substrate for studying predictions of the changes in tonicity and extracellular volume caused by hyperglycemia because these predictions fail, by and large, to account for changes in the external balance of sodium, potassium, and water observed in hyperglycemic syndromes occurring in patients with preserved renal function. The predictions suggest that the baseline state of extracellular volume and the degree of hyperglycemia are major factors influencing the magnitude of abnormalities in the tonicity and extracellular volume resulting from DH, while transfers of solute between the intracellular compartment and the extracellular compartment have relatively smaller effects. Edematous patients are at risk for greater hypertonicity and larger increases in their extracellular volume than euvolemic -- or, even less, hypovolemic -- patients with the same degree of hyperglycemia. Studies reporting the treatment of DH with only insulin therapy can be used to test these theoretical predictions and to analyze the relationship between solute and fluid abnormalities and clinical manifestations.

Background: The use of androgen deprivation therapy (ADT) for prostate cancer has increased substantially in recent years, exposing more men to potential treatment complications, including osteoporosis and fractures., Objective: To determine whether men treated with ADT for prostate cancer received osteoporosis screening, prevention, or treatment., Design: Cross-sectional observational study using a retrospective review of electronic medical records., Subjects: One hundred seventy-four patients with prostate cancer on ADT or status-post orchiectomy enrolled in primary care at the New Mexico Veterans Affairs Health Care System as of July 2005., Measurements: Patient demographics, tumor characteristics (Gleason score, stage, last PSA value, documented bone metastases), history of hip or vertebral fracture, osteoporosis risk factors (number of ADT shots, diabetes, smoking, heavy alcohol use or prescriptions for corticosteroids, thyroid hormone or dilantin). We defined recommended management as performing DXA scans or prescribing bisphosphonates, calcitonin, calcium or vitamin D., Results: Just 60 of 174 (34%) patients received recommended osteoporosis management based on DXA scans (13%) or treatment with oral or IV bisphosphonates (21%), calcitonin (1%), calcium (16%) or vitamin D (10%). On multivariate analysis, bone metastases, higher last PSA, and younger age at diagnosis were associated with recommended management, whereas Hispanic race/ethnicity was inversely associated., Conclusions: Most men treated with ADT for prostate cancer did not receive osteoporosis screening, prevention or treatment. Evidence for advanced cancer though not risk factors for osteoporosis or fracture-was associated with receiving osteoporosis management. Further research is needed to identify optimal strategies for screening, prevention, and treatment in this population.

To test the feasibility of calculating, in the absence of peritoneal transport studies, the dose (daily drain volume) of continuous peritoneal dialysis (CPD) that will produce a high probability of adequate fractional peritoneal urea clearance (Kpt/Vurea), we randomly separated 619 clearance studies in patients on continuous ambulatory peritoneal dialysis (CAPD) with 4 daily exchanges into a derivation (n = 322) and a validation (n = 297) group. In the derivation group, the dialysate-to-plasma urea concentration ratio (D/Purea) was < or = 0.799 within the lowest 5% of the studies. By the urea clearance formula, a D/Purea value of 0.799 will produce weekly Kpt/Vurea values of 1.70 or better if the ratio of the daily drain volume to plasma water (Dv/V) is > or = 0.304 L/L. Among the 56 studies in the validation group with Dv/V values of 0.304 L/L or more, 52 (92.9%) had weekly Kpt/Vurea values of 1.70 or better. Assuming a suitable (low) D/Purea value for a given CPD treatment, it is possible to derive the dose of dialysis (the Dv/V ratio) that will provide adequate peritoneal urea clearance levels regardless of peritoneal transport characteristics. This method is applicable to the prescription of CPD for patients lacking studies of peritoneal transport. Anuric patients on CAPD with 4 daily exchanges require a Dv/V value of 0.304 L/L or better to have a > or = 0.9 probability of achieving a weekly Kpt/Vurea of 1.70 or better.