Value-based evaluation of dialysis versus conservative care in older patients with advanced chronic kidney disease: a cohort study.

BACKGROUND: Conservative care is argued to be a reasonable treatment alternative for dialysis in older patients with advanced chronic kidney disease (CKD). However, comparisons are scarce and generally focus on survival only. Comparative data on more patient-relevant outcomes are needed to truly foster shared decision-making on an individual level, and cost comparison is needed to assess value of care. METHODS: We conducted a retrospective observational single-center cohort study in 366 patients aged ≥70 years with advanced CKD, who chose dialysis (n = 240) or conservative care (n = 126) after careful counselling by a multidisciplinary team in a non-academic teaching hospital in The Netherlands. Using a value-based health care approach (value = outcomes/cost): survival, health-related quality of life-cross-sectionally assessed with the Kidney Disease Quality of Life Short Form™-treatment burden, and treatment costs were evaluated. RESULTS: The overall survival benefit of patients on a dialysis pathway compared with patients on conservative care diminished or lost significance in patients aged ≥80 years or with severe comorbidity. There were no differences between patients managed conservatively and dialysis patients on physical and mental health summary scores (all P > 0.1). Patients on conservative care had 352.7 hospital free days per year versus 282.7 in patients on a dialysis pathway, calculated from treatment decision (adjusted incidence rate ratio: 1.15, 95% confidence interval: 1.09 to 1.21, P <  0.001). Annual treatment costs were lower in patients on conservative care (adjusted cost ratio: 0.43, 95% confidence interval: 0.28 to 0.67, P <  0.001). CONCLUSIONS: In this study, conservative care is shown to be a viable treatment option in older patients with advanced CKD, particularly in the oldest old and those with severe comorbidity. By achieving similar outcomes at lower treatment burden and treatment costs, value was generated for older patients choosing conservative care and society.

Ongoing effects of eConsultation in nephrology on hospital referral rates: An observational study.

INTRODUCTION: eConsultation in nephrology is an innovative way for general practitioners (GPs) to consult a nephrologist. Studies have shown that questions from GPs can be answered and intended referrals can be avoided by eConsultation. However, follow-up data are lacking. The primary aim of this study was therefore to assess whether patients for whom a referral to the outpatient clinic of a medical specialist was avoided in the short term were not then referred for the same problem within one year after the eConsultation. METHODS: All eConsultations sent between June 2017 and April 2018 to seven nephrologists in three different hospitals in The Netherlands were included. Exclusion criteria were duplications and missing data on follow-up. Data were obtained from the eConsultation application forms and from GP medical records. RESULTS: A total of 173 eConsultations were included. Of the 32 patients for whom a referral was initially prevented, 91% (95% confidence interval 75-98) had not been referred to a specialist for the same problem within one year after the eConsultation. DISCUSSION: eConsultation in the field of nephrology can prevent referrals in the long term. It can therefore contribute to a more modern and efficient health-care system in which chronic care is provided by GPs in close proximity to patients, while specialist support is easily available and accessible through eConsultation when necessary.

Reanalysis of the physical and mental health summary scores of dialysis versus conservative care in older patients with advanced chronic kidney disease: a critical appraisal.

OBJECTIVE: Non-dialytic conservative care is argued to be a reasonable treatment alternative for dialysis in selected older patients with advanced chronic kidney disease. We evaluated patient-relevant outcomes including health-related quality of life in a previous study. However, the scoring algorithm we used to calculate the physical and mental component summary scores of the Short Form-36 (SF-36) turned out to differ from comparable studies on this topic. The aim of this critical appraisal was to reanalyze the SF-36 summary scores in our patient cohort (≥ 70 years) using the more widely used scoring algorithm. RESULTS: Patients on conservative care (n = 23) had lower physical and mental component summary scores compared to patients not yet started on dialysis (n = 39), but similar compared to patients on dialysis (n = 34). These findings were similar to our original findings and did not change the conclusions. Several scoring algorithms are used for the SF-36 summary scores. Researchers should be aware of this fact and should use the same scoring algorithm across similar studies in a specific field to increase comparability. Using the more widely used scoring algorithm, the recalculated SF-36 summary scores of our patient cohort can now be compared to other studies.

Comparative Survival among Older Adults with Advanced Kidney Disease Managed Conservatively Versus with Dialysis.

BACKGROUND AND OBJECTIVES: Outcomes of older patients with ESRD undergoing RRT or conservative management (CM) are uncertain. Adequate survival data, specifically of older patients, are needed for proper counseling. We compared survival of older renal patients choosing either CM or RRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective survival analysis was performed of a single-center cohort in a nonacademic teaching hospital in The Netherlands from 2004 to 2014. Patients with ESRD ages ≥70 years old at the time that they opted for CM or RRT were included. Patients with acute on chronic renal failure needing immediate start of dialysis were excluded. RESULTS: In total, 107 patients chose CM, and 204 chose RRT. Patients choosing CM were older (mean±SD: 83±4.5 versus 76±4.4 years; P<0.001). The Davies comorbidity scores did not differ significantly between both groups. Median survival of those choosing RRT was higher than those choosing CM from time of modality choice (median; 75th to 25th percentiles: 3.1, 1.5-6.9 versus 1.5, 0.7-3.0 years; log-rank test: P<0.001) and all other starting points (P<0.001 in all patients). However, the survival advantage of patients choosing RRT was no longer observed in patients ages ≥80 years old (median; 75th to 25th percentiles: 2.1, 1.5-3.4 versus 1.4, 0.7-3.0 years; log-rank test: P=0.08). The survival advantage was also substantially reduced in patients ages ≥70 years old with Davies comorbidity scores of ≥3, particularly with cardiovascular comorbidity, although the RRT group maintained its survival advantage at the 5% significance level (median; 75th to 25th percentiles: 1.8, 0.7-4.1 versus 1.0, 0.6-1.4 years; log-rank test: P=0.02). CONCLUSIONS: In this single-center observational study, there was no statistically significant survival advantage among patients ages ≥80 years old choosing RRT over CM. Comorbidity was associated with a lower survival advantage. This provides important information for decision making in older patients with ESRD. CM could be a reasonable alternative to RRT in selected patients.

Partial inhibition of nitric oxide synthesis in vivo does not inhibit glucose production in man.

In the liver, paracrine interaction between Kupffer cells and hepatocytes influences glucose metabolism. In vitro in rats, nitric oxide (NO), a paracrine mediator, inhibits several pathways of hepatic glucose production. The role of NO on glucose production has not been studied in vivo in humans. Glucose production was measured during N(G)-monomethyl-L-arginine, monoacetate salt (L-NMMA) infusion, an inhibitor of NO synthesis in vivo, in 6 healthy men fasting 23 hours in a saline-controlled crossover study. During L-NMMA infusion, NO output decreased 40% to 50%, peripheral vascular resistance increased approximately 22%, and cardiac output (CO) decreased approximately 14%. The decrease in glucose production was not different between L-NMMA and saline. Glucose concentration, substrate supply, and glucoregulatory hormone concentrations were not different; epinephrine was lower with L-NMMA. A 40% to 50% inhibition of NO synthesis in vivo in humans does not affect glucose production during short-term fasting. The hypothesis that NO is an important modulator of basal glucose production in healthy humans in vivo should therefore be rejected.

[Agranulocytosis/granulocytopenia after long-term use of thiamazole]. / Agranulocytose na langdurig gebruik van thiamazol.

Agranulocytosis/granulocytopenia is a rare side effect of thyreostatics. Earlier publications state that for thiamazole this side effect occurs during the first few months of treatment. In two patients this thiamazole-induced agranulocytosis/granulocytopenia only occurred after years of treatment. A 53-year-old man presented with fever after a visit to Suriname. He had used thiamazole for 12 years for Graves' hyperthyroidism. The second patient, a 31-year-old woman, presented at the emergency department with fever and sore throat after 13 years of intermittent treatment with thiamazole. Both patients had an agranulocytosis/granulocytopenia and leukopenia. This was thought to be a side effect of thiamazole and blood values normalised after cessation of therapy. Both patients were treated empirically with broad-spectrum antibiotics during the agranylocytic period. They then received radioactive sodium iodide. To our knowledge this case report is the first to describe agranulocytosis/granulocytopenia following long-term treatment with thiamazole.

Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock.

OBJECTIVE: To establish the heterogeneity of hemodynamic responses to dobutamine in patients with septic shock and to identify the predictive factors of these hemodynamic responses. DESIGN: Prospective study. SETTING AND PATIENTS: A total of 12 patients with septic shock in a tertiary medical intensive care unit. INTERVENTIONS: A 20-min dobutamine infusion at 5 microg.kg(-1).min(-1) with subsequent increments to 8, 12.6, and 20 microg.kg(-1).min(-1), on two consecutive days. Responses were dichotomized into changes in heart rate (HR) or stroke volume index (SVI) of >10% and < or =10% at the maximal dobutamine infusion. MEASUREMENTS AND MAIN RESULTS: No differences were found in survival, Acute Physiology and Chronic Health Evaluation II score, maximal dobutamine doses, or pharmacokinetics of dobutamine between HR and SVI groups. In DeltaHR > 10% vs. DeltaHR < or = 10%, baseline HR was lower, and baseline mixed venous oxygen tension and saturation were higher. During dobutamine infusion, mean arterial pressure decreased in DeltaHR > 10%. Cardiac index and the systemic oxygen delivery index increased and the systemic vascular resistance index decreased at unchanged SVI. Pressure work index increased and the ratio of the diastolic to systolic aortic pressure time indices decreased but not to <0.6. In DeltaHR < or = 10%, systemic vascular resistance index and the ratio of the diastolic to systolic aortic pressure time indices decreased (but remained >0.6) without changes in SVI or cardiac index. Baseline hemodynamic and metabolic variables did not differ between SVI groups. In DeltaSVI > 10%, cardiac index increased with dobutamine, but Pao2 and the systemic oxygen delivery index decreased. In DeltaSVI < or = 10%, HR and the systemic oxygen delivery index increased; mean arterial pressure, left ventricular stroke work index, systemic vascular resistance index, and the ratio of the diastolic to systolic aortic pressure time indices decreased. CONCLUSIONS: Patients with a positive chronotropic response to dobutamine had lower baseline HR values, and a chronotropic rather than inotropic response predicted an increase in cardiac index and systemic oxygen delivery index. Incremental dosages of dobutamine did not compromise indirectly measured myocardial oxygen balance.

In vivo interaction of endotoxin and recombinant bactericidal/permeability-increasing protein (rBPI23): hemodynamic effects in a human endotoxemia model.

The cardiovascular derangement that results from the administration of endotoxin in healthy subjects is qualitatively similar to what is observed in patients in septic shock. The biological response to endotoxin is attributed in part to cytokine release. In experimental endotoxemia, recombinant bactericidal/permeability increasing protein (rBPI(23)) has shown a protective effect by binding endotoxin with the subsequent inhibition of the endotoxin-induced cytokine release and of neutrophil activation. In a controlled, blinded crossover study the early cardiovascular effects of rBPI(23) were investigated in an experimental endotoxemia model in humans. The beat-to-beat changes in arterial pressure and cardiac output following infusion of endotoxin (40 EU/kg body weight) and rBPI(23) (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg) were studied for 2 hours in 8 healthy male adults. Endotoxin or rBPI(23) alone did not induce significant cardiovascular changes. Endotoxin following rBPI(23) infusion elicited a fall in total peripheral resistance with its nadir after 4 minutes to 40% (range 16-53; P <.001) of control level. Mean arterial pressure showed little change, and the fall in total peripheral resistance was associated with a reflex increase in heart rate and cardiac output (32%; range 43-106). Changes in cardiovascular variables in the subsequent 2 hours were not significant. In vitro activation of the contact system by, respectively, rBPI(23), LPS, and LPS-rBPI(23) complexes was assessed. Following incubation with rBPI(23), LPS, and LPS-rBPI(23) complexes, complex levels were generated at levels comparable to those observed in the buffer control. The rapid vasodilatation by endotoxin administered concomitantly with rBPI(23) is not mediated by complement or contact system activation. The early vasodilatation is compensated by an increase in cardiac output, which therefore does not result in arterial hypotension. The monitoring of continuous cardiac output allows for the detection of rapid effects on systemic flow and conductance that go unnoticed in a recording of arterial pressure.