Antimicrobial use and microbiological testing in district general hospital ICUs of the Veneto region of north-east Italy.

International - predominantly American - studies undertaken in the ICUs of teaching centres show that inadequate antibiotic therapy increases mortality and length of stay. We sought to ascertain whether this also pertains to smaller ICUs in the Veneto region of north-east Italy. To the best of our knowledge, this is the first such survey in the Veneto area or in Italy as a whole. A retrospective, observational study was performed across five general-hospital ICUs to examine appropriateness of microbiological sampling, empirical antibiotic adequacy, and outcomes. Among 911 patients (mean age, 65.8 years ± 16.2 SD; median ICU stay, 17.0 days [IQR, 8.0-29.0]), 757 (83.1 %) were given empirical antibiotics. Treatment adequacy could be fully assessed in only 212 patients (28.0 %), who received empirical treatment and who had a relevant clinical sample collected at the initiation of this antibiotic (T0). Many other patients only had delayed microbiological investigation of their infections between day 1 and day 10 of therapy. Mortality was significantly higher among the 34.9 % of patients receiving inadequate treatment (48.6 % vs 18.80 %; p < 0.001). Only 32.5 % of combination regimens comprised a broad-spectrum Gram-negative ß-lactam plus an anti-MRSA agent, and many combinations were irrational. Inadequate treatment was frequent and was strongly associated with mortality; moreover, there was delayed microbiological investigation of many infections, precluding appropriate treatment modification and de-escalation. Improvements in these aspects and in antibiotic stewardship are being sought.

Performance evaluation of the automated nucleated red blood cell count of five commercial hematological analyzers.

INTRODUCTION: Recent automated hematology analyzers (HAs) can identify and report nucleated red blood cells (NRBC) count as a separate population out of white blood cells (WBC). The aim of this study was to investigate the analytical performances of NRBC enumeration on five top of the range HAs. METHODS: We evaluated the within-run and between-day precision, limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) of XE-2100 and XN-module (Sysmex), ADVIA 2120i (Siemens), BC-6800 (Mindray), and UniCel DxH 800 (Beckman Coulter). Automated NRBC counts were also compared with optical microscopy (OM). RESULTS: The limits of detection for NRBC of the BC-6800, XN-module, XE-2100, UniCel DxH 800, and ADVIA 2120i are 0.035×109 /L, 0.019×109 /L, 0.067×109 /L, 0.038×109 /L, and 0.167×109 /L, respectively. Our data indicated excellent performance in terms of precision. The agreement with OM was excellent for BC-6800, XN-module, and XE-2100 (Bias 0.023, 0.019, and 0.033×109 /L, respectively). ADVIA 2120i displayed a significant constant error and UniCel DxH 800 both proportional and small constant error. CONCLUSION: Regards to NRBC counting, the performances shown by BC-6800, XN-module, and XE-2100 are excellent also a low count, ADVIA 2120i and UniCel DxH 800 need to be improved.

Comparing the performance of three panels rules of blood smear review criteria on an Italian multicenter evaluation.

BACKGROUND: The aims of this study were to compare the diagnostic accuracy of blood smear review criteria, by means of three different panel rules, those proposed by: the International Consensus Group for Hematology [41-ICGH rules], the Italian Survey [IS rules] and the Working Group on Hematology-SIBioC (WGH) consensus rules (WGH rules). METHODS: This study is based on 2707 peripheral blood (PB) samples referred for routine hematological testing to the WGH-associated laboratories displaced all over the Italian territory. The PB samples were processed on seven different hematology analyzers (HAs): Advia 2120i, XE-2100, BC-6800, ABX Pentra, XN-1000, Cell-DYN Sapphire, and DxH800, respectively. All the results provided by the HAs were analyzed through the application of three different blood smear review criteria: that is, the 41-ICGH, IS, and WGH rules. Finally, data were compared with those obtained by optical microscopy (OM), as the current gold standard. RESULTS: The overall the agreement OM classification with ICGH, IS, and WGH panel rules is 0.83, 0.83, and 0.85, respectively. The false negatives are 2.1%, 3.0%, and 2.9%, while false positives are 15.1%, 13.7%, and 11.7%, respectively. All the seven HAs showed variable interinstrument performance, as three different criteria for OM review were adopted on each of them from time to time. CONCLUSION: These results presented show that the customization of validation rules is necessary for enhancing the quality of hematological testing and optimizing workflow.

Increased serum beta 2-microglobulin concentrations in hyperthyroid states.

Serum beta 2-microglobulin concentrations were determined in 21 untreated hyperthyroid patients (12 with Graves' disease, and nine with toxic nodular adenoma) and in 20 healthy controls. All subjects had normal serum creatinine concentrations and urine analysis. Both total and free thyroid hormones were significantly higher in the hyperthyroid groups than in controls. Beta 2-microglobulin concentrations were significantly increased in both groups of hyperthyroid patients compared with controls. No difference was found in the thyroid hormone and beta 2-microglobulin concentrations between both sets of patients. The beta 2-microglobulin and thyroid hormone concentrations were not correlated. These data show that hyperthyroidism is another cause of increased beta 2-microglobulin production along with viral infections, immunologically mediated diseases, and malignant neoplasms. The increased serum beta 2-microglobulin concentration in thyroid hyperfunction is probably related to metabolic rate, even if autoimmunity might contribute to its overproduction.

[Bone metabolism in primary hypothyroidism in the adult]. / Studio del metabolismo osseo nell'ipotiroidismo primitivo dell'adulto.

The aim of the study was to investigate bone metabolism in adult onset idiopathic myxedema. We studied 13 untreated patients (11 women and 2 men, age ranging 24-64 years) and, as a control group 15 healthy subjects (13 women and 2 men, age ranging 24-64 years). The hypothyroid group had significantly lower urinary excretion of hydroxyproline (4.40 +/- 0.63 vs. 8.60 +/- 1.3 mg/g, p less than 0.05) and serum concentration of osteocalcin (4.45 +/- 0.41 vs. 7.76 +/- 0.55 ng/ml, p less than 0.001). This low urinary excretion of hydroxyproline points to reduced osteoclastic bone resorption, while the low serum level of osteocalcin supports the view that osteoblastic bone formation is sluggish, too. Therefore bone metabolism in adult myxedema is characterized by a general reduction of remodelling. The stimulating actions of thyroid hormones on both bone resorption and new synthesis are further supported by the positive correlations between free hormone fractions and either urinary hydroxyproline and serum osteocalcin. Serum calcium, phosphorus, urinary calcium and phosphorus, and serum calcitrophic hormones (vitamin D, calcitonin, parathyroid hormone, measured as intact molecule) did not differed between the two groups; this finding might be related to the low fraction of active bone in hypothyroidism. The slow bone turnover seems to have few clinical consequences, but replacement therapy might produce accelerated osteoporosis, perhaps as a result of bone hypersensitivity to thyroid hormones.

[Serum levels of the tartrate-resistant isoenzyme, acid phosphatase, for the evaluation of bone remodeling in hyperthyroidism]. / Il dosaggio sierico dell'isoenzima tartrato resistente della fosfatasi acida nella valutazione del rimodellamento osseo nell'ipertiroidismo.

Tartrate-resistant acid phosphatase (TRAP) is one of the acid phosphatase isoenzymes. It is secreted by osteoclasts so it has been proposed as a marker of bone resorption. Bone turnover is high in hyperthyroidism due to an increase in both bone resorption and formation. The aim of the study was to measure serum TRAP as well as other markers of bone metabolism in 20 fertile age females affected by Graves-disease; 11 patients were also studied after euthyroid state was attained by means of a 6 month course of methimazole treatment. TRAP was measured with the colorimetric method using p-nitrophenylphosphate as substrate. Free thyroid hormones, TSH, serum calcium (corrected for albumin concentration), phosphate, osteocalcin, alkaline phosphatase, parathormone intact molecule, and urinary excretions of calcium, phosphate and hydroxyproline were measured, too. Twenty-eight healthy fertile women made up the control group. Untreated patients had a significant increase of TRAP, osteocalcin, serum calcium, alkaline phosphatase and urinary excretion of calcium and hydroxyproline. A significant fall in all these parameters but alkaline phosphatase was disclosed comparing patients before and after treatment, nevertheless only urinary calcium became not significantly different from the controls. TRAP showed a significant correlation with free T3 levels but not with hydroxyproline excretions. This survey on fertile age women with Graves' disease shows a significant increase in serum concentration of TRAP, which decreases, but doesn't get normalization, when euthyroidism is attained by a six month course of methimazole therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical validation of PD Adequest software: modeling error assessment.

OBJECTIVE: PD ADEQUEST software (Baxter Healthcare, Deerfield, IL, U.S.A.) is used in peritoneal dialysis for calculating the indices of dialysis efficiency and for the mathematical simulation of the results of various dialysis regimens. The aim of our study was to quantify the modeling errors and find the methods which give best results. DESIGN: Nonrandomized, repeated measurement, clinical validation study. PATIENTS: The study included 78 patients on continuous ambulatory peritoneal dialysis (PD), daytime ambulatory PD, and automated PD. MEASUREMENTS: We used 207 collections of dialysate and urine associated with peritoneal equilibration tests (PETs) performed with different glucose concentrations (1.36%, 2.27%, 3.86%). The measured urea Kt/V, creatinine clearance (CRCL) and ultrafiltration (UF) were compared with the same data simulated mathematically using the PD ADEQUEST software version 1.4. RESULTS: The Kt/V, CRCL, and UF measured values were significantly correlated and in agreement with modeled data [concordance correlation (rc) was 0.849, 0.839, 0.625 respectively]. The errors (modeled - measured) were: Kt/V = -0.04 +/- 0.27 (p = ns), CRCL = 2.1 +/- 7.7 L (p < 0.001), UF = -121 +/- 711 mL (p = 0.016). Applying ANOVA to both the peritoneal transport data calculated by PD ADEQUEST (mass transfer area coefficient of the solutes, fluid reabsorption, and hydraulic permeability) and the modeling errors, significant differences were found in relation to the PET glucose concentrations. CONCLUSION: PD ADEQUEST proves to be a useful instrument in peritoneal dialysis, although there is undoubtedly still room for improvement in its prediction efficacy, which is influenced by the glucose concentration used in the PET.

Compliance study in peritoneal dialysis using PD Adequest software.

Poor compliance in peritoneal dialysis (PD) is a significant cause of dropout and morbidity. PD Adequest software, which, through a mathematical model, predicts the effect of the dialysis prescription on the basis of the peritoneal transport, may be used to identify the noncompliant patient. Fifty patients from two dialysis centers, aged 65.9 +/- 1.5 years and on PD for 28.6 +/- 4.7 months, were studied. A peritoneal equilibration test (PET) was carried out and 24-hour urine and dialysate were collected. Total weekly creatinine clearance (CrCl, L/week/1.73 m2) was calculated, as well as the glomerular filtration rate [(GFR), mL/min, mean CrCl and urea nitrogen clearance (UNCI)]. The dialytic schedules used were then introduced into the program and the parameters were recalculated using the software model. Nine patients considered noncompliant from their case histories were used to assess the differences of reference between expected and measured values. The control group was significantly different from the noncompliant group in the percentage of the CrCl and the serum creatinine (sCR) differences. The noncompliance threshold value was calculated from the mean of the lower 95% confidence interval of the compliant group and the higher one of the noncompliant group (-5.3%) for CrCl and vice versa for sCR (+10%), which behaved to the contrary. Reassessing the patients, 11 (22%) were identified as probably noncompliant.

Serum bone GLA-protein in hypercalcemia of primary hyperparathyroidism and malignancy.

Serum bone GLA-protein, a modern and sensitive marker of bone turnover, was measured in 15 patients with primary hyperparathyroidism, 18 patients with hypercalcemia of malignancy, 41 patients with bone metastasis without hypercalcemia, and 29 healthy subjects. Serum bone GLA-protein was increased in primary hyperparathyroidism (17.6 +/- 3.9 ng/ml) and normal in hypercalcemia of malignancy (5.2 +/- 2.8 ng/ml; p less than 0.001 vs hyperparathyroidism) and in normocalcemic patients with bone metastases. In primary hyperparathyroidism parathyroid hormone correlated positively with urinary calcium excretion (p less than 0.05) and with urinary hydroxyproline excretion (p less than 0.001). The sensitivity of serum bone GLA-protein measurements in differentiating between primary hyperparathyroidism and hypercalcemia of malignancy was 91% and the specificity 84%. Thus this marker appears to be a useful tool for the differential diagnosis of hypercalcemias.

Peritoneal dialysis prescription: the "Clearance Peak" model.

Creatinine clearance (CRCL) was studied in 20 patients on CAPD in relation to the dwell times (DT), in order to establish a personalised dialysis schedule with the best clearance (CL) results, while respecting the patient's life-style. By calculating the CRCL from the two exchanges with dwell-times of 4 and 8 hours (2 I, 2.27%), curves (2nd degree polynomial regression) were plotted with three points (0h, 4h, 8h) for CRCL and the ultrafiltration rate (UF) as a function of the DT. The DT corresponding to the CRCL peak (CLPeak-time) was calculated for each subject with the first derivative of the function. On the basis of the CRCL obtained with the three most common DT (4h, 6h, 8h), we divided the patients into three categories (CLPeak-time < 5h: "fast", 5-7h: "normal"; > 7h: "slow") for the best CRCL correspondence of the 4h, 6h or 8h exchanges respectively. Also the 8h/4h ratio was used to determine CLPeak-time. For each of the three categories there is a corresponding dialysis schedule for the best CRCL and UF results of the exchanges with DT of 4, 6 and 8 hours, plus the theoretical calculation of the daily CRCL obtainable ("fast": APD; "normal": CAPD 4 exchanges/DAPD 4 exchanges; "slow": CAPD 4 exchanges). The "CLPeak" dialysis prescription model therefore identifies the most advantageous DT for each patient by using the CRCL values of two 2.27% exchanges of 4 and 8h respectively. Functional classification into three categories may give a rational orientation to dialysis prescription in order to reach the maximum CRCL possible with the individual peritoneal transport rates.

A new biosensor for continuous monitoring of the spent dialysate urea level in standard hemodialysis.

This study gives the results in terms of precision and repeatability of a new on-line urea monitoring system (Ureascan P2 Hospal) capable of measuring the urea concentrations in the spent dialysate. The Ureascan P2 Hospal (UP2H), fitted on single-pass dialysis machines (Integra-Hospal), functions by the presence of a disposable mini-reactor containing urease. The passage through the reactor of a minimum quantity of spent dialysate from the filter diluted with a pH 7 buffer solution (1 ml/min) increases its ionic strength, which is detected by a differential measurement of conductivity in proportion to the urea concentration in the dialysis liquid. We studied 13 dialysis sessions, with bicarbonate buffer, in 8 anuric patients. From 4 to 7 dialysate samples were taken during each treatment to determine the urea and 65 samples were analysed overall. Urea values from the UP2H were compared with those measured on the Dimension Du Pont analyser. Simple linear regression analysis showed an excellent correlation between the 2 measuring methods (r=0.987; p<0.001). The Bland-Altman test gave an average difference between the urea values measured with the UP2H and in the laboratory of 1.3+/-1.2 mg/dl. The agreement limits between 2 SD were -1.2 mg/dl and +3.8 mg/dl respectively. In conclusion, the UP2H we have developed has proved to be a reliable and very useful instrument for adapting, through the urea kinetic mathematical models, the dialysis dose for individual patients.

Hyperinsulinism reduction associated with icodextrin treatment in continuous ambulatory peritoneal dialysis patients.

Glucose absorption from peritoneal dialysis solutions causes a chronic stimulation of insulin secretion, which leads to hyperinsulinism. The use of solutions without glucose should correct this metabolic derangement together with the associated cardiovascular risk. To verify this hypothesis, we studied the entire non diabetic continuous ambulatory peritoneal dialysis (CAPD) population of our center: 27 patients with a mean age of 62 +/- 15 years, and a median 17 months on treatment. Morning fasting serum insulin was 32.8 +/- 9.3 microU/mL; glucose, 104.4 +/- 21.8 mg/dL; triglycerides, 162.4 +/- 125.7 mg/dL; cholesterol, 221.9 +/- 54.7 mg/dL; intact parathyroid hormone (iPTH), 212 +/- 189 pg/mL; fibrinogen, 519 +/- 112 mg/dL; body mass index, 24.1 +/- 4.1; and daily erythropoietin subcutaneous therapy dose, 17 +/- 6 U/kg. Insulin sensitivity, measured as ISI-HOMA (insulin sensitivity index, derived from the homeostasis model assessment) was 2.4 +/- 0.7. Daily glucose load, calculated from dialytic schedules, was 135 +/- 38 g. Of the 27 patients, 12 were treated with standard glucose solutions during the day and with one icodextrin dwell during the night for a median of 9 months (range: 1-28). The remaining 15 patients were treated with standard glucose solutions. The icodextrin group showed significantly lower serum insulin levels (28.6 +/- 6.0 microU/mL vs 36.1 +/- 10.2 microU/mL, p = 0.021) and significantly higher ISI-HOMA values (2.7 +/- 0.5 vs 2.2 +/- 0.7, p = 0.041) than the control group. The two groups showed no significant differences for glucose, triglycerides, cholesterol, iPTH, fibrinogen, body mass index, or erythropoietin therapy dose. Daily glucose load was lower in the icodextrin group, but without reaching statistical significance (128 +/- 31 g vs 142 +/- 43 g). This study shows, in a preliminary way, that the chronic use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

Continuous tidal peritoneal dialysis (CTPD) prescription and adequacy targets.

NKF-DOQI guidelines suggest a Kt/V value of 2.1 and a creatinine clearance (CRCL) value of 63 L/1.73 m2 of body surface area per week as minimum targets in continuous cycling peritoneal dialysis (CCPD). Those targets are obtained by adapting the CAPD guidelines. The aim of our study was to verify the possibility of reaching the suggested targets with continuous tidal peritoneal dialysis (CTPD) and to check target modification in this automated treatment. Eight anuric patients underwent four consecutive CTPD sessions with increasing total prescribed volumes (17 L, 22 L, 27 L, and 32 L; night 9 h; fill 2.2 L; tidal 75%, day 2 dwells). The Kt/V increase was significant (P = 0.012), unlike that of CRCL, with larger volumes. Two patients did not reach target Kt/V, and four did not reach target CRCL. The volume normalized for 1.73 m2 corresponding to DOQI targets was 19.6 +/- 2.6 L for Kt/V and 20.2 +/- 2.4 for CRCL. The overall Kt/V was 2.29 +/- 0.66 and CRCL was 57.3 +/- 16.5 L/1.73 m2. CRCL/Kt/V overall ratio was 25.6 +/- 4.7 and significantly different from the target ratio (63/2.1 = 30, P < 0.001). The CRCL/Kt/V ratio showed a significant decrease with larger volumes (P = 0.001, linear trend P < 0.001). Adequacy targets can be reached only in some patients on CTPD even with high dialysis volumes. The changes in the CRCL/Kt/V ratio in relation to dialysis volume can be considered for adaptation and evaluation of adequacy targets in automated treatments.

Low sodium concentration solution in normohydrated CAPD patients.

The aim of this study was to examine the possibility of increasing sodium and water removal with peritoneal dialysis. Ten patients aged 67.3 +/- 6.2 years, on continuous ambulatory peritoneal dialysis (CAPD) for 28.1 +/- 13.9 months, with no episodes of peritonitis for at least 2 months and clinically normohydrated, gave their informed consent to undergo two consecutive peritoneal equilibration tests (PETs) with dialysis solution at a sodium concentration of 126 mEq/L (low sodium) and 132 mEq/L (normal sodium), both with 2.5% glucose. Net ultrafiltration and sodium mass transfer were 319.4 +/- 178.5 and 443.2 +/- 234.4 mL (p = 0.0346) and 27.7 +/- 24.5 and 28.2 +/- 27.1 mEq (p = NS), respectively. There were no variations in natremia or the transport indices of the studied solutes or in the arterial pressure or heart rate. All patients showed drowsiness or torpor during the low sodium PET and one had cramps. The 126 mEq/L sodium dialysis solution showed no advantages compared to the more common solution, 132 mEq/L. However, further study is necessary to check the potentiality of solutions with different sodium and glucose compositions for both acute and chronic use.

Total clearance and extracellular volume with 125I-iothalamate in peritoneal dialysis.

To assess treatment adequacy by calculating total clearance (CL) in patients on peritoneal dialysis (PD), fluids must be collected over 24 hours, a laborious procedure and prone to inaccuracy. CL calculation from the plasma disappearance curve of an injected tracer has none of the above inconveniences. We therefore compared creatinine clearance CR-CL with CL calculated from the plasma disappearance curve of 125I-iothalamate (IO) injected in a single intravenous bolus. Twelve patients aged 63 (44-80) years and on PD for four (1-44) months were studied in hospital. Nine plasma samples were taken for IO-CL after a bolus of 21 kBq/kg of tracer. The least-squares biexponential fitting according to Gauss-Newton-Raphson was then carried out: [Aexp(-at) + Bexp(-bt)], and clearance was calculated by the formula, IO-CL = dose/AUC, where AUC = A/a + B/b. Both CLs were normalized for 1.73 m2 of body surface. Agreement (r = 0.746, p = 0.005) for the CR-CL (6.8 +/- 1.9 mL/min) and IO-CL (7.6 +/- 1.9 mL/min) was good, with a difference of 0.9 +/- 1.4 mL/min (t = 2.182, p = 0.052). Extracellular volume (ECV), calculated from the IO plasma disappearance curve with the formula, ECV = dose/ bAUC, and including the endoperitoneal fluid, was 19.8 +/- 2.9 L (29.5 +/- 6.2% body weight).

Calcium lactate interference in measuring creatinine in peritoneal dialysis fluids by the Jaffé kinetic method.

Creatinine measurements in peritoneal dialysis fluids using the Jaffé method have poor specificity due to interfering substances. We have checked to see if calcium lactate, in addition to glucose, interferes with the Jaffé kinetic measurement. Eight samples were prepared with increasing concentrations of glucose (960-3890 mg/dL) and eight were prepared with the same glucose content plus 7 mg/dL of calcium lactate, all without creatinine; in addition, 96 samples with increasing concentrations of glucose (1500-4000 mg/dL), calcium lactate (3-7.5 mg/dL), and creatinine (0.75-4.5 mg/dL) were prepared. There was a 0.31 +/- 0.13 mg/dL glucose interference on the Jaffé kinetic measurement in the first series, with an exponential trend. Interference was greater with calcium lactate and glucose: 0.50 +/- 0.16 mg/dL with the same trend. Data from the second series confirm the overestimation: 0.54 +/- 0.05 mg/dL (32.6%) with an exponential trend. The interference of glucose, creatinine, and calcium lactate on the Jaffé kinetic measurement was obtained by multi-variate regression. The single effects of glucose2 and glucose are predominant, but both creatinine and calcium lactate have a significant effect. Our study highlights the nonlinear glucose interference on creatinine measurement with the Jaffé kinetic method and the linear interference of both calcium lactate and creatinine.

[Serum osteocalcin in hyperthyroidism]. / L'osteocalcina sierica nell'ipertiroidismo.

Several bone metabolism biochemical parameters were measured to evaluate the increased serum osteocalcin (sBGP) in hyperthyroidism. Twenty patients (19 women and 1 man, aged 22-69) and 20 age and sex-matched healthy subjects were examined. The following serum measurements were performed: calcium, phosphate, mid-molecule PTH, calcitonin, 25OH vitD, alkaline phosphatase, total and free thyroid hormones; urinary excretion of calcium, hydroxyproline and creatinine was also measured. The results (mean +/- standard error) show significant increases of sBGP (16.4 +/- 1.02 ng/mL; p less than 0.001), serum calcium (10.1 +/- 0.1 mg/dL; p less than 0.001), alkaline phosphatase (144.0 +/- 11.7 UI/L; p less than 0.001), urinary calcium (315.6 +/- 48.5 mg/g urinary creatinine; p less than 0.001) and hydroxyproline (43.0 +/- 6.1 mg/g urinary creatinine; p less than 0.001). A significant correlation between total and free thyroid hormones and sBGP was found. Accelerated bone turnover in hyperthyroid patients is therefore confirmed: both osteoclastic bone resorption, as suggested by increased serum and urinary calcium and urinary hydroxyproline, and osteoblastic bone formation, as suggested by increased serum osteocalcin and alkaline phosphatase, are stimulated.