Lean six sigma methodologies improve clinical laboratory efficiency and reduce turnaround times.

BACKGROUND: Organizing work flow is a major task of laboratory management. Recently, clinical laboratories have started to adopt methodologies such as Lean Six Sigma and some successful implementations have been reported. This study used Lean Six Sigma to simplify the laboratory work process and decrease the turnaround time by eliminating non-value-adding steps. METHODS: The five-stage Six Sigma system known as define, measure, analyze, improve, and control (DMAIC) is used to identify and solve problems. The laboratory turnaround time for individual tests, total delay time in the sample reception area, and percentage of steps involving risks of medical errors and biological hazards in the overall process are measured. RESULTS: The pre-analytical process in the reception area was improved by eliminating 3 h and 22.5 min of non-value-adding work. Turnaround time also improved for stat samples from 68 to 59 min after applying Lean. Steps prone to medical errors and posing potential biological hazards to receptionists were reduced from 30% to 3%. CONCLUSION: Successful implementation of Lean Six Sigma significantly improved all of the selected performance metrics. This quality-improvement methodology has the potential to significantly improve clinical laboratories.

Reference interval of pregnancy-associated plasma protein-a in healthy men and non-pregnant women.

OBJECTIVE: The serum pregnancy-associated plasma protein-A (PAPP-A) concentration is a predictor of ischemic cardiac events and renal impairment. However, the reference interval of PAPP-A has not been determined. This study determined the reference interval of PAPP-A in men and non-pregnant women. METHODS: The study enrolled 126 apparently healthy individuals (52 males and 74 females). The mean age of the men and women was 34.7 (range 20-66) years and 34.6 (range 18-65) years, respectively. Serum PAPP-A concentrations were determined using an ultrasensitive enzyme-linked immunoassay kit. Reference intervals were calculated using the bootstrap method. RESULTS: The results for three subjects were outliers, so the reference interval of PAPP-A was calculated using the data for 123 subjects. PAPP-A was undetectable in 26 subjects. The reference interval of PAPP-A for men and women (with the 90% confidence interval) was <22.9 ng/mL (19.7-23.3) and <33.6 ng/mL (25.2-36.7), respectively. In male subjects, serum PAPP-A levels of smokers [3.10 (UD, 7.30)ng/mL] were significantly lower than that of non-smokers [11.00 (UD, 24.4)ng/mL] (p<0.001) and there was a positive correlation between serum PAPP-A levels and subjects' age (r=0.439; p<0.001). CONCLUSIONS: The reference interval of PAPP-A differed for men and non-pregnant women. In clinical practice, <22.9 ng/mL for men and <33.6 ng/mL for non-pregnant women may be used as reference intervals for PAPP-A.

Indirect reference intervals estimated from hospitalized population for thyrotropin and free thyroxine.

AIM: To establish indirect reference intervals from patient results obtained during routine laboratory work as an alternative to laborious and expensive producing of their own reference range values according to international instructions. METHODS: All results for thyrotropin (TSH) and free thyroxine (T4) that were stored in our laboratory information system between 2004 and 2008 were included in this study. After a logarithmic transformation of the raw data, outliers were excluded. Non-parametric reference intervals were estimated statistically after visual observation of the distribution using stem-and-leaf plots and histograms. A standard normal deviation test was performed to test the significance of differences between sub-groups. RESULTS: There was no significant difference in serum TSH or free T4 concentrations between male and female participants. Because no differences were found within the time span of the study, combined reference intervals were calculated. Indirect reference values were 0.43-3.93 mU/L for TSH and 11.98-21.33 pmol/L for free T4. CONCLUSION: Using patient laboratory data values is a relatively easy and cheap method of establishing laboratory-specific reference values if skewness and kurtosis of the distribution are not too large.

Macrophage depletion delays progression of neuropathic pain in diabetic animals.

Despite the fact that it is a frequent diabetic complication, the mechanisms underlying the manifestation of diabetic neuropathic pain remain poorly understood. In this study, we hypothesized that the depletion of peripheral macrophages with liposome-encapsulated clodronate (LEC) can prevent, at least delay, the progression of diabetes-induced neuropathic pain. Therefore, the aim of this study was to evaluate the effects of macrophage depletion on mechanical allodynia and thermal hyperalgesia in the streptozotocin (STZ)-induced rat model of diabetic neuropathy. LEC was intravenously administrated to rats three times with 5-day intervals. A single intravenous injection of STZ caused an increase in the average blood glucose levels and a decrease in body weight. Although LEC treatment did not affect the body weight gain, the blood glucose level was lower and serum insulin level higher in LEC-treated diabetic rats than in that of diabetic rats. In addition, LEC treatment alleviated the excessive damage in beta cells in diabetic rats. Diabetic animals displayed marked mechanical allodynia and thermal hyperalgesia. While the treatment of diabetic rats with LEC did not significantly change the thermal withdrawal latency, diabetes-induced decrease in mechanical paw withdrawal threshold was significantly corrected by the LEC treatment. The results of this study show that thermal hyperalgesia and mechanical allodynia induced by diabetes may be associated with alterations in blood glucose level. Depletion of macrophages with LEC in diabetic rats may reduce mechanical allodynia without affecting thermal hyperalgesia. Taken together, these results suggested that depletion of macrophages in diabetes may partially postpone the development of diabetic neuropathic pain.

Biochemical indicators and cardiac function tests in chronic alcohol abusers.

AIM: To determine the effect of chronic alcohol abuse on cardiac function, antioxidant system, trace elements, and liver function tests. METHODS: Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), superoxide dismutase (SOD), malondialdehyde (MDA), as well as zinc, magnesium, and copper were assayed in 25 chronic alcoholic patients and their 25 healthy relatives matched in age and gender. Echocardiographic parameters were evaluated for subjects. RESULTS: Mean corpuscular volume (96.7 fL vs 92.4 fL) and mean corpuscular hemoglobin levels (31.4 pg vs 30.5 pg) were found to be significantly increased in the patient group (P=0.002 and P=0.048, respectively). The results of the SOD and MDA assays showed no significant differences between the two groups. AST (38.7 U/L vs 22.1 U/L) and GGT (104.2 U/L vs 34.2 U/L) levels were found to be significantly increased in the patient group compared with controls (P=0.005 and P<0.001, respectively). Magnesium (1.6 mmol/L vs 1.8 mmol/L) and zinc levels (14.9 micromol/L vs 19.2 micromol/L) were significantly decreased, whereas copper levels (19.3 micromol/L vs 17.9 micromol/L) were increased in alcoholics (P=0.042, P<0.001 and P=0.003, respectively). Echocardiographic examination showed a significant decrease in mitral and tricuspid ratio of peak early and atrial flow velocity (E/A ratio) in alcoholics. CONCLUSION: Decrease in mitral and tricuspid E/A ratios accompanied with low levels of magnesium and zinc, and increased levels of copper indicate that alcoholics already have heart muscle disease even chronic alcohol exposure.

Protective effect of L-arginine intake on the impaired renal vascular responses in the gentamicin-treated rats.

The purpose of this study was to investigate the effect of gentamicin (100 mg/kg/day, i.p.) treatment on endothelium-dependent and -independent vasodilation in isolated perfused rat kidney, and the effect of amino acid L-arginine (in the drinking water, 2.25 g/l) on renal dysfunction induced by gentamicin. When gentamicin-treated groups were compared with the control group, it was observed that BUN and creatinine levels increased significantly. Also, the relaxant responses induced by acetylcholine, sodium nitroprusside and pinacidil decreased. Histopathological examination indicated acute tubular necrosis in this group. In animals treated with gentamicin together with L-arginine, there was a significant amelioration in the BUN and creatinine levels. The vasodilator responses were similar to those of the control group. Histopathological examination indicated only hydropic degeneration in tubular epithelium of kidney. Co-administration of L-NG-nitroarginine methyl ester (L-NAME) (112.5 mg/l), an inhibitor of nitric oxide synthase, and L-arginine to rats treated with gentamicin did not change the protective effect of L-arginine. In rats receiving L-NAME alone, the level of BUN and creatinine and vasodilation to acetylcholine were not significantly different when compared to those of the control group, while relaxant responses to sodium nitroprusside and pinacidil were increased. These results suggest that gentamicin leads to an impairment in vascular smooth muscle relaxation in addition to acute tubular necrosis in the rat kidney. Supplementation of L-arginine has an important protective effect on gentamicin-induced nephropathy.