Individual, sociodemographic, and lifestyle influence on blood chromium, cobalt, and nickel levels in healthy population living in Belgrade, Serbia.

The rapid trend of industrialization and urbanization can lead to greater exposure of the general population to chromium, cobalt, and nickel. Their total body burden from all routes of recent exposure, as well as interindividual variability in exposure levels, metabolism, and excretion rates, are reflected in the blood metal concentrations. The main goals in this study were as follows: observing the reference levels of chromium, cobalt, and nickel in the blood of the population living in Belgrade, identification of individual and sociodemographic factors that most affect their blood levels, and comprehension of recent exposure to chromium, cobalt, and nickel. Blood was sampled from 984 participants, voluntary blood donors, who agreed to participate in this study. Individual and sociodemographic data were collected using questionnaire adapted for different subpopulations. Blood metal analyses were measured using ICP-MS method (7700×, Agilent, USA). Our study provided reference values of chromium, cobalt, and nickel in blood for adult population (18-65 years) and confirmed that blood cobalt and nickel levels were mostly influenced by age and gender, and age, respectively. Furthermore, weight status affected blood chromium and cobalt levels, while national origin affected blood chromium levels. The present study highlighted the importance of human biomonitoring studies to monitor exposure status and identify subpopulations with increased exposure to chromium, cobalt, and nickel.

Association of clozapine and norclozapine levels with patient and therapy characteristics-focus on interaction with valproic acid.

PURPOSE: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. METHODS: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients' data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. RESULTS: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. CONCLUSION: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.

Integrating moving average control procedures into the risk-based quality control plan in small-volume medical laboratories.

Introduction: The modern approach to quality control (QC) in medical laboratories implies the development of a risk-based control plan. This paper aims to develop a risk-based QC plan for a laboratory with a small daily testing volume and to integrate the already optimized moving average (MA) control procedures into this plan. Materials and methods: A multistage bracketed QC plan for ten clinical chemistry analytes was made using a Westgard QC frequency calculator. Previously, MA procedures were optimized by the bias detection simulation method. Results: Aspartate aminotransferase, HDL-cholesterol and potassium had patient-risk sigma metrics greater than 6, albumin and cholesterol greater than 5, creatinine, chlorides, calcium and total proteins between 4 and 5, and sodium less than 4. Based on the calculated run sizes and characteristics of optimized MA procedures, for 6 tests, it was possible to replace the monitoring QC procedure with an MA procedure. For the remaining 4 tests, it was necessary to keep the monitoring QC procedure and introduce MA control for added security. Conclusion: This study showed that even in a laboratory with a small volume of daily testing, it is possible to make a risk-based QC plan and integrate MA control procedures into that plan.

Moving average procedures as an additional tool for real-time analytical quality control: challenges and opportunities of implementation in small-volume medical laboratories.

INTRODUCTION: Moving average (MA) is one possible way to use patient results for analytical quality control in medical laboratories. The aims of this study were to: (1) implement previously optimized MA procedures for 10 clinical chemistry analytes into the laboratory information system (LIS); (2) monitor their performance as a real-time quality control tool, and (3) define an algorithm for MA alarm management in a small-volume laboratory to suit the specific laboratory. MATERIALS AND METHODS: Moving average alarms were monitored and analysed over a period of 6 months on all patient results (total of 73,059) obtained for 10 clinical chemistry parameters. The optimal MA procedures were selected previously using an already described technique called the bias detection simulation method, considering the ability of bias detection the size of total allowable error as the key parameter for optimization. RESULTS: During 6 months, 17 MA alarms were registered, which is 0.023% of the total number of generated MA values. In 65% of cases, their cause was of pre-analytical origin, in 12% of analytical origin, and in 23% the cause was not found. The highest alarm rate was determined on sodium (0.10%), and the lowest on calcium and chloride. CONCLUSIONS: This paper showed that even in a small-volume laboratory, previously optimized MA procedures could be successfully implemented in the LIS and used for continuous quality control. Review of patient results, re-analysis of samples from the stable period, analysis of internal quality control samples and assessment of the analyser malfunctions and maintenance log have been proposed for the algorithm for managing MA alarms.

Death due to consumption of ibogaine: case report.

Ibogaine is a psychotropic indole alkaloid extracted from the roots of the Tabernanthe iboga shrub from the Apocynaceae family. Depending on the taken dose, it can lead to stimulant effects, euphoria, visual and auditory hallucinations, along with auditory, olfactory, and gustatory synesthesia. In addition to its historical usage in spiritual rituals of African tribes, these days iboga extract presents a prohibited, alternative drug widely used as a part of addiction treatment. Ibogaine used in opioid withdrawal is associated with serious side effects and sudden deaths. Besides its main use as an anti-addiction medication in alternative medicine, in moderate doses (from 100mg to 1g) ibogaine most commonly causes a "trance-like state".In this paper, we report the case of a heroin addict who died suddenly 5-12 hours after oral ingestion of powder labeled Tabernanthe iboga which had been bought online and used in the process of detoxification during an addiction treatment. The man was found dead in a rented apartment, where he was undergoing the addiction treatment.External examination revealed no lesions other than nonspecific injuries on the legs. The autopsy showed congestion of internal organs and pulmonary edema. Histopathological analysis of the heart showed neither macroscopic nor microscopic abnormalities. The concentration of ibogaine was 3.26mg/L. Moreover, systematic toxicological analyses of biological samples showed the presence of morphine and codeine. These data suggest that death, which occurred unnaturally after initiation of the "treatment", was probably the result of the cardiovascular effects caused by the ibogaine powder.The presented case highlights the worldwide problem of various products being widely available over the internet and the danger associated with consumption thereof.

Effect of urine adulterants on commercial drug abuse screening test strip results.

Immunochromatographic strips for urine drug screening tests (UDSTs) are common and very suitable for drug abuse monitoring, but are also highly susceptible to adulterants kept in the household, which can significantly alter test results. The aim of this study was to see how some of these common adulterants affect UDST results in practice and whether they can be detected by sample validity tests with pH and URIT 11G test strips. To this end we added household chemicals (acids, alkalis, oxidizing agents, surfactants, and miscellaneous substances) to urine samples positive for amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), tetrahydrocannabinol, heroin, cocaine, or benzodiazepines (diazepam or alprazolam) and tested them with one-component immunochromatographic UDST strips. The UDST for cocaine resisted adulteration the most, while the cannabis test produced the most false negative results. The most potent adulterant that barely changed the physiological properties of urine specimens and therefore escaped adulteration detection was vinegar. Besides lemon juice, it produced the most false negative test results. In conclusion, some urine adulterants, such as vinegar, could pass urine specimen validity test and remain undetected by laboratory testing. Our findings raise concern about this issue of preventing urine tampering and call for better control at sampling, privacy concerns notwithstanding, and better sample validity tests.

Optimizing moving average control procedures for small-volume laboratories: can it be done?

INTRODUCTION: Moving average (MA) means calculating the average value from a set of patient results and further using that value for analytical quality control purposes. The aim of this study was to examine whether the selection, optimization and validation of MA procedures can be performed using the already described bias detection simulation method and whether it is possible to select appropriate MA procedures for a laboratory with a small daily testing volume. MATERIALS AND METHODS: The study was done on four analytes: creatinine, potassium, sodium and albumin. All patient results of these tests processed during six months were taken from the laboratory information system. Using the MA Generator software, different MA procedures were analysed. Different inclusion criteria, calculation formulas, batch sizes and weighting factors were tested. Selection of optimal MA procedures was based on their ability to detect simulated biases of different sizes. After optimization, the validation of MA procedures was done. The results were presented by bias detection curves and MA validation charts. RESULTS: Simple MA procedures for albumin and sodium without truncation limits were selected as optimal. Exponentially weighted MA procedures were found optimal for creatinine and potassium, with the upper truncation limits of 150 µmol/L and 6 mmol/L, respectively. CONCLUSIONS: It has been experimentally confirmed that it is possible to perform the selection, optimization and validation of MA procedures using the bias detection simulation method. Also, it is possible to define MA procedures optimal for a laboratory with a small daily testing volume.

Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans.

Rhamnolipids are biodegradable low toxic biosurfactants which exert antimicrobial and anti-biofilm properties. They have attracted much attention recently due to potential applications in areas of bioremediation, therapeutics, cosmetics and agriculture, however, the full potential of these versatile molecules is yet to be explored. Based on the facts that many naturally occurring lipopeptides are potent antimicrobials, our study aimed to explore the potential of replacing rhamnose in rhamnolipids with amino acids thus creating lipopeptides that would mimic or enhance properties of the parent molecule. This would allow not only for more economical and greener production but also, due to the availability of structurally different amino acids, facile manipulation of physico-chemical and biological properties. Our synthetic efforts produced a library of 43 lipopeptides revealing biologically more potent molecules. The structural changes significantly increased, in particular, anti-biofilm properties against Candida albicans, although surface activity of the parent molecule was almost completely abolished. Our findings show that the most active compounds are leucine derivatives of 3-hydroxy acids containing benzylic ester functionality. The SAR study demonstrated a further increase in activity with aliphatic chain elongation. The most promising lipopeptides 15, 23 and 36 at 12.5 µg/mL concentration allowed only 14.3%, 5.1% and 11.2% of biofilm formation, respectively after 24 h. These compounds inhibit biofilm formation by preventing adhesion of C. albicans to abiotic and biotic surfaces.

Sodium nitrite food poisoning in one family.

Sodium nitrite is used as a coloring agent or preservative in food, as well as an antimicrobial agent in meat and fish and some cheeses. In high amounts it can be toxic for humans, causing methemoglobinemia. This is an unusual and potentially fatal condition in which hemoglobin is oxidized to methemoglobin (MHb), reducing the amount of oxygen that is released from hemoglobin, similar to carbon monoxide poisoning. MHb levels of 70% are generally lethal, but the existence of underlying anemia, acidosis, respiratory compromise, and cardiac disease may exacerbate the toxicity of MHb. We present a case of poisoning with sodium nitrite in three family members after eating homemade sausages given to them by their neighbor who was a butcher. According to the findings of the veterinary inspectorate in charge of food control in this case, the concentration of sodium nitrite in the homemade sausages was about 3.5 g per 1 kg of meat, almost 30 times higher than allowed according to legislation. In this case report, a 70-year-old man died about 7 h after consuming the meal, while two women, 53 and 67 years of age, respectively, were admitted to a toxicology clinic the following day due to food poisoning, with the maximum concentration of MHb in blood of 33.7 and 20.4%, respectively. They were discharged 3 days later. The autopsy of the deceased man showed sodium nitrite poisoning with a relatively low concentration of MHb in his blood - 9.87%. Death was attributed to the exacerbation of hypertensive and ischemic heart disease, resulting from accidental sodium nitrite poisoning. The presented cases illustrate the necessity of close cooperation between the authorities, medical staff, veterinary inspectorate, and forensic pathologists in determining the source of poisoning, the cause of death of the victim, and preventing the outbreak of poisoning among a greater number of consumers.

Unnatural and Violent Death in Cases with High Blood Alcohol Concentration- Autopsy Study.

The use of alcohol increases the risk of dying from unnatural or violent causes. The presented study explored the distribution of age, gender, cause, and circumstances of death in persons who died in an unnatural and violent manner, with a blood alcohol concentration (BAC) higher than 0.3 g/dL, and where the cause of death was not alcohol intoxication. We defined the control (0 < BAC < 0.3 g/dL) and study (BAC ≥ 0.3 g/dL) groups, as in subjects with these concentrations, there is a significant risk of gross intoxication, stupor, and death. The subjects from the study group were older, with no difference in gender distribution. Traffic accidents were the most common fatal event in both groups, followed by suicides. Other accidents (choking on food and exposure to fire) were more frequent in the study group. Compared to the control group, subjects from the study group were older persons whose deaths were mainly accidental.

Laboratory Information System - Where are we Today?

Wider implementation of laboratory information systems (LIS) in clinical laboratories in Serbia has been initiated ten years ago. The first LIS in the Railway Health Care Institute has been implemented nine years ago. Before the LIS was initiated, manual admission procedures limited daily output of patients. Moreover, manual entering of patients data and ordering tests on analyzers was problematic and time consuming. After completing tests, laboratory personnel had to write results in patient register (with potential errors) and provide invoices for health insurance organisation. First LIS brought forward some advantages with regards to these obstacles, but it also showed various weaknesses. These can be summarised in rigidity of system and inability to fulfil user expectation. After 4 years of use, we replaced this system with another LIS. Hence, the main aim of this paper is to evaluate advant ages of using LIS in laboratory of the Railway Health Care Institute and also to discuss further possibilities for its application. After implementing LIS, admission procedure has proven to be much faster. LIS enabled electronic requests, barcoded specimens prevent identification errors, bidirectional interface replaces redundant data entry steps, QC data are transferred automatically, results are electronically validated and automatically archived in data base, billing information is transferred electronically, and more. We also use some advanced options, like delta check, HIL feature, quality indicators and various types of reports. All steps in total testing process are drastically improved after the implementation of LIS, which had a positive impact on the quality of issued laboratory results. However, we expect development of some new features in the future, for example auto-verification and inventory management. On the example of the laboratory of the Railway Health Care Institute, we show that it is crucial that laboratory specialists have the main role in defining desirable characteristics of LIS which institution aims to buy. This paper suggests that the main feature of LIS should be the flexibility of system and capability of adjustment to user needs and requests.

The influence of alcohol on pedestrians: A different approach to the effectiveness of the new traffic safety law.

OBJECTIVE: The aim of this study was to explore the effects of the new traffic safety law on pedestrian mortality by exploring hazardous behaviors of pedestrians in terms of alcohol use and blood alcohol concentration (BAC). METHODS: A retrospective autopsy study was performed, covering a 7-year period (from 2006 to 2012), including cases of fatally injured pedestrians who died at the scene of the incident. Blood samples obtained from the femoral vein during autopsy were analyzed for BAC. The entire sample was divided into 2 groups. The first included cases from 2006 to 2009, at which time the old traffic safety law was in force, and the second included cases from 2010 to 2012, under the new traffic safety law. RESULTS: A total of 247 cases were examined, covering a 7-year period. The average age was 57.5 ± 19.7 years (median 61.0 years) with a significant male predominance of 147 men to 100 women. This predominance also applied to alcohol use (54 vs. 13). The results show a significant decrease in the total annual number of fatally injured pedestrians, starting from 2009, compared to previous years, reaching a low in 2010, one year after implementation of the new traffic safety law. In contrast, the proportion of alcohol-intoxicated pedestrians showed no significant difference in the years preceding and following the new traffic safety law, nor did the annual distribution of BAC or mean BAC before and after application of the new law. CONCLUSION: The present study indicates that the new traffic safety law has been quite effective in reducing pedestrian mortality. However, alcohol consumption and intoxication in pedestrians remains a fairly important factor in motor vehicle accidents involving pedestrians, because the proportion of pedestrians positive for alcohol, the proportion of severely intoxicated pedestrians with BAC > 1 g/L, and annual mean BAC have remained unchanged.

The effects of a new traffic safety law in the Republic of Serbia on driving under the influence of alcohol.

The aim of the study presented here has been to see what the effects of the new traffic safety law are, 2 years into its initial implementation, on driving under the influence of alcohol. Until the end of 2009, the legal limit for blood concentration for drivers in Serbia was 0.5g/l; however, the new traffic safety law stipulates the new limit to be 0.3g/l. A retrospective autopsy study was performed over a 6-year period (from 2006 to 2011) whose sample covered cases of fatally injured drivers who had died at the scene of the incident, before being admitted to hospital. A total of 161 fatally injured drivers were examined for their blood alcohol concentration. The average age for these drivers was 40.2±15.4 years, with a significant male predominance of 152 men to 9 women (χ(2)=152.000, p<0.001). This study has shown no decrease in the ratio of drivers under the influence of alcohol vs. all drivers (Pearson χ(2)=4.415, df=5, p=0.491), nor in the number of drivers under the influence of alcohol (Pearson χ(2)=6.629, df=5, p=0.250), nor a decrease in the mean blood alcohol concentration in drivers (1.72±0.87 vs. 1.68±0.95g/l, t=0.177, df=80, p=0.860). The conclusion of this study is that the new law has had a limited effect on driving under the influence of alcohol, which still remains one of the major human factors, responsible for road-traffic crashes in Serbia.