Paclitaxel and Therapeutic Drug Monitoring with Microsampling in Clinical Practice.

Paclitaxel is an anticancer agent efficacious in various tumors. There is large interindividual variability in drug plasma concentrations resulting in a wide variability in observed toxicity in patients. Studies have shown the time the concentration of paclitaxel exceeds 0.05 µM is a predictive parameter of toxicity, making dose individualization potentially useful in reducing the adverse effects. To determine paclitaxel drug concentration, a venous blood sample collected 24 h following the end of infusion is required, often inconvenient for patients. Alternatively, using a microsampling device for self-sampling would facilitate paclitaxel monitoring regardless of the patient's location. We investigated the feasibility of collecting venous and capillary samples (using a Mitra® device) from cancer patients to determine the paclitaxel concentrations. The relationship between the venous plasma and whole blood and venous and capillary blood (on Mitra®) paclitaxel concentrations, defined by a Passing-Bablok regression, were 0.8433 and 0.8569, respectively. Demonstrating a clinically acceptable relationship between plasma and whole blood paclitaxel concentration would reduce the need to establish new target concentrations in whole blood. However, in this study, comparison of venous and capillary blood using Mitra® for sampling displayed wide confidence intervals suggesting the results from the plasma and whole blood on this device may not be interchangeable.

LC-MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring.

Background: Optimizing antimicrobial therapy to attain drug exposure that limits the emergence of resistance, effectively treats the infection, and reduces the risk of side effects is of a particular importance in critically ill patients, in whom normal functions are augmented or/and are infected with pathogens less sensitive to treatment. Achievement of these goals can be enhanced by therapeutic drug monitoring (TDM) for many antibiotics. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method is presented here for simultaneous quantification of ten antimicrobials: cefazolin (CZO), cefepime (CEP), cefotaxime (CTA), ceftazidime (CTZ), ciprofloxacin (CIP), flucloxacillin (FLU), linezolid (LIN), meropenem (MER), piperacillin (PIP) and tazobactam (TAZ) in human plasma. Methods: Plasma samples were precipitated with acetonitrile and injected into the LC-MS/MS. Chromatographic separation was on a Waters Acquity BEH C18 column. Compounds were eluted with water and acetonitrile containing 0.1 % formic acid, using a gradient (0.5-65 % B), in 3.8 min. The flow rate was 0.4 mL/min, and the run time was 5.8 min. Results: The calibration curves were linear across the tested concentration ranges (0.5-250, CZO, CEP, CTA, CTZ and FLU; 0.2-100, MER and TAZ; 0.1-50, CIP and LIN and 1-500 mg/L, PIP). The intra and inter-day imprecision was < 11 %. Accuracy ranged from 95 to 114 %. CTZ and MER showed ionization suppression while CIP showed ionization enhancement, which was normalized with the use of the internal standard. Conclusion: An LC-MS/MS method for simultaneous quantification of ten antimicrobials in human plasma was developed for routine TDM.

Mitigating analyte to stable isotope labelled internal standard cross-signal contribution in quantitative liquid chromatography-tandem mass spectrometry.

Background: Utilising stable isotope labelled internal standards (SIL-IS) in quantitative LC-MS/MS drug analysis is the most widely used approach to normalise for variability during sample quantification processes. However, compounds containing atoms such as Sulphur, Chlorine or Bromine, could potentially cause cross-signal contribution to the SIL-IS from the naturally occurring isotopes, resulting in non-linear calibration curves. A simple, novel method of mitigating the effect is presented here. It entails monitoring of a less abundant SIL-IS isotope, as the precursor ion, of a mass that has no/minimal isotopic contribution from the analyte isotopes. Methods: Experiments were conducted on two LC-MS/MS analysers: Waters Xevo TQ-S and Shimadzu 8050. Flucloxacillin (FLX) was used as an example. Two transitions were selected for FLX (m/z 454 â†’ 160 â†’ 295) and one for each of the SIL-IS isotopes (m/z 458 â†’ 160 for the isotope 457 g/mol and m/z 460 â†’ 160 for the isotope 459 g/mol). Assay biases were assessed at three SIL-IS concentrations: 0.7, 7 and 14 mg/L for each isotope. Results: When using the SIL-IS isotope m/z 458 â†’ 160 at a concentration of 0.7 mg/L, biases were up to 36.9 % on both instruments. Increasing the SIL-IS concentration to 14 mg/L, reduced the bias to 5.8 %. Using the less abundant isotope, m/z 460 â†’ 160, resulted in biases of 13.9 % at an SIL-IS concentration of 0.7 mg/L. Conclusions: Applying this method will mitigate cross-signal contribution from the analyte isotopes to the corresponding SIL-IS, minimise the use of SIL-IS, and, thereby, reduce overall cost.

Decarbonisation of eastern European economies: monitoring, economic, social and security concerns.

Background: Decarbonisation of the European economy is one of the main strategic goals of energy transition in the European Union (EU), which aims to become a leader in this process by 2050 and to include other European countries making thus the European continent the first carbon neutral region in the world. Although decarbonisation is an important goal of the EU, the models for monitoring the progress of this process have not yet been clearly defined, and views on the social, economic, and security implications in terms of prioritising decarbonisation are conflicting. The main objective of this paper is to determine the methodological correctness of the existing method of decarbonisation monitoring, to develop a new monitoring model indicating the differences in the EU and European countries that are non-EU and to point out the underlying social, economic and security implications that must certainly find their place in the decision-making process in this field. Results: The main results showed that there is no clearly defined model for monitoring the success of decarbonisation, while the indicators that are commonly used for this purpose make a model that, as the analysis shows-is methodologically incorrect. In the case of EU countries, the following indicators proved to be the most reliable: consumption-based CO 2 and share in global CO 2 . For non-EU countries, the best monitoring indicators are CO 2 per unit of GDP, consumption-based CO 2 , and renewable energy consumption. These indicators can explain 99% of the variance in decarbonisation success. Conclusions: The basic conclusion of the paper is that even before the implementation, the decarbonisation monitoring model should be defined and methodologically tested, and the use of a single model for all EU countries or for all countries is not recommended. It is proposed to simplify the monitoring model, with an emphasis on monitoring of consumption-based CO 2 , which proved to be the most efficient in all sampled countries. The current method of monitoring is based exclusively on environmentally related indicators while ignoring the fact that decarbonisation is associated with almost all aspects of development. The additional social, economic and security aspects need to be developed and included in the further monitoring process.

Measurement of 5- fluorouracil, capecitabine and its metabolite concentrations in blood using volumetric absorptive microsampling technology and LC-MS/MS.

5-fluorouracil (5-FU) and its oral formulation, capecitabine, are widely used in treating a range of malignancies, either alone or in combination with other antineoplastic drugs. Body surface area-based dosing is used for these agents, despite this approach leading to substantial variability in drug exposure and often resulting in either toxicity or treatment failure. Tailoring therapeutic regimens for individual patients using therapeutic drug monitoring (TDM) has been shown to significantly reduce toxicity and improve cancer outcomes. However, for optimum TDM, sample timing is crucial, along with the need for a venepuncture blood sample to obtain the plasma currently used for 5-FU measurement. In addition to complex blood sample handling requirements, large sample volume and frequent sampling required for pharmacokinetic analysis is another barrier to successfully implementing TDM in a healthcare setting. Microsampling is an alternative collection method to venepuncture, which, combined with the now readily available liquid chromatography mass spectrometry (LC-MS/MS) technology, overcomes the plasma-associated issues. It also has the significant advantage of enabling at home and remote sampling, thus facilitating 5-FU TDM in clinical practice. A LC-MS/MS method for simultaneous measurement of capecitabine, 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine and 5-FU using Mitra® microsampling devices for sample collection was developed. A Shimadzu 8060 LC-MS/MS equipped with electrospray ionisation source interface, operated in positive and negative ion modes, with reversed-phase chromatographic separation was employed for sample analysis. Samples were extracted from Mitra® devices using acetonitrile containing stable isotope-labelled internal standards, sonicated, evaporated under vacuum and resuspended in 0.1 % formic acid before injection into the LC-MS/MS. Chromatographic separation was on a Luna Omega Polar C18 (100 × 2.1 mm, 1.6 µm) column with gradient elution of 0.1 % formic acid in water and acetonitrile. Total run time was 5 min, with the injection volume of 1 µL. The intra and inter-day imprecision ranged from 3.0 to 8.1 and 6.3-13.3 % respectively. Accuracy ranged from 95 -114 % for all analytes. Lower limit of quantification with imprecision of < 19 % and accuracy between 89 and 114 % was 0.05 mg/L for 5-FU and 10 µg/L for other analytes. Assays were linear from 0.05 to 50 mg/L for 5-FU and 10-10,000 µg/L for all other analytes. Analytes were stable on Mitra® devices for up to 9 months at room temperature, 2 years at -30 ℃ and 3 days at 50 ℃. The method was successfully applied for the analysis of samples from patients undergoing cancer treatment with 5-FU and capecitabine. Microsampling using volumetric absorptive microsampling proved to be as reliable as conventional blood collection for 5-FU and capecitabine. This sampling technique may lead to less invasive and better-timed sample collection for TDM, supporting dose optimization strategy.

Chemical and microbial evaluation of biscuits made from wheat flour substituted with wheat sprouts.

The aim of this work was to produce biscuits from wheat flour substituted with different amounts of wheat sprout powder (2.5-7.5%). The biscuits were subjected to chemical, phytochemical, and microbial evaluations. The crude protein, fat, and ash contents and the energy value of the biscuits increased with increasing percentage of wheat sprout powder. Adding sprouts resulted in higher values of phenolics, alpha-tocopherol, and antioxidant activity. There was no statistically significant difference in the contents of total phenolics and alpha-tocopherol between biscuits supplemented with 5% sprouts and biscuits substituted with 7.5% sprouts. The phenolic content in biscuits containing 7.5% sprouts was 245 mg gallic acid equivalents (GAE)/100 g dm compared with 110 mg GAE/100 g dm in control biscuits. Antioxidant activity was the highest in biscuits substituted with 7.5% sprouts. All levels of substitution of wheat flour with wheat sprouts had an effect on the nutritional properties of biscuits, but the substitution level of 2.5-5% is recommended for the improvement of their sensorial properties. The biscuits produced had a low microbial load and were microbiologically safe. Escherichia coli, Salmonella spp., and sulfite-reduction clostridia were not detected in any sample during the period of investigation from 2 to 60 days of storage.

A Temporal Profile of pro-abstinence-oriented Constructs from The Modified Theory of Planed Behavior in a Slovenian Clinical Sample of Treated Alcoholics - an 18-year Follow-up.

INTRODUCTION: Using the modified Theory of Planned Behaviour (mTPB), different indicators of therapeutic success were studied to understand pro-abstinence behavioural orientation during an 18-year after-care period following a 3-month intensive alcoholism treatment. The indicators were: perceived needs satisfaction (NS), normative differential (ND), perceived alcohol utility (UT), beliefs about treatment programme benefits (BE) and behavioural intentions (BI). METHODS: The sample of 167 patients who consecutively started an intensive alcoholism treatment programme has been followed-up for 18 years, using standardised ailed instruments at the end of the treatment, and in the years 4-5, 9 and 18 of follow-up. The last data collection was completed by 32 subjects in 2010. The analysis followed the standard explore-analyse-explore approach. After the initial descriptive exploration of data, multivariate analysis of variance (MANOVA) in SPSS statistical package was set to explore between-groups and within-groups differences over time. RESULTS: At the between-group level, BI remained stable at the same level as at the end of the treatment programme, whereas BE and UT robustly changed over time and levelled off after 10 years of follow-up. NS and ND show a trend of pro-abstinent orientation and level off after 10 years of follow-up, although the trend is not significant. The same results were confirmed by the within-subject level. CONCLUSIONS: Studied constructs stabilised after ten years of follow-up, apart from BI. The latter suggests that BI level needed for completion of an intensive treatment programme suffices for the maintenance of abstinence when accompanied by the change in perception of alcohol usefulness.

Enhancement and Suppression of Ionization in Drug Analysis Using HPLC-MS/MS in Support of Therapeutic Drug Monitoring: A Review of Current Knowledge of Its Minimization and Assessment.

High-performance liquid chromatography coupled with tandem mass spectrometry is commonly used for quantitation of analytes in biological matrices, because of the selectivity, sensitivity, and high throughput offered by this technique. However, the presence of both suppression and enhancement of ionization (SEI) by matrix components is an increasingly recognized impediment to accurate results. The existence of SEI indicates that ionization efficiency is a result of the chemical environment seen by both the analyte and internal standard during ion formation. SEI is influenced by the type and the make of ion source used, mobile-phase composition, extent of sample preparation, and the ability to chromatographically separate other compounds that may influence ionization of the analyte and/or internal standard. A comprehensive review of the phenomenon of SEI in high-performance liquid chromatography coupled with tandem mass spectrometry was conducted, and a summary of salient papers relating to therapeutic agents in biological matrices is presented. Suggestions for approaches to minimize, normalize, or assess SEI and its deleterious effect on accuracy and sensitivity, and hence the validity of quantitative results, are provided. Consideration is also given to a strategy to test for SEI, including the number of samples from different sources that are required to adequately test for SEI.

The structure of paranoia in the general population.

BACKGROUND: Psychotic phenomena appear to form a continuum with normal experience and beliefs, and may build on common emotional interpersonal concerns. AIMS: We tested predictions that paranoid ideation is exponentially distributed and hierarchically arranged in the general population, and that persecutory ideas build on more common cognitions of mistrust, interpersonal sensitivity and ideas of reference. METHOD: Items were chosen from the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II) questionnaire and the Psychosis Screening Questionnaire in the second British National Survey of Psychiatric Morbidity (n = 8580), to test a putative hierarchy of paranoid development using confirmatory factor analysis, latent class analysis and factor mixture modelling analysis. RESULTS: Different types of paranoid ideation ranged in frequency from less than 2% to nearly 30%. Total scores on these items followed an almost perfect exponential distribution (r = 0.99). Our four a priori first-order factors were corroborated (interpersonal sensitivity; mistrust; ideas of reference; ideas of persecution). These mapped onto four classes of individual respondents: a rare, severe, persecutory class with high endorsement of all item factors, including persecutory ideation; a quasi-normal class with infrequent endorsement of interpersonal sensitivity, mistrust and ideas of reference, and no ideas of persecution; and two intermediate classes, characterised respectively by relatively high endorsement of items relating to mistrust and to ideas of reference. CONCLUSIONS: The paranoia continuum has implications for the aetiology, mechanisms and treatment of psychotic disorders, while confirming the lack of a clear distinction from normal experiences and processes.

Effects of a computer-based cognitive exercise program on age-related cognitive decline.

We developed a 'senior friendly' suite of online 'games for learning' with interactive calibration for increasing difficulty, and evaluated the feasibility of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can improve key aspects of cognitive ability with the aid of such games. Sixty community-dwelling senior volunteers were randomized to either an online game suite designed to train multiple cognitive abilities, or to a control arm with online activities that simulated the look and feel of the games but with low level interactivity and no calibration of difficulty. Study assessment included measures of recruitment, retention and play-time. Cognitive change was measured with a computerized assessment battery administered just before and within two weeks after completion of the six-week intervention. Impediments to feasibility included: limited access to in-home high-speed internet, large variations in the amount of time devoted to game play, and a reluctance to pursue more challenging levels. Overall analysis was negative for assessed performance (transference effects) even though subjects improved on the games themselves. Post hoc analyses suggest that some types of games may have more value than others, but these effects would need to be replicated in a study designed for that purpose. We conclude that a six-week, moderate-intensity computer game-based cognitive intervention can be implemented with high-functioning seniors, but the effect size is relatively small. Our findings are consistent with Owen et al. (2010), but there are open questions about whether more structured, longer duration or more intensive 'games for learning' interventions might yield more substantial cognitive improvement in seniors.

Heroin addict with gangrene of the extremities, rhabdomyolysis and severe hyperkalemia.

INTRODUCTION: Long-time consumption of narcotics leads to altered mental status of the addict. It is also connected to damages of different organic systems and it often leads to appearance of multiple organ failure. Excessive narcotics consumption or abuse in a long time period can lead to various consequences, such as atraumatic rhabdomyolysis, acute renal failure and electrolytic disorders. Rhabdomyolysis is characterized by injury of skeletal muscle with subsequent release of intracellular contents, such as myoglobin, potassium and creatine phosphokinase. In heroin addicts, rhabdomyolysis is a consequence of the development of a compartment syndrome due to immobilization of patients in the state of unconsciousness and prolonged compression of extremities, direct heroin toxicity or extremities ischemia caused by intraluminal occlusion of blood vessels after intraarterial injection of heroin. Severe hyperkalemia and the development of acute renal failure require urgent therapeutic measures, which imply the application of either conventional treatment or a form of dialysis. CASE REPORT: We presented a male patient, aged 50, hospitalized in the Emergency Center Kragujevac due to altered mental status (Glasgow Coma Score 11), partial respiratory insufficiency (pO2 7.5 kPa, pCO2 4.3 kPa, SpO2 89%), weakness of lower extremities and atypical electrocardiographic changes. Laboratory analyses, carried out immediately after the patient's admission to the Emergency Center, registered the following disturbances: high hyperkalemia level (K+ 9.9 m mol/L), increased levels of urea (30.1 mmol/L), creatinine (400 micromol/L), creatine phosphokinase--CK (12,0350 IU/L), CK-MB (2500 IU/L) and myoglobin (57000 microg/L), with normal levels of troponin I (< 0.01 microg/L), as well as signs of anemia (Hgb 92 g/L, Er 3.61 x 10(12)/L), infection (C-reactive proteine 184 microg/mL, Le 16.1 x 10(9)/L) and acidosis (base excess--18.4 mmol/L, pH 7.26. Initial examination of the patient revealed swelling and paleness of the right lower leg, signs of gangrene of the right foot and the 1st and the 4th toes of the left foot. The patient had normal values of arterial pressure (130/80 mmHg) and heart rate (64/min(-1)); roentgenographic lungs examination and computerized tomography (CT) brain examination did not reveal pathological changes in lung and brain parenchyma; toxicological analyses confirmed the presence of heroin in patient's organism. The patient was treated by intensive conventional treatment (infusion of crystalloid solutions, 8.4% solution of sodium bicarbonate, i.v. infusion of diuretics, calcium gluconate and short-acting insulin), and also by antibiotics and anticoagulants. Normalization of kalemia and fast regression of electrocardiographic changes were registered. The patient refused the suggested surgical treatment (fasciotomy, foot amputation). After stabilization of kidney function and improvement of his mental state, the patient agreed to undergo surgical procedure. Therefore, on the day 30 of hospitalization the above-knee amputation of the right leg was performed, and on the day 38 the transmetatarsal amputation of the left foot was carried out. After 46 days of hospital treatment, the patient was released and sent to home treatment. CONCLUSION: The routine laboratory diagnostics, which implies determining of the levels of potassium, urea, creatinine and CK in the serum of all hospitalized heroin addicts can contribute to timely detection of hyperkalemia and acute kidney weakness and undertaking of appropriate therapeutic measures.

The present global financial and economic crisis poses an additional risk factor for mental health problems on the employees.

BACKGROUND: The global financial and economic crisis starting in 2007 led to a deterioration of several socio-economic determinants of mental health. The aim of this cross-sectional study was to examine the impact of the present economic crisis on the depression and anxiety levels of the employed in the private and public sector in Slovenia. SUBJECTS AND METHODS: Altogether 1592 employees completed an internet based self-reported questionnaire. Data about perceived impact of the economic crisis, several socio-demographic, socioeconomic, and health parameters were collected. Depression symptoms were assessed by the Center for Epidemiological Studies-Depression Scale and anxiety symptoms by the Spielberger State-Inventory. Regression models were used 1) to explore the associations of the economic crisis with the level of depression and anxiety symptoms while controlling for some sociodemographic and work characteristic variables, and 2) to understand the relationship between some potentially important socioeconomic variables and the perception of the economic crisis. RESULTS: Depressive and anxiety scores were significantly increased among 590 (46.6%) employees being affected by the economic crisis. The level of depressive symptoms was significantly associated with perceived impact by the crisis, recent sick leave, reported injuries sustained at work, benzodiazepine and analgesic use, the lack of emotional support, and trust in crisis telephone lines. The level of anxiety symptoms yielded the robust association with the level of depression symptoms, reported injuries sustained on the way to work and education. CONCLUSIONS: The economic crisis poses an additional risk factor for mental health problems which clinicians should internalize and become more aware of them. Symptoms of depression and anxiety can be masked in high-utilizers of medical care with physical complaints or psychoactive drug use.

Early cannabis use and estimated risk of later onset of depression spells: Epidemiologic evidence from the population-based World Health Organization World Mental Health Survey Initiative.

Early-onset cannabis use is widespread in many countries and might cause later onset of depression. Sound epidemiologic data across countries are missing. The authors estimated the suspected causal association that links early-onset (age <17 years) cannabis use with later-onset (age > or =17 years) risk of a depression spell, using data on 85,088 subjects from 17 countries participating in the population-based World Health Organization World Mental Health Survey Initiative (2001-2005). In all surveys, multistage household probability samples were evaluated with a fully structured diagnostic interview for assessment of psychiatric conditions. The association between early-onset cannabis use and later risk of a depression spell was studied using conditional logistic regression with local area matching of cases and controls, controlling for sex, age, tobacco use, and other mental health problems. The overall association was modest (controlled for sex and age, risk ratio = 1.5, 95% confidence interval: 1.4, 1.7), was statistically robust in 5 countries, and showed no sex difference. The association did not change appreciably with statistical adjustment for mental health problems, except for childhood conduct problems, which reduced the association to nonsignificance. This study did not allow differentiation of levels of cannabis use; this issue deserves consideration in future research.

Cross-national differences in clinically significant cannabis problems: epidemiologic evidence from 'cannabis-only' smokers in the United States, Mexico, and Colombia.

BACKGROUND: Epidemiological studies show wide variability in the occurrence of cannabis smoking and related disorders across countries. This study aims to estimate cross-national variation in cannabis users' experience of clinically significant cannabis-related problems in three countries of the Americas, with a focus on cannabis users who may have tried alcohol or tobacco, but who have not used cocaine, heroin, LSD, or other internationally regulated drugs. METHODS: Data are from the World Mental Health Surveys Initiative and the National Latino and Asian American Study, with probability samples in Mexico (n = 4426), Colombia (n = 5,782) and the United States (USA; n = 8,228). The samples included 212 'cannabis only' users in Mexico, 260 in Colombia and 1,724 in the USA. Conditional GLM with GEE and 'exact' methods were used to estimate variation in the occurrence of clinically significant problems in cannabis only (CO) users across these surveyed populations. RESULTS: The experience of cannabis-related problems was quite infrequent among CO users in these countries, with weighted frequencies ranging from 1% to 5% across survey populations, and with no appreciable cross-national variation in general. CO users in Colombia proved to be an exception. As compared to CO users in the USA, the Colombia smokers were more likely to have experienced cannabis-associated 'social problems' (odds ratio, OR = 3.0; 95% CI = 1.4, 6.3; p = 0.004) and 'legal problems' (OR = 9.7; 95% CI = 2.7, 35.2; p = 0.001). CONCLUSIONS: This study's most remarkable finding may be the similarity in occurrence of cannabis-related problems in this cross-national comparison within the Americas. Wide cross-national variations in estimated population-level cumulative incidence of cannabis use disorders may be traced to large differences in cannabis smoking prevalence, rather than qualitative differences in cannabis experiences. More research is needed to identify conditions that might make cannabis-related social and legal problems more frequent in Colombia than in the USA.

[Successful treatment of polymedicamentous poisoning with metoprolol, diltiazem and cilazapril].

INTRODUCTION: Poisoning caused by drugs with cardiodepressive effects is an urgent condition in medicine which is associated with high mortality rate regardless of modern therapeutic methods. Accidental or intentional poisoning whit these drugs produces heart activity depression and cardiovascular collapse as consequences. Current therapy for severe poisoning caused by beta-blockers and calcium channel blockers includes both unspecific and specific antidote therapy whit glucagon, as well as application of adrenergic drugs, calcium, phosphodiesterase inhibitors and hyperinsulinemia/euglycemia therapy. However, even whit the application of these drugs, prompt measures of unspecific detoxication therapy and cardiopulmonary reanimation are crucial for survival of patients with severe poisoning. CASE REPORT: A 28-year-old female patient was hospitalized for cardiogenic shock and altered state of conscioussnes (Glasgow coma score = 4), caused by acute poisoning with 2 g of metoprolol (Presolol), 1.8 g of diltiazem (Cortiazem) and 50 mg of cilazapril (Zobox). Prolonged cardiopulmonary resuscitation was applied during the first 16 hours of hospitalization, including administration of crystaline solutions (8 L), 17 mg of adrenaline, 4 mg of atropine, 4 mg of glucagone and 1.6 g of dopamine, with electro-stimulation by temporary pacemaker and mechanical ventilation. In a defined time period, normalized state of consciousness was registered, mechanical ventilation was stopped and normal heart activity and hemodynamic stability were accomplished. During hospitalization the patient was treated for mild pneumonia and after ten days, completely recovered, was released and sent to home treatment. CONCLUSION: Prompt measures of cardiopulmonary resuscitation and multidisciplinary treatment in intensive care units significantly increase the chances of complete recovery of a patient with severe poisoning caused by drugs with cardiodepressive efects.

Physical health problems among patients seeking treatment for alcohol use disorders: a study in six European cities.

The present study investigates physical health problems among patients with alcohol use disorders at alcohol treatment agencies in six European cities. The sample comprised 315 patients with a primary alcohol use disorder. Data were collected at admission to treatment using a structured research protocol, and ratings were made by a medically qualified physician subsequent to a physical examination of the patient. Physical health problems were extremely common: 79% of the sample had at least one problem, and 59% had two or more problems. Health problems were often serious, and 60% had at least one health problem that required treatment. The most common problems were gastrointestinal and liver disorders, but about a quarter of the sample had cardiovascular or neurological problems. Frequency of drinking, duration of alcohol use disorder, and severity of alcohol dependence were associated with increased physical morbidity. Current smoking status and age were also associated with poorer physical health. Older drinkers had more physical health problems although they were less severely alcohol dependent than their younger counterparts. The high prevalence of physical health problems among problem drinkers provides opportunities of screening for alcohol use disorders not only in specialist alcohol treatment services but also in other health-care settings. It is recommended that alcohol treatment agencies should provide a full routine health screen of patients at admission to treatment with provision or referral to appropriate treatment.