Total costs of inpatient treatment for COVID-19 in a tertiary hospital in Serbia.

BACKGROUND: Our study aimed to identify the total costs of inpatient treatment for coronavirus disease 2019 (COVID-19) in a tertiary institution in Serbia, an upper-middle-income country in Southeast Europe. METHODS: An observational, retrospective, cost-of-illness study was performed from the perspective of the National Health Insurance Fund and included a cohort of 78 females and 118 males admitted to the COVID-19 ward units of a tertiary center during the first wave of the pandemic. RESULTS: The median of the total costs in the non-survivors subgroup (n =43) was 3,279.16 Euros [interquartile range (IQR): 4,023.34; range: 355.20-9,909.61) which is higher than in the survivors (n =153) subgroup 747.10 Euros (IQR: 1,088.21; 46.71-3,265.91). The cut-off value of 156.46 Euros regarding the total costs per day was estimated to have 95.3 % sensitivity and 91.5 % specificity for predicting patients' dismal prognosis, with the area under the curve (AUC) of 0.968 (95 % confidence interval: 0.940-0.996, p <0.001). CONCLUSIONS: Direct medical inpatient treatment costs for COVID-19 represent a significant economic burden. The link between increased costs and an ultimate unfavorable outcome should be further explored.HIPPOKRATIA 2022, 26 (2):62-69.

The influence of CYP2C8*3 on carbamazepine serum concentration in epileptic pediatric patients.

The aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

Effect of physical effectiveness on digestibility of ration for cows in early lactation.

A study was conducted to investigate the effects of a diet particle size on nutrient digestibility in cows in early lactation. Treatments were diets with forage to concentrate ratio 43:57% in diet dry matter, with four different physically effective fibres (peNDF) content based on different cut length of corn silage and alfalfa haylage. The physical effectiveness factors (pef) and peNDF content of TMRs (total mixed ration) were determined using Penn State Particle Separator (PSPS) with two (pef8.0 , peNDF8.0) or three (pef1.18, peNDF1.18) sieves. The reducing of cut length of forages and particle size of diets did not affect on dry matter intake, while decreased peNDF intake by 16.34 and 8.83%, for peNDF8.0 and peNDF1.18 respectively. Apparent total tract digestibility of the nutrients was measured using two indicators: acid insoluble ash (AIA) and acid detergent insoluble lignin (ADL). Decreasing of forages cut length significantly increased apparent total tract digestibility of neutral detergent fibre (NDF) from 48.39% to 53.84% and from 53.9% to 58.66%, of crude protein from 73.96% to 79.24% and from 71.56% to 77.90%, with contemporary decreasing of non-fibre carbohydrate from 90.89% to 84.81% and from 91.99% to 86.80%, with AIA or ADL as indicator respectively. Dietary value of net energy for lactation (NEL) and energy intake was not affected by the peNDF content of the diet.

Advantages of isolated application of fibrin glue over suture in preservation of second-grade spleen lesion.

OBJECTIVES: The aim of this procedure was to assess the safety and efficiency of glue application in the treatment of lienal second-degree lesions, compared with traditional suture method of treatment. BACKGROUND: The spleen is the most frequently injured intra-abdominal structure regardless of injury mechanisms. Fibrin glue is a useful bio-adhesive for safe and efficient treatment of diffuse parenchymatous spleen haemorrhages. METHODS: Seventy dogs under intravenous anaesthesia were subdued to spleen incision in length of 5 cm and depth of 2 cm. Forty animals from the experimental group were treated with fibrin glue preservation, and 30 animals from the control group were treated with suture. Removed spleens were histologically analyzed. No animal was sacrificed. RESULTS: The application of fibrin glue allowed reparation to be accomplished in all cases. The effectiveness of primary repair was registered in 95 %, with only 5 % of cases requiring an application of fibrin omentoplasty. Secondary bleeding was registered only in 1 (2.5 %) case. Preservation with suture is primarily effective only in 40 %, requires additional repair in 23 %, and even 37 % of cases are not feasible. This method is characterized by mortality of 21 %, secondary haemorrhage (32 %), appearance of focal necrosis (42 %) and abscess (11 %). CONCLUSIONS: Application of FG is a method of choice in cases of second-degree transcapsular spleen lesions and it has a considerable advantage over suture (Tab. 4, Fig. 6, Ref. 24).

[Lead point as a poor prognostic factor in the therapy of invagination in children].

UNLABELLED: Invagination is specific form of bowel opstruction that is seen in 1-4 children per 1000 births, usually in the period from 3 to 12 months of age. In 90-95 % reason for invagination in unknown so we called this forms idiopathic. In 5-10% invagination is caused by specific leading point. THE AIM of this retrospective study was to determinate prognostic valye of used biochemical tests (hemograms, glucosa, electrolites ( levels of Na+, K+, Ca+ and Cl-) and to prove bad influence of existing "leading point" in therapy of invagination (weather it will be surgical or hydrostatic desinvagination). METHODS: We analised 65 patients with invagination. We devided all our patients into 2 groups: first group consisted patients with idiopathic forms of invagination, and the other one were patients with invagination coused by specific leading point. RESULTS proved that leading point in invagination has great implications on clinical presentation, laboratory results, diagnostic and therapeutic procedure, and finaly in prognosis.

Extracorporeal shock wave lithotripsy in the management of pediatric urolithiasis.

The main objective of this paper was to evaluate the efficacy and safety of the management of pediatric urolithiasis by extracorporeal shock wave lithotripsy (ESWL). Between November 1988 and July 2000, 165 renal stones, 53 ureteral stones, and 5 bladder stones were treated in 126 pediatric patients using Siemens Lithostar lithotriptor. The ESWL treatments ranging from 1 to 7 were needed per patient (mean: 2.1). One ESWL session was performed for 49.6% of stones, two for 24.6%, three for 13.0 %, four for 5.6% and > 4 for 8.2%. The success rate for renal stone units (asymptomatic fragments less than 4 mm) was 88.2%, stone-free rate was 49.0%. The stone-free rate for ureteral stone units was 87.5%, but was 75% for bladder stones. The overall results of ESWL treatment in 126 children was satisfactory: the success rate was 90.5%, stone-free rate was 51.6%, residual fragments > 4 mm were 9.5%. General anesthesia was required in 65 children (136 treatments) under the age of 10, and only in 18 children (40 treatments) in the age 11-14. Auxiliary procedures, such as double J stent and percutaneous nephrostomy (PCN) were used in 19 and 7 patients, respectively. Perirenal hematoma in one patient and hematomas in enteric wall in another one patient were the only major complications managed conservatively without consequences. Low energy lithotripsy with the Siemens Lithostar in our series of pediatric patients was safe and relatively effective.

Axillary recurrence after modified radical mastectomy.

Optimal management for axillary recurrence is poorly understood. The aim of this study was to evaluate the risk factors for overall survival in the patients with axillary recurrence. Data of 1098 patients were collected from breast cancer registers from Clinic for Oncology Nis between 1990-1995. All patients underwent modified radical mastectomy. Axillary recurence was diganosed in 43 (3.92%) patients. Most patients were presented with a localized, palpable axillary mass 30 (69.77%). Cox multivariate analysis of prognostic factors for breast cancer-specific survival showed that node status HR 4.69 (1.50 to 14.72), tumor size HR 3.18 (0.90 to 11.26) and axillary radiotherapy HR 1.99 (0.69 to 5.75) had statistically significant effect on breast cancer mortality. Log-rank (54.21 p < 0.001) analysis showed significant difference for overall survival among women with a axillary recurrence based on different cancer stages. Tumor size and node status were the most important prognostic factors in women with axillary recurrence.

Separation of peptides utilizing ultrahigh-temperature micellar electrokinetic chromatography.

The use of ultrahigh column temperatures, up to 110 degrees C, in micellar electrokinetic capillary chromatography was investigated. The number of plates generated per unit time increased from 0.22 to 12.8 plates/s for separations at 15 degrees C and 110 degrees C, respectively. Ultrahigh-temperature micellar electrokinetic capillary chromatography was used for the separation of cyclic undecapeptides (cyclosporins). A minimum resolution of 1.39 was calculated for a critical peak pair at 110 degrees C, which is more than a 50% increase over resolution generated at 40 degrees C. During a run time of more than 90 min at 110 degrees C and at pH 9.3, no sample degradation or solvent boiling was observed.

Evaluation of ODS-AQ stationary phase for use in capillary electrochromatography.

The aim of this study was to evaluate the applicability of ODS-AQ packing material as a stationary phase in capillary electrochromatography (CEC). The electroosmotic flow created on an ODS-AQ stationary phase was measured at different mobile phase compositions and at different column temperatures. It was observed that the electroosmotic flow generated in the column increased by 50% when the temperature of the system was raised from 20 degrees C to 60 degrees C, while all other conditions were kept constant. The electroosmotic flow produced by the ODS-AQ stationary phase was found to be comparable to the flow generated in a column packed with Nucleosil bare-silica material. In addition, a set of polar compounds (D-lysergic acid diethylamide derivatives) was utilized to determine the influence of temperature and mobile phase composition on their chromatographic behavior on an ODS-AQ stationary phase in a CEC mode. A linear relationship between the solute retention factor and column temperatures was seen over the temperature range studied (20 degrees C to 60 degrees C). A quadratic function was used to describe the changes in the solute retention factors with variation of acetonitrile concentration in the mobile phase.

High temperature and temperature programming in capillary electrochromatography.

In electrochromatography, solvent electrophoretic mobility and solute partitioning are temperature dependent processes. If temperature variations are controlled, solute selectivity and analysis times can be tailored. In this study the feasibility of temperature programming in capillary electrochromatography (CEC) was demonstrated using a reversed-phase CEC mode. The outcome of programmed separations was compared with isothermal, isocratic and isorheic (constant flow) separations. The combined effects of column temperature and mobile phase flow-rate changes during the separation run, resulted in up to a 50% reduction in the separation run time, without adversely affecting the quality of separation. For capillary electrochromatography, temperature programming may be a valuable alternative to solvent programming modes because of the great technical difficulties associated with carrying out solvent gradient elution.

Reversed-phase liquid chromatographic separation of complex samples by optimizing temperature and gradient time I. Peak capacity limitations.

The separation of samples that contain more than 15 to 20 analytes (n > 15-20) is typically difficult and usually requires gradient elution. We have examined the reversed-phase liquid chromatographic separation of 24 samples with 8 < or = n < or = 48 as a function of temperature T and gradient time tG. The required peak capacity was determined for each sample, after selecting T and tG for optimum selectivity and maximum sample resolution. Comparison of these results with estimates of the maximum possible peak capacity in reversed-phase gradient elution was used to quantify the maximum value of n for some required sample resolution (when T and tG have been optimized). These results were also compared with literature studies of similar isocratic separations as a function of ternary-solvent mobile phase composition, where the proportions of methanol (MeOH), tetrahydrofuran (THF) and water were varied simultaneously. This in turn provides information on the relative effectiveness of these two different method development procedures (optimization of T and tG vs. % MeOH and % THF) for changing selectivity and achieving maximum resolution.

Reversed-phase liquid chromatographic separation of complex samples by optimizing temperature and gradient time II. Two-run assay procedures.

By optimizing column temperature T and gradient time tG, complex samples can often be separated by means of reversed-phase high-performance liquid chromatography (RP-LC). Conclusions reached in Part I suggest that the complete separation of such samples will be difficult, however, when more than 15-20 components are present in the sample. An alternative approach is to carry out two separations with different conditions (T, tG) in each run. The combination of results from these two runs then allows the total analysis of the sample, providing that every sample component is adequately resolved in one run or the other. Examples of this approach, carried out by means of computer simulation, are shown here for several samples of varying complexity. Also considered is the ability of a single separation where T and tG are optimized to enable the separation and analysis of one or more individual sample components from complex mixtures (e.g., drugs in animal plasma), including the resolution of isomeric compounds from each other.

Simultaneous variation of temperature and gradient steepness for reversed-phase high-performance liquid chromatography method development. I. Application to 14 different samples using computer simulation.

The optimized reversed-phase HPLC separation of 14 different samples is reported, based on simultaneous changes in temperature and gradient steepness. Four experimental runs are required for each sample, following which preferred conditions can be predicted using computer simulation software (DryLab). The overall accuracy and effectiveness of this method development approach is discussed, with particular attention to the use of resolution maps provided by the software. These maps are useful for maximizing resolution for the total sample, for optimizing the separation of a smaller number of selected sample compounds, and as an initial step in the separation of more demanding samples.

HPLC separation of oligonucleotides in isocratic and temperature-programming mode.

In HPLC, temperature programming and isocratic separation were investigated for resolving a mixture of nucleotide polymers. A mixture of short oligonucleotides pd(A)(12)(-)(18) was resolved in less than 4 min by utilizing isocratic separation. The method is sensitive to organic modifier concentration; a 0.5% change of organic modifier in the mobile phase leads to more than doubling of the total analysis time. Temperature programming was used to optimize the separation of larger oligonucleotides pd(A)(25)(-)(30) and pd(A)(40)(-)(60). When the column temperature was changed by programming during the separation, the analysis time was 75% less than for an isocratic/isothermal run. The low amounts of ion-pairing agent in the mobile phase (between 5 and 10 mM) make these methods suitable for electrospray ionization mass spectrometry.

Combination of column temperature gradient and mobile phase flow gradient in microcolumn and capillary column high-performance liquid chromatography.

The combination of several gradient modes (solvent, temperature, and flow programming) is rarely used in HPLC analysis. In this work, the separations obtained utilizing simultaneous flow and temperature gradient in capillary column and microcolumn HPLC were compared with the separations performed under isocratic, isothermal, and isorheic (constant flow) conditions. When the mobile phase flow rate and the column temperature were changed simultaneously during the separation run, the analysis time was shortened up to 50%, while the separation efficiency was preserved. The separations obtained with combined temperature and flow gradients show high reproducibility (relative standard deviation <2.0%), comparable to the reproducibility normally seen with a mobile phase gradient. For capillary HPLC, simultaneous temperature and flow programming is the method of choice because of the great technical difficulties involved in performing solvent gradient elution.

Combined use of temperature and solvent strength in reversed-phase gradient elution. I. Predicting separation as a function of temperature and gradient conditions.

It has been shown previously that computer simulation based on two initial experiments can predict separation in reversed-phase gradient elution as a function of gradient conditions (gradient steepness, gradient range and gradient shape) and column conditions (column length, flow-rate and particle size). The present study extends this capability for changes in temperature. Four initial experiments (two different gradient times, two different temperatures) provide input data that allow predictions of separation as a function of temperature as well as gradient and column conditions. A semi-empirical relationship, tR = a + bT, is able to relate gradient retention time tR to column temperature T (other conditions constant). The accuracy of this approach has been evaluated for 102 solutes and a variety of experimental conditions, including the use of five different HPLC instruments (four different models).