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Introduction: Prescribing trends in maintenance therapy of patients with primary psychotic disorders (PSD) may vary worldwide. Present study aimed to investigate prescription patterns in a sample of outpatients with PSD from Serbia.Methods: In a sample of 73 PSD outpatients we analysed the rate of antipsychotic polypharmacy and psychotropic polypharmacy, concomitant continual benzodiazepine use, and associations between therapy, psychotic symptoms and quality of life.Results: Maintenance therapy (median daily dose 321 mg of chlorpromazine equivalents) predominantly consisted of monotherapy with second generation antipsychotics (45.2%), followed by antipsychotic polypharmacy based on first and second generation combination (25.0%). The median number of psychotropic drugs was 3. Benzodiazepines were continually prescribed to more than 60% of patients (mean daily dose 2.9 ± 2.0 mg lorazepam equivalents). Patients with benzodiazepine use had significantly more psychotropic medications and more antipsychotic polypharmacy, poorer quality of life and more severe psychopathology in comparison to another group.Conclusion: The present study demonstrated new information regarding the prescription patterns of psychotropic drugs in outpatients with PSD in Serbia, amplified with clinically relevant information. This study also revealed distinct prescription patterns concerning antipsychotic/benzodiazepine polypharmacy. Overall, such findings are likely to contribute to improving clinical practice and care for patients with PSD in general.KeypointsPresent exploratory research aimed to elucidate trends of antipsychotics polypharmacy and concomitant use of psychotropic medications including benzodiazepines in the maintenance treatment of outpatients with schizophrenia and other psychotic disorders, amplified with clinically relevant information (symptoms and quality of life).'Antipsychotic (AP) polypharmacy' was defined as concurrent use of more than one AP for at least 1 month; 'Psychotropic polypharmacy' was defined as the combination of AP and a different class of psychotropic drugs medication for at least one month.The median number of prescribed psychotropic drugs was 3 (mean 3.1 ± 1.1) and the average AP daily dose was moderate (median 321 mg of chlorpromazine equivalents). However, the rates of AP polypharmacy (45.2%) and benzodiazepine prescription on a continual basis (>60%) found in our sample could be considered relatively high.Outpatients with higher AP daily dose and higher BPRS symptom score were receiving more benzodiazepines.For improvement of the local, as well as general clinical practice and care for patients with psychotic disorders, and for education in psychiatry, such analyses need to be done on a regular basis and on larger samples.
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Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Pacientes Ambulatoriais/estatística & dados numéricos , Polimedicação , Padrões de Prática Médica/estatística & dados numéricos , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Prevenção Secundária/estatística & dados numéricos , Adulto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Sérvia , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Due to the pandemic, the entire staff employed in healthcare institutions were directly exposed to longer working hours and unstable working conditions. Based on these facts, the research in this article aims to find out more about employees' satisfaction with working conditions and management's engagement in preserving their health and safety. Thus, a multiple-criteria decision analysis (MCDA) model based on the analyzed attitudes and opinions of employees was formed to reveal the interdependencies between working conditions resulting from the undertaken management activities, employee satisfaction and workplace safety. The results show that both nurses and drivers were least satisfied with working conditions during the pandemic while indicating those workplaces to be the most endangered. Additionally, the proposed model can be successfully applied to any type of organization to identify insufficiently effective management activities, address them accordingly and thereby improve the level of employee satisfaction.
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COVID-19 , Instalações de Saúde , Satisfação no Emprego , Humanos , COVID-19/epidemiologia , Adulto , Feminino , Masculino , Local de Trabalho/psicologia , Inquéritos e Questionários , Pandemias , Saúde Ocupacional , SARS-CoV-2 , Pessoa de Meia-IdadeRESUMO
Biopolymers represent a great resource for the development and utilization of new functional materials due to their particular advantages such as biocompatibility, biodegradability and non-toxicity. "Intelligent gels" sensitive to different stimuli (temperature, pH, ionic strength) have different applications in many industries (e.g., pharmacy, biomedicine, food). This review summarizes the research efforts presented in the patent and non-patent literature. A discussion was conducted regarding biopolymer-based hydrogels such as natural proteins (i.e., fibrin, silk fibroin, collagen, keratin, gelatin) and polysaccharides (i.e., chitosan, hyaluronic acid, cellulose, carrageenan, alginate). In this analysis, the latest advances in the modification and characterization of advanced biopolymeric formulations and their state-of-the-art administration in drug delivery, wound healing, tissue engineering and regenerative medicine were addressed.
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The objectives of this study are the synthesis of thermosensitive poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate), p(NiPAm-HPMet), hydrogels and the analysis of a drug-delivery system based on piroxicam, as a model drug, and synthesized hydrogels. A high pressure liquid chromatography method has been used in order to determine both qualitative and quantitative amounts of unreacted monomers and crosslinkers from polymerized hydrogels. Swelling kinetics and the order of a swelling process of the hydrogels have been analyzed at 10 and 40 °C. The copolymers' thermal properties have been monitored by the differential scanning calorimetry (DSC) method. DSC termograms have shown that melting occurs in two temperature intervals (142.36-150.72 °C and 153.14-156.49 °C). A matrix system with incorporated piroxicam has been analyzed by using FTIR and SEM methods. Structural analysis has demonstrated that intermolecular non-covalent interactions have been built between side-groups of copolymer and loaded piroxicam. Morphology of p(NiPAm-HPMet) after drug incorporation indicates the piroxicam presence into the copolymer pores. Kinetic parameters of the piroxicam release from hydrogels at 37 °C and pH 7.4 indicate that the fluid transport mechanism corresponds to Fickian diffusion. As a result, formulation of thermosensitive p(NiPAm-HPMet) hydrogels with incorporated piroxicam could be of interest for further testing as a drug carrier for modulated and prolonged release, especially for topical administration.
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The aim of this study was to examine homopolymeric poly(N-isopropylacrylamide), p(NIPAM), hydrogels cross-linked with ethylene glycol dimethacrylate as carriers for sulfanilamide. Using FTIR, XRD and SEM methods, structural characterization of synthesized hydrogels before and after sulfanilamide incorporation was performed. The residual reactants content was analyzed using the HPLC method. The swelling behavior of p(NIPAM) hydrogels of different crosslinking degrees was monitored in relation to the temperature and pH values of the surrounding medium. The effect of temperature, pH, and crosslinker content on the sulfanilamide release from hydrogels was also examined. The results of the FTIR, XRD, and SEM analysis showed that sulfanilamide is incorporated into the p(NIPAM) hydrogels. The swelling of p(NIPAM) hydrogels depended on the temperature and crosslinker content while pH had no significant effect. The sulfanilamide loading efficiency increased with increasing hydrogel crosslinking degree, ranging from 87.36% to 95.29%. The sulfanilamide release from hydrogels was consistent with the swelling results-the increase of crosslinker content reduced the amount of released sulfanilamide. After 24 h, 73.3-93.5% of incorporated sulfanilamide was released from the hydrogels. Considering the thermosensitivity of hydrogels, volume phase transition temperature close to the physiological temperature, and the satisfactory results achieved for sulfanilamide incorporation and release, it can be concluded that p(NIPAM) based hydrogels are promising carriers for sulfanilamide.
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The purposes of this study are the polymerization of temperature-sensitive copolymers based on N-isopropyl acrylamide and 10 mol % of 2-hydroxypropylmethacrylate, characterisations of their thermal, morphological and swelling properties, as well as the analysis of potential application in drug-delivery systems. Acetaminophen, the representative of non-steroidal anti-inflammatory drugs, was used as a model drug in this study. It is a common pain relief drug, which is also used for fever treatment. However, oral administration comes with certain health risks, mainly the overdose and frequent administration of up to four times a day. The goal of applying temperature-sensitive hydrogel is to enable extended administration once a day, depending on the body temperature. The swelling behavior of the obtained poly(N-isopropyl acrylamide-co-2-hydroxypropylmethacrylate) (p(NIPA/HPMA)) hydrogels and their temperature-sensitivity, kinetics and order of swelling processes at 18 and 38 °C were analyzed. The thermal properties of these hydrogels were observed by the DSC method, and the obtained thermograms showed both melting and glass transitions. The drug delivery system of p(NIPA/HPMA) hydrogels with loaded acetaminophen was analyzed using scanning electron microscopy and Fourier transform infrared spectroscopy methods. Structural analysis of FTIR spectra indicates that non-covalent intermolecular interactions of the type of hydrogen bonds were formed among functional groups of acetaminophen and side-chains of p(NIPA/HPMA) hydrogels. The surface structure of p(NIPA/HPMA) hydrogels after drug loading indicates the acetaminophen presence into the pores of the hydrogel network, and their loading efficiency was higher than 92%. Qualitative and quantitative analysis of acetaminophen, determined by the high-pressure liquid chromatography method, showed that about 90-99% of the loaded amount was released from p(NIPA/HPMA) hydrogels within 24 h. Kinetic parameters of the acetaminophen release under simulated gastrointestinal conditions were determined. Based on obtained results, the drug delivery system of temperature-sensitive p(NIPA/HPMA) hydrogels with loaded acetaminophen could be suitable for additional investigation for modulated drug administration, e.g., for extended drug administration.
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Curcumin comes from the plant species Curcuma longa and shows numerous pharmacological activities. There are numerous curcumin formulations with gels or cyclodextrins in order to increase its solubility and bioavailability. This paper presents the formulation of complex of curcumin with 2-hydroxypropyl-ß-cyclodextrin in a thermosensitive hydrogel, based on N-isopropylmethacrylamide and N-isopropylacrylamide with ethylene glycol dimethacrylate as a crosslinker. The product was characterized by chemical methods and also by FTIR, HPLC, DSC, SEM, XRD. The results show that synthesis was successfully done. With an increase in the quantity of crosslinker in the hydrogels, the starting release and the release rate of curcumin from the formulation of the complex with hydrogels decreases. The release rate of curcumin from the gel complex formulation is constant over time. It is possible to design a formulation that will release curcumin for more than 60 days. In order to determine the mechanism and kinetics of curcumin release, various mathematical models were applied by using the DDSolver package for Microsoft Excel application. The Korsmeyer-Peppas model best describes the release of curcumin from the gel formulation of the complex, while the values for the diffusion exponent (0.063-0.074) shows that mechanism of the release rate is based on diffusion.
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The aim of this study is to investigate the possibility of using electrospun polylactide (PLA) fibers as a carrier of the phytoestrogen biochanin A. Polylactide fibers were prepared with different contents of biochanin A by using an electrospinning method at specific process parameters. The obtained electrospun polylactide fibers, as carriers of biochanin A, were characterized by means of different methods. The presented results showed that the mechanical properties of PLA have not changed significantly in the presence of biochanin A. Scanning electron microscopy showed that the fine fiber structure is retained without visible deformations and biochanin A crystals on the surface of the fibres. The analysis by infrared spectroscopy showed that there are no strong interactions between polylactide and biochanin A molecules, which is a good prerequisite for the diffusion release of biochanin A from PLA fibers.The release of biochanin A from PLA fibers in buffer solution pH 7.4 at 37 °C was monitored by applying the HPLC method. The rate and time of the release of biochanin A from PLA fibers is in correlation with the amount of the active ingredient in the matrix of the carrier and follows zero-order kinetics. PLA fibers with biochanin A exhibit concentration-dependent activity on proliferation and migration of L929 fibroblasts in direct culture system in vitro, and proved to be suitable for a potential formulation for use in wound healing.
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In this study, poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate) hydrogels were synthesized using free radical initiated copolymerization method. Four hydrogels with different cross-linker concentrations were prepared. Semi-crystalline, cross-linked copolymer networks were confirmed by FTIR, SEM and XRD analysis. Variation of swelling behaviour was monitored gravimetrically and thermo-responsiveness has been noticed. An application of synthesized thermo-responsive hydrogels as carriers for the modulated release of anti-inflammatory model drug was investigated. Moreover, naproxen loading into these hydrogels was also determined using FTIR, SEM and XRD techniques and release was analyzed using HPLC method at simulated physiological conditions. Swelling kinetic and mechanism of water transport, as well as diffusion of naproxen through the hydrogels were analyzed. Thus, the aim of this work was to study various compositions of obtained hydrogels and their possibility of application as a thermo-responsive carrier for prolonged naproxen release in order to evaluate as a potential candidate for drug carrier in future pharmaceutical applications.
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The temperature- and pH-responsive poly(N-isopropylacrylamide-co-acrylic acid), p(NIPAM-co-AA), copolymer was synthesized by free radical polymerization and examined as a carrier for modified release of biochanin A. Biochanin A is a biologically active methoxylated isoflavone which exhibits estrogenic and other pharmacological activities. Due to its poor aqueous solubility and extensive first-pass metabolism, biochanin A has low bioavailability. The aim of this work was to incorporate biochanin A into the synthesized p(NIPAM-co-AA) copolymer and to examine its release at the body temperature and pH values that correspond to pH values of vaginal and rectal cavities. The amount of released biochanin A was monitored by the ultra-visible spectroscopy (UV-Vis) method. The structure of synthesized p(NIPAM-co-AA) copolymer and copolymer with incorporated biochanin A were characterized by using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) methods. The content of residual monomers in the synthesized copolymer was analyzed by using the high-pressure liquid chromatography (HPLC) method. The swelling behavior of p(NIPAM-co-AA) copolymer was monitored in relation to the temperature and pH values of the surrounding medium. For modelling the process of p(NIPAM-co-AA) copolymer swelling, the full three-level factorial design was applied.
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Essential oils (EOs) have historically been used for centuries in folk medicine, and nowadays they seem to be a promising control strategy against wide spectra of pathogens, diseases, and parasites. Studies on free-living nematodes are scarce. The free-living microbivorous nematode Panagrolaimus sp. was chosen as the test organism. The nematode possesses extraordinary biological properties, such as resistance to extremely low temperatures and long-term survival under minimal metabolic activity. Fifty EOs from 22 plant families of gymnosperms and angiosperms were tested on Panagrolaimus sp. The aims of this study were to investigate the in vitro impact of EOs on the psychrophilic nematode Panagrolaimus sp. in a direct contact bioassay, to list the activity of EOs based on median lethal concentration (LC50), to determine the composition of the EOs with the best nematicidal activity, and to compare the activity of EOs on Panagrolaimus sp. versus plant parasitic nematodes. The results based on the LC50 values, calculated using Probit analysis, categorized the EOs into three categories: low, moderate and highly active. The members of the laurel family, i.e., Cinnamomum cassia and C. burmannii, exhibited the best nematicidal activity. Aldehydes were generally the major chemical components of the most active EOs and were the chemicals potentially responsible for the nematicidal activity.
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Poly(N-isopropylmethacrylamide) (p(NiPMAm)) is one of the lesser known homopolymers that has significant potential for designing new "intelligent" materials. The aims of this work were the synthesis a series of cross-linked p(NiPMAm) hydrogels by the free radical polymerization method and the application of gamma-ray radiation for additional cross-linking. The synthesized p(NiPMAm) hydrogels were structurally characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The amount of unreacted monomers was analyzed using high pressure liquid chromatography (HPLC) to evaluate conversion of monomers into polymers. The swelling behavior was monitored in dependence of pH and temperature changes. The previous aim of gamma-ray radiation was the further the cross-linkage of the obtained hydrogel sample in the gelatinous, paste-like state, but the gamma-ray radiation caused decomposition. After absorbing irradiation doses, they transformed into the liquid phase. The results obtained by the gel permeation chromatography (GPC) method indicated that only oligomers and monomers were present in the irradiated liquid material, without molecules with a higher average molar mass, i.e., that the decomposition of the hydrogels occurred. Additionally, the irradiated liquid material was analyzed using the static headspace gas chromatography mass spectrometry (HSS-GC/MS) and gas chromatography/flame ionization detection (HSS-GC/FID) methods. The presence of unchanged initiator molecule and a dominant amount of four new molecules that were different from homopolymers and the reactant (monomer and cross-linker) were determined.
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This study presents 3 case reports of patients who experienced anginous pain during treatment with capecitabine. The interruption of capecitabine and sublingual or intravenous nitroglycerine treatment lead to recovery. Rechallenge of capecitabine with dose reduction of 30% lead to repeated anginous pain in 2 patients. Treatment with capecitabine had been replaced with weekly bolus 5FU-LV, without further cardiotoxicity. The literature contains data from about 50 patients who experienced cardiotoxicity during capecitabine treatment. The most frequent manifestations of capecitabine cardiotoxicity included: anginous pain in 38/53 (71.7%), arrhythmia in 6/53 (11.3%), myocardial infarction in 6/53 (11.3%). Cardiotoxicity of capecitabine lead to death in 6/53 (11.3%) patients. Risk factors for cardiotoxicity are associated with the grade 4 and the fatal outcome of cardiotoxicity (p = 0.035, p = 0.015), but not with the symptom recurrence upon capecitabine rechallenge (p = 0.18). The combination chemotherapy regimens are associated with the grade 4 of cardiotoxicity (p = 0.048), but not with the fatal outcome (p = 0.3). Rechallenge of capecitabine lead to symptoms recurrence in 10/16 patients. Neither the dose reduction of capecitabine (p = 0.18) nor the additional medical prophylaxis (p = 0.37) were important for the outcome of capecitabine rechallenge.