The placebo effect is a psychobiological phenomenon in which patients' expectations, prior experiences, and social context influence health outcomes, even in the absence of active pharmacological treatment. Key mechanisms include expectancy, verbal suggestion, classical conditioning, and social-contextual factors, underpinned by neurobiological processes involving endogenous opioids, Dopamine, and related neural circuits. In mental health and psychotherapy, placebo effects are particularly relevant, as the therapeutic alliance, empathy, and belief in treatment can significantly enhance outcomes. Ethical applications such as open-label and dose-extending placebos preserve patient autonomy while leveraging expectancy and learning to improve clinical results. Recognizing and integrating placebo mechanisms into clinical practice highlights the interaction of psychological, neurobiological, and ethical factors, offering a holistic approach to treatment and enhancing therapy outcomes in conditions like depression, anxiety, and chronic pain.
Teucrium montanum L. (TM) is a perennial species of the Lamiaceae family, traditionally used in folk medicine for its diverse therapeutic properties. Although previous studies have explored the biological activity of TM extracts, their effects on skin cells have not been investigated. This study examined the cytotoxic and antioxidant effects of two methanolic extracts of T. montanum (TM1 and TM2), obtained from serpentinite and limestone, across a concentration range of 12.5-400 µg/mL on human keratinocyte (HaCaT) cells. Both extracts showed a concentration-dependent cytotoxic effect in the MTT assay, with no significant impact on cell survival up to 100 µg/mL. At higher concentrations (200 and 400 µg/mL), cell viability decreased significantly, with TM1 exhibiting greater cytotoxicity than TM2. Antioxidant potential was assessed by the H2DCFDA assay, revealing that neither extract altered basal reactive oxygen species (ROS) levels, but higher concentrations increased ROS formation under H2O2-induced oxidative stress. These results suggest that TM1 and TM2 are well tolerated at lower concentrations, but may induce oxidative stress and cytotoxicity at higher concentrations. The findings highlight the importance of dose optimisation for potential therapeutic or cosmetic applications of TM extracts and further phytochemical characterisation to identify the active constituents responsible for these effects.
Microencapsulation is a widely applied strategy for protecting bioactive compounds by entrapping them within a polymeric or lipid-based shell, thereby enhancing their stability and enabling controlled release. In recent years, the growing number of applications of cannabinoids has driven increasing interest in microencapsulation as a strategy to overcome challenges related to poor aqueous solubility, chemical instability, and limited bioavailability. The aim of this review is to summarize and evaluate commonly employed microencapsulation techniques for obtaining cannabinoid delivery systems. A systematic literature search was conducted using the PubMed, SCOPUS, EBSCO, and Embase databases, resulting in the selection of over 50 original research articles and reviews. The search strategy employed combinations of keywords including cannabis AND microencapsulation methods, cannabinoids AND microencapsulation techniques, hempseed oil AND spray-drying OR coacervation technology, and cannabis industry AND microencapsulation. The findings indicate that the most frequently investigated microencapsulation techniques for cannabinoids include spray-chilling, spray-cooling, fluidized-bed coating, liposomal entrapment, extrusion, freeze-drying, coacervation, and emulsification. These techniques differ in their encapsulation efficiency, scalability, particle size distribution, and suitability for specific delivery routes. Overall, microencapsulation has demonstrated significant potential to improve the physicochemical stability of cannabinoids, protect them from environmental degradation, and enable controlled or targeted release. In conclusion, microencapsulation represents a promising and rapidly evolving approach for the development of advanced cannabinoid formulations, offering innovative solutions for enhanced stability, defined delivery performance, leading to potential of therapeutic applicability.
The college years are critical to students' health as they face various challenges, including social influences and unhealthy lifestyles. Limited access to health services in residence halls increases the risk of unhealthy behaviours. The aim of this study was to investigate students' attitudes towards public health services for primary prevention in dormitories and to make suggestions for improvement. A cross-sectional study was conducted using a questionnaire among students living in halls of residence. The survey explored students' views on healthcare and the availability of preventive services for students living away from home. A total of 996 students participated (response rate 99.1%). Most were unemployed (83.9%). The most frequent preventive visits were to dentists (34.4% twice a year, 24.7% once a year), while 37.7% never visited a gynaecologist/urologist. The majority (68.6%) stated that a pharmacy was necessary in their dormitories. Basic health services include general practitioners (82.3%) and psychologists (21.4%). Attitudes towards health centres varied significantly by place of residence (p<0.001). Primary prevention should be improved by health centres with student-friendly opening hours and additional activities that promote access to healthcare and awareness of prevention.
From patients' perspective, the use of antibiotics to treat urinary tract infections (UTIs) in Serbia is unexplored, and therefore the aim of this study is to examine antibiotic use among these patients. An online cross-sectional study using snowball sampling was conducted during the winter of 2020/21 using a validated Google Docs questionnaire. The study included 236 female patients with a mean age of 34.9 ± 14.2 years. Most of the patients perceived UTI symptoms as severe (62.3%) and disruptive for their daily routines (51.3%). The majority of the patients (77.1%) used antibiotics by doctors' prescriptions. Other patients used antibiotics on their own and their selection. Self-treatment with antibiotics was associated with perceived symptom severity (p=0.006) and residence (p=0.017). In total, 17 different antibiotics were reported as being used for UTI treatment and the most frequent were fluoroquinolones (30.3%), cephalosporins (21.2%), and sulfonamides (15.7%). The highest consistency with national and European guidelines in doctors' decisions on antibiotic therapy was observed for treating UTIs in pregnant women (80.0%). These findings emphasize the need for education of healthcare professionals and clinical practice improvement in making rational antibiotic prescribing decisions.
Customer satisfaction reflects the quality of pharmaceutical services and depends on various factors, such as the quality of services, pharmacists' skills and customer' demographic characteristics. Positive experiences strengthen customer trust and loyalty. Research into user satisfaction is an important tool for improving services. The aim of the work was the analysis of user satisfaction with pharmacy services in Serbia over the last twelve years. Annual reports on user satisfaction in pharmacies from 2013 to 2024 were analyzed. Based on key indicators, a report was prepared comparing satisfaction over the years, taking into account various factors and service quality. With the exception of 2020, public, private and health center pharmacies participated every year. The highest response rate was recorded in 2015. More than 60% of users visit a pharmacy more than five times a year, usually waiting less than five minutes. The highest level of satisfaction with the availability of medicines was recorded in 2021, while overall satisfaction with services peaked in 2022. User satisfaction has remained stable, indicating good availability and quality of pharmaceutical services. The results may contribute to further improvement in practice.
The purpose of this systematic review was to analyze and summarize telepharmacy evaluation methods. A systematic review of articles was conducted in accordance with the PRISMA guidelines, using proper inclusion criteria. After the initial keyword search, duplicate check and screening for titles and abstracts, 22 papers entered the next phase, which was deep analysis. Most of the studies included in the in-depth analysis were classified as retrospective and were mainly focused on drug dispensing and pharmacotherapeutics monitoring and management. According to the Donabedian model, in 16 cases researchers analyzed processes, while 9 times the focus was set on the outcome. Using the ECHO model, it was found that 13 analyses were focused on clinical outcomes, 11 on humanistic, while economic outcome issues were explored in 2 papers. Risk of bias assessment showed that the highest risk of bias came from attrition bias. There are no unique recommendations on how telepharmacy evaluation should be performed. Interestingly, ECHO telepharmacy evaluation marginalized economic outcome issues, even though these outcomes are often a decision factor when it comes to the implementation. Our results confirm that stronger study designs and more rigorous evaluation methods are recognized as necessary so that new trends could be identified.
Pharmacists have the potential to address gaps in primary healthcare by providing pharmaceutical services in home care settings, particularly in response to the challenges faced by the Norwegian healthcare system. Their integration into primary care teams could enhance care quality, reduce the burden on physicians, and improve treatment accessibility and efficiency, as demonstrated in other countries. This study explores pharmacists' perspectives on the challenges and opportunities associated with implementing pharmaceutical home care services in Norway, considering international experiences and trends. A qualitative study was conducted between July and August 2024, involving interviews with pharmacists from various Norwegian pharmacies. Transcripts were analysed to identify categories and themes. Ten pharmacists participated, and the data were structured into 19 categories grouped into six themes: (i) the concept and implementation of home pharmaceutical services, (ii) benefits, (iii) challenges, (iv) impact on daily practice and training needs, (v) evaluation and teamwork, and (vi) patient outcomes and the use of digital tools. Findings indicate that home-based pharmaceutical services could improve healthcare quality in Norway, but their implementation involves challenges such as resource limitations and training needs. Recommendations include developing targeted strategies and support mechanisms to overcome these barriers, in order to ensure optimal benefits while maintaining high standards in pharmaceutical home care services.
Venous leg ulcers (VLUs) account for most lower extremity wounds. Wound management include cleansing, debridement, infection control and applying wound dressing. There exist various types of dressings which can maintain adequate moisture, offer protection, and support the reepithelization of VLUs. The aim of this study is to evaluate the cost-effectiveness of the antimicrobial wound dressing containing ionic silver (Aquacel® Ag+Extra™) in the treatment of VLUs compared to conventional gauze dressing in Serbia. The data regarding the effectiveness and frequency of dressings for both the Aquacel® Ag+Extra™ and conventional dressing were obtained from literature sources. Only direct costs were considered, and values were taken from the published price list of health services or procurement procedures. Sensitivity analyses were performed. The total cost per patient for Aquacel® Ag+Extra™ was 34,178.76 RSD, while the total cost for gauze was 82,800.90 RSD. Besides lower costs, antimicrobial wound dressing shows higher effectiveness than the gauze, implying that Aquacel® Ag+Extra™ is the dominant strategy. The sensitivity analysis supports the robustness of the results. The use of antimicrobial wound dressing containing ionic silver is the preferred option for the treatment of VLUs due to lower costs and the higher curing rate of the wounds.
According to the World Health Organization, pharmacovigilance is a science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. Since the underreporting of adverse drug reactions (ADRs) remains a significant global issue, reporting ADRs is essential for the success of pharmacovigilance programs. By systematically monitoring and reporting ADRs at the primary, secondary, and tertiary levels of healthcare, pharmacovigilance plays a crucial role in protecting public health. In addition to facilitating the early identification and prevention of negative consequences, reporting also contributes to improving the quality of healthcare services. This article presents a narrative review aimed at synthesizing available literature and regulatory documents related to pharmacovigilance and ADR reporting across various levels of healthcare, with particular emphasis on the national context in Serbia and relevant international comparisons.
Modern trends in nutrition imply the daily intake of fresh fruits and vegetables, with the statement that they are important sources of natural antioxidants that protect the body from oxidative stress and can contribute to the prevention of many chronic diseases. In these recommendations, green vegetables with high total phenolics content (TPC) are especially highlighted. However, one must ask whether the high total phenolics content of green vegetables, such as Brussels sprouts, cabbage, broccoli, parsley, borecole and spinach, is a reliable indicator of antioxidant activity for regulating free radicals in the body. The aim of this work is the spectrophotometric determination of TPC of hydromethanol extracts of selected green vegetables and its correlation with their antioxidant potential. For this purpose, DPPH and ABTS radical scavenging tests of extracts were performed. The obtained results indicate that Brussels sprouts and parsley exhibit the highest antioxidative activities, while cabbage extract shows lower values. The Pearson correlation used to test the correlation between the TPC obtained for green vegetable extracts and the results of the DPPH and ABTS tests shows a moderate correlation between TPC and ABTS values, whereas the correlation for TPC and DPPH is statistically significant.
Gadobutrol (Gadovist®) is a macrocyclic, extracellular gadolinium-based contrast agent widely used in magnetic resonance imaging. This study aims to assess the genotoxic and cytotoxic potential of gadobutrol in human G0 phase lymphocytes and circulating lymphocytes. The Sister Chromatid Exchange (SCE) assay, a fast, sensitive, and reliable method for evaluating genotoxicity, was employed. Genotoxic effects were assessed by measuring SCE frequency, while cytotoxicity was determined using the mitotic index (MI). Peripheral blood samples from two healthy donors were treated in vitro with three different concentrations of gadobutrol for 24 hours in G0 phase lymphocytes and 72 hours in circulating lymphocytes. The results indicated that gadobutrol did not exhibit cytotoxic effects in either cell type. However, at the highest concentration (25 mM), gadobutrol significantly increased the formation of SCE in circulating lymphocytes (p < 0.05), while no significant genotoxic effect was observed in G0 phase lymphocytes (p > 0.05). These findings suggest that gadobutrol, although not cytotoxic, may induce genotoxic effects in a concentration-dependent manner in circulating lymphocytes. Further studies are needed to explore the clinical implications of these findings.
In this study, the extended thermodynamic approach was used to quantitatively explain the effect of counterions, both of chaotropic agents and ionic strength modifiers, in variable (vI) and constant ionic strength (cI) systems on the retention behavior of 23 fully protonated basic analytes. Nine series of experiments (at three pH values for NaPF6, KPF6 and NH4PF6) with vI and nine series of experiments (at three pH values for NaPF6, KPF6 and NH4PF6) with ionic strength kept constant with NaCl, KCl and NH4Cl were performed. The experimentally determined retention factors were modeled using the extended thermodynamic approach and the processes occurring in the stationary phase and in the mobile phase and their influence on retention in the investigated chaotropic chromatography systems were rationalized. In both vI and cI systems, ion pair formation in the stationary phase proved to be dominant over ion pair formation in the mobile phase. In the KPF6_vI systems, these interactions with the stationary phase were even more pronounced than in the other systems. Although both K+ and NH4+ are chaotropic in nature, the formation of ion pairs in the stationary phase was favored by the presence of NH4+ only at its rather high concentrations as in cI systems.
Measurement uncertainty plays a critical role in ensuring the reliability, accuracy, and regulatory compliance of analytical results in pharmaceutical quality control. This study presents a comprehensive comparison of the Top-down and Bottom-up approaches for estimating the uncertainty associated with the quantitative determination of Meloxicam in injectable dosage forms using a validated HPLC method. The Top-down approach, based on method validation data, yielded an expanded uncertainty of ±0.336 mg per injection, while the Bottom-up approach (incorporating uncertainties from volumetric equipment, reference standards, and molar mass) produced a broader value of ±0.646 mg per injection. The results highlight the complementary nature of both approaches and support the integration of their respective strengths to improve the robustness of uncertainty estimation. The proposed methodology is applicable to other methods within pharmaceutical quality control.
Live biotherapeutic products (LBPs) are gaining significant medical importance as a new approach in the prevention and treatment of various conditions in the female population. This study investigated the design, development, and evaluation of immediate-release (IR) vaginal dosage forms containing live Lactobacillus spp., with the aim of enabling fast and effective drug delivery in the vaginal environment. Capsule and tablet formulations were developed using different excipients and appropriate manufacturing processes (encapsulation and direct compression) and systematically evaluated for their robustness and performance. The results demonstrated that all capsule formulations exhibited suitable flowability and uniformity of dosage units, with hard gelatine capsules (HGC) providing the most favourable disintegration times compared to hydroxypropyl methylcellulose (HPMC) and pullulan capsules. Tablet formulations based on microcrystalline cellulose (MCC) achieved optimal hardness, friability, and disintegration, especially under lower compression forces, confirming MCC's multifunctional role as a filler, binder, and disintegrant. Importantly, both dosage forms maintained Lactobacillus viability with only minor losses (~0.5 log), preserved the acidic vaginal environment (pH 4.2), and demonstrated robustness under simulated biorelevant conditions. These findings highlight that IR vaginal capsules and tablets can be effectively tailored to deliver live biotherapeutics with rapid onset of action, thereby advancing microbiome-based strategies for women's health.
The utilization of phytotherapy is essential in the Algerian Sahara, where endemic plants such as Otoglyphis pubescens are used to address certain health issues. However, discrepancies in knowledge and application of these botanical resources may lead to toxicity and reduced efficacy. A questionnaire was prepared and interviews conducted among herbalists and common population to collect data according to the objectives set. Ethnobotany indices were calculated and comparison was made between the different subgroups of the sampled population. The most commonly used vernacular names for Otoglyphis pubescens are: Gartoufa, Gritfa, and Wazwaza. This plant is endemic and grows wild. The most commonly used parts are the whole aerial parts dried in the shade. This plant is used as herbal tea. The most commonly used preparation methods are maceration and infusion. This plant is used mainly for its therapeutic properties to address issues related to the treatment of digestive, genitourinary, and respiratory problems, and fever. According to the analysed indices, the interviewed populations showed high knowledge of the uses of O. pubescens, with subpopulations such as married individuals, females, persons aged over 60 years, the less educated, and the unemployed noting superior use of the plant. Variations are noted in the answers of the interviewed subjects and differences stood comparing to data reported in the literature, but close responses patterns were noted between the herbalists and the common population.
Cyclosporine A (CsA) is an immunosuppressive used in both children and adult transplant recipients, as well as patients with autoimmune diseases such as nephrotic syndrome. Therapeutic drug monitoring (TDM) of CsA is essential due to its significant interindividual and intraindividual pharmacokinetic variability, narrow therapeutic index and the risk of organ rejection or autoimmune disease relapse at subtherapeutic levels, as well as the potential for serious adverse effects with overexposure. In pediatric patients, CsA pharmacokinetics can be significantly influenced by developmental physiological factors, necessitating even greater attention to TDM in this vulnerable population. This paper explores the key challenges associated with TDM in children, the clinical rationale for its use, clinical settings where it is applied and future perspectives, including the potential of model-informed precision dosing (MIPD).
Cough and cold represent some of the most prevalent indications for using herbal medicinal products in pediatric care across European countries. These herbal medicines are generally regarded as safe, with their efficacy predominantly classified as good to very good. Traditional herbal medicinal products based on mucilaginous herbal drugs like Althaeae radix, Malvae folium, Lichen islandicus and Plantaginis lanceolatae folium are used in the treatment of oral and pharyngeal inflammations and associated dry cough. For productive coughs, herbal medicinal products with well-established use, based on Hederae folium, or a range of traditional herbal medicinal products containing Primulae radix, Thymi herba, and other aromatic drugs and essential oils are administered. It is important to note that products containing essential oils and certain aromatic herbal drugs are contraindicated in children under 2 to 2.5 years of age due to the risk of laryngospasm. In the pediatric population, products derived from Matricariae flos, Pelargonii radix, Tiliae flos and Sambuci flos are used to relieve various cold symptoms. Use is restricted to children over a certain age, mostly due to lack of safety data, and in some cases due to the possibility of certain adverse effects.
Three-dimensional (3D) printing offers a versatile platform for producing personalized, age-appropriate dosage forms that address the specific therapeutic and administration needs of the pediatric population. Among several oral dosage forms that can be prepared by 3D printing, chewing lozenges offer numerous advantages, especially for the pediatric population. This study illustrates a formulation development and selection of process parameters for 3D-printed chewing lozenges containing propranolol hydrochloride as a model drug, with potential application in the pediatric population. It also highlights the advantages of 3D printing using the semi-solid material extrusion method. Gelatin and sodium alginate were used as carriers for 3D printing. Immersion time in the calcium chloride solution (tim) and lozenges shape were varied, while the following tests were performed: the assessment of organoleptic properties, mass and thickness variations, melting and disintegration time, drug content and dissolution rate. Initially, the key 3D printing parameters for lozenge production were identified, and then the appropriate formulation was selected. Subsequent testing demonstrated that the shape of lozenges, along with variations in tim, influenced the pharmaceutical-technological characteristics. A formulation based on the combination of gelatin and sodium alginate in 1:3 ratio, immersed for 60 seconds in a calcium chloride solution, was found to be suitable for 3D printing of chewable lozenges.
Orodispersible films (ODFs) emerged as a patient-friendly dosage form that is particularly suitable for pediatric therapy, where swallowing difficulties often interfere with adherence to therapy. In this study, the preparation of ODFs using semi-solid extrusion (SSE) 3D printing was investigated as an alternative to the conventional solvent casting method. Four hydrophilic polymers - hydroxypropyl cellulose (HPC), polyethylene glycol-polyvinyl alcohol graft copolymer (PVA-PEG), maltodextrin (MDX) and sodium alginate (SA) - were used either individually or in binary blends, with caffeine selected as the model active ingredient. Films were printed on an Ultimaker 2+ system and evaluated for uniformity, thickness, porosity, moisture content, mechanical strength, disintegration and drug release. Formulations containing only MDX or PVA-PEG exhibited poor printability due to leakage and spreading, while other systems showed reproducible film deposition and satisfactory dimensional stability. Binary blends generally resulted in increased film thickness. SA-based films showed the lowest porosity and moisture absorption, while HPC films exhibited favorable mechanical properties. The investigated samples achieved rapid disintegration and complete release of the caffeine. These results confirm the potential of SSE 3D printing as a versatile manufacturing platform for customizable ODFs that enable precise dosing and patient-centric design for pediatric drugs.
