Search results for: physiological barriers to drug delivery

Authors: Sergio A. Bernal-Chavez, Sergio Alcalá-Alcalá, Doris A. Cerecedo-Mercado, Adriana Ganem-Rondero

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The prevalence of people with chronic wounds has increased dramatically by many factors including smoking, obesity and chronic diseases, such as diabetes, that can slow the healing process and increase the risk of becoming chronic. Because of this situation, the improvement of chronic wound treatments is a necessity, which has led to the scientific community to focus on improving the effectiveness of current therapies and the development of new treatments. The wound formation is a physiological complex process, which is characterized by an inflammatory stage with the presence of proinflammatory cells that create a proteolytic microenvironment during the healing process, which includes the degradation of important growth factors and cytokines. This decrease of growth factors and cytokines provides an interesting strategy for wound healing if they are administered externally. The use of nanometric drug delivery systems, such as polymer nanoparticles (NP), also offers an interesting alternative around dermal systems. An interesting strategy would be to propose a formulation based on a thermosensitive hydrogel loaded with polymeric nanoparticles that allows the inclusion and application of a platelet lysate (PL) on damaged skin, with the aim of promoting wound healing. In this work, NP were prepared by a double emulsion-solvent evaporation technique, using polylactic-co-glycolic acid (PLGA) as biodegradable polymer. Firstly, an aqueous solution of PL was emulsified into a PLGA organic solution, previously prepared in dichloromethane (DCM). Then, this disperse system (W/O) was poured into a polyvinyl alcohol (PVA) solution to get the double emulsion (W/O/W), finally the DCM was evaporated by magnetic stirring resulting in the NP formation containing PL. Once the NP were obtained, these systems were characterized by morphology, particle size, Z-potential, encapsulation efficiency (%EE), physical stability, infrared spectrum, calorimetric studies (DSC) and in vitro release profile. The optimized nanoparticles were included in a thermosensitive gel formulation of Pluronic® F-127. The gel was prepared by the cold method at 4 °C and 20% of polymer concentration. Viscosity, sol-gel phase transition, time of no flow solid-gel at wound temperature, changes in particle size by temperature-effect using dynamic light scattering (DLS), occlusive effect, gel degradation, infrared spectrum and micellar point by DSC were evaluated in all gel formulations. PLGA NP of 267 ± 10.5 nm and Z-potential of -29.1 ± 1 mV were obtained. TEM micrographs verified the size of NP and evidenced their spherical shape. The %EE for the system was around 99%. Thermograms and in infrared spectra mark the presence of PL in NP. The systems did not show significant changes in the parameters mentioned above, during the stability studies. Regarding the gel formulation, the transition sol-gel occurred at 28 °C with a time of no flow solid-gel of 7 min at 33°C (common wound temperature). Calorimetric, DLS and infrared studies corroborated the physical properties of a thermosensitive gel, such as the micellar point. In conclusion, the thermosensitive gel described in this work, contains therapeutic amounts of PL and fulfills the technological properties to be used in damaged skin, with potential application in wound healing and tissue regeneration.

Keywords: growth factors, polymeric nanoparticles, thermosensitive hydrogels, tissue regeneration

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Authors: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

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Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

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Authors: Shamila Manie, Soraya Maart, Ayesha Osman

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Introduction: People diagnosed with multidrug resistant pulmonary tuberculosis (MDR-PTB) is subjected to prolonged hospitalization in South Africa. It has thus become essential for research to shift its focus from a purely medical approach, but to include social and environmental factors when looking at the impact of the disease on those affected. Aim: To explore the factors affecting individuals with multi-drug resistant pulmonary tuberculosis during long-term hospitalization using the comprehensive ICF core-sets for obstructive pulmonary disease (OPD) and cardiopulmonary (CPR) conditions at Brooklyn Chest Hospital (BCH). Methods: A quantitative descriptive, cross-sectional study design was utilized. A convenient sample of 19 adults at Brooklyn Chest Hospital were interviewed. Results: Most participants reported a decrease in exercise tolerance levels (b455: n=11). However it did not limit participation. Participants reported that a lack of privacy in the environment (e155) was a barrier to health. The presence of health professionals (e355) and the provision of skills development services (e585) are facilitators to health and well-being. No differences exist in the functional ability of HIV positive and negative participants in this sample. Conclusion: The ICF Core Sets appeared valid in identifying the barriers and facilitators experienced by individuals with MDR-PTB admitted to BCH. The hospital environment must be improved to add to the QoL of those admitted, especially improving privacy within the wards. Although the social grant is seen as a facilitator, greater emphasis must be placed on preparing individuals to be economically active in the labour for when they are discharged.

Keywords: multidrug resistant tuberculosis, MDR ICF core sets, health-related quality of life (HRQoL), hospitalization

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Authors: Mostafa Mabrouk, Basma E. Abdel-Ghany, Mona Moaness, Bothaina M. Abdel-Hady, Hanan H. Beherei

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Tissue engineering became a promising field for bone repair and regenerative medicine in which cultured cells, scaffolds and osteogenic inductive signals are used to regenerate tissues. The annual cost of treating bone defects in Egypt has been estimated to be many billions, while enormous costs are spent on imported bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. The current study is aimed at developing a more strategic approach in order to speed-up recovery after bone damage. This will reduce the risk of fatal surgical complications and improve the quality of life of people affected with such fractures. 3D scaffolds loaded with cheap nano-particles that possess an osteogenic effect were prepared by nano-electrospinning. The Microstructure and morphology characterizations of the 3D scaffolds were monitored using scanning electron microscopy (SEM). The physicochemical characterization was investigated using X-ray diffractometry (XRD) and infrared spectroscopy (IR). The Physicomechanical properties of the 3D scaffold were determined by a universal testing machine. The in vitro bioactivity of the 3D scaffold was assessed in simulated body fluid (SBF). The bone-bonding ability of novel 3D scaffolds was also evaluated. The obtained nanofibrous scaffolds demonstrated promising microstructure, physicochemical and physicomechanical features appropriate for enhanced bone regeneration. Therefore, the utilized nanomaterials loaded with the drug are greatly recommended as cheap alternatives to growth factors.

Keywords: bone regeneration, cheap scaffolds, nanomaterials, active molecules

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Authors: Bhupendra G. Prajapati, Alpesh R. Patel

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The aim of this research work is to develop sustained release multi-particulates dosage form of Dexketoprofen trometamol, which is the pharmacologically active isomer of ketoprofen. The objective is to utilization of active enantiomer with minimal dose and administration frequency, extended release multi-particulates dosage form development for better patience compliance was explored. Drug loaded and sustained release coated pellets were prepared by fluidized bed coating principle by wurster coater. Microcrystalline cellulose as core pellets, povidone as binder and talc as anti-tacking agents were selected during drug loading while Kollicoat SR 30D as sustained release polymer, triethyl citrate as plasticizer and micronized talc as an anti-adherent were used in sustained release coating. Binder optimization trial in drug loading showed that there was increase in process efficiency with increase in the binder concentration. 5 and 7.5%w/w concentration of Povidone K30 with respect to drug amount gave more than 90% process efficiency while higher amount of rejects (agglomerates) were observed for drug layering trial batch taken with 7.5% binder. So for drug loading, optimum Povidone concentration was selected as 5% of drug substance quantity since this trial had good process feasibility and good adhesion of the drug onto the MCC pellets. 2% w/w concentration of talc with respect to total drug layering solid mass shows better anti-tacking property to remove unnecessary static charge as well as agglomeration generation during spraying process. Optimized drug loaded pellets were coated for sustained release coating from 16 to 28% w/w coating to get desired drug release profile and results suggested that 22% w/w coating weight gain is necessary to get the required drug release profile. Three critical process parameters of Wurster coating for sustained release were further statistically optimized for desired quality target product profile attributes like agglomerates formation, process efficiency, and drug release profile using central composite design (CCD) by Minitab software. Results show that derived design space consisting 1.0 to 1.2 bar atomization air pressure, 7.8 to 10.0 gm/min spray rate and 29-34°C product bed temperature gave pre-defined drug product quality attributes. Scanning Image microscopy study results were also dictate that optimized batch pellets had very narrow particle size distribution and smooth surface which were ideal properties for reproducible drug release profile. The study also focused on optimized dexketoprofen trometamol pellets formulation retain its quality attributes while administering with common vehicle, a liquid (water) or semisolid food (apple sauce). Conclusion: Sustained release multi-particulates were successfully developed for dexketoprofen trometamol which may be useful to improve acceptability and palatability of a dosage form for better patient compliance.

Keywords: dexketoprofen trometamol, pellets, fluid bed technology, central composite design

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Authors: Sanjay Kumar Behera, Kanhu Charan Patra

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A GIS-based method has been applied for the determination of soil erosion and sediment yield in a small watershed in Ong River basin, Odisha, India. The method involves spatial disintegration of the catchment into homogenous grid cells to capture the catchment heterogeneity. The gross soil erosion in each cell was calculated using Universal Soil Loss Equation (USLE) by carefully determining its various parameters. The concept of sediment delivery ratio is used to route surface erosion from each of the discretized cells to the catchment outlet. The process of sediment delivery from grid cells to the catchment outlet is represented by the topographical characteristics of the cells. The effect of DEM resolution on sediment yield is analyzed using two different resolutions of DEM. The spatial discretization of the catchment and derivation of the physical parameters related to erosion in the cell are performed through GIS techniques.

Keywords: DEM, GIS, sediment delivery ratio, sediment yield, soil erosion

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Authors: Jie Gao

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The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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Authors: P. S. Jain, K. D. Bobade, S. J. Surana

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A simple, selective, precise and Stability-indicating High-performance thin-layer chromatographic method for analysis of Naftopidil both in a bulk and in pharmaceutical formulation has been developed and validated. The method employed, HPTLC aluminium plates precoated with silica gel as the stationary phase. The solvent system consisted of hexane: ethyl acetate: glacial acetic acid (4:4:2 v/v). The system was found to give compact spot for Naftopidil (Rf value of 0.43±0.02). Densitometric analysis of Naftopidil was carried out in the absorbance mode at 253 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r2=0.999±0.0001 with respect to peak area in the concentration range 200-1200 ng per spot. The method was validated for precision, recovery and robustness. The limits of detection and quantification were 20.35 and 61.68 ng per spot, respectively. Naftopidil was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation and thermal conditions. This indicates that the drug is susceptible to acid, base, oxidation and thermal conditions. The degraded product was well resolved from the pure drug with significantly different Rf value. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of investigated drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of Naftopidil in bulk drug and pharmaceutical formulation.

Keywords: naftopidil, HPTLC, validation, stability, degradation

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Authors: Samson F. Agberotimi, Rachel B. Asagba, Choja Oduaran

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Disturbing rate of use of different substances such as cannabis, alcohol, as well as pharmaceutical drugs among Nigerian youth in recent times has been affirmed in the literature. There is, however, a paucity of literature addressing the pattern of usage of such drugs, especially for clinical relevance and intervention planning. The present study investigated the prevalence and pattern of drug usage among youth in Ogbomoso, Nigeria. A cross-sectional survey involving 92 purposively selected participants comprising of 82 males and 10 females aged between 15 and 24 years was conducted. A measure of drug involvement and demographic characteristics was administered to the participants. Descriptive analysis was done using the SPSS v.21. Cannabis (79.4%), alcohol (77.2%), codeine (70.7%), tobacco (65.2%) and tramadol (47.8%) are the five most frequently used substances. However, the majority of the users of tobacco (68.3%) and alcohol (62.0%) are casual users indicating a mild level of use of the substances among the participants. On the other hand, 49.2% of the codeine users, 27.3% of the tramadol users, and 21.9% of the cannabis users reported harmful/intensive levels of use. Furthermore, the results revealed individuals at the pathological level of use as 28.8% for cannabis, 25.0% for tramadol, and 21.6% for codeine, and thus require clinical/therapeutic intervention. In conclusion, cannabis remains the most frequently used substance among youths. However, there appears to be a shift from the use of conventional psychoactive substances to pharmaceutical/prescription drugs such as codeine and tramadol. The findings of this study raised the need for both preventive and therapeutic interventions addressing the problem of substance use disorder among youth in contemporary society.

Keywords: Ogbomoso, pattern of drug use, prevalence of drug use, youth

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Authors: Abeer Amayri, Akif A. Bulgak

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Due to today’s globalization as well as outsourcing practices of the companies, the Supply Chain (SC) performances have become more dependent on the efficient movement of material among places that are geographically dispersed, where there is more chance for disruptions. One such disruption is the quality and delivery uncertainties of outsourcing. These uncertainties could lead the products to be unsafe and, as is the case in a number of recent examples, companies may have to end up in recalling their products. As a result of these problems, there is a need to develop a methodology for selecting suppliers globally in view of risks associated with low quality and late delivery. Accordingly, we developed a two-stage stochastic model that captures the risks associated with uncertainty in quality and delivery as well as a solution procedure for the model. The stochastic model developed simultaneously optimizes supplier selection and purchase quantities under price discounts over a time horizon. In particular, our target is the study of global organizations with multiple sites and multiple overseas suppliers, where the pricing is offered in suppliers’ local currencies. Our proposed methodology is applied to a case study for a US automotive company having two assembly plants and four potential global suppliers to illustrate how the proposed model works in practice.

Keywords: global supply chains, quality, stochastic programming, supplier selection

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Authors: Vipin Saini, Sunil Kamboj, Suman Bala, A. Pandurangan

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The present research is aimed at fabrication of multiple-unit controlled-release tablet formulation of aceclofenac by employing acrylic polymers as the release controlling excipients for drug multi-particulates to achieve the desired objectives of maintaining the same controlled release characteristics as that prior to their compression into tablet. Various manufacturers are successfully manufacturing and marketing aceclofenac controlled release tablet by applying directly coating materials on the tablet. The basic idea behind development of such formulations was to employ aqueous acrylics polymers dispersion as an alternative to the existing approaches, wherein the forces of compression may cause twist of drug pellets, but do not have adverse effects on the drug release properties. Thus, the study was undertaken to illustrate manufacturing of controlled release aceclofenac multiple-unit tablet formulation.

Keywords: aceclofenac, multiple-unit tablets, acrylic polymers, controlled-release

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Authors: Kayum Fokoue Carole

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This paper aims at verifying the effectiveness of reaching target populations while paying attention to their cultural background when communicating new knowledge, ideas or technology in a multicultural world. Our case study is an experiment on the communication of knowledge on breast cancer in three sub-Saharan countries (Ghana, Tchad, and Cameroon health). The methodology consisted of submitting a semi-structured questionnaire to local populations in some localities in these target countries in order to determine the cultural barriers hindering the effective communication of knowledge on breast cancer. Once this done, sensitization documents on breast cancer were translated into Ewe (Ghana), Mbaye (Tchad), Ghomala’, Ewondo, and Fufulde (Cameroon). In each locality, a sensitization programme was organised for two groups. For one group, the cultural barriers discovered were taken into consideration while communicating during the programme whereas in the other group, they were not. Another questionnaire was disseminated after three months to verify the level of appropriation of those who attended the campaign based on Chumbow’s appropriation theory. This paper, therefore, discusses some spiritual beliefs, representations and practices in the target African communities hindering effective communication of issues on breast cancer in the target localities. Findings reveal that only 38% of respondents in the group of those for whom cultural barriers were not taken into account during the programme had a high level of appropriation while for the other group, 86% had a high level of appropriation. This is evidence that the communication of issues on breast cancer can be more effective by reaching different populations in a language they best master while paying attention to their culture. Therefore, international communication of new knowledge should be culturally contextualised. Suggestions at the end of the paper are directed towards the achievement of these goals. The present work promotes international partnership in addressing and resolving global health preoccupations since research findings from one community/country can be mutualized in partnership with other communities and countries.

Keywords: cultural barriers, communication, health, breast cancer

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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Additive manufacturing technologies producing drug dosage forms aimed at personalized medicine applications are promising strategies with several advantages over the conventional production methods. One of the emerging technologies is 3D printing which reduces manufacturing steps and thus allows a significant drop in expenses. A decrease in material consumption is also a highly impactful benefit as the tested drugs are frequently expensive substances. In addition, 3D printed dosage forms enable increased patient compliance and prevent misdosing as the dosage forms are carefully designed according to the patient’s needs. The incorporation of multiple drugs into a single dosage form further increases the degree of personalization. Our research focuses on the development of 3D printed tablets incorporating multiple drugs (candesartan, losartan) and thermoplastic polymers (e.g., KlucelTM HPC EF). The filaments, an essential feed material for 3D printing,wereproduced via hot-melt extrusion. Subsequently, the extruded filaments of various formulations were 3D printed into tablets using an FDM 3D printer. Then, we have assessed the influence of the internal structure of 3D printed tablets and formulation on dissolution behaviour by obtaining the dissolution profiles of drugs present in the 3D printed tablets. In conclusion, we have developed tablets containing multiple drugs providing modified release profiles. The 3D printing experiments demonstrate the high tunability of 3D printing as each tablet compartment is constructed with a different formulation. Overall, the results suggest that the 3D printing technology is a promising manufacturing approach to dual tablet preparation for personalized medicine.

Keywords: 3D printing, drug delivery, hot-melt extrusion, dissolution kinetics

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Authors: Sperisa Distantina, Fadilah, Mujtahid Kaavessina

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Crosslinked konjac glucomannan and kappa carrageenan film were prepared by chemical crosslinking using glutaraldehyde (GA) as the crosslinking agent. The effect crosslinking on the swelling degree was investigated. Konjac glucomanan and its mixture with kappa carragenan film was immersed in GA solution and then thermally cured. The obtained crosslinked film was washed and soaked in the ethanol to remove the unreacted GA. The obtained film was air dried at room temperature to a constant weight. The infrared spectra and the value of swelling degree of obtained crosslinked film showed that glucomannan and kappa carrageenan was able to be crosslinked using glutaraldehyde by film immersion and curing method without catalyst. The crosslinked films were found to be pH sensitive, indicating a potential to be used in drug delivery polymer system.

Keywords: crosslinking, glucomannan, carrageenan, swelling

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Authors: Muhammad Imran Din

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The aim of this study was to understand the interaction between multi-walled carbon nano tubes (MCNTs) and anticancer agents and evaluate the drug-loading ability of MCNTs. Batch adsorption experiments were carried out for adsorption of 5-Fluorouracil (5-FL) using MCNTs. The effect of various operating variables, viz., adsorbent dosage, pH, contact time and temperature for adsorption of 5-Fluorouracil (5-FL) has been studied. The Freundlich adsorption model was successfully employed to describe the adsorption process. It was found that the pseudo-second-order mechanism is predominant and the overall rate of the 5-Fluorouracil (5-FL) adsorption process appears to be controlled by the more than one-step. Thermodynamic parameters such as free energy change (ΔG°), enthalpy change (ΔH°) and entropy change (ΔS°) have been calculated respectively, revealed the spontaneous, endothermic and feasible nature of adsorption process. The results showed that carbon nano tubes were able to form supra molecular complexes with 5-Fluorouracil (5-FL) by π-π stacking and possessed favorable loading properties as drug carriers.

Keywords: drug, adsorption, anticancer, 5-Fluorouracil (5-FL)

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Authors: Oscar Conrad Pili De Jesus

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In consonance with the UN Convention on Rights for People with Disabilities, countries are mandated to provide a barrier-free environment through adherence to universal design and full participation of persons with disabilities (PWDs) in planning and implementation, but there is little action in incorporating universal design in the public environment. Travelling freely and independently is paramount to the needs of the PWDs to participate in daily activities ahead of them, and it contributes to the advancement of their inclusion in society, in which universal design is a catalyst to provide seamless access and mobility. This study aims to determine the barriers to incorporating the concept of universal design in transportation projects in Southeast Asian countries. Based on a literature review and using the accessible journey chain as a framework, barriers are identified and categorized in the components of public transport within the context of utilization of the transport mode, the built environment within the transport infrastructure, and the first and last miles of travel. Some findings in the study which constitute solutions to creating a barrier-free environment were identified as information to guide the future research agenda in efficiently incorporating universal design in transportation projects in Southeast Asian countries. The study reflected that the focus of most literature is on the built environment, noting that there is a need for future studies to investigate universal design in the context of the public transport component in the active journey chain.

Keywords: public transportation, barriers, universal design, persons with disabilities, accessible journey chain

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Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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Authors: Ruijie Fan, Hao Xu

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Due to the increasing demand for resources, solid waste disposal is becoming an increasingly important issue to be addressed. Solid waste is not only hazardous to human health but also has a negative impact on the environment. The main sources of solid waste are metals, glass, food, plastics, paper, and electrical waste. Different types of waste may require different treatments. The UK currently lags behind other countries, such as Japan and Germany, in terms of waste management. Although the UK is catching up through various incentives, waste management education in the UK still faces challenges. Education requires a lot of work before the UK can achieve a circular economy. This paper first presents the latest information on the five main types of solid waste in the UK today. It delves into the current state of waste paper management in the UK, in addition to gathering information from the literature on the current state of waste management education in the UK as a whole. Potential barriers to the disposal of each waste type in the UK are identified, along with potential barriers to education in the UK. This study was based on a pragmatic philosophy to find possible solutions for these barriers, including questionnaires to conduct an in-depth investigation. In addition, the questionnaire analysis reveals a correlation between educational attainment and individual waste management behaviour and attitudes. This research guides inspiration on the current problems of waste management in the UK.

Keywords: circular economy, education, solid waste, waste management

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Authors: Sagar R. Patil, Dinesh R. Gawade, Sudhir N. Divekar

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One of the medical devices we found when we visit a hospital care unit such device is ‘patient monitoring system’. This device (patient monitoring system) informs doctors and nurses about the patient’s physiological signals. However, this device (patient monitoring system) does not have a remote monitoring capability, which is necessitates constant onsite attendance by support personnel (doctors and nurses). Thus, we have developed a Remote Wireless Patient Monitoring System using some biomedical sensors and Android OS, which is a portable patient monitoring. This device(Remote Wireless Patient Monitoring System) monitors the biomedical signals of patients in real time and sends them to remote stations (doctors and nurse’s android Smartphone and web) for display and with alerts when necessary. Wireless Patient Monitoring System different from conventional device (Patient Monitoring system) in two aspects: First its wireless communication capability allows physiological signals to be monitored remotely and second, it is portable so patients can move while there biomedical signals are being monitor. Wireless Patient Monitoring is also notable because of its implementation. We are integrated four sensors such as pulse oximeter (SPO2), thermometer, respiration, blood pressure (BP), heart rate and electrocardiogram (ECG) in this device (Wireless Patient Monitoring System) and Monitoring and communication applications are implemented on the Android OS using threads, which facilitate the stable and timely manipulation of signals and the appropriate sharing of resources. The biomedical data will be display on android smart phone as well as on web Using web server and database system we can share these physiological signals with remote place medical personnel’s or with any where in the world medical personnel’s. We verified that the multitasking implementation used in the system was suitable for patient monitoring and for other Healthcare applications.

Keywords: patient monitoring, wireless patient monitoring, bio-medical signals, physiological signals, embedded system, Android OS, healthcare, pulse oximeter (SPO2), thermometer, respiration, blood pressure (BP), heart rate, electrocardiogram (ECG)

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Authors: Shraddha Acharya, Sharad Kumar Sharma, Ratna Bhattarai, Bhagwan Maharjan, Deepak Dahal, Serpahine Kaminsa

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Background: Drug-resistant (DR) tuberculosis (TB) continues to be a threat in Nepal, with an estimated 2800 new cases every year. The treatment of DR-TB with second line TB drugs is complex and takes longer time with comparatively lower treatment success rate than drug-susceptible TB. Delay in treatment initiation for DR-TB patients might further result in unfavorable treatment outcomes and increased transmission. This study thus aims to determine median time taken to initiate second-line treatment among Rifampicin Resistant (RR) diagnosed TB patients and to assess the proportion of treatment delays among various type of DR-TB cases. Method: A retrospective cohort study was done using national routine electronic data (DRTB and TB Laboratory Patient Tracking System-DHIS2) on drug resistant tuberculosis patients between January 2020 and December 2022. The time taken for treatment initiation was computed as– days from first diagnosis as RR TB through Xpert MTB/Rif test to enrollment on second-line treatment. The treatment delay (>7 days after diagnosis) was calculated. Results: Among total RR TB cases (N=954) diagnosed via Xpert nationwide, 61.4% were enrolled under shorter-treatment regimen (STR), 33.0% under longer treatment regimen (LTR), 5.1% for Pre-extensively drug resistant TB (Pre-XDR) and 0.4% for Extensively drug resistant TB (XDR) treatment. Among these cases, it was found that the median time from diagnosis to treatment initiation was 6 days (IQR:2-15.8). The median time was 5 days (IQR:2.0-13.3) among STR, 6 days (IQR:3.0-15.0) among LTR, 30 days (IQR:5.5-66.8) among Pre-XDR and 4 days (IQR:2.5-9.0) among XDR TB cases. The overall treatment delay (>7 days after diagnosis) was observed in 42.4% of the patients, among which, cases enrolled under Pre-XDR contributed substantially to treatment delay (72.0%), followed by LTR (43.6%), STR (39.1%) and XDR (33.3%). Conclusion: Timely diagnosis and prompt treatment initiation remain fundamental focus of the National TB program. The findings of the study, however suggest gaps in timeliness of treatment initiation for the drug-resistant TB patients, which could bring adverse treatment outcomes. Moreover, there is an alarming delay in second line treatment initiation for the Pre-XDR TB patients. Therefore, this study generates evidence to identify existing gaps in treatment initiation and highlights need for formulating specific policies and intervention in creating effective linkage between the RR TB diagnosis and enrollment on second line TB treatment with intensified efforts from health providers for follow-ups and expansion of more decentralized, adequate, and accessible diagnostic and treatment services for DR-TB, especially Pre-XDR TB cases, due to the observed long treatment delays.

Keywords: drug-resistant, tuberculosis, treatment initiation, Nepal, treatment delay

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Authors: Malesa Kgashane Johannes

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The ineffective use of contraceptives among married couples has always been a challenge. This article discusses the culture-religious normative barriers that infringe on married women’s rights, justice, and dignity. The study was qualitative in nature and focused on understanding how religion and culture contribute to women’s ineffective use of contraceptives within marriage. Exploratory, descriptive, and contextual designs were applied. Twenty-eight (28) participants were interviewed, and the data was analysed through Tesch’s steps of qualitative analysis. The findings of the study highlighted the role played by religion and culture as barriers to women’s effective use of contraceptives within marriage.

Keywords: women, contraceptives, religion, culture, marriage

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Authors: Behcet Al, Şener Cindoruk, Suat Zengin, Mehmet Murat Oktay, Mehmet Mustafa Sunar, Hatice Eroglu, Cuma Yildirim

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Objective: In present study we aimed to investigate the chronic drug use due to chronic diseases in patients admitted to emergency department. Materials-Methods: 144 patients who applied to emergency department (ED) of medicine school of Gaziantep University between June 2013 and September 2013 with chronic diseases and use chronic drugs were included. Information about drugs used by patients were recorded. Results: Of patients, half were male, half were female, and the mean age was 58 years. The first three common diseases were diabetes mellitus, hypertension and coronary artery diseases. Of patients, %79.2 knew their illness. Fifty patients began to use drug within three months, 36 patient began to use within the last one year. While 42 patients brought all of their drugs with themselves, 17 patients brought along a portion of drugs. While three patients stopped their medication completely, 125 patients received medication on a regular basis. Fifty-two patient described the drugs with names, 13 patients described with their colors, 3 patients described by grammes, 45 patients described with the size of the tablet and 13 patients could not describe the drugs. Ninety-two patients explained which kind of drugs were used for each diseases, 17 patient explained partly, and 35 patients had no idea. Hundred patients received medication by themselves, 44 patients medications were giving by their relatives and med carers. Of medications, 140 were written by doctors directly, three medication were given by pharmacist; and one patient bought the drug by himself. For 11 patients the drugs were not harmonious to their diseases. Fifty-one patients admitted to the ED two times within last week, and 73 admitted two times within last month. Conclusion: The majority of patients with chronic diseases and use chronic drugs know their diseases and use the drugs in order, but do not have enough information about their medication.

Keywords: chronic disease, drug use, emergency department, medication

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Authors: Krishna Dahiya, Esha Charaya

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Induction of labour is a common obstetrical intervention. Around 1 in every 4 patient undergo induction of labour for different indications Purpose: To study the efficacy of the combination of Foley bulb and vaginal misoprostol in comparison to vaginal misoprostol alone for cervical ripening and induction of labour. Methods: A prospective randomised study was conducted on 150 patients with term singleton pregnancy admitted for induction of labour. Seventy-five patients were induced with both Foley bulb, and vaginal misoprostol and another 75 were given vaginal misoprostol alone for induction of labour. Both groups were then compared with respect to change in Bishop score, induction to the active phase of labour interval, induction delivery interval, duration of labour, maternal complications and neonatal outcomes. Data was analysed using statistical software SPSS version 11.5. Tests with P,.05 were considered significant. Results: The two groups were comparable with respect to maternal age, parity, gestational age, indication for induction, and initial Bishop scores. Both groups had a significant change in Bishop score (2.99 ± 1.72 and 2.17 ± 1.48 respectively with statistically significant difference (p=0.001 S, 95% C.I. -0.1978 to 0.8378). Mean induction to delivery interval was significantly lower in the combination group (11.76 ± 5.89 hours) than misoprostol group (14.54 ± 7.32 hours). Difference was of 2.78 hours (p=0.018,S, 95% CI -5.1042 to -0.4558). Induction to delivery interval was significantly lower in nulliparous women of combination group (13.64 ± 5.75 hours) than misoprostol group (18.4±7.09 hours), and the difference was of 4.76 hours (p=0.002, S, 95% CI 1.0465 to 14.7335). There was no difference between the groups in the mode of delivery, infant weight, Apgar score and intrapartum complications. Conclusion: From the present study it was concluded that addition of Foley catheter to vaginal misoprostol have the synergistic effect and results in early cervical ripening and delivery. These results suggest that the combination may be used to achieve timely and safe delivery in the presence of an unfavorable cervix. A combination of the Foley bulb and vaginal misoprostol resulted in a shorter induction-to-delivery time when compared with vaginal misoprostol alone without increasing labor complications.

Keywords: Bishop score, Foley catheter, induction of labor, misoprostol

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Authors: Chang Liu, Hanwen Zhang, Vikash Sharma, Don Eliseo Lucerno-Prisno III, Emmanuel Yujuico, Maulik Chokshi, Prashanthi Krishnakumar, Bach Xuan Tran, Giang Thu Vu, Kamilla Anna Pinter, Shenglan Tang

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Background and Aims: Globally, many health systems focus on hospital-based healthcare models targeting acute care and disease treatment, which are not effective in addressing the challenges of ageing populations, chronic conditions, multi-morbidities, and increasingly unhealthy lifestyles. Recently, integrated care programs on chronic diseases have been developed, piloted, and implemented to meet such challenges. However, integrated care programs in the Asia-Pacific region vary in the levels of integration from linkage to coordination to full integration. This study aims to identify and analyze existing cases of integrated care in the Asia-Pacific region and identify the facilitators and barriers in order to improve existing cases and inform future cases. Methods: The study is a comparative study, with a combination approach of desk-based research and key informant interviews. The selected countries included in this study represent a good mix of lower-middle income countries (the Philippines, India, Vietnam, and Fiji), upper-middle income country (China), and high-income country (Singapore) in the Asia-Pacific region. Existing integrated care programs were identified through the scoping review approach. Trigger, history, general design, beneficiaries, and objectors were summarized with barriers and facilitators of integrated care based on key informant interviews. Representative case(s) in each country were selected and comprehensively analyzed through deep-dive case studies. Results: A total of 87 existing integrated care programs on chronic diseases were found in all countries, with 44 in China, 21 in Singapore, 12 in India, 5 in Vietnam, 4 in the Philippines, and 1 in Fiji. 9 representative cases of integrated care were selected for in-depth description and analysis, with 2 in China, the Philippines, and Vietnam, and 1 in Singapore, India, and Fiji. Population aging and the rising chronic disease burden have been identified as key drivers for almost all the six countries. Among the six countries, Singapore has the longest history of integrated care, followed by Fiji, the Philippines, and China, while India and Vietnam have a shorter history of integrated care. Incentives, technologies, education, and performance evaluation would be crucial for developing strategies for implementing future programs and improve already existing programs. Conclusion: Integrated care is important for addressing challenges surrounding the delivery of long-term care. To date, there is an increasing trend of integrated care programs on chronic diseases in the Asia-Pacific region, and all six countries in our study set integrated care as a direction for their health systems transformation.

Keywords: integrated healthcare, integrated care delivery, chronic diseases, Asia-Pacific region

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Authors: Ibrahim M. Labouta, Marwa H. El-Wakil, Hayam M. Ashour, Ahmed M. Hassan, Manal N. Saudi

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The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Among the wide variety of heterocycles that have been explored for developing c-Met kinase inhibitors, the 1,2,4-triazines have been rarely investigated, although they are well known in the literature to possess antitumor activities. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives possessing N-acylarylhydrazone moiety and another series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-MP in order to explore their “double-drug” effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antiproliferative activity and four compounds showed potent inhibitory activity more than the reference drug Foretinib against one or more cancer cell lines. The obtained results revealed that the potent compounds are highly selective to A549 (lung adenocarcinoma) cancer cell line. The c-Met kinase inhibitory activity of the potent derivatives is still under investigation. The present study clearly demonstrates that the 1,2,4-triazine core ring exhibits promising antitumor activity with potential c-Met kinase inhibitory activity.

Keywords: 1, 2, 4-triazine, antitumor, c-Met inhibitor, double-drug

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Authors: Lucy Horrobin, Rebecca Fores

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Background: Muay Thai is an increasingly popular combat sport worldwide. Further academic research in the sport will contribute to its professional development. This research sought to produce normative data in relation to the physical and physiological characteristics of professional Muay Thai boxers, as, currently no such data exists. The ultimate aim being to inform appropriate training programs and to facilitate coaching. Methods: N = 9 professional, adult, male Muay Thai boxers were assessed for the following anthropometric, physical and physiological characteristics, using validated methods of assessment: body fat, hamstring flexibility, maximal dynamic upper body strength, lower limb peak power, upper body muscular endurance and aerobic capacity. Raw data scores were analysed for mean, range and SD and where applicable were expressed relative to body mass (BM). Results: Results showed similar characteristics to those found in other combat sports. Low percentages of body fat (mean±SD) 8.54 ± 1.16 allow for optimal power to weight ratios. Highly developed aerobic capacity (mean ±SD) 61.56 ± 5.13 ml.min.kg facilitate recovery and power maintenance throughout bouts. Lower limb peak power output values of (mean ± SD) 12.60 ± 2.09 W/kg indicate that Muay Thai boxers are amongst the most powerful of combat sport athletes. However, maximal dynamic upper body strength scores of (mean±SD) 1.14 kg/kg ± 0.18 were in only the 60th percentile of normative data for the general population and muscular endurance scores (mean±SD) 31.55 ± 11.95 and flexibility scores (mean±SD) 19.55 ± 11.89 cm expressed wide standard deviation. These results might suggest that these characteristics are insignificant in Muay Thai or under-developed, perhaps due to deficient training programs. Implications: This research provides the first normative data of physical and physiological characteristics of Muay Thai boxers. The findings of this study would aid trainers and coaches when designing effective evidence-based training programs. Furthermore, it provides a foundation for further research relating to physiology in Muay Thai. Areas of further study could be determining the physiological demands of a full rules bout and the effects of evidence-based training programs on performance.

Keywords: fitness testing, Muay Thai, physiology, strength and conditioning

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Authors: Frista Dearetha Marasabessy, Usep Suhud, Mohammad Rizan

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The study objective was to compare influencing factors on customer retention of two brands – SimPATI and IM3 – of telecommunication services owned by Telkomsel and Indosat, two giant mobile telecommunication providers in Indonesia. The authors applied predictor variables including perceived tariff, perceived quality, switching barriers, and customer satisfaction. These variables were used after reviewing literature in quantitative studies on consumer behaviour relating to telecommunication services. This study used indicators adopted and adapted from literature. The quantitative data were gathered in Jakarta, involving 205 subscribers of SimPATI and 202 subscribers of IM3. The authors selected respondents purposively. Data were analysed using both exploratory and confirmatory factor analyses. Two fitted models were developed confirming factors that were involved in customer retention as stated on the proposed model: perceived tariff, perceived quality, switching barriers, and customer satisfaction. However, parts of the hypotheses were rejected.

Keywords: customer retention, switching barriers, telecommunication providers, structural equation model, SimPATI, IM3, Indonesia

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Authors: Harish K. Chandrawanshi, Mithun S. Rajput, Neelima Choure, Purnima Dey Sarkar, Shailesh Jain

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The present research study aimed to fabricate and evaluate biodegradable nanoparticles of aromatase inhibitor letrozole, intended for breast cancer therapy. Letrozole loaded poly(D,L-lactide-co-glycolide acid) nanoparticles were prepared by solvent evaporation method using dichlorometane as solvent (oil phase) and polyvinyl alcohol (PVA) as aqueous phase. Prepared nanoparticles were characterized by particle size, infrared spectra, drug loading efficiency, drug entrapment efficiency and in vitro release and also evaluated for in vivo anticancer activity. The high speed homogenizer was used to produce stable nanoparticles of mean size range 198.35 ± 0.04 nm with high entrapment efficiency (69.86 ± 2.78%). Percentage of drug and homogenization speed significantly influenced the particle size, entrapment efficiency and release (p<0.05). The nanoparticles show significant in vivo anticancer activity against Ehrlich ascites carcinoma in mice. The significant system sustained the release of letrozole drug effectively and further investigation could exhibit its potential usefulness in breast cancer therapy.

Keywords: breast cancer/therapy, letrozole, nanoparticles, PLGA

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Authors: Siphesihle Hlongwane

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Background: Globally, alcohol consumption, smoking, and the use of illicit drugs kill more than 11.8 million people each year. In sub-Saharan Africa, substance abuse is responsible for more than 6.4% of all deaths recorded and about 4.7% of all Disability Adjusted Life Years (DALYs), with numbers still expected to grow if no drastic measures are taken to curb and address drug use. In a setting where substance use is rife, understanding contextual factors that influence an individual’s perceived eligibility to seek rehabilitation is paramount. Using the candidacy framework, we unpack how situational factors influence an individual’s perceived eligibility for healthcare uptake in adolescents and youth with substance use disorder (SUD). Methods: The candidacy framework is concerned with how people consider their eligibility for accessing a health service. The study collected and analyzed primary qualitative data to answer the research question. Data were collected between January and July 2022 on participants aged between 18 and 35 for drug users and 18 to 60 for family members. Participants include 20 previous and current drug users and 20 family members that experience the effects of addiction. A pre-drafted semi-structured interview guide was administered to a conveniently sampled population supplemented with a referral sampling method. Data were thematically analyzed using the NVivo 12pro software to manage the data. Findings: Our findings show that people with substance use disorders are aware of their drug use habits and acknowledge their candidacy for health services. Candidacy for health services is also acknowledged by those around them, such as family members and peers, and as such, information on the navigation of health services for drug users is shared by those who have attended health services, those affected by drug use, and this includes health service research by family members to identify accessible health services. While participants reported willingness to quit drug use if assistance is provided, the permeability of health care services is hindered by both individual determinations to quit drug use from long-time use and the availability of health services for drug users, such as rehabilitation centers. Our findings also show that drug users are conscious and can articulate their ailments; however, the hunt for the next dose of drugs and long waiting cues for health service acquisition overshadows their claim to health services. Participants reported a mixture of treatments prescribed, with some more gruesome than others prescribed, thus serving as both a facilitator and barrier for health service uptake. Despite some unorthodox forms of treatments prescribed in health care, the majority of those who enter treatment complete the process of treatment, although some are met with setbacks and sometimes relapse after treatment has finished. Conclusion: Drug users are able to ascertain their candidacy for health services; however, individual and environmental characteristics relating to drug use hinder the use of health services. Drug use interventions need to entice health service uptake as a way to improve candidacy for health use.

Keywords: substance use disorder, rehabilitation, drug use, relapse, South Africa, candidacy framework

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Authors: Wanwimon Mekwimon

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Drug addiction is a serious problem in Thailand which has occurred continuously and repeatedly and enormously impacting health and economy of drug users. The indigenous wisdom and folk medicine is an attractive alternative choice, especially in detoxification and rehabilitation period. There are two objectives: First is to study about rehabilitation process and the curing for drug eaters and 2nd is to investigate the effectiveness of the curing and rehabilitation process by indigenous wisdom at Tamkrabok monastery, Pra-Puttabat district, Saraburi province. The main informants are 10 curers, 15 patients and 17 after-1-year rehabilitators. In the process, the semi-structured questionnaire is administered, the data are analyzed and proved by triangulation. The curing and rehabilitation process which use herbal remedies has a period of 15 days (5 days for detoxification and 10 days for recovery period) and the occupational training and self-consciousness awakening were delivered. The follow-up process includes twice-a-month recall for 6 months, follow-up letters and in depth interview with their families. The outcome of 1 year post-treatment was 94% (16 from 17). There are many reasons for not relapsing: the recovering patients have drawn on their inner strength, self-awareness and coping skill as well as their family and social support while rehabilitation process which includes difficulties in contacting with family members. They can void themselves from high risk situations to relapse. Recommendations: The follow-up system should be improved for continuous quality improvement, there should be the qualification standard for herbal remedies and the comparison among rehabilitation process of Tamkrabok and another methods are to be guideline for the further development.

Keywords: rehabilitation, drug addiction, Thai indigenous knowledge, herbal remedies

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