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    Novel Design and Analysis of an Oral Cannabidiol (Cbd) Therapeutic Delivery System for Pain Management
    (University of the Witwatersrand, Johannesburg, 2023-11) Khan-Flear, Faryal; Adeyemi, Samson A.; Kondiah, Pierre P. D.; Choonara, Yahya E.
    Cannabidiol (CBD) is a non-psychoactive cannabinoid used for its antinociceptive, analgesic and anti-inflammatory properties in chronic pain. The endocannabinoid system (ECS) influences CBD: receptor binding to generate or regulate antinociceptive responses, producing centrally acting analgesia predominantly through Cannabinoid receptor 1 (CB1) abundant in the brain and spinal cord. In contrast, Cannabinoid receptor 2 (CB2) modulates inflammatory responses in immune system cells and tissues. Most oral medications can have inefficient absorption ability and insufficient therapeutic bioavailability due to the solubility of active ingredients and dosage form dissolution. Although the high lipophilicity of CBD enables it to cross the blood-brain barrier (BBB), which prevents the entry of most systematically administered drugs, the oil-soluble CBD is poorly soluble in water, resulting in erratic, incomplete absorption and poor drug bioavailability, preventing therapeutic doses from reaching specific receptors and regions in the brain. Directly ingested CBD also undergoes hepatic and intestinal metabolism, further contributing to therapeutic insufficiencies. Lipid-Based Drug Delivery Systems (LBDDS) can circumvent the drug's hysicochemical properties and the body's protective biological barriers to enhance drug-receptor interaction and elicit a biological response. Lipid combinations in self-emulsifying lipid formulations (SELF) create liposome nanocarriers that entrap and release CBD, providing a non-invasive, transitory, regionally selective delivery method. Nanoliposomes restrict therapeutic delivery to targeted areas, minimizing systemic toxicity and improving drug bioavailability. Manipulating the physical, chemical, and mechanical aspects of nano-liposomes and the material properties of their constituents concerning human anatomy and physiology can help or hinder therapeutic efficiency, drug safety, and delivery. Most therapeutic nanoliposome designs fall within 50–100 nm, facilitating passive transport across the BBB enabling drug receptor binding at brain and spinal cord receptor sites. Modulator uptake and interactions with host cells, enhanced uptake by target cells, and limits accumulation in specific tissues. Nanoliposomes smaller than 100 nm also extend blood circulation by evading renal, hepatic, and immunogenic sequestration and clearance by the mononuclear phagocyte system (MPS), the reticuloendothelial system (RES), opsonization, modulator uptake and interactions with host cells, limited accumulation in specific tissues, low uptake by target cells. This experiment used established system predictors such as HLB and LogP values, Poulton's Lipid Classification System (LCS), Biopharmaceutics Classification System (BCS), Lipinski's Rule of 5 (Ro5), FBDD Rule of 3 (Ro3), Biopharmaceutics Drug Disposition Classification System (BDDCS) to evaluate the critical quality attributes of two optimized formulations able to deliver CBD to the brain and spinal cord. Both formulations consisted of a phospholipid (soy lecithin), unmodified vegetable oils (coconut, olive/castor oil), surfactants (Span 80 and Tween 20), and a cosolvent (ethyl acetate) in the same ratios with the same ingredients, except that the olive oil in one formulation replaced castor oil in the other. These formulations molecularly dispersed CBD in the polymeric matrix of an unstable amorphous solid dispersion (ASD), improving drug solubility and bioavailability compared to crystalline forms. Thermodynamically unstable ASD must be assessed for quality, stability, and resilience to design helpful dosage forms. Both optimized validation batches successfully encapsulated CBD in liposomes in the eutectic ASD mixtures, as reflected in Fourier transform infrared spectroscopy (FTIR) spectrograms and the Differential scanning calorimetry (DSC). The olive oil-containing formulation produced self-micro-emulsifying drug delivery system (SMEDDS). At the same time, the castor oil preparation formed a self-nano-emulsifying drug delivery system (SNEDDS), accounting for the differences in particle size, size distribution, zeta potential, rheology, morphology, drug release and cell culture analysis. The differences arose due to the oils' unique fatty acid composition and chemistry. Drug release test results of each formulation loaded in hydroxypropyl methylcellulose (HPMC) capsules showed good timing for capsule dissolution and a burst release preceding sustained release over 48 hours. Drug release test results established cell viability in culture studies. The positive cell proliferation indicated that the CBD concentrations released by both formulations were non-toxic to mouse embryonic fibroblasts (NIH/3T3) and human embryonic kidney epithelial cell (HEK 293) cultures. Although both formulations yielded favourable results, the analysis indicated that the castor oil formulation was more robust and, therefore, suitable as a nanocarrier for CBD.
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    Identification of third year midwifery skills that could benefit from simulated practice prior to clinical midwifery placements
    (2021) Singaram, Kerry-Ann
    Neophyte midwifery students often feel anxious and inadequate during their clinical placements, as they are expected to perform midwifery skills as early as their first day in the clinical environment. Midwifery educators are seeking out creative ways to create practice opportunities for their students with regards to skills practice, and simulation as a teaching strategy offers a learning environment for safe practice of skills. The use of simulation in midwifery is a fairly new concept, and its future growth is dependent upon research to provide a sound base from which it may grow and develop to meet the needs of the students. The purpose of the study was to identify key midwifery skills that could be taught and practiced using simulation prior to student midwives’ clinical placements that would better equip student midwives to manage their midwifery clinical placements. Findings from the study could serve as a foundational basis for future midwifery simulated programs. The research design and method was qualitative in nature and data was collected from focus group discussions with fourth-year student nurses and their respective midwifery lecturers. Clinical facilitators who are based in the clinical environment and responsible for the training of third year midwifery students were invited to participate in the study, however, were unable to attend. The researcher felt that, this created a limitation to the study as they might have added additional information or a different perspective about novice midwifery skills training. Findings identified specific midwifery skills that could benefit from simulated practice as well as how best skills could be practiced within facilitation of simulation in third year midwifery practice. Summary of findings included the identification of the following midwifery skills that participants identified as being important with regards to simulated practice: completion of documentation; vaginal examinations; management of second stage of labour and offering of psychological support. IV, Participants together with the researcher gives suggestions on how best simulation can be facilitated for developing confidence in neophyte student midwives before their first clinical placement. Based on the findings of this research, recommendations were made to guide midwifery lecturers when planning simulation activities.
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    Experiences of professional nurses in providing support to student nurses in the clinical practice environment of a private hospital in Gauteng
    (2021) Jones, Jennifer
    Quality in nursing education is a global focus due to the many challenges facing healthcare the world over. Clinical learning is an important component in nursing training and nursing experiences during clinical placement are crucial to prepare the student to become safe, competent Professional Nurses. However recent studies have shown that the students’ clinical training is not always effective in preparing them for their future role. Support in the clinical environment by the Professional Nurse is crucial to assist the student to develop confidence and competence to transition into the Professional Nurse role. The objective of this study was to describe the experiences of Professional Nurses in providing support to student nurses in the clinical practice environment of a private hospital. An exploratory qualitative study using in depth interviews of fifteen Professional Nurses was done. The data collected was then analysed using thematic analysis. The identified themes and categories were discussed to offer meaning and insight. The study provided an understanding of how support of the student nurse is currently experienced and perceived by the Professional Nurse in the clinical practice environment with a view to identifying ways of improving support to the student nurse in the future. It was found that the clinical environment is unpredictable and whilst the Professional Nurses acknowledged they needed to support the student, it was often challenging to do this effectively leaving them feeling frustrated and disappointed. The study took place during the COVID -19 pandemic which caused major disruptions to the everyday functioning and operations of hospitals globally, and the study site was no exception. Recommendations to improve support to the student nurse were made in the areas of Clinical Practice, Nursing Education and Research.
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    The impact of lower limb amputation on quality of life: a study done in the Johannesburg Metropolitan area, South Africa
    (University of the Witwatersrand, Johannesburg, 2010-01-29T07:15:06Z) Godlwana, Lonwabo L.
    Background: The impact of non-traumatic lower limb amputation on participant’s quality of life (QOL) is unknown. In an effort to provide better care for people with lower limb amputation, there is a need to first know the impact of this body changing operation on people’s quality of life. Aim of the study: To determine the impact of lower limb amputation on QOL in people in the Johannesburg metropolitan area during their reintegration to their society/community of origin. Objectives: 1. To establish the pre-operative and post-operative:  QOL of participants (including the feelings, experiences and impact of lower limb amputation during the time when they have returned home and to the community).  The functional status of participants.  Household economic and social status of these participants. 2. To establish factors influencing QOL. Methods: A longitudinal pre (amputation) test –post (amputation) test study utilized a combination of interviews to collect quantitative data and in-depth semi-structured interviews to gather qualitative data. Consecutive sampling was used to draw participants (n=73) for the interviews at the study sites pre-operatively. The three study sites were Chris Hani Baragwanath Hospital, Charlotte Maxeke Johannesburg General Hospital and Helen Joseph Hospital. Participants were then followed up three months later for post-operative interviews and key informants were selected for in-depth interviews (n=12). Inclusion criteria: Participants were included if they were scheduled for first time unilateral (or bilateral amputation done at the same time) lower limb amputation. The participants were between the ages of 36-71 years. Exclusion criteria: Participants who had an amputation as a result of traumatic or congenital birth defects were excluded from the study. Participants with comorbidities that interfered with function pre-operatively were not included. Procedures: Ethics: Ethical clearance was obtained from the Committee for Research on Human Subjects at the University of the Witwatersrand and permission was obtained from the above hospitals. Participants gave consent before taking part in the study. Instrumentation: A demographic questionnaire, the EQ-5D, the Modified Household Economic and Social Status Index (HESSI), the Barthel Index (BI) and semi-structured in-depth interviews were used. Data collection: Participants were approached before the operation for their preoperative interviews using the above questionnaires and then followed up postoperatively using the same questionnaires and some were selected to participate in semi-structured in-depth interviews three months later. Pilot study: The demographics questionnaire and the modified HESSI were piloted to ensure validity and reliability. iii Data analysis: Data were analyzed using the SPSS Version 17.0 and STATA 10.0. The significance of the study was set at p=0.05. All continuous data are presented as means, medians, standard deviations and confidence intervals (CI 95%). Categorical data are presented as frequencies. Pre and post operative differences were analyzed using Wilcoxon Signed-rank test. A median regression analysis (both the univariate and multivariate regression) was done to establish factors influencing QOL. Pre and post operative differences in the EQ-5D items and the BI items were analyzed using Chi square/Fischer’s exact depending on the data. Data were pooled for presentation as statistical figures in tables. Both an intension to treat analysis and per protocol analysis were used. A grounded theory approach was used to analyze the concepts, categories and themes that emerged in the qualitative data. Results: Twenty-four participants (33%) had died by the time of follow up. At three months, n=9 (12%) had been lost to follow up and 40(55%) was successfully followed up. The preoperative median VAS was 60 (n=40). The postoperative median VAS was 70. The EQ-5D items on mobility and usual activities were reported as having deteriorated significantly postoperatively (p=0.04, p=0.001respectively) while pain/discomfort had improved (p=0.003). There was no improvement in QOL median VAS from the preoperative status to three months postoperatively The preoperative median total BI score was (n=40). The postoperative median total BI score was 19. There was a reduction in function (median BI) from the preoperative status to three months postoperatively (p<0.001). The ability to transfer was improved three months postoperatively (p=0.04). Participants were also found to have a decreased ability to negotiate stairs (p<0.001). Mobility was significantly reduced three months postoperatively (p=0.04). During the postoperative stage (n=40), 38% of the participants were married. Most (53%) of the participants had no form of income. The highest percentage of participants in all instances (35%) had secondary education (grade10-11), while 25% had less than grade 5. Only one participant was homeless, 18% lived in shacks, 55% lived in homes that were not shared with other families. People with LLA in the Johannesburg metropolitan area who had no problem with mobility preoperatively (EQ-5D mobility item), who were independent with mobility (BI mobility item) preoperatively, who were independent with transfer preoperatively (BI transfer item) had a higher postoperative quality of life (postoperative median EQ-5D- VAS) compared to people who were dependent or had problems with these functions preoperatively. Being females was a predictor of higher reported quality of life compared to being male. Emerging themes from the qualitative data were psychological, social and religious themes. Suicidal thoughts, dependence, poor acceptance, public perception about body image, phantom limb related falls and hoping to get a prosthesis were reported. Some reported poor social involvement due to mobility problems, employment concerns, while families and friends were found to be supportive. Participants had faith in God. Conclusion: Participants’ QOL and function were generally scored high both preoperatively and postoperatively but there was a significant improvement in QOL and a significant reduction in function after three months although participants were generally still functionally independent. Good mobility preoperatively is a predictor of good QOL postoperatively compared to people with a poor preoperative mobility status. Generally, most participants had come to terms with the amputation and were managing well while some expressed that they were struggling with reintegration to their community of origin three months postoperatively with both functional and psychosocial challenges.
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    Record review of patients with brain abscess and empyema.
    (University of the Witwatersrand, Johannesburg, 2010-01-22T10:28:25Z) Schwenke, Katherine Linda
    Studies of patients presenting with brain abscess (BA) and Empyema are not routinely focused on occupational therapy (OT). There is a paucity of literature on deficits other than hemiplegia. Aims of this study were to determine the relationship between BA, Empyema, motor and other deficits and whether an OT intervention protocol is needed. Record review was used to establish clinical presentation trends. Hemiplegia was the most common motor deficit and the majority scored below the norm on the Beery- Buktenika Developmental Test of Visual Motor Integration (VMI). Patients with Brain Abscess generally had more significant deficits than those with Empyema for both motor and process deficits. Part B followed up a small sample (n=8) which indicated clinical improvement on the VMI test with the score on the supplemental test of motor coordination remaining a concern. Occupational Therapy is recommended to address these issues based on the Occupational Therapy Practice Framework-II.