List of Titles

Quick View

Infant health: a community-based assessment and educational intervention in two rural communities in the Eastern Cape.

- Kuzeeko, Faith

Authors: Kuzeeko, Faith
Date: 2021
Subjects: Angus Gillis Foundation (South Africa) , Infants -- Mortality -- South Africa , Infants -- Health and hygiene -- South Africa , Breastfeeding -- South Africa -- Eastern Cape , Infants -- Care -- Equipment and supplies , Infants -- Care -- South Africa -- Eastern Cape -- Case studies , Children -- Mortality -- South Africa , High throughput screening (Drug development)
Language: English
Type: text , Thesis , Masters , MPharm
Identifier: http://hdl.handle.net/10962/170837 , vital:41964
Description: South Africa is on track to attaining the 2030 Agenda on reducing under-five deaths to 25 deaths per 1000 live births at its current momentum, however an unacceptable amount of infants are still at risk from preventable illnesses. Malnutrition is the major underlined cause of infant mortality rates in South Africa. Exclusive breastfeeding rates are low nationwide due to low exposure to breastfeeding information, some mothers having other commitments and others having breastfeeding difficulties. Implementation and expansion of simple, cost-effective interventions, such as exclusive breastfeeding for six months to reduce and/or prevent infant mortality rates, remains low in South Africa. The aim of the study was to determine one infant health issue of major concern to participants in two rural villages in the Eastern Cape, namely Glenmore and Ndwayana. The identified infant health issue was used to design an educational intervention in the villages. This was the second phase of this study. A community-based participatory approach was utilized in which the Angus Gillis Foundation, a non-profit organization that works in these communities, was one of the stakeholders. Stock status of WHO priority medicines for infants, semi-structured interviews and focus group discussions were carried out during the baseline study. The intervention phase contained pre-2 intervention semi-structured interviews with ten pregnant women followed by an educational intervention with nine out of the ten; and finally, a post-intervention with seven out of the ten women. A questionnaire was completed by members of the Angus Gillis Foundation to provide feedback on the sustainability of the intervention. Semi-structured interviews revealed that medicines stocked at the clinic parallel those indicated in the WHO priority medicines list for infants. The results from the focus group discussions indicated that mothers do not exclusively breastfeed their infants during the first six months. Pre- and post-intervention results on exclusive breastfeeding illustrated a positive change in participants’ knowledge and intent to breastfeed exclusively for six months. They showed a better understanding of the importance of exclusive breastfeeding and indicated a more focussed intention and confidence to carry out optimal breastfeeding practices. In the questionnaire the members of the Angus Gillis Foundation stated that the intervention is sustainable as it was linked with the existing networks. These include educational programs carried out in the villages by the foundation together with positive health champions, community health workers and women self-help groups; which will be able to build on the present knowledge base. Finally, the study also included the design of a booklet on the identified infant health issue. In conclusion, participants highlighted lack of understanding regarding breastfeeding as an issue of concern during the baseline phase of the study. This community-based educational intervention improved the understanding of breastfeeding among the participants, resulting in a positive change in perception with regards to exclusive breastfeeding practices.
Full Text:

Quick View

Lipid nanocarriers : a novel approach to delivering ophthalmic clarithromycin

- Makoni, Pedzisai Anotida

Authors: Makoni, Pedzisai Anotida
Date: 2021
Subjects: Clarithromycin , Nanomedicine , Nanostructures , Antibiotics , Eye -- Diseases -- Treatment , Ocular pharmacology , Ophthalmic drugs , Karatitis -- Chemotherapy
Language: English
Type: text , Thesis , Doctoral , PhD
Identifier: http://hdl.handle.net/10962/171678 , vital:42109 , 10.21504/10962/171678
Description: The feasibility of incorporating clarithromycin (CLA) into innovative solid lipid nanoparticles (SLN) and nanostructured lipi d carriers (NLC) using hot emulsification ultrasonication (HEUS) was investigated. This approach was investigated in an attempt to address the shortcomings associated with the use of lyophilized parenteral formulations administered via the ocular route suc h as toxic reactions, intolerance and patient discomfort due to frequent insti llation of topical solutions of CLA. In particular, sustained release approaches to delivery may enhance precorneal retention, increase ocular availability and permit dose reduction or use of a longer dosing frequency when treating ocular non - tuberculous m ycobacterial (NTM) keratitis infections. This approach may potentially improve the delivery of CLA to the eye, thereby addressing some or all of the unmet clinical needs described vide infra . Prior to initiating pre - formulation, formulation development a nd optimization studies of CLA - loaded SLN and/or NLC, Design of Experiments (DoE), specifically a Central Composite Design (CCD) was used in conjunction with Response Surface Methodology (RSM) to develop and optimize a suitable method for the quantitative determination of CLA in pharmaceutical formulations and for monitoring CLA release from SLN and/or NLC in vitro . A simple, accurate, precise, sensitive and stability - indicating reversed phase - high performance liquid chromatography (RP - HPLC) method with ele ctrochemical (EC) detection was developed, validated and optimized for the in vitro analysis of CLA loaded SLN and/or NLC formulations. Pre - formulation studies were undertaken to investigate the thermal stability of CLA and bulk lipids to facilitate the s election of lipid excipients for the manufacture of nanocarriers in addition to establishing compatibility of CLA with the excipients. It was established that CLA was thermostable up to a temperature of approximately 300 °C thereby indicating that HEUS cou ld be used for the manufacture of CLA - loaded SLN and/or NLC. Lipid screening revealed that CLA i s, in general, poorly soluble in solid and liquid lipids however a combination of stearic acid (SA) and Transcutol ® HP (THP) exhibited the best dissolution pote ntial for CLA of all lipids tested . Stearic acid appears to exist as polymorphic form B prior to exposure to heat however occurs as the form C polymorph following heating at 85 °C for one hour. The best ratio for the mixture of SA and THP for the manufactu re of CLA - NLC ii was an 80:20 ( w/w ) ratio of SA: THP as the two lipids are miscible in this ratio and exhibited the greatest dissolution potential for CLA. Furthermore, an investigation of binary mixtures of CLA/SA and SA/Transcutol ® HP, in addition to eutect ic mixtures of CLA, SA and Transcutol ® HP, revealed no obvious interaction between CLA and the lipids selected for the production of the nanocarriers. Due to the relatively high solubility of CLA in THP in comparison to SA, NLC are likely to exhibit a hig her loading capacity (LC) and encapsulation efficiency (EE) for CLA than SLN. Consequently the feasibility of incorporating CLA (10% w/w ) into NLC was investigated and evaluation of the production of SLN was not undertaken as the production of these might not result in the manufacture of a delivery technology with a high EE and LC for CLA. Tween ® 20 was used as the surfactant as it is readily available, exhibits little or no cytotoxicity and is relatively cheap. Polyethylene glycol (PEG) was used as a coati ng polymer to impart muco - adhesive properties the formulated CLA - NLC. Response surface methodology (RSM) in conjunction with DoE, specifically a Box - Behnken Design (BBD) used as a screening design was used to identify a formulation composition which would produce a product that would meet the pre - defined target critical quality attributes (CQA) for the nanoparticles viz. particle size (PS) in the nano - range, polydispersity index (PDI) < 0.5, Zeta Potential (ZP) ≥ ± 30 mV, and EE > 80%. The formulation composition identified was subsequently used for the optimization of the manufacturing parameters viz. sonication time and amplitude, using a Central Composite Design (CCD) . The LC and EE, in vitro CLA release, cytotoxicity, osmolarity, pH, degree of crystallinity and lipid modification, elemental analysis and surface morphology of the optimized batch was investigated and mon itored to ensure that CLA - loaded NLC, of the desirable quality, had been produced. On the day of manufacture the mean PS and PDI of the optimized CLA - loaded NLC formulation adjusted to physiological osmolarity (250 – 450 mOsm/kg) was 461.9 ± 40.16 nm and 0. 523 ± 0.104, respectively. The ZP for the optimized NLC generated on the day of manufacture using HPLC grade water as the dispersion medium was - 20.5 ± 4.82 mV. The pH and osmolarity of the optimized CLA - loaded NLC formulation was 7.76 ± 0.01 and 316 ± iii 2 m Osm/Kg, respectively and the EE was 88.62 ± 0.23 %. The optimized NLC exhibited a decreased crystallinity in comparison to the bulk lipid materials. DSC, WAXS and FT - IR revealed that CLA was molecularly dispersed in the nanocarriers. The optimized CLA - load ed NLC exhibited muco - adhesive properties, when tested under stationary conditions using laser doppler anemometry (LDA). The optimized formulation also exhibited sustained release of CLA over 24 hours during in vitro release testing and CLA release was bes t described using the Baker - Lonsdale model . The cumulative % CLA released over 24 hours was 56.13 ± 0.23% and mass balance analysis revealed 41.38 ± 0.02% CLA had been retained in the NLC. In vitro cytotoxicity testing revealed that the optimized CLA - NLC w ere less cytotoxic to HeLa cells when compared to CLA alone and further confirmed that the lipids and excipients used in these studies were of GRAS status . Stability studies revealed that the EE reduced over 28 days by 14.42% and 5.14% when stored at 4 °C and 22 °C , respectively. In addition, the particle size increased from the nm to μm range for samples stored at 22 °C. The findings are a good starting point but require further optimization to ensure prolongation of stability. In addition , the technology requires additional developmental studies and a powder for reconstitution for use as a single - dose considered as single dose packaging may be a solution to the compromised formulation stability observed in these studies. The CLA - NLC produced in these stu dies exhibit sound product attributes which serve as a useful foundation for the novel delivery of antibiotics to the eye. The results suggest that the optimized NLC have the potential to enhance precorneal retention and increase ocular availability of CLA , which in turn may be useful to reduce the required dose and dosing frequency when administering CLA as a reconstituted solution to treat susceptible organisms that infect ocular tissues.
Full Text:

Quick View

A drug utilisation review of lithium at a public sector psychiatric hospital

- Mapfumo, Charlotte

Authors: Mapfumo, Charlotte
Date: 2020-04
Subjects: Lithium -- Therapeutic use , Psychiatric hospitals -- South Africa -- Grahamstown , Drug utilization , Psychiatric hospital care , Manic-depressive illness , Lithium -- Toxicology , Drug monitoring
Language: English
Type: text , Thesis , Masters , M.Pharm
Identifier: http://hdl.handle.net/10962/150541 , vital:38983
Description: Bipolar disorder (BD) is a common mental condition that affects about 60 million people globally. Lithium is among the drugs of choice used to treat BD and other affective disorders such as schizoaffective disorder (SD). Lithium is a mood stabiliser with antimanic, antidepressant and anti-suicidal properties. Lithium has complex mechanisms of action and a narrow therapeutic index (NTI). Therapeutic drug monitoring (TDM) is a vital component of lithium therapy due to its NTI. Lithium toxicity can occur at therapeutic levels and is characterised by symptoms such as blurred vision and convulsions. Lithium interacts with a number of drugs resulting in lithium toxicity or diminished effects of lithium. Symptoms of lithium toxicity range from abdominal pain, convulsions and death. Lithium use is associated with serious adverse effects on renal and thyroid function. Other adverse effects include tremor and weight gain. Monitoring of lithium serum levels, renal and thyroid function are therefore recommended for patients on lithium therapy. Monitoring of these parameters assists in the early detection of any problems associated with lithium use. The metabolic monitoring of lithium is vital due to the adverse effect profile of lithium and the current South African Standard Treatment Guidelines Hospital level: Adults, do not have any recommendations for the monitoring of metabolic parameters. The National Institute for Health and Care Excellence (NICE) may be used and adapted for the South African setting. Aim and Objectives: The general aim of the study was to conduct a drug utilisation review (DUR) on lithium through investigating its prescribing and monitoring patterns in both inpatients and outpatients at Fort England Hospital. Methodology: The study was in the form of a retrospective DUR. Data was collected from 40 files (n=40) of patients who were on treatment with lithium between 1 January 2017-31 December 2017 at Fort England Hospital. The data was collected retrospectively for both in- and outpatients. Compliance of the monitoring requirements with both South African and international guidelines was analysed. Results and Discussion: In 87.50% (n=37) of the cases, patients had been on lithium therapy before 2017 with most patients (n=13; 37.50%) being maintained on 500 mg of lithium. Non-compliance with the South African and NICE guidelines for renal baseline monitoring was 65.00% (n=26) in both guidelines. Non-compliance for baseline thyroid monitoring was 70.00% (n=28) for both guidelines. There was non-compliance in 45.00% (n=18) of the cases for lithium serum level monitoring for both guidelines. Non-compliance with follow-up renal monitoring was 47.50% (n=19) for both guidelines. Compliance with the NICE guidelines for follow-up metabolic monitoring was 67.50% (n=27). Conclusion: There was non-compliance in most cases leaving room for clinical improvement in the monitoring of lithium. Healthcare professionals should be educated on the recommended monitoring guidelines to promote the rational use of lithium in South Africa. Pharmacists should be more involved in the TDM of lithium to promote its safe and effective use.
Full Text:

Quick View

Application of quality by design to the manufacture of a multiparticulate prednisone dosage form

- Manda, Arthur

Authors: Manda, Arthur
Date: 2020-04
Subjects: Drugs -- Quality control , Drugs -- Design -- Quality control , Drugs -- Dosage forms , Drug development -- Quality control , Pharmaceutical industry -- Quality control , Prednisone , High throughput screening (Drug development)
Language: English
Type: text , Thesis , Masters , MSc (Pharmacy)
Identifier: http://hdl.handle.net/10962/117986 , vital:34583
Description: For many years, quality by testing was the only approach to guarantee quality of drug products before the Food and Drug Administration launched the concept of current Good Manufacturing Practice. In order to gain more knowledge of the manufacturing process, a new system known as Quality by Design was introduced into the pharmaceutical industry. Quality by Design is based on thorough understanding of how materials, process parameters and interaction thereof impact final product quality. Quality by Design is a systematic approach to product development which ensures that quality is built into a product during product development and not just tested into it. The aim of Quality by Design is to achieve optimum product quality with consistent dosage form performance and minimal risk of failure in patients. The objective of these studies was to implement a Quality by Design approach to establish a design space for the development and manufacture of a safe, effective and stable multi-partite solid oral dosage form for prednisone as an alternative to currently marketed prednisone formulations. Multi-particulate dosage forms offer significant advantages over conventional technologies. In addition to lowering the incidence of gastrointestinal irritation they exhibit a reduced risk of dose dumping and a large surface area which favours dissolution. Furthermore, their free flowing nature facilitates reproducible capsule filling and consequently uniformity of dosing. Different multi-particulate dosage forms exist however a multiple-unit pellet system was investigated during these studies. Quality by Design principles were used to develop and establish a reversed-phase high performance liquid chromatographic method for quantifying prednisone from solid oral dosage forms. A Central Composite Design was used to generate multivariate experiments and to investigate the impact of input variables on the quality and performance of the analytical method. The optimized method was validated according to International Council for Harmonization guidelines and was found to be linear, precise, accurate and specific for the quantitation of prednisone. Pre-formulation studies were conducted and included the assessment of particle size, particle shape, powder flow properties and compatibility studies. Carr’s index, Hausner ratio and the Angle of Repose were used to evaluate powder flow properties and results generated from all studies suggest the need for adding a glidant and lubricant to improve pellet flow. The images generated from Scanning Electron Microscopy were used to analyze particle shape and size. Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy were used to evaluate API-excipient compatibility. All excipients investigated were found to be compatible with prednisone and suitable for formulation development studies. Extrusion-spheronization was used to manufacture prednisone pellets. Extrusion-spheronization is a multi-step process involving many factors. Quality risk management tools particularly an Ishikawa Fishbone (cause and effect) diagram and failure mode and effects analysis were used to narrow down potentially significant factors to a reasonable number that could be investigated experimentally. Risk priority numbers were used to quantify risk and factors above a set threshold value were considered to be of high risk. A total of eleven risk factors were identified as high. A Plackett-Burman study was conducted to narrow down the eleven high risk factors to identify the most impactful factors viz., microcrystalline cellulose content, sodium starch glycolate content, extrusion speed and spheronization time. Evaluation of four factors was carried over to optimization studies using a Box-Behnken Design and following identifaction of the optimum process settings and excipient content a design space for the manufacture of a multi-partite dosage form containing prednisone was established.
Full Text:

Quick View

Evaluating the prescribing and management practices of clozapine at a public sector psychiatric hospital

- Mukoko, Vimbisai Millicent

Authors: Mukoko, Vimbisai Millicent
Date: 2020-04
Subjects: Clozapine , Schizophrenia -- Chemotherapy , Schizophrenia -- South Africa -- Treatment
Language: English
Type: text , Thesis , Masters , M.Pharm
Identifier: http://hdl.handle.net/10962/123266 , vital:35422
Description: Approximately one percent (1%) of the South African population suffers from schizophrenia. Clozapine has proven to be more effective than conventional antipsychotics in the treatment of schizophrenia, particularly in alleviating positive symptoms. Clozapine is primarily indicated for treatment-resistant schizophrenia due to its severe adverse effect profile. The prescribing guidelines recommend a trial of at least two different antipsychotic drugs before the initiation of clozapine. At least one should be a non-clozapine second generation antipsychotic. Compared to other atypical antipsychotics, clozapine poses the greatest risk of causing a haematological event, such as neutropenia and agranulocytosis. Agranulocytosis (estimated prevalence of 1.3%) is a life-threatening adverse effect. Common adverse effects include weight gain and metabolic syndrome, hypersalivation and constipation. These can also predispose the patient to co-morbid diseases which further complicate their current diagnosis. Haematological and metabolic monitoring is paramount throughout the duration of clozapine therapy. International (NICE guidelines, Clozapine REMS, and Maudsley prescribing guidelines) and national (South African STGs, SASOP treatment guidelines and the SAMF) guidelines recommend these monitoring patterns to assist with the prevention and management of the adverse effects of clozapine.
Full Text:

Quick View

Evaluating the prescribing and management practices of venlafaxine at a public sector psychiatric hospital

- Naidu, Bavika

Authors: Naidu, Bavika
Date: 2020-04
Subjects: Venlafaxine , Anxiety disorcers -- Treatment , Depression, Mental -- Treatment
Language: English
Type: text , Thesis , Masters , M.Pharm
Identifier: http://hdl.handle.net/10962/123200 , vital:35414
Description: Neuropsychiatric conditions have been ranked third in South Africa according to some of the most recent reviews of disease burden, following human immunodeficiency virus/acquired immune deficiency syndrome and other infectious diseases (Bateman, 2012:70; South African Depression and Anxiety Group, 2018). For depressive disorders, the conventional selective serotonin reuptake inhibitors (e.g. fluoxetine), are common first-step treatments due to their relatively low toxicity and high tolerability (Rush et al., 2006:1231). The class of selective noradrenaline reuptake inhibitors (e.g. venlafaxine) is relatively new on the market. The first SNRI to be marketed in the United States was venlafaxine immediate-release (IR). It was approved by the United States FDA in 1993 (Sansone and Sansone, 2014:37) and was soon followed by the introduction of a micro-encapsulated extended-release (XR) formulation in 1997. Currently there is no published or readily available information concerning the prescribing and management patterns of venlafaxine as well as the incidence and types of adverse effects experienced by patients in the public health sector of South Africa besides the established increased in blood pressure.
Full Text:

Quick View

Preparation, characterization and optimization of carbamazepine based pellets prepared by extrusion-spheronization technique

- Makoni, Kudzai Gabriella

Authors: Makoni, Kudzai Gabriella
Date: 2020-04
Subjects: Carbamazepine , Pharmacokinetics , Anticonvulsants , Drugs -- Controlled release , Drugs -- Dosage forms , Tablets (Medicine) , Drugs -- Administration , High performance liquid chromatography , International Conference on Harmonisation , Experimental design
Language: English
Type: Thesis , Masters , MSc (Pharmacy)
Identifier: http://hdl.handle.net/10962/140478 , vital:37893
Description: Carbamazepine (CBZ) is an oral antiepileptic drug (AED) that is prescribed as a first-line treatment for partial seizures. CBZ is a class II compound according to the Biopharmaceutical Classification System (BCS), hence it exhibits low aqueous solubility and high gastrointestinal tract (GIT) permeability...
Full Text:

Quick View

Collaborative health literacy development: a World Health Organization workplace health promotion approach to address tobacco use

- Duxbury, Theodore Orlando

Authors: Duxbury, Theodore Orlando
Date: 2019
Subjects: Tobacco use -- Health aspects , Smoking -- Health aspects , Employee health promotion , Employee health promotion -- Computer programs , Rhodes University -- Employees -- Tobacco use
Language: English
Type: text , Thesis , Masters , MPharm
Identifier: http://hdl.handle.net/10962/104116 , vital:29930
Description: Background: Non-Communicable Diseases (NCDs) are a major global public health threat and tobacco use in particular is the leading cause of preventable illness and mortality globally. Furthermore, vulnerable and socially disadvantaged people get sicker and die sooner, especially because they are at higher risk of being exposed to harmful products such as tobacco and have limited access to health services. Tobacco use also has a major impact on the workplace, adversely affecting work productivity and increasing absenteeism. Both the living and work environments, therefore, play an important role in contributing towards the NCD epidemic. Demographics, culture, behaviour change reluctance and health literacy are all factors which exacerbate tobacco prevalence in South Africa. Workplace health promotion, however, is not well established in many workplaces. This study aimed to develop, implement and evaluate the effectiveness of a culturallysensitive and contextually-appropriate collaborative workplace health promotion literacy programme on tobacco use, utilizing tailored health information leaflets and the Rhodes University peer educators support staff, guided by the World Health Organization Workplace Health Promotion Framework. Method: The research was conducted using a participatory action research approach, which involved four phases: Firstly, the Exploratory phase assessed tobacco-related health promotion policies and practices at Rhodes University; and established facilitating and constraining factors related to tobacco use. Secondly, the Educational health promotion phase involved designing and testing a health promotion educational intervention to address tobacco use related challenges, which took the form of culturally sensitive and appropriate health information leaflets to be used as an educational intervention Thirdly, in the Implementation phase health promotion training workshops were conducted with volunteering Rhodes University Peer Educators. Finally, an Evaluation phase involved evaluating the tobacco health promotion programme presented to the Rhodes University Peer Educators through a focus group discussion; and evaluating Peer Educator recall on the tobacco related health information discussed during the training workshops through a post-post intervention questionnaire. Eight semi-structured interviews (SSIs) and seven focus group discussions (FGDs) were conducted with support staff, peer educators and key stakeholders to establish the need for a comprehensive workplace health promotion initiative, and to identify the facilitating and constraining factors to conducting such an initiative on tobacco use at the University. Three health information leaflets (HILs) were developed collaboratively with the Peer Educators following a series of scientific, end-user testing approaches. The HILs were tested for readability, comprehension, actionability and suitability. A four-day health promotion training programme was conducted to improve user friendliness, memory retention and recall of the HILs by the peer educators and to improve tobacco related health literacy aspects. The participants’ memory recall was evaluated using a pre- and post-, and post-post-intervention questionnaire to evaluate knowledge transfer. The study participants were also equipped with the completed HILs to distribute to their peers and to use as reference sources of information when needed in future. Results: The peer educators and institutional management supported the need for a tobacco workplace health promotion intervention. The intervention and evaluation phase of this study proved that health information material developed was readable, actionable, suitable, userfriendly, culturally sensitive and contextually appropriate. The workshops resulted in a significant increase in the participants’ tobacco related health knowledge. Through the adoption of a collaborative approach to the research, the participants felt empowered and ready to be agents of change amongst their peers in the workplace. Recommendations: The collective use of external expert reviewers, end-user testing techniques and validated computer programmes are recommended to improve the validity of health promotion research outcomes. A longitudinal study that focus on behaviour change, specifically, with health evaluation and monitoring aspects could be conducted as the next step to this study.
Full Text:

Quick View

Workplace health promotion at Rhodes University: harmful use of alcohol

- Marara, Praise

Authors: Marara, Praise
Date: 2019
Subjects: Chronic diseases -- South Africa , Health education -- South Africa , Drinking of alcoholic beverages -- Health aspects -- South Africa , Employees -- Alcohol use -- South Africa , Employee health promotion -- South Africa , Rhodes University -- Employees -- Health and hygiene
Language: English
Type: text , Thesis , Masters , MPharm
Identifier: http://hdl.handle.net/10962/67444 , vital:29088
Description: Background: Non-communicable diseases (NCDs) are responsible for 38 million deaths annually, which translates to 68% of global deaths every year. Incidence and prevalence of NCDs are increasing rapidly and the poor bear a disproportionate burden. The increase in NCDs has been primarily due to a proliferation of modifiable risk factors, such as unhealthy diet, physical inactivity, tobacco use, and excessive alcohol consumption. Substance abuse, mainly of alcohol, is a common cause of health problems in almost all countries across the globe. Alcohol abuse is a major contributor to the global burden of diseases and accounts for 3.3 million deaths, approximately 5.9% of all global deaths, annually. Alcohol misuse is the fifth leading risk factor for premature death and disability and is the top risk factor among people between 15 and 49 years of age. The rise of harmful use of alcohol in South Africa contributes to the disease burden faced by the country, with alcohol-related disorders making up 44.6% of all alcohol-attributable disabilities. Strategies to reduce harmful use of alcohol include national policies and educational interventions including health promotion. Health promotion is a common practice in the prevention of NCDs, but workplace health promotion has not yet been well established in many workplaces. Identification of past workplace initiatives and exploring their facilitating and limiting factors is thus important to consider when planning future initiatives. Raising awareness on harmful use of alcohol through workplace health promotion projects can help to prevent and reduce alcohol-related problems. For these health promotion activities to succeed, they need to be developed with consideration of factors such as the environment, culture, and socio-economic standing of the intended target population. Method: This study, conducted at Rhodes University, followed a mixed methods research approach and consisted of two phases. The first phase of the current study was a needs assessment and involved working with the key stakeholders. Using the Community Based Participatory Research approach and the Centres for Disease Control and prevention workplace health model to guide the research, five semi-structured interviews were conducted with key stakeholders to identify factors affecting workplace health promotion, and their opinions on how to improve these initiatives were sought. The participants were asked to identify areas on which the intended intervention should focus, as well as to identify their preferred means of communicating health messages. During this phase, a group of peer educators who volunteered their involvement in the health promotion project focusing on harmful use of alcohol was also identified. The second phase of this project aimed to address concerns raised in the first phase through a health promotion initiative for support staff that focuses on the prevention of NCDs diseases through reducing alcohol related harm. During the educational health promotion phase of the study, three health information leaflets based on harmful use of alcohol were designed. These leaflets went through a series of evaluations by the researchers’ peers, support staff during a pilot study, peer educators and other health professionals to assess content validity, context specificity, and cultural appropriateness for the target group. The health information leaflets were then used as written materials in the educational intervention of the project and were also used to design a poster. Through participatory involvement, a facilitator’s manual on harmful use of alcohol was developed, which was used during the workshops in the implementation phase of the research. The facilitator’s manual was modified based on provided feedback on improving the content of the facilitator’s manual. The readability of the manual was also performed to make it suitable for the end users. The peer educators were also trained through workshops to enable them to promote and raise awareness on harmful use of alcohol to others in the workplace. Workshops were participatory in nature and were also equipped with the completed health information leaflets to distribute to their peers and to use as reference sources of information when needed. Results: Participants in the semi-structured interviews reported that some health promotion initiatives have previously been attempted and advertised to support staff, but there was poor participant participation. Peer educators reported that these initiatives were not communicated to them and venues and work commitments sometimes were barriers to participation in these projects. The peer educators suggested incentivising initiatives for better participation. Another key suggestion was to inform and to include their managers and supervisors in these initiatives so they are permitted to take time off work. Health education material like posters or leaflets were also proposed as modes of delivering health information. During the design of the material to be used for this project’s intended intervention, the health information leaflets were deemed readable, suitable, actionable, context-specific, and culturally appropriate. Workshops conducted during Phase 2 of the study proved to be valuable in training peer educators. Peer educators also deemed the workshops useful, and reported their readiness to be agents of change in the workplace. Conclusions: Based on the input of key stakeholders and peer educators, there is currently no health promotion policy at Rhodes University, especially with respect to NCDs health promotion policies and protocols for NCDs. Health promotion initiatives, especially for support staff, that address NCDs have previously been attempted at the university but were not successful. Factors affecting workplace health promotion were identified. Knowledge of these factors was useful when implementing the health promotion project on harmful use of alcohol. The health leaflets were deemed suitable for use by the target population. Peer educators who went through the workshops and were provided with the facilitators’ manuals concluded that the sessions were useful in their continued participation in the health promotion project. Continued involvement of the Wellness Office and peer educators can assist in ensuring the sustainability of this workplace health initiative.
Full Text:

Quick View

A medicinal chemistry study in nitrogen containing heterocycles

- Lunga, Mayibongwe Junior

Authors: Lunga, Mayibongwe Junior
Date: 2018
Subjects: Indole , Tetrazoles , Antimalarials , Heat shock proteins , Plasmodium falciparum
Language: English
Type: Master's theses , text
Identifier: http://hdl.handle.net/10962/63521 , vital:28430
Description: Heterocyclic structures have found extensive utility in the field of medicinal chemistry, as prominent regions of pharmacophores resulting in numerous drug treatments for many diseases. Accordingly, in this project we explored the respective antimalarial and anticancer activity exhibited by compounds featuring nitrogen containing indole and tetrazole heterocycles respectively. This thesis therefore comprises of two distinct parts. Part 1. Following the development of resistance towards traditional antimalarial therapy such as chloroquine and emerging resistance towards artemisinin combination therapies, the WHO reported the urgent need for new, effective drugs and identification of new drug targets to combat the Plasmodium falciparum parasite. In 2015 the parasite was the cause of 429 000 deaths, the majority occurring in the sub-Saharan region of Africa. This highlights the failing effectiveness of vector control strategies, reiterating the need to develop alternative control and treatment strategies. In response to this need we wanted to expand and further describe the SAR of the indole based series, indolyl-3-ethanone-α- thioethers, previously synthesized in our laboratory. These compounds were found to exhibit antimalarial activity with compounds 2.26 and 2.27 exhibiting activity against P. falciparum 3D7 in the nanomolar range. Based on these compounds we synthesized compounds 3.21 and 3.24 – 3.32 following a three step reaction pathway. Our results in this study, indicate that compound 3.28, a pnitrothiophenol analogue of 2.27 was the most active of the compounds we synthesized and furthermore was superior in activity against Plasmodium compared to 2.27. This result indicated that the presence of p-NO2 is important in enhancing anti-plasmodial activity. Comparing compounds 3.25 and 3.26 with an oxygen on the ether bridge to compounds 3.29 and 3.30 with a sulfur, we observed an increase in hydrophilicity coupled to a decrease in anti-plasmodial activity in the compounds, thus, highlighting the importance of sulfur for enhanced activity. Furthermore, we investigated bioisosteric replacement of the 5-chloro substituent present in hit compounds 2.27 and 3.28, with an electron withdrawing nitrile (3.27) and electron donating methyl (3.29) and methoxy (3.31) substituents. These substituents decreased anti-plasmodial activity, confirming that a chlorine substituent is optimal for biological activity. This study furthered our understanding of the SAR of indolyl-3-ethanone-α- thioethers for the development of potent anti-plasmodial lead compounds. Part 2. Triple negative breast cancer (TNBC), which disproportionately affects women of sub-Saharan Africa, is unresponsive to hormone-based therapies. This emergence presents a population of patients devoid of effective drug treatment, signaling the urgent need to develop new effective therapies with novel drug targets. Therefore, we identified our target in TNBC cells as the protein-protein interaction between the co-chaperones HOP and HSP90. We reasoned that a disruption of this interaction would ultimately result in cancer cell death via the degradation of essential oncogenic client proteins. Following a fragment screening campaign, which identified several acid and tetrazole containing hits (4.56 – 4.58) which bound to HOP, with low anticancer activity, we sought to develop synthetic methodology to elaborate our fragment hits synthesizing tetrazole containing fragments to target TNBC cell lines. We therefore proceeded to synthesize a range of multi substituted fragments (4.59 – 4.63), utilizing a nitrile (4.66) to access tetrazoles via 1,3-cycloaddition and an acid by nitrile hydrolysis. We successfully synthesized the tetrazole and acid fragments which are currently undergoing characterization for activity against TNBC. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
Full Text:

Quick View

Showing items 21 - 40 of 229