Exposure to antibiotics is an important factor influencing the development of bacterial resistance.  In an era where very few new antibiotics are being developed, a strategy for the development of optimal dosing regimen and combination treatment that reduces the rate of resistance development and overcome existing resistance is of utmost importance. In addition, the optimal dosing in subpopulations is often not fully elucidated. The aim of this thesis was to develop pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PKPD) models that characterize the interaction of antibiotics with bacterial growth, killing and resistance over time, and can be applied to guide optimization of dosing regimens that enhance the efficacy of mono- and combination antibiotic therapy. A mechanism-based PKPD model that incorporates the growth, killing kinetics and adaptive resistance development in Escherichia coli against gentamicin was developed based on  in vitro time-kill curve data. After some adaptations, the model was successfully applied for similar data on colistin and meropenem alone, and in combination, on one wild type and one meropenem-resistant strain of Pseudomonas aeruginosa. The developed population PK model for colistin and its prodrug colistin methanesulfonate (CMS) in combination with the PKPD model showed the benefits for applying a loading dose for this drug. Simulations predicted the variability in bacteria kill to be larger between dosing occasions than between patients. A flat-fixed loading dose followed by an 8 or 12 hourly maintenance dose with infusion duration of up to 2 hours was shown to result in satisfactory bacterial kill under these conditions. Pharmacometric models that characterize the time-course of drug concentrations, bacterial growth, antibacterial killing and resistance development were successfully developed. Predictions illustrated how PKPD models based on in vitro data can be utilized to guide development of antibiotic dosing, with examples advocating regimens that (i) promote bacterial killing and reduce risk for toxicity in preterm and term newborn infants receiving gentamicin, (ii) achieve a fast initial bacterial killing and reduced resistance development of colistin in critically ill patients by application of a loading dose, and (iii) overcome existing meropenem resistance by combining colistin and meropenem

This thesis is focused on the analysis and development of Ensembles of Neural Networks. An ensemble is a system in which a set of heterogeneous Artificial Neural Networks are generated in order to outperform the Single network based classifiers. However, this proposed thesis differs from others related to ensembles of neural networks [1, 2, 3, 4, 5, 6, 7] since it is organized as follows. In this thesis, firstly, an ensemble methods comparison has been introduced in order to provide a rank-based list of the best ensemble methods existing in the bibliography. This comparison has been split into two researches which represents two chapters of the thesis. Moreover, there is another important step related to the ensembles of neural networks which is how to combine the information provided by the neural networks in the ensemble. In the bibliography, there are some alternatives to apply in order to get an accurate combination of the information provided by the heterogeneous set of networks. For this reason, a combiner comparison has also been introduced in this thesis. Furthermore, Ensembles of Neural Networks is only a kind of Multiple Classifier System based on neural networks. However, there are other alternatives to generate MCS based on neural networks which are quite different to Ensembles. The most important systems are Stacked Generalization and Mixture of Experts. These two systems will be also analysed in this thesis and new alternatives are proposed. One of the results of the comparative research developed is a deep understanding of the field of ensembles. So new ensemble methods and combiners can be designed after analyzing the results provided by the research performed. Concretely, two new ensemble methods, a new ensemble methodology called Cross-Validated Boosting and two reordering algorithms are proposed in this thesis. The best overall results are obtained by the ensemble methods proposed. Finally, all the experiments done have been carried out on a common experimental setup. The experiments have been repeated ten times on nineteen different datasets from the UCI repository in order to validate the results. Moreover, the procedure applied to set up specific parameters is quite similar in all the experiments performed. It is important to conclude by remarking that the main contributions are: 1) An experimental setup to prepare the experiments which can be applied for further comparisons. 2) A guide to select the most appropriate methods to build and combine ensembles and multiple classifiers systems. 3) New methods proposed to build ensembles and other multiple classifier systems.

During its first few decades, the People¡¦s Liberation Army Air Force strategy was primarily formulated to support the ground forces¡¦ needs. Serious changes in the way the PLAAF thought about its future really began as a result of Deng Xiaoping¡¦s 1985 ¡§strategic decision¡¨ that directed the armed forces to change from preparation for an ¡§early, major, and nuclear war¡¨ to preparation for ¡§local war.¡¨ These changes included writing new teaching materials, conducting research on combination of offensive and defensive capabilities, and doing research on campaign and strategic theory. Wang Hai initiated the concept of combination of offensive and defensive operations in 1987, but it did not receive much publicity. Since the Gulf war, the PLAAF has been grappling with the demands of a radically changed its strategy that underscored the technological obsolescence of their armaments and so fundamentally affected the missions of the air forces that its traditional training principles and objective were largely inapplicable to. In late 1999, the PLAAF¡¦s commander, Liu Shunyao, began to emphasize the need to fight offensive battles and declare PLAAF¡¦s strategy of combination of offensive and defensive operations to build a People¡¦s Liberation Army capable of waging ¡§local war under high-tech conditions.¡¨ In a future high-tech local war, the PLAAF will be called up as the first one to encounter the enemy and fight until the last minute. It is gradually transitioning from a support service into an independent one and from a national territory air defense type of air force into one that conducts combination of offensive and defensive operations. The PLAAF is working on its way to reform its military conformation, adjust its military training guidelines and renew its old equipment. By establishing an all-weather and attack-defense air force to battle in a modern high-tech environment, it is expected to acquire the full ability to perform ¡§local war under high-tech conditions.¡¨ The purposes of the thesis are as follows: 1. Illustrate the tendency and contents of current air power theories and wars. 2. Illustrate the stages of PLAAF¡¦s development and the roles and performances it takes on in the wars. 3. Clarify the theoretic contents of PLAAF¡¦s air power in each stage. 4. Conclude the present and future contents and actions of the PLAAF¡¦s air power on the theoretic and practical aspects. 5. Analyze the future developments and challenges of PLAAF¡¦s air power. Expected to focus on the discussion on the theoretic and practical aspects, the thesis was organized as a modal for explaining the PLAAF¡¦s air power and to be used as the referential basis to illustrate the developments of the past, present and future PLAAF¡¦s air power.

In this dissertation, a study is conducted to develop a probability based load and resistance factor design criterion for structural members considering the local conditions of Turkey. The Advanced First Order Second Moment (AFOSM) procedure is utilized as the probabilistic method of analysis. Various sources of uncertainties associated with concrete compressive strength, yielding and ultimate strength of reinforcing steel bars and the dimensions of beams, columns and shear walls are analyzed and quantified. The resistance statistics for different failure modes of different types of reinforced concrete structural members are computed by using the resistance parameters within the framework of reliability analysis. Structural load effects of dead, live, wind, snow and earthquake loads are analyzed considering the uncertainties in these loads. For different load combinations, the safety levels corresponding to the current design practice are evaluated in terms of the reliability indexes for reinforced concrete beam, column and shear wall design in flexure and shear, and also column design in combined action of flexure and axial load. Depending on this evaluation and the reliability index values reported from other countries, target reliability indexes are selected for different load combinations and different failure modes of structural members. Finally, a new set of load and resistance factors corresponding to selected target reliabilities and levels of uncertainties are proposed for each different failure modes of the structural members considered in this study, separately.

A model has been developed which simulates a system consisting of a horizontal and vertical ground-coupled heat exchanger connected in parallel to the same heat pump. The model was used in computer simulations to investigate how the annual minimum and mean fluid temperatures at the heat pump varied as several parameters of the combined system were changed. A comparison was also made between different control settings for fluid flow rate distribution between the two exchangers. For the case when the flow rate distribution was not controlled, the effect of viscosity differences between a colder and warmer exchanger was investigated. The short term effects of letting the vertical heat source rest during the warm summer months was then tested. Lastly, the results of the model was compared to a simple 'rule of thumb' that have been used in the industry for this kind of combined system. The results show that using a combined system might not always result in increased performance, if the previously existing exchanger is a vertical ground-coupled heat exchanger. The effects of viscosity differences on the flow distribution seems to be negligible, especially for high net flows. Controlling the fluid flow rates seems to only be worth the effort if the the pipe lengths of the two combined exchangers differ heavily. Letting the vertical ground-coupled heat exchanger rest during summer was shown to in some cases yield an increased short-term performance in addition to the already known positive long term effects. The rule of thumb was shown to recommend smaller dimensions for combination systems than the more realistic analytical model.

Conditions for the establishment of family oriented organization are analysed in this Master's work. Half-standardized (N=63) qualitative and quantitative (N=111) surveys were done. For the processing of qualitative data narrative method was chosen and quantitative data was analysed using to the Wilcoxon's test. Also analysis of documents describing the situation of family and professional roles' combination was done. Held hypotheses proved out only partially. Combination of family and professional roles is important only for the members of university which have children themselves and for a few managing persons and it goes in more informal way. There are some cases when both - family and professional interests - are met, but in the most cases it depends on the situation, circumstances and person's relations with the managers.Recommendations for the combination of family and professional roles, as one of the main factors for the creation of family oriented university, are proposed in this Master's work.

Rural schools in South Africa often face numerous challenges that are largely aggravated by low numbers of learners, low numbers of teachers and a shortage of teaching and learning resources, to mention a few. Hence, the provision of one teacher per grade is perceived as a luxury in many rural schools. Consequently, such challenges have led to many rural schools being affected by multi-grade teaching. Multi-grade classes have more than one grade in one classroom, usually those grades that are close to each other. For instance, Grade R and Grade One learners will be taught in one class by the same teacher. This research study therefore focused on teachers’ pedagogical content knowledge for teaching literacy in a multi-grade foundation phase class. The teaching of reading in isiZulu Home Language was singled out as the literacy component to be investigated. Teachers at the foundation phase need to have a distinctive body of knowledge as they have to be able to blend content in literacy and the appropriate methods of teaching each literacy component. They need to understand how to organize each component of the content and how to deliver it accurately to learners through appropriate methodologies. Moreover, it is imperative to understand that it is a complex process for teachers to intersect content knowledge and pedagogical knowledge. The process becomes even more complex for teachers who teach in a multi-grade class. Reading as a literacy component was put under a particular lens as teaching and assessing this literacy component in a multi-grade context is highly challenging. This was an exploratory case study that was embedded in a qualitative research methodology. A primary school from Ndwedwe Circuit in the KwaZulu-Natal province was purposively sampled. Empirical data for this study were collected from this rural school because it was practising multi-grade teaching in all phases. To collect the data, teachers teaching multi-grade classes were interviewed using semi-structured interviews. Observations were also done during the teaching process and relevant documents were analysed. The documents that were interrogated included daily, weekly and monthly work plans, class timetables, and the school’s calendar. The findings suggested that teachers relied on traditional methods of teaching as the context was complex and beyond their professional capabilities. This study was therefore aimed at contributing to the discourse of how teachers in rural contexts can be trained on multi-grade teaching in order to provide them with appropriate pedagogical knowledge and skills that will empower them to support teaching and learning across grades. / Thesis (M. Ed.)-University of KwaZulu-Natal, Durban, 2012.

South African prescribers have a large choice of combination analgesic preparations available for prescribing. According to Desmeules et al. (2003:8) the advantages of combining analgesics include increasing the duration of analgesia, widening the spectrum of efficacy, improved patient compliance and reduced parenteral abuse potential. According to McMahon (1975:13) one of the principle arguments against fixed-dose combinations is that the physician surrenders flexibility in managing his patient. Combination analgesics may expose patients to ingredients not necessary for pain relief in their particular condition (Beaver, 1984). Rigas (1997:454) explains that the value of pharmaco-economics in providing cost-effective pharmacologic treatment for pain must not only be seen as a containment effort, but rather as a valuation effort. Meaningful economic analyses based on empiric information about cost and a range of subjective and objective outcomes are needed to minimise cost without compromising care. The objective of this study was to review and interpret the prescribing patterns of combination analgesics and the cost associated with their usage for the period 2001-2006 in a section of the private healthcare sector in South Africa. This research can be classified as a quantitative, retrospective drug utilisation review study. Data were obtained from a medicine claims database, and the study population consisted of all combination analgesic prescriptions (Mims® category 3.3) for the period 1 January 2001 to 31 December 2002 and 1 January 2004 to 31 December 2006. Prescribing Patterns of Combination Analgesics in the Private Health Care Sector. Firstly pain and the treatment thereof with combination analgesics were investigated from the literature to understand the disease and to determine the prevalence and treatment thereof. Secondly, managed health care, drug utilisation review, pharmacoeconomics and pharmaco-epidemiology were investigated from the literature to understand these concepts. The influence of the South African government on the medicine pricing regulations was discussed. Thirdly, through the empirical investigation the utilisation patterns of combination analgesics were reviewed, analysed and interpreted. It was determined that combination analgesic drugs represented 8.87% (n=261 907) of all medicine claimed during 2001 (N=2 951 326), decreased to 7.20% (n=381 809) during 2004 (N=5 305 846) after which it increased to 7.92% (n=187 745) in 2006 (N=2 370 572). Between 2001 (N=R379 708 489.00) and 2006 (N=R279 160 832.00) the cost percentage of the combination analgesic drugs decreased from 4.95% (n=R18 798 202.42) to 3.15% (n=R8 791 228.57). The average cost per combination analgesic drugs decreased from R71.77 ± 61.67 to R46.83 ± 43.41 between 2001 and 2006. This decrease was of no practical significance (d<0.8). The average number of combination analgesics per prescription stayed relatively constant varying between 1.01 ± 0.11 in 2001 and 1.02 ± 0.13 in 2006. The percentage generic combination analgesic drugs claimed increased from 29.63% (n=77 608) in 2001 to 66.37% (n=124 600) in 2006 (N=261 907 for 2001 and N=187 745 for 2006) even though generic medicine items claimed by the total database only increased from 26.79% (n=790 548) in 2001 to 40.27% (n=954 561) during 2006 (N=2 951 326 for 2001 and N=2 370 572 for 2006). The combination of ibuprofen 200mg, paracetamol 250mg and codeine phosphate 10mg (e.g. Myprodol® capsules, Mybulen® capsules, Gen-payne® capsules and Ibupain Forte® capsules) represented the active ingredient combination with the highest prevalence for the entire study period, increasing from 28.44% (n=74 483) in 2001 to 33.08% (n=62 100) in 2006 of all combination analgesics prescribed (N=261 907 for 2001 and N=187 745 for 2006). Generic substitution influenced the prevalence of the innovator medicine item, Myprodol® Capsules dramatically, causing a decrease from 23.16% (n=60 631) in 2001 to 3.77% (n=7 084) in 2006 representation of all combination analgesic prescribed. In 2006, the generics of Myprodol® Capsules e.g. Dentopain Forte®, Mybulen® Capsules, Gen-payne® and Ibupain Forte® represented 23.79% (n=44651) of all combination analgesics claimed. Recommendations were derived regarding certain aspects of the clinical and economical management of pain e.g. the implication of generic substitution with regard to cost and prescribing patterns, and the decreasing cost of combination analgesics which might encourage abuse, needs further investigation. South African prescribers have a large choice of combination analgesic preparations available for prescribing. According to Desmeules et al. (2003:8) the advantages of combining analgesics include increasing the duration of analgesia, widening the spectrum of efficacy, improved patient compliance and reduced parenteral abuse potential. According to McMahon (1975:13) one of the principle arguments against fixed-dose combinations is that the physician surrenders flexibility in managing his patient. Combination analgesics may expose patients to ingredients not necessary for pain relief in their particular condition (Beaver, 1984). Rigas (1997:454) explains that the value of pharmaco-economics in providing cost-effective pharmacologic treatment for pain must not only be seen as a containment effort, but rather as a valuation effort. Meaningful economic analyses based on empiric information about cost and a range of subjective and objective outcomes are needed to minimise cost without compromising care. The objective of this study was to review and interpret the prescribing patterns of combination analgesics and the cost associated with their usage for the period 2001-2006 in a section of the private healthcare sector in South Africa. This research can be classified as a quantitative, retrospective drug utilisation review study. Data were obtained from a medicine claims database, and the study population consisted of all combination analgesic prescriptions (Mims® category 3.3) for the period 1 January 2001 to 31 December 2002 and 1 January 2004 to 31 December 2006. Prescribing Patterns of Combination Analgesics in the Private Health Care Sector. Firstly pain and the treatment thereof with combination analgesics were investigated from the literature to understand the disease and to determine the prevalence and treatment thereof. Secondly, managed health care, drug utilisation review, pharmacoeconomics and pharmaco-epidemiology were investigated from the literature to understand these concepts. The influence of the South African government on the medicine pricing regulations was discussed. Thirdly, through the empirical investigation the utilisation patterns of combination analgesics were reviewed, analysed and interpreted. It was determined that combination analgesic drugs represented 8.87% (n=261 907) of all medicine claimed during 2001 (N=2 951 326), decreased to 7.20% (n=381 809) during 2004 (N=5 305 846) after which it increased to 7.92% (n=187 745) in 2006 (N=2 370 572). Between 2001 (N=R379 708 489.00) and 2006 (N=R279 160 832.00) the cost percentage of the combination analgesic drugs decreased from 4.95% (n=R18 798 202.42) to 3.15% (n=R8 791 228.57). The average cost per combination analgesic drugs decreased from R71.77 ± 61.67 to R46.83 ± 43.41 between 2001 and 2006. This decrease was of no practical significance (d<0.8). The average number of combination analgesics per prescription stayed relatively constant varying between 1.01 ± 0.11 in 2001 and 1.02 ± 0.13 in 2006. The percentage generic combination analgesic drugs claimed increased from 29.63% (n=77 608) in 2001 to 66.37% (n=124 600) in 2006 (N=261 907 for 2001 and N=187 745 for 2006) even though generic medicine items claimed by the total database only increased from 26.79% (n=790 548) in 2001 to 40.27% (n=954 561) during 2006 (N=2 951 326 for 2001 and N=2 370 572 for 2006). The combination of ibuprofen 200mg, paracetamol 250mg and codeine phosphate 10mg (e.g. Myprodol® capsules, Mybulen® capsules, Gen-payne® capsules and Ibupain Forte® capsules) represented the active ingredient combination with the highest prevalence for the entire study period, increasing from 28.44% (n=74 483) in 2001 to 33.08% (n=62 100) in 2006 of all combination analgesics prescribed (N=261 907 for 2001 and N=187 745 for 2006). Generic substitution influenced the prevalence of the innovator medicine item, Myprodol® Capsules dramatically, causing a decrease from 23.16% (n=60 631) in 2001 to 3.77% (n=7 084) in 2006 representation of all combination analgesic prescribed. In 2006, the generics of Myprodol® Capsules e.g. Dentopain Forte®, Mybulen® Capsules, Gen-payne® and Ibupain Forte® represented 23.79% (n=44651) of all combination analgesics claimed. Recommendations were derived regarding certain aspects of the clinical and economical management of pain e.g. the implication of generic substitution with regard to cost and prescribing patterns, and the decreasing cost of combination analgesics which might encourage abuse, needs further investigation. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2008.

The survival for high-grade glioma patients is poor and the treatment may cause severe side effects. A common obstacle in the treatment is chemoresistance. To improve the quality of life and prolong survival for these patients prognostic biomarkers and new approaches for chemotherapy are needed. To this end, a strategy to evade chemoresistance was evaluated by combining chemotherapeutic drugs with agents inhibiting resistance mechanisms identified by a bioinformatic analysis (paper I). The prognostic value of 13 different proteins was analyzed in this thesis (papers II-IV). Two of them, p38 mitogen-activated protein kinase (MAPK) and protein tyrosine phosphatase non-receptor type 6 (PTPN6, also known as SHP1) were analyzed for their potential as targets in combination chemotherapy (in paper III and IV, respectively).   We found that: PTPN6 expression and methylation status may be important for survival of anaplastic glioma patients, p38 MAPK phosphorylation may be a potential negative prognostic biomarker for high-grade glioma patients and FGF2 expression may be a potential negative prognostic biomarker for proneural glioma patients. PTPN6 may be a useful target for combination chemotherapy with cisplatin, melphalan or bortezomib in high-grade gliomas. The following drug combinations; camptothecin combined with an EGFR or RAC1 inhibitor, imatinib combined with a Notch or RAC1 inhibitor, temozolomide combined with an EGFR or FAK inhibitor and vandetanib combined with a p38 MAPK inhibitor may be useful combination chemotherapy for high-grade gliomas.

South African prescribers have a large choice of combination analgesic preparations available for prescribing. According to Desmeules et al. (2003:8) the advantages of combining analgesics include increasing the duration of analgesia, widening the spectrum of efficacy, improved patient compliance and reduced parenteral abuse potential. According to McMahon (1975:13) one of the principle arguments against fixed-dose combinations is that the physician surrenders flexibility in managing his patient. Combination analgesics may expose patients to ingredients not necessary for pain relief in their particular condition (Beaver, 1984). Rigas (1997:454) explains that the value of pharmaco-economics in providing cost-effective pharmacologic treatment for pain must not only be seen as a containment effort, but rather as a valuation effort. Meaningful economic analyses based on empiric information about cost and a range of subjective and objective outcomes are needed to minimise cost without compromising care. The objective of this study was to review and interpret the prescribing patterns of combination analgesics and the cost associated with their usage for the period 2001-2006 in a section of the private healthcare sector in South Africa. This research can be classified as a quantitative, retrospective drug utilisation review study. Data were obtained from a medicine claims database, and the study population consisted of all combination analgesic prescriptions (Mims® category 3.3) for the period 1 January 2001 to 31 December 2002 and 1 January 2004 to 31 December 2006. Prescribing Patterns of Combination Analgesics in the Private Health Care Sector. Firstly pain and the treatment thereof with combination analgesics were investigated from the literature to understand the disease and to determine the prevalence and treatment thereof. Secondly, managed health care, drug utilisation review, pharmacoeconomics and pharmaco-epidemiology were investigated from the literature to understand these concepts. The influence of the South African government on the medicine pricing regulations was discussed. Thirdly, through the empirical investigation the utilisation patterns of combination analgesics were reviewed, analysed and interpreted. It was determined that combination analgesic drugs represented 8.87% (n=261 907) of all medicine claimed during 2001 (N=2 951 326), decreased to 7.20% (n=381 809) during 2004 (N=5 305 846) after which it increased to 7.92% (n=187 745) in 2006 (N=2 370 572). Between 2001 (N=R379 708 489.00) and 2006 (N=R279 160 832.00) the cost percentage of the combination analgesic drugs decreased from 4.95% (n=R18 798 202.42) to 3.15% (n=R8 791 228.57). The average cost per combination analgesic drugs decreased from R71.77 ± 61.67 to R46.83 ± 43.41 between 2001 and 2006. This decrease was of no practical significance (d<0.8). The average number of combination analgesics per prescription stayed relatively constant varying between 1.01 ± 0.11 in 2001 and 1.02 ± 0.13 in 2006. The percentage generic combination analgesic drugs claimed increased from 29.63% (n=77 608) in 2001 to 66.37% (n=124 600) in 2006 (N=261 907 for 2001 and N=187 745 for 2006) even though generic medicine items claimed by the total database only increased from 26.79% (n=790 548) in 2001 to 40.27% (n=954 561) during 2006 (N=2 951 326 for 2001 and N=2 370 572 for 2006). The combination of ibuprofen 200mg, paracetamol 250mg and codeine phosphate 10mg (e.g. Myprodol® capsules, Mybulen® capsules, Gen-payne® capsules and Ibupain Forte® capsules) represented the active ingredient combination with the highest prevalence for the entire study period, increasing from 28.44% (n=74 483) in 2001 to 33.08% (n=62 100) in 2006 of all combination analgesics prescribed (N=261 907 for 2001 and N=187 745 for 2006). Generic substitution influenced the prevalence of the innovator medicine item, Myprodol® Capsules dramatically, causing a decrease from 23.16% (n=60 631) in 2001 to 3.77% (n=7 084) in 2006 representation of all combination analgesic prescribed. In 2006, the generics of Myprodol® Capsules e.g. Dentopain Forte®, Mybulen® Capsules, Gen-payne® and Ibupain Forte® represented 23.79% (n=44651) of all combination analgesics claimed. Recommendations were derived regarding certain aspects of the clinical and economical management of pain e.g. the implication of generic substitution with regard to cost and prescribing patterns, and the decreasing cost of combination analgesics which might encourage abuse, needs further investigation. South African prescribers have a large choice of combination analgesic preparations available for prescribing. According to Desmeules et al. (2003:8) the advantages of combining analgesics include increasing the duration of analgesia, widening the spectrum of efficacy, improved patient compliance and reduced parenteral abuse potential. According to McMahon (1975:13) one of the principle arguments against fixed-dose combinations is that the physician surrenders flexibility in managing his patient. Combination analgesics may expose patients to ingredients not necessary for pain relief in their particular condition (Beaver, 1984). Rigas (1997:454) explains that the value of pharmaco-economics in providing cost-effective pharmacologic treatment for pain must not only be seen as a containment effort, but rather as a valuation effort. Meaningful economic analyses based on empiric information about cost and a range of subjective and objective outcomes are needed to minimise cost without compromising care. The objective of this study was to review and interpret the prescribing patterns of combination analgesics and the cost associated with their usage for the period 2001-2006 in a section of the private healthcare sector in South Africa. This research can be classified as a quantitative, retrospective drug utilisation review study. Data were obtained from a medicine claims database, and the study population consisted of all combination analgesic prescriptions (Mims® category 3.3) for the period 1 January 2001 to 31 December 2002 and 1 January 2004 to 31 December 2006. Prescribing Patterns of Combination Analgesics in the Private Health Care Sector. Firstly pain and the treatment thereof with combination analgesics were investigated from the literature to understand the disease and to determine the prevalence and treatment thereof. Secondly, managed health care, drug utilisation review, pharmacoeconomics and pharmaco-epidemiology were investigated from the literature to understand these concepts. The influence of the South African government on the medicine pricing regulations was discussed. Thirdly, through the empirical investigation the utilisation patterns of combination analgesics were reviewed, analysed and interpreted. It was determined that combination analgesic drugs represented 8.87% (n=261 907) of all medicine claimed during 2001 (N=2 951 326), decreased to 7.20% (n=381 809) during 2004 (N=5 305 846) after which it increased to 7.92% (n=187 745) in 2006 (N=2 370 572). Between 2001 (N=R379 708 489.00) and 2006 (N=R279 160 832.00) the cost percentage of the combination analgesic drugs decreased from 4.95% (n=R18 798 202.42) to 3.15% (n=R8 791 228.57). The average cost per combination analgesic drugs decreased from R71.77 ± 61.67 to R46.83 ± 43.41 between 2001 and 2006. This decrease was of no practical significance (d<0.8). The average number of combination analgesics per prescription stayed relatively constant varying between 1.01 ± 0.11 in 2001 and 1.02 ± 0.13 in 2006. The percentage generic combination analgesic drugs claimed increased from 29.63% (n=77 608) in 2001 to 66.37% (n=124 600) in 2006 (N=261 907 for 2001 and N=187 745 for 2006) even though generic medicine items claimed by the total database only increased from 26.79% (n=790 548) in 2001 to 40.27% (n=954 561) during 2006 (N=2 951 326 for 2001 and N=2 370 572 for 2006). The combination of ibuprofen 200mg, paracetamol 250mg and codeine phosphate 10mg (e.g. Myprodol® capsules, Mybulen® capsules, Gen-payne® capsules and Ibupain Forte® capsules) represented the active ingredient combination with the highest prevalence for the entire study period, increasing from 28.44% (n=74 483) in 2001 to 33.08% (n=62 100) in 2006 of all combination analgesics prescribed (N=261 907 for 2001 and N=187 745 for 2006). Generic substitution influenced the prevalence of the innovator medicine item, Myprodol® Capsules dramatically, causing a decrease from 23.16% (n=60 631) in 2001 to 3.77% (n=7 084) in 2006 representation of all combination analgesic prescribed. In 2006, the generics of Myprodol® Capsules e.g. Dentopain Forte®, Mybulen® Capsules, Gen-payne® and Ibupain Forte® represented 23.79% (n=44651) of all combination analgesics claimed. Recommendations were derived regarding certain aspects of the clinical and economical management of pain e.g. the implication of generic substitution with regard to cost and prescribing patterns, and the decreasing cost of combination analgesics which might encourage abuse, needs further investigation. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2008.