The objectives of this study were to assess patient activation levels, to assess association between sociodemographic characteristics and patient activation, to assess association between health status characteristics and patient activation, and to assess association between patient activation and medication adherence among Medicare beneficiaries with type 2 diabetes. A retrospective cohort study was conducted using data from the 2009 through 2013 Medicare Current Beneficiary Survey (MCBS). Patient activation was measured with the Patient Activation Supplement in the MCBS and was categorized as low, moderate, and high levels based on activation scores. Medication adherence was assessed with proportion of days covered (PDC) using Medicare Part D administrative records from the MCBS within a period of six months after measurement of patient activation. The sample included Medicare beneficiaries who completed the MCBS Patient Activation questionnaire, who were diagnosed with type 2 diabetes, and who were 18 or older. Beneficiaries were excluded if they responded “Not ascertained,” “Not Applicable,” “Don’t know” or “Refused” to more than 50 percent of the Patient Activation questions, did not have continuous Medicare Part A and Part D coverage throughout the assessment period, had less than two Medicare Part D claims for an antidiabetic medication throughout the assessment period, used insulin during the assessment period, resided in long-term care facilities, or had Alzheimer’s disease, dementia, mental retardation or mental disorder. All analyses were conducted in SAS 9.4 for Unix environment. An <i>a priori</i> alpha level of 0.05 was used to determine significance. Bivariate and multivariable weighted ordinal logistic regression were applied for assessing associations. A total of 571 individuals met sample selection criteria. The mean age was 72.4 years. Of the 571 persons in the sample, 27.5 percent were at low activation level, 38.7 percent were at moderate activation level, and 33.7 percent were at high activation level. Approximately three-fourths of the sample persons were adherent to antidiabetic medications. Low activation was more likely to be found in males, less educated patients, and patients without arrhythmia. Ex-smokers as compared to non-smokers and overweight patients as compared to those with healthy weight were less likely to report low activation. In multivariable logistic analysis adjusting for race, gender, osteoporosis, Charlson Comorbidity Index score, and number of prescribed medications, patient activation level was not significantly associated with medication adherence. Non-Whites and patients with a Charlson Comorbidity Index score of 1 as compared to those with a score of 0 were more likely to be non-adherent. A lower number of prescribed medications was associated with higher odds of non-adherence.

The present study involved the analyses of the Texas Medicaid prescription claims data. The population studied was made up of subjects between 10 and 18 years who had at least 2 prescriptions of the same oral antidiabetic (OAD) medication from January 1, 2006 through December 31, 2009. Twelve months’ data for each subject were analyzed. The main aim of the study was to describe OAD medication use patterns in the study population, assess trends in Medication Possession Ratio (MPR) and persistence in the study population and determine the relationship between age and MPR and between age and persistence while controlling for covariates. Results of the descriptive statistics, multiple and logistic regression analyses are reported. The average age (± SD) of the 3,109 eligible subjects was 14 (± 2) years; minority populations made up the majority (87%) of the population; 67% of the population were females; and 91% were on the OAD metformin. The overall mean MPR (± SD) for the population was 45% (± 27). A significant negative relationship between MPR and age was reported while controlling for covariates (p<0.0001). Among the covariates, white race and male were significantly associated with a higher MPR, holding other variables constant. When adherence was dichotomized (MPR < 80% and MPR >= 80%), logistic regression analysis also found that age was significantly and negatively related to MPR (p < 0.0001). In addition, the white race and male were again significantly related to a higher level of adherence, holding other variables constant. The overall mean days to non-persistence (± SD) was 108 days (± 86). Persistence was significantly and negatively associated with age, holding other variables constant (p < 0.0001). Among the covariates, white race was significantly related to longer persistence. In conclusion, adherence and persistence are generally low in the study population. Age, gender and race were significantly associated with adherence. Being younger, male, and white were significantly associated with a higher level of adherence, while being younger and white were significantly associated with longer persistence. Healthcare providers therefore need to intensify efforts to improve adherence in pediatric patients especially those at the brink of adulthood. / text

Background and Aims: Type 2 diabetes mellitus (T2DM) is a chronic progressive condition characterised by hyperglycaemia due to insulin deficiency with or without insulin resistance. The prevalence of diabetes is increasing rapidly worldwide and it has a significant burden on health care resources with estimated costs of up to 10% of health expenditure in the UK. With an ageing population, people are now living longer with diabetes which consequently leads to increased multimorbidity and polypharmacy. Some previous studies have not assessed the effect of demographic or geographic factors (such as age, gender, UK nation and social deprivation) on the incidence and prevalence of T2DM in the UK over the past decade. In addition, detailed reports on the patterns of comorbidities in T2DM patients are sparse. Patients with T2DM are at a two-fold higher risk for cardiovascular (CV) disease. Some earlier studies assessing the CV risk associated with available therapies have been inconclusive in determining the preferred regimens. This thesis aimed to: i) assess the incidence and prevalence of T2DM in the UK; ii) investigate and compare mortality risk between T2DM patients and patients without diabetes and explore if it explains the observed prevalence rates; iii) examine the patterns of comorbidities in T2DM patients and matched comparators without diabetes; and iv) assess the comparative CV risk associated with second-line diabetes therapies. Methods: All the studies in this thesis used data from the UK Clinical Practice Research Datalink. Access to linked national hospitalisation, deprivation and mortality data was obtained for the individual studies. Annual overall and gender-specific incidence and prevalence of T2DM were calculated for the study period 2004-2014. Rates were standardised by age bands, gender, neighbourhood social deprivation, and UK nation and expressed per 10,000 person-years (PYRs) with 95% confidence intervals (95% CI). For the mortality analysis, T2DM patients (cases) were matched to patients without diabetes (controls) on age, gender and general practice. Annual mortality rates for the matched T2DM and patients without diabetes were calculated and compared. Cox regression analysis was used to examine the effect of important covariates on the risk for all-cause mortality in the matched cohort and calculate hazard ratios (HR) and 95% CI. The multimorbidity profile in T2DM cases and matched controls, registered in English general practices, were also examined. Annual prevalence rates of 18 physical and mental health comorbidities were determined between 2004 and 2014 using linked primary care and hospitalisation records. For the CV risk analysis, patients prescribed a second-line medication after greater than or equal to90days of metformin monotherapy between 1998 and 2011 were identified. Using a retrospective cohort study design, inverse probability of treatment-weighted time-varying Cox regression models were used to estimate HRs and 95% CI for developing a major CV event (myocardial infarction, stroke, acute coronary syndrome, unstable angina, coronary revascularisation, or CV death) associated with second-line therapies after adjusting for clinically important CV risk factors. Results: The prevalence of T2DM nearly doubled from 320.62 (95% CI: 318.83; 322.41) in 2004 to 526.36 per 10,000 PYR (95% CI: 523.81; 528.91) in 2014, whereas the incidence was relatively stable with overall rate of 43.07 per 10,000 PYR (95% CI: 40.06; 46.09). Gender-specific incidence and prevalence rates were markedly higher in men than women. Between 2004 and 2014, the prevalence increased from 380.31 (95% CI: 377.48; 383.13) to 625.45 (95% CI: 621.37; 629.52) in men and from 268.56 (95% CI: 266.22; 270.90) to 437.28 (95% CI: 433.94; 440.62) in women. Overall, older individuals, men, and residents in the most deprived locations were more likely to have T2DM. Wales and Northern Ireland had higher prevalence rates than the other UK nations. In the all-cause mortality analysis, 20,312 (11.5%) patients with T2DM died, as compared with 79,951 (9.1%) controls. The adjusted survival model showed that patients with T2DM were at significantly greater risk for mortality in comparison with patients without diabetes (HR: 1.26, 95% CI: 1.20; 1.32). Mortality rates decreased over time in both cases and controls. The multimorbidity study showed that comorbidities were more prevalent in patients diagnosed with T2DM in comparison with patients without diabetes. The number of patients with two comorbidities increased between 2004 and 2014. The prevalence of cardiovascular disease (CVD) in T2DM patients was double that of matched control patients. DPP-4 inhibitors, thiazolidinediones and sulphonylureas add-on therapies to metformin were the most commonly-prescribed second-line therapies. The time-varying survival models showed that DPP-4 inhibitors (HR: 0.78, 95% CI: 0.55; 1.11) and thiazolidinediones (HR: 0.68, 95% CI: 0.54; 0.85) add-on therapies were associated with lower risk for major CVD compared to sulphonylurea add-on therapy when all added to initial metformin. Conclusions: The prevalence of T2DM is increasing rapidly in the UK. Patients with T2DM are at significantly greater risk for mortality than patients without diabetes. However, with the declining mortality rates over the past decade, patients are now living longer to develop comorbidities. CVD was the most prevalent comorbidity in T2DM cases in comparison with people without diabetes. This is important as CVD is the main cause of mortality in patients with T2DM. Thiazolidinedione combination with metformin was associated with significantly lower CV risk in comparison with sulphonylurea add-on therapies to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitors add-on therapies. These real-world findings add to the existing knowledge on the epidemiology of T2DM, provide novel insight on the patterns of multimorbidity in these patients and clinically relevant evidence on the CV risk associated with commonly-prescribed second-line regimens. Future larger studies are needed to confirm the observed CV benefits associated with antidiabetic therapies.

Magister Pharmaceuticae - MPharm / Diabetes Mellitus, one of the major diseases affecting human population all over the world has caused significant morbidity and mortality. The management of this condition has raised the demand of safe and cost effective remedial measures due to several side effects associated with the present use of modern medicines. Thus, it is crucial to explore other options for diabetes management such as the use of medical plants. Cnicus benedictus L. is one of the known plant species used by traditional medicine practitioners in South Africa for the treatment of various ailments including inflammatory conditions, pain and diabetes. Even though the plant species has been extensively studied, scientifically, no evidence exists in literature to corroborate the claim made by traditional medicine practitioners of its therapeutic success in the treatment of diabetes and pain. Therefore, the objectives of this present study were: to investigate the antidiabetic activity of C. benedictus using leaf methanol extract of the plant species on animal model involving male and female Albino rats; to investigate the antinociceptive activity of the plant species on mice; to determine the safety profile of the plant by investigating the acute toxicity and to carry out HPLC study in order to characterize the plant species. Animals were divided into groups of six each and fasted overnight prior to the induction of diabetes in rats using Streptozocin (STZ). The plasma glucose was measured at intervals of 30 min for 4 hours by means of a glucometer. Cnicus benedictus (100 – 400 mg/kg, i.p.) significantly reduced the blood glucose concentrations of fasted normal rats with percentage maximum reduction ranging from 46 to 79% and chlorpropramide (250 mg/kg, i.p.) significantly reduced the blood glucose concentrations of fasted normal rats by 84%. Cnicus benedictus (100 – 400 mg/kg, i.p.) significantly reduced the blood glucose concentrations of STZinduced diabetic rats with percentage maximum reduction ranging from 44.82 to 66.04% and chlorpropramide (250 mg/kg, i.p.) significantly reduced the blood glucose concentration of STZ-induced diabetic rats by 71.71%. In the oral glucose tolerance test, administration of leaf methanol extract of Cnicus benedictus (100 – 400 mg/kg, i.p.) following oral glucose load on fasted normoglycaemic rats significantly reduced the increased blood glucose concentrations with percentage maximum reduction ranging from 42.45 to 70.75%. Chlorpropramide (250 mg/kg, i.p.) following oral glucose load on fasted normoglycaemic rats significantly reduce the increased blood glucose concentration with a percentage maximum reduction of 79.04%. In acetic acid writhing test, animals were divided into groups of eight per dose. Cnicus benedictus (25-400 mg/kg, i.p.) significantly reduced the number of writhes in mice with percentage inhibition of the writhes ranging from 67.95 to 73.71%. Indomethacin (20 mg/kg, i.p.) and paracetamol (500 mg/kg, i.p.) significantly reduced the number of writhes in mice with percentage inhibition of 75.44 and 69.18% respectively. Combined treatment of lowest and sub-effective doses of C.benedictus (12.5 mg/kg, i.p.) and indomethacin (10 mg/kg, i.p.) significantly reduced the writhes with a percentage inhibition of 58.32%. In hot plat test, animals were divided into groups of eight per dose. Cnicus benedictus (25-400 mg/kg, i.p.) significantly delayed the reaction times of the mice to hot-plate thermal stimulation. Morphine (10 mg/kg, i.p.) significantly delayed the reaction time of the mice to the hot-plate stimulation. The no-adverse-effect-level (NOAEL) of leaf methanol extract of Cnicus benedictus was obtained at 3200 mg/kg (p.o.) and the LD50 value of the plant species was found to be 4000 mg/kg (p.o.). The HPLC fingerprint of the leaf methanol extract of Cnicusbenedictus showed distinct peaks at the following retention times of 6.387, 14.628, 18.431, 23.228 and 29.829 min. In conclusion, the data obtained showed that leaf methanol extract of Cnicus benedictus possesses both antidiabetic and antinocipetive activities. / National Research Foundation (NRF)

Philosophiae Doctor - PhD / Diabetes mellitus (DM), being one of the most common metabolic disorders with an elevated morbidity and mortality rate around the world. It is characterised by deficiency in insulin secretion or degradation of secreted insulin. Many internal and external factors such as oxidative stress, obesity and sedentary lifestyle among others have been suggested as the major causes of these cell alterations. Diabetes I and II are the most common types of diabetes. Treatment of type I requires insulin injection, while type II can be managed using different synthetic antidiabetic agents. However, their effectiveness is limited as a result of low bioavailability, high cost of drug production, and unfavourable side effects. There is a great need to develop alternative and more active antidiabetic drugs from natural sources. Natural products are a well-known source for the discovery of new scaffold for drugs discovery, and South Africa is one of the most important megaflora with high percentage of endemism. / 2023-12-01

Fármacos pouco solúveis em água são um dos maiores desafios encontrados em formulação de comprimidos, uma vez que, se não adequadamente formulados, podem apresentar problemas de dissolução e de biodisponibilidade. O presente trabalho teve como objetivo produzir comprimidos de glibenclamida 5 mg (hipoglicemiante oral pouco solúvel) utilizando diferentes processos visando a melhoria da dissolução do fármaco e comparar a liberação in vitro (perfil de dissolução) das formulações entre si, bem como em relação ao medicamento referência no Brasil, Daonil&#174;. Foram obtidas 19 formulações por compressão direta empregando dispersão sólida, complexação com ciclodextrina ou micronização do fármaco. Os comprimidos foram analisados quanto ao aspecto, peso médio, dureza, friabilidade, teor e eficiência de dissolução. Os resultados indicaram que, dentre os processos estudados, a utilização de complexos glibenclamida-&#946;-ciclodextrina e glibenclamida micronizada, promoveram uma melhora da dissolução do fármaco. O superdesintegrante Explocel&#174; promoveu significativa melhoria no perfil de dissolução em todas as formulações em que estava presente. A utilização do complexo glibenclamida-&#946;-ciclodextrina com o Explocel&#174; apresentou perfil de dissolução estatisticamente semelhante ao Daonil&#174;, além de atender aos demais requisitos físico-químicos. / Slightly soluble drugs are one of the largest challenges found in tablet formulation, once, if not appropriately formulated, they can present dissolution and bioavailability problems. The present work had as objective to produce 5 mg glibenclamide (practically insoluble hipoglicemic drug) tablets using different processes which aim at enhancing drug dissolution and to compare the in vitro release (dissolution profile) of these formulations with each other as well as with the reference medicine in Brazil, Daonil&#174;. 19 diferent formulations were obtained through direct compression using solid dispersion, cyclodextrin complexion or micronization of the drug. The tablets were also analyzed in relation to aspect, medium weight, hardness, friability, assay and dissolution eficiency. The results indicated that, among the studied processes, an enhancement of the dissolution rate of the drug have arisen from the use of the glibenclamide-&#946;-cyclodextrin complex and the micronized glibenclamide. The disintegrant Explocel&#174; promoted enhancement in the dissolution rate in all the formulations in which it was present. The use of the glibenclamide-&#946;-cyclodextrin complex with Explocel&#174; have presented the best dissolution profile, statistically similar to Daonil&#174;, besides accomplishing the other physico-chemical requirements.

Fármacos pouco solúveis em água são um dos maiores desafios encontrados em formulação de comprimidos, uma vez que, se não adequadamente formulados, podem apresentar problemas de dissolução e de biodisponibilidade. O presente trabalho teve como objetivo produzir comprimidos de glibenclamida 5 mg (hipoglicemiante oral pouco solúvel) utilizando diferentes processos visando a melhoria da dissolução do fármaco e comparar a liberação in vitro (perfil de dissolução) das formulações entre si, bem como em relação ao medicamento referência no Brasil, Daonil&#174;. Foram obtidas 19 formulações por compressão direta empregando dispersão sólida, complexação com ciclodextrina ou micronização do fármaco. Os comprimidos foram analisados quanto ao aspecto, peso médio, dureza, friabilidade, teor e eficiência de dissolução. Os resultados indicaram que, dentre os processos estudados, a utilização de complexos glibenclamida-&#946;-ciclodextrina e glibenclamida micronizada, promoveram uma melhora da dissolução do fármaco. O superdesintegrante Explocel&#174; promoveu significativa melhoria no perfil de dissolução em todas as formulações em que estava presente. A utilização do complexo glibenclamida-&#946;-ciclodextrina com o Explocel&#174; apresentou perfil de dissolução estatisticamente semelhante ao Daonil&#174;, além de atender aos demais requisitos físico-químicos. / Slightly soluble drugs are one of the largest challenges found in tablet formulation, once, if not appropriately formulated, they can present dissolution and bioavailability problems. The present work had as objective to produce 5 mg glibenclamide (practically insoluble hipoglicemic drug) tablets using different processes which aim at enhancing drug dissolution and to compare the in vitro release (dissolution profile) of these formulations with each other as well as with the reference medicine in Brazil, Daonil&#174;. 19 diferent formulations were obtained through direct compression using solid dispersion, cyclodextrin complexion or micronization of the drug. The tablets were also analyzed in relation to aspect, medium weight, hardness, friability, assay and dissolution eficiency. The results indicated that, among the studied processes, an enhancement of the dissolution rate of the drug have arisen from the use of the glibenclamide-&#946;-cyclodextrin complex and the micronized glibenclamide. The disintegrant Explocel&#174; promoted enhancement in the dissolution rate in all the formulations in which it was present. The use of the glibenclamide-&#946;-cyclodextrin complex with Explocel&#174; have presented the best dissolution profile, statistically similar to Daonil&#174;, besides accomplishing the other physico-chemical requirements.

Syzygium cordatum is a medicinal plant indigenous to South Africa and Mozambique, commonly used to treat stomach aches, diabetes, respiratory problems and tuberculosis. In spite of the folklore use, adequate scientific data to credit its widespread traditional use is lacking. The objectives of this study were: to evaluate and validate scientifically the successful therapeutic claims by traditional medicine practitioners that Syzygium cordatum is effective in treating diarrhoea and diabetes / to determine the effects of the plant extract on gastrointestinal transit of a charcoal meal in mice / to determine the effects on castor oilinduced intestinal fluid accumulation / to determine the safety profile of the plant by carrying out acute toxicology study and to carry out preliminary screening of the active compounds present in the plant using standard phytochemical analytical procedures. The aqueous leaf extract of Syzygium cordatum (3.125 -50mg/kg, p.o) significantly reduced the faecal output caused by castor oil (0.7ml). All the doses used, reduced faecal output from 100% produced by castor oil to between 40 and 61%. S.cordatum (6.25 &ndash / 50mg/kg, p.o) significantly and in a dose dependent manner, delayed the onset of castor oil-induced diarrhoea.

The present study is a retrospective cohort analysis which sought to examine adherence to medications used in managing painful diabetic peripheral neuropathy (PDPN) and to determine their association with oral antidiabetic (OAD) medication adherence using the Texas Medicaid prescription claims database. The study objectives were to: 1) provide a description of PDPN and OAD medication use among the study subjects; 2) determine if PDPN medication adherence differs among individual PDPN agents (i.e., tricyclic antidepressants, gabapentin, pregabalin and duloxetine); 3) determine if pre-index OAD and post-index OAD medication adherence differs among mono, dual, and triple OAD therapies; and 4) determine if PDPN medication adherence is related to post-index OAD medication adherence while controlling for covariates. Study participants were adult (≥18 years) Medicaid beneficiaries prescribed OAD and PDPN medications. The index date was the first PDPN prescription. Data were extracted from June 1, 2003 to October 31, 2009 and prescription claims were analyzed over an 18-month study period (i.e., 6 months pre-index and 12 months post index period). Medication possession ratio (MPR) was used as a proxy measure of medication adherence. An MPR less than 80 percent was regarded as being non-adherent to prescribed medication, while an MPR greater than or equal to 80 percent was regarded as being adherent to prescribed medication. Objective 1 was addressed using descriptive statistics (i.e., mean, standard deviation, frequency). Univariate analysis (ANOVA) was employed to address Objectives 2 and 3. Multivariate analyses (i.e., multiple linear regression and logistic regression) were conducted to address Objective 4. For the logistic regression MPR was dichotomized at the cut-off value of 80 percent. A total of 4,277 patients met the study’s inclusion criteria. The overall mean MPR (±SD) for PDPN medications was 75.4 percent (±23.9). Mean MPR (±SD) was highest for duloxetine (85.6% ±18.2) and was lowest for pregabalin (69.4% ±24.9). Mean MPR differed significantly among individual PDPN medications (p<0.0001). The overall mean MPR (±SD) for OAD medications in the pre and post-index period was 73.0 percent (±24.3) and 64.5 percent (±25.6) respectively. In both pre and post-index periods, mean MPR differed significantly among mono, dual, and triple OAD therapies (p<0.0001). In the pre-index period, mean MPR (±SD) was highest for monotherapy users (75.4% ±24.7) and was lowest for triple therapy users (63.9% ±22.9). Similarly, mean MPR (±SD) was highest for monotherapy users (69.0% ±26.1) and was lowest for triple therapy users (52.9% ±21.8) in the post-index period. After controlling for the covariates, PDPN adherence (i.e., MPR) was statistically significant (p<0.0001) and positively related to post-index OAD adherence (i.e., MPR). PDPN patients who were non-adherent (i.e., MPR<80%) to their PDPN medications (or neuropathic pain medications), compared to those who were adherent (MPR≥80%), were significantly less likely to be adherent to their OAD medications [Odds Ratio (OR) = 0.626, 95% CI=0.545-0.719]. In addition, post-index OAD adherence (i.e., MPR) did not differ significantly (p>0.05) when pregabalin, duloxetine and gabapentin users were individually compared to tricyclic antidepressants users. In conclusion, PDPN patients who were adherent (i.e., MPR≥80%) to their PDPN medications, compared to those who were not adherent (i.e., MPR<80%), were more adherent to their OAD medications. Also, adherence to OAD medications was independent of the type of PDPN medication used. PDPN patients need to be educated regularly that neuropathic pain medications only relieve the pain associated with the neuropathy but achieving adequate glycemic control remains the only established approach for slowing down the progression of the neuropathy and other complications associated with the diabetes. / text

Syzygium cordatum is a medicinal plant indigenous to South Africa and Mozambique, commonly used to treat stomach aches, diabetes, respiratory problems and tuberculosis. In spite of the folklore use, adequate scientific data to credit its widespread traditional use is lacking. The objectives of this study were: to evaluate and validate scientifically the successful therapeutic claims by traditional medicine practitioners that Syzygium cordatum is effective in treating diarrhoea and diabetes / to determine the effects of the plant extract on gastrointestinal transit of a charcoal meal in mice / to determine the effects on castor oilinduced intestinal fluid accumulation / to determine the safety profile of the plant by carrying out acute toxicology study and to carry out preliminary screening of the active compounds present in the plant using standard phytochemical analytical procedures. The aqueous leaf extract of Syzygium cordatum (3.125 -50mg/kg, p.o) significantly reduced the faecal output caused by castor oil (0.7ml). All the doses used, reduced faecal output from 100% produced by castor oil to between 40 and 61%. S.cordatum (6.25 &ndash / 50mg/kg, p.o) significantly and in a dose dependent manner, delayed the onset of castor oil-induced diarrhoea.