| 1. |
- Blom, Dirk Jacobus, et al.
(författare)
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The therapeutic management of South African dyslipidaemic patients at very high cardiovascular risk (CARDIO TRACK) : a cross-sectional study
- 2020
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Ingår i: Cardiovascular Journal of Africa. - : Clinics Cardive Publishing. - 1995-1892. ; 31:5, s. 245-251
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dyslipidaemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. At the time the study was conducted, guidelines recommended a low-density lipoprotein cholesterol (LDL-C) target of less than 1.8 mmol/l and a reduction of at least 50% if the baseline LDL-C was between 1.8 and 3.5 mmol/l in patients with either very high cardiovascular risk or established atherosclerosis. In South Africa, there is a paucity of data on attainment of LDL-C goal in patients with very high cardiovascular risk who are on maximum tolerated statin with or without ezetimibe. Objective: The aim was to assess the percentage of very high cardiovascular risk South African patients with dyslipidaemia not reaching an LDL-C goal of less than 1.8 mmol/l, despite maximum tolerated statin with or without ezetimibe. Methods: This was a multi-centre, observational, cross-sectional study conducted at 15 private healthcare sector sites and one public sector site. Adults (> 18 years) with very high cardiovascular risk of familial hypercholesterolaemia receiving stable, maximum-tolerated statin therapy for at least four weeks prior to their latest lipid profile were enrolled into the study, and electronic case report forms were completed after written informed consent was provided. LDL-C goal attainment was modelled. first assuming an increase in the statin dose to the registered maximum, followed by the addition of ezetimibe or a PCSK9-inhibitor. Results: In total, 507 patients were screened. of whom 492 were eligible for study participation. One patient was excluded from the analysis because of a missing LDL-C value. Most participants were male (male 329. 67%; female 162, 33%). Most patients were either obese (223. 46.0%) or overweight (176. 36.3%). Hypertension and diabetes mellitus were frequent co-morbidities and were found in 381 (77.6%) and 316 (64.4%) patients. respectively. Eighty (16.3%) patients reported current smoking Only 68 (13.8%) patients were taking ezetimibe in addition to a statin. Reasons for not using ezetimibe included no requirement jot ezetimibe in the opinion of the treating physician (229, 48.7%). cost (149. 31.7%), physician's choice (39, 8.3%), or other (53, 11.3%), Only 161 (32.8%) of the patients attained their goal LDL-C level. In our modelling analysis. increasing the statin dose to the registered maximum and adding ezetimibe brought an additional 34.5% of patients to goal. while adding a PCSK9-inhibitor, irrespective of any other changes to lipid-lowering therapy brought over 90% of not-at-goal patients to goal. Conclusion: Most study participants were not at LDL-C goal despite maximum-tolerated statin, highlighting the need for treatment intensification in this high-risk population. Although intensifying treatment by adding a PCSK9-inhibitor brought more patients to goal, the initial addition of ezetimibe would be more reasonable, given the cost of PCSK9-inhibitors.
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| 2. |
- Duthaler, Urs, et al.
(författare)
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The effect of food on the pharmacokinetics of oral ivermectin
- 2020
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 75:2, s. 438-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ivermectin is an older anthelminthic agent that is being studied more intensely given its potential for mass drug administration against scabies, malaria and other neglected tropical diseases. Its pharmacokinetics (PK) remain poorly characterized. Furthermore, the majority of PK trials are performed under fasted-state dosing conditions, and the effect of food is therefore not well known. To better plan and design field trials with ivermectin, a model that can account for both conditions would be valuable.Objectives: To develop a PK model and characterize the food effect with single oral doses of ivermectin.Patients and methods: We performed a population-based PK analysis of data pooled from two previous trials of a single dose of 12mg ivermectin, one with dosing after a high-fat breakfast (n=12) and one with fasted-state dosing (n=3).Results: The final model described concentration-time profiles after fed and fasted dosing accurately, and estimated the food effect associated with relative bioavailability to 1.18 (95% CI 1.10-1.67).Conclusions: In this analysis, the effect of a high-fat breakfast compared with a fasted-state administration of a single oral dose of 12mg ivermectin was minimal.
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| 3. |
- Jacobson, Barry, et al.
(författare)
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Safety and Efficacy of Enoxaparin in Pregnancy : A Systematic Review and Meta-Analysis
- 2020
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 37:1, s. 27-40
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Forskningsöversikt (refereegranskat)abstract
- IntroductionInternational guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence of the benefit and harm associated with specific low molecular weight heparins such as enoxaparin is dated. No current systematic review and meta-analysis describing the safety and efficacy of enoxaparin for thromboembolism and thromboprophylaxis during pregnancy exists.MethodsPubMed, Embase, and Cochrane databases were searched on August 17, 2018 for clinical trials or observational studies in pregnant women receiving enoxaparin; patients with a prosthetic heart valve were excluded. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model, and heterogeneity was measured using the I2 statistic.ResultsOf the 485 records identified in the search, 24 studies published clinical trials, and observational studies were found dating back to 2000. Only one observational cohort and one randomized control trial focused on the use of enoxaparin for thromboprophylaxis and therefore efficacy was not assessed; the other studies included women with recurrent pregnancy loss (15 studies), history of placental vascular complications (five studies), and recurrent in vitro fertilization failure (two studies) and were therefore analyzed in terms of safety only. Bleeding events were non-significantly more often reported for enoxaparin compared to untreated controls (RR 1.35 [0.88–2.07]) but less often reported for enoxaparin versus aspirin (RR 0.93 [0.62–1.39]); thromboembolic events, thrombocytopenia, and teratogenicity were rarely reported events; in patients with a history of recurrent pregnancy loss, encouragingly the rates of pregnancy loss were significantly lower for enoxaparin compared to untreated controls (RR 0.58 [0.34–0.96]) and enoxaparin + aspirin versus aspirin alone (RR 0.42 [0.32–0.56]) as well as observably lower for enoxaparin versus aspirin alone (RR 0.39 [0.15–1.01]), though significant heterogeneity was observed (I2 > 60).ConclusionLiterature on the efficacy and safety of enoxaparin for thromboembolism and thromboprophylaxis remains scanty, and therefore efficacy was not assessed; in terms of safety, when including other indications for enoxaparin in pregnancy, we found that enoxaparin was associated with significantly lower complications than aspirin. Given differences in study design and study heterogeneity, pregnancy loss results should be interpreted with caution. Moreover, reports of thromboembolic events, thrombocytopenia, and congenital malformations were rare.
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| 4. |
- Mbanya, Jean Claude, et al.
(författare)
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Management of adult patients with type 1 diabetes mellitus in Africa : A post-hoc cohort analysis of 12 African countries participating in the International Diabetes Management Practices Study (Wave 7)
- 2020
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Ingår i: Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0025-7974 .- 1536-5964. ; 99:25
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Tidskriftsartikel (refereegranskat)abstract
- There is a paucity of information on real world management of African adult patients with type 1 diabetes mellitus (T1DM). We aimed to describe a cohort of African adults with T1DM. The International Diabetes Management Practices Study is an observational survey conducted from 2005 to 2017. Data were collected in seven individual waves from countries in Asia, Africa, East Europe, and Latin America. Wave 7 was conducted from 2016 to 2017 and the African cohort included 12 countries. Questionnaires were administered to clinicians and patients. Analyses were mainly descriptive. Logistic regressions were performed to identify predictive factors for glycaemic control. A total of 788 patients were enrolled in the study. HbA1c values were available for 712 patients; only 16.6% had HbA1c values <7%. A total of 196 (24.9%) reported being hospitalized in the preceding year, with the most common reasons being diabetic ketoacidosis (58.1%, 93/160) and hypoglycaemia (31.1%; 52/167). Over half of the patients (55.4%) stated that the cost of test strips limited regular glycemic monitoring; a minority of patients (15%, 120/788) received structured diabetes education. Predictors of HbA1c <7% included patients receiving diabetes education (odds ratio [OR] [95% confidence interval, CI] = 2.707 [1.157-6.335]P = .022), following a healthy diet and exercise plan (OR [95% CI] = 2.253 [1.206-4.209],P< .001) and self-managing (monitoring glucose levels and adjusting insulin accordingly) (OR [95% CI] 2.508 [1.500-4.191]P < .001). African adults with T1DM have suboptimal glycemic control with almost one-quarter reporting hospitalization within the preceding year. Most patients felt comfortable with self-adjustment of insulin dose but said that the cost of test strips was the main factor that limited regular monitoring. Reducing direct costs of testing strips and insulin, and improving education will address major challenges within these settings.
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| 5. |
- Mim, Sabiha R., et al.
(författare)
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Optimal dosing of gliclazide-A model-based approach
- 2023
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : John Wiley & Sons. - 1742-7835 .- 1742-7843. ; 133:1, s. 59-72
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Tidskriftsartikel (refereegranskat)abstract
- Gliclazide was approved as a treatment for type 2 diabetes in an era before model-based drug development, and consequently, the recommended doses were not optimised with modern methods. To investigate various dosing regimens of gliclazide, we used publicly available data to characterise the dose-response relationship using pharmacometric models. A literature search identified 21 published gliclazide pharmacokinetic (PK) studies with full profiles. These were digitised, and a PK model was developed for immediate- (IR) and modified-release (MR) formulations. Data from a gliclazide dose-ranging study of postprandial glucose were used to characterise the concentration-response relationship using the integrated glucose-insulin model. Simulations from the full model showed that the maximum effect was 44% of the patients achieving HbA1c <7%, with 11% experiencing glucose <3 mmol/L and the most sensitive patients (i.e., 5% most extreme) experiencing 35 min of hypoglycaemia. Simulations revealed that the recommended IR dose (320 mg) was appropriate with no efficacy gain with increased dose. However, the recommended dose for the MR formulation may be increased to 270 mg, with more patients achieving HbA1c goals (i.e., HbA1c <7%) without a hypoglycaemic risk higher than the resulting risk from the recommended IR dose.
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| 6. |
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| 7. |
- Naidoo, Poobalan, et al.
(författare)
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Access to novel anti-diabetic agents in resource limited settings : A brief commentary
- 2023
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Ingår i: World Journal of Diabetes. - : Baishideng Publishing Group Inc.. - 1948-9358. ; 14:7, s. 939-941
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of diabetes mellitus is increasing in resource limited settings. Simultaneously, there has been an increase in the number of novel therapies for the management of diabetes mellitus. However, use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings. Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes, and thus most likely to benefit from the therapy, are less likely to have negative budget impact for funders. To improve access, and reduce morbidity and mortality, requires alignment amongst key stakeholders including patient advocacy groups, health care professional councils, national departments of health, the pharmaceutical industry, treasury and finance departments.
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| 8. |
- Naidoo, P., et al.
(författare)
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Mechanisms for sustainable post-trial access : A perspective
- 2021
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Ingår i: SOUTH AFRICAN JOURNAL OF BIOETHICS AND LAW. - : HEALTH & MEDICAL PUBLISHING GROUP. - 1999-7639. ; 14:3, s. 77-78
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Tidskriftsartikel (refereegranskat)abstract
- Clinical trials are essential to establish the safety and efficacy of investigational products, contributing to risk/benefit assessments that ultimately determine whether these products meet the criteria for market authorisation. Clinical trials are also an important source of revenue and expertise generation for countries in which they are conducted. In developing countries, they represent substantial foreign direct investment. In spite of the substantial capital input that clinical trials require, the issue of funding post-trial access to beneficial therapies remains contentious, especially in resource-limited settings. In this article, we explore this situation and propose mechanisms to establish 'win-win' situations where both patients and clinical trial sponsors derive benefit from post-trial access programmes in low- and middle-income countries.
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| 9. |
- Naidoo, Poobalan, et al.
(författare)
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Real-world evidence and product development : Opportunities, challenges and risk mitigation
- 2021
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Ingår i: Wiener Klinische Wochenschrift. - : Springer. - 0043-5325 .- 1613-7671. ; 133:15-16, s. 840-846
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Forskningsöversikt (refereegranskat)abstract
- Real-world evidence (RWE) is derived from real-world data (RWD) sources including electronic health records, claims data, registries (disease, product) and pragmatic clinical trials. The importance of RWE derived from RWD has been once again demonstrated during the coronavirus disease 2019 (COVID-19) pandemic, as it can improve patient care by complementing information obtained from traditional clinical trial programs. Additionally, RWE can generate insights into disease mechanisms, epidemiology, patient flows in and out of healthcare systems, and drivers and barriers to optimal clinical care in real-world settings. Identifying unmet medical needs is crucial as it often can inform which investigational new drugs enter clinical trial testing, and RWE studies from hospital settings have contributed substantial progress here. RWE can also optimize the design of clinical studies, inform benefit risk assessments and use networks of pragmatic studies to help with clinical trial feasibilities and eventual trial initiation. The challenges of RWD include data quality, reproducibility and accuracy which may affect validity. RWD and RWE must be fit for purpose and one must be cognizant of inherent biases.
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| 10. |
- Raal, Frederick J., et al.
(författare)
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PCSK9 Inhibitors : From Nature's Lessons to Clinical Utility
- 2020
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Ingår i: Endocrine, Metabolic & Immune Disorders - Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5303 .- 2212-3873. ; 20:6, s. 840-854
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Forskningsöversikt (refereegranskat)abstract
- Background: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel class of non-statin lipid lowering therapy that reduce LDL-cholesterol by 50 - 6044,. PCSK9 inhibitors decrease LDL-cholesterol by preventing intracellular degradation of LDL receptors; subsequently, a greater number of LDL-receptors arc available on the cell surface to extract circulating LDL. Objective: To describe the origins of PCSK9 inhibitors and their current use in clinical practice. Methods: We performed a narrative review of the PCSK9 inhibitor class of drugs Results: Current data indicate that PCSK9 inhibitors effectively reduce LDL-cholesterol and are well tolerated and safe. PCSK9 inhibitors have also been shown to reduce cardiovascular event rates in patients with stable atherosclerotic cardiovascular disease and in patients with a recent (up to one year) acute coronary syndrome. Given the costs, chronicity of the treatment and the potential budget impact, PCSK9 inhibitors are often limited to patients with the highest absolute risk for major adverse cardiovascular events despite optimal treatment with high-intensity statin and ezetimibe. Conclusion: PCSK9 inhibitors have a favorable safety, efficacy and tolerability profile. Post marketing safety surveillance and real-world studies are needed to further support the long-term safety profile of this class of medicine.
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