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1.
Adv Ther ; 37(1): 27-40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31673991

RESUMO

INTRODUCTION: International 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. METHODS: PubMed, 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. RESULTS: Of 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). CONCLUSION: Literature 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. FUNDING: Sanofi.

2.
Pan Afr Med J ; 33: 313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692862

RESUMO

The role of a Medical Science Liaison (MSL) is of growing importance to pharmaceutical, biotechnology, diagnostic and medical device companies. Through scientific engagement MSLs add value to clinical practice, ultimately benefiting patients. The MSL role is dynamic and encompasses in-depth product and disease knowledge together with the ability to communicate relevant, unbiased scientific information concisely and timely. Tasks are focused on contributing towards the advancement of medical knowledge, scientific data generation and dissemination. Professional relationships are developed, fostering collaboration between external experts and typically the medical affairs departments of pharmaceutical companies through a credible liaison. Through such relationships, critical insights are shared that shape the development pipeline, promote successful clinical translation and guide the market deployment strategy of therapeutic interventions through-out their life cycle. Despite the rising number of MSLs in the field and the implicit medical value of the role, there remains a lack of understanding for what the roles of a MSL entails. In Africa, where exponential growth of the pharmaceutical industry is expected, the number of MSLs will increase rapidly. Given the complexities of the African continent, the MSLs in this burgeoning environment will face various challenges including remote locations, time-constraints, regulatory and bureaucratic hurdles and importantly physician misperception of the MSL role that collectively may thwart the goal of meaningful scientific engagement; but these challenges can be surmounted through astute proactive planning and utilization of opportunities including digital communication strategies.


Assuntos
Comunicação , Comportamento Cooperativo , Indústria Farmacêutica/organização & administração , África , Humanos , Indústria Manufatureira/organização & administração , Papel Profissional
3.
Cardiovasc J Afr ; 30(5): 279-284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512717

RESUMO

BACKGROUND: Alirocumab reduces low-density lipoprotein cholesterol (LDL-C) levels by up to 61%. The ODYSSEY Open-Label Extension study investigated the effect of alirocumab in patients with heterozygous familial hypercholesterolaemia (HeFH) over 144 weeks. METHODS: Eligible patients with HeFH had completed an earlier double-blind, randomised, placebo-controlled parent study. Patients were initiated on 75 mg alirocumab Q2W subcutaneous (SC) unless baseline LDL-C was > 8.9 mmol/l, in which case they received 150 mg alirocumab Q2W. Dose titration to 150 mg Q2W was at the investigator's discretion. RESULTS: The study enrolled 167 patients and the parent study mean (± SD) baseline LDL-C level was 3.65 ± 1.9 mmol/l. Mean LDL-C level was reduced by 48.7% at week 144; mean on-treatment LDL-C was 2.30 ± 1.24 mmol/l. Eight patients reported injection-site reactions, with one treatment discontinuation. Treatment emergent anti-drug antibodies were identified in five patients but these did not affect the efficacy. CONCLUSIONS: Alirocumab effectively and safely reduced LDL-C in these patients.

4.
Cardiovasc J Afr ; 30(1): 15-23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30720848

RESUMO

The International Cholesterol Management Practice Study (ICLPS) South Africa investigated achievement of European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline low-density lipoprotein cholesterol (LDL-C) targets in real-world clinical practice. Demographic data, clinical characteristics, cardiovascular risk factors, lipid-modifying medications, lipid values and investigator's assessment of cardiovascular risk were recorded for 396 patients on stable lipid-modifying therapy. Most (98.7%) patients received statins; 25.1% of statin-treated patients were receiving high-intensity statins. Overall, 41.4% of patients achieved their LDL-C target; among 354 (89.4%) patients in whom cardiovascular disease risk, based on ESC Systematic Coronary Risk Estimation (SCORE) was calculated, achievement rate was 14.3% for moderate-risk (n = 7), 59.3% for high-risk (n = 123) and 32.3% for very high-risk patients (n = 223). Half of Asian (54.7%) and black African (53.2%) patients were at LDL-C target compared with 29.8% of European/Caucasian and 27.3% of 'other' patients. Improved guideline adherence and greater use of combination therapy may increase LDL-C goal achievement.


Assuntos
Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Padrões de Prática Médica , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Fidelidade a Diretrizes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Medição de Risco , Fatores de Risco , África do Sul/epidemiologia , Fatores de Tempo , Resultado do Tratamento
5.
Int J Infect Dis ; 79: 37-43, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30292891

RESUMO

BACKGROUND: The World Health Organization (WHO) recommends the use of adjunctive urine lipopolysaccharide lipoarabinomannan (LAM) testing in hospitalized HIV-infected persons with suspected tuberculosis (TB) and a CD4 count <100cells/ml. However, the recommendation is conditional, and uptake by individual treatment programmes depends on perceived additional benefit. The aim of this study was to determine whether adjunctive LAM testing has additional clinical benefits including a reduction in healthcare-related use of resources. METHODS: A post hoc analysis was performed of a published multicentre, multi-country, randomized controlled trial that showed an approximate 20% mortality benefit in HIV-infected hospitalized patients who underwent adjunctive LAM testing as part of their diagnostic workup. In that parent study, adult HIV-infected hospitalized patients with suspected TB (n=2528) were randomly allocated to either routine diagnostics (smear microscopy, Xpert MTB/RIF, and culture; n=1271), or routine diagnostics plus adjunctive urine LAM testing (n=1257). Data were further analyzed to determine whether there were other potential benefits of LAM usage based on CD4 count and illness severity. Aspects evaluated included: (1) the reduction in number of diagnostic sputum samples tested, (2) the utilization of additional imaging, (3) disease resolution based on follow-up signs and symptoms of illness severity, and (4) the reduction in hospital readmission. RESULTS: Adjuvant LAM did not reduce the number of diagnostic sputum samples requested, the need for additional imaging, or the hospital readmission rate. However, adjunctive LAM was associated with a more rapid rate of disease resolution (dyspnoea) in the severely ill subgroup. Higher LAM grade (grades 4 and 5), compared to lower grade positivity (≤3), was associated with lower use of ultrasound, lower Karnofsky performance score, lower CD4 cell count, and shorter time to culture positivity. CONCLUSIONS: Although, adjunct LAM was associated with a mortality benefit in the parent study, no benefit could be demonstrated in the secondary analysis with respect to the number of diagnostic sputum samples requested, the use of additional imaging, or hospital readmission rates. However, given the limitations of the present study, further appropriately designed studies are required to determine the effect of adjunct urine LAM on the utilization of healthcare resources.


Assuntos
Coinfecção , Infecções por HIV/complicações , Lipopolissacarídeos/urina , Tuberculose/diagnóstico , Adulto , Contagem de Linfócito CD4 , Utilização de Instalações e Serviços , Hospitalização , Humanos , Tuberculose/complicações , Tuberculose/diagnóstico por imagem , Tuberculose/mortalidade
6.
Pan Afr Med J ; 30: 171, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30455800

RESUMO

We report a case of Marfan syndrome (MFS) in a South African patient, which is extraordinary because of the large constellation of clinical, radiological and vascular anomalies in a single patient. A literature search from 1950 to date did not show a similar report of such extensive clinical characteristics of MFS.


Assuntos
Síndrome de Marfan/diagnóstico , Adolescente , Humanos , Masculino , Síndrome de Marfan/fisiopatologia , África do Sul
7.
Pan Afr Med J ; 29: 223, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30100977

RESUMO

Traditionally, minimal potential organ donor referrals emanate from general medicine departments. We use a clinical vignette to draw attention to challenges related to referral of potential organ donors from general internal medicine departments. In addition, we provide potential solutions to overcome challenges and reflect on the ethical issues of non-referral of potential organ donors. It is hoped that this paper will increase the awareness of organ donation in the medical fraternity in Africa and thus mitigate critical shortages of organs for transplantation.


Assuntos
Transplante de Órgãos/ética , Doadores de Tecidos/provisão & distribução , Obtenção de Tecidos e Órgãos/ética , Adolescente , Humanos , Masculino , Encaminhamento e Consulta/ética , África do Sul , Doadores de Tecidos/ética
8.
JMIR Res Protoc ; 7(6): e163, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29959115

RESUMO

BACKGROUND: Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. Current South African guidelines recommend titrating lipid-lowering therapy (LLT) to low-density lipoprotein cholesterol (LDL-C) targets stratified by cardiovascular risk. The LDL-C goal for very high-risk patients is <1.8 mmol/L. In international studies, approximately 30% of patients do not achieve this goal despite receiving maximally tolerated statin doses. There is, however, a paucity of data on LDL-C goal achievement in very high-risk South African patients receiving maximal statin doses. OBJECTIVE: The goal of the research it to assess LDL-C goal achievement in, and clinical characteristics of, very high cardiovascular risk dyslipidemic patients receiving maximal tolerated statin doses with or without ezetimibe. METHODS: This is an observational, cross-sectional South African registry study that plans to include up to 30 sites and 500 study participants. Adult patients with very high cardiovascular risk status receiving stable, maximally tolerated statin doses (with or without ezetimibe) will be eligible for inclusion. RESULTS: Funding has been awarded and enrollment began on November 15, 2017, and was completed on April 13, 2018, with 507 participants. Database lock was done on June 21, 2018. The statistical analysis has commenced and we expect the final clinical study report to be completed by October 2018. CONCLUSIONS: This study will document the adequacy of LLT in those at highest risk and will thus fill an important data gap in South Africa. This data may be useful in assessing the need for novel LLTs like proprotein convertase subtilisin/kexin 9 inhibitors that substantially lower cholesterol levels in addition to optimal statin therapy. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9248.

9.
Vasc Health Risk Manag ; 14: 137-143, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950852

RESUMO

Paraoxonase-1 (PON1) is a high-density lipoprotein-associated esterase and is speculated to play a role in several human diseases including diabetes mellitus and atherosclerosis. Low PON1 activity has been associated with increased risk of major cardiovascular events, therefore a variety of studies have been conducted to establish the cardioprotective properties and clinical relevance of PON1. The major aim of this review was to highlight the important studies and to subsequently assess if PON1 has clinical relevance. A review of the literature showed that there is currently insufficient data to suggest that PON1 has clinical relevance. It is our opinion that robust studies are required to clarify the clinical relevance of PON1.


Assuntos
Arildialquilfosfatase/genética , Doenças Cardiovasculares/genética , Polimorfismo Genético , Animais , Arildialquilfosfatase/química , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/enzimologia , Predisposição Genética para Doença , Humanos , Fenótipo , Conformação Proteica , Medição de Risco , Fatores de Risco , Relação Estrutura-Atividade
10.
Orthop Res Rev ; 10: 73-81, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30774462

RESUMO

Knee osteoarthritis is a chronic degenerative joint disease characterized by destruction of articular cartilage with resultant para-articular bone changes. It is a major cause of disability in older persons and is managed by surgical and nonsurgical interventions. Pharmacotherapy includes acetaminophen, nonsteroidal anti-inflammatory agents, and intra-articular steroids. Another treatment option is viscosupplementation with intra-articular injection of hyaluronan (HA). The full mechanism of action of exogenous HA is uncertain, but studies indicate that it may promote endogenous HA production, reduce inflammation, prevent degeneration of cartilage and promote cartilage regeneration. Clinically, HA may improve symptoms of osteoarthritis and delay time to total knee replacement surgery. However, clinical studies are heterogenous and of varying quality, and thus there is a need for more robust studies to determine the place of viscosupplementation in the management of knee osteoarthritis.

11.
Clin Pharmacol ; 8: 141-153, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27713650

RESUMO

AIM: To determine the effective dose of glibenclamide by quantifying the dose-response relationship in South African type 2 diabetic patients. PATIENTS AND METHODS: A total of 24 type 2 diabetic patients participated in a glibenclamide dose-escalation study during which glibenclamide, glucose, and insulin concentrations were quantified, while the dose of glibenclamide was progressively increased. All except four subjects contributed data on all dose-escalation steps; however, data from all 24 patients were included in the model-based analysis. Pharmacokinetic/pharmacodynamic (PKPD) relationships were modeled using the software Nonmem®. Six models were utilized to explore the effect of alternative glibenclamide dose and plasma concentration inputs on various metrics of glucose response. RESULTS: Six models adequately described the experimental data. The effective dose for a glucose-lowering effect suggested by PKPD modeling is less than 5 mg/day. Doses beyond 5 mg/day do not meaningfully add to glibenclamide effects on blood-glucose response. CONCLUSION: The effective dose of glibenclamide, suggested by PKPD modeling, is less than 5 mg/day. Higher doses of glibenclamide, eg, 15 mg/day as originally recommended by the manufacturer, do not produce further decrease in the blood glucose level but may predispose the patients to adverse effects.

13.
JMIR Res Protoc ; 5(3): e145, 2016 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-27491324

RESUMO

BACKGROUND: The high prevalence and incidence of type 2 diabetes mellitus (DM), and its associated morbidity and mortality, has prompted growing international interest and effort in the primary prevention of this disease. Primary prevention is possible since type 2 DM is preceded by prediabetes, offering a window opportunity to treat patients, and prevent the emergence of advanced disease. Sitagliptin is an oral dipeptidyl peptidase-IV inhibitor that preserves existing beta cell function and increases beta cell mass. These two effects have been demonstrated both in vitro and in animal studies, and current clinical data show that sitagliptin is safe. Metformin, a biguanide, reduces insulin resistance and inhibits hepatic gluconeogenesis, and has an excellent safety profile. The combination of metformin and sitagliptin, targeting both characteristics of prediabetes (insulin resistance and progressive beta cell degeneration), may potentially slow or halt the progression from prediabetes to type 2 DM. This paper describes the rationale and design of the Sitagliptin and Metformin in PreDiabetes (SiMePreD) study. OBJECTIVE: The aim of this study is to determine the effect of sitagliptin and metformin on progression from prediabetes to type 2 DM. The objectives of the study are to determine the effects of metformin and placebo on glycemic endpoints, the effects of sitagliptin and metformin on glycemic endpoints, the effects of metformin and placebo on incidence of cardiovascular disease and death, and the effects of sitagliptin and metformin on incidence of cardiovascular disease and death. METHODS: This is a randomized, double-blind, multicenter clinical study that will determine if the combination of metformin and sitagliptin is effective in preventing the progression from prediabetes to type 2 DM. The study will contain two arms (metformin/sitagliptin and metformin/placebo). Primary endpoints include the number of subjects progressing from prediabetes to type 2 DM, the number of cardiovascular events, and the number of deaths. The planned duration of the study is five years, and 410 subjects will be included in each group. Data analyses will include clinically relevant measures (eg, numbers needed to treat and numbers needed to harm) and will be performed according to the intention-to-treat principle. RESULTS: This study is currently in the process of acquiring research funding. CONCLUSIONS: The SiMePreD study is the first study to investigate the utility of sitagliptin in combination with metformin for the primary prevention of type 2 DM. .

14.
Clin Pharmacol ; 8: 83-92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27471411

RESUMO

AIM: The aim of this study was to describe the pharmacokinetics (PK) of glibenclamide in poorly controlled South African type 2 diabetic subjects using noncompartmental and model-based methods. METHODS: A total of 24 subjects with type 2 diabetes were administered increasing doses (0 mg/d, 2.5 mg/d, 5 mg/d, 10 mg/d, and 20 mg/d) of glibenclamide daily at 2-week intervals. Plasma glibenclamide, glucose, and insulin determinations were performed. Blood sampling times were 0 minute, 30 minutes, 60 minutes, 90 minutes, and 120 minutes (post breakfast sampling) and 240 minutes, 270 minutes, 300 minutes, 330 minutes, 360 minutes, and 420 minutes (post lunch sampling) on days 14, 28, 42, 56, and 70 for doses of 0 mg, 2.5 mg, 5.0 mg, 10 mg, and 20 mg, respectively. Blood sampling was performed after the steady state was reached. A total of 24 individuals in the data set contributed to a total of 841 observation records. The PK was analyzed using noncompartmental analysis methods, which were implemented in WinNonLin(®), and population PK analysis using NONMEM(®). Glibenclamide concentration data were log transformed prior to fitting. RESULTS: A two-compartmental disposition model was selected after evaluating one-, two-, and three-compartmental models to describe the time course of glibenclamide plasma concentration data. The one-compartment model adequately described the data; however, the two-compartment model provided a better fit. The three-compartment model failed to achieve successful convergence. A more complex model, to account for enterohepatic recirculation that was observed in the data, was unsuccessful. CONCLUSION: In South African diabetic subjects, glibenclamide demonstrates linear PK and was best described by a two-compartmental model. Except for the absorption rate constant, the other PK parameters reported in this study are comparable to those reported in the scientific literature. The study is limited by the small study sample size and inclusion of poorly controlled type 2 diabetic subjects.

15.
S Afr Med J ; 106(2): 169-71, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26821896

RESUMO

BACKGROUND: The Health Professions Council of South Africa requires that a research project be submitted and passed before registration as a specialist. OBJECTIVE: To describe surgical registrars' perceptions of the compulsory research project. METHOD: Ethics clearance was received before commencing the study. A questionnaire was developed to collect feedback from surgical registrars throughout South Africa (SA). Completed questionnaires underwent descriptive analysis using MS Excel. Fisher's exact test and the χ2 test were used to compare perceptions of the research-experienced and research-naive groups. RESULTS: All medical schools in SA were sampled, and 51.5% (124/241) of surgical registrars completed the questionnaire. Challenges facing registrars included insufficient time (109/124), inadequate training in the research process (40/124), inadequate supervision (31/124), inadequate financial resources (25/124) and lack of research continuity (11/124). Of the registrars sampled, 67.7% (84/124) believed research to be a valuable component of training. An overwhelming percentage (93.5%, 116/124) proposed a dedicated research block of time as a potential solution to overcoming the challenges encountered. Further proposals included attending a course in research methodology (79/124), supervision by a faculty member with an MMed or higher postgraduate degree (73/124), and greater research exposure as an undergraduate (56/124). No statistically significant differences were found between the perceptions of the research-experienced and research-naive groups. CONCLUSION: Challenges facing surgical registrars in their efforts to complete their research projects were identified and solutions to these problems proposed. It is heartening that respondents have suggested solutions to the problems they encounter, and view research as an important component of their careers.

16.
Cardiovasc J Afr ; 25(2): 83-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24844554

RESUMO

Sulphonylureas (SUs) are oral anti-diabetic drugs (OADs) that were introduced more than 60 years ago. Clinicians are familiar with their use and they remain extensively used. However, the SU class is associated with adverse effects of weight gain and hypoglycaemia. In addition, their effects on cardiovascular events remain contentious. Newer classes of anti-diabetic agents have been developed and these agents are weight neutral (di-peptidyl peptidase IV inhibitors), while others reduce weight (glucagon-like peptide analogues and sodium glucose co-transporter inhibitors). Furthermore, the newer agents are less likely to cause hypoglycaemia and have a potentially better cardiovascular safety profile. However, the newer agents are more costly than SUs and their long-term safety is unknown. It is therefore likely that SUs will continue to be used, and more so in resource-limited settings. One may mitigate the adverse effects of weight gain and hypoglycaemia associated with the SU class by using members within this class that are less probable to cause these adverse effects. Furthermore, the specific SU must be used at the lowest effective therapeutic dose. In patients at high risk of SU-induced hypoglycaemic episodes (frail, clinically significant renal impairment), or patients in whom hypoglycaemic episodes may have devastating effects (bus drivers), newer anti-diabetic agents may be a justifiable alternative option.


Assuntos
Diabetes Mellitus Tipo 2/economia , Hipoglicemiantes/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/economia , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/economia , Resultado do Tratamento
17.
Clin Pharmacol ; 6: 63-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24741335

RESUMO

BACKGROUND: The purpose of this study was to investigate the effect of glibenclamide dose escalation on blood glucose and insulin in patients with poorly controlled type 2 diabetes. METHODS: Twenty-two subjects with type 2 diabetes were administered increasing doses (0, 2.5, 5, 10, and 20 mg/day) of glibenclamide at 2-week intervals. Glibenclamide, glucose, and insulin determinations were performed. RESULTS: The decrease in mean blood glucose from zero dose was 20%, 22%, 26%, and 28% for doses of 2.5, 5, 10, and 20 mg/day, respectively, which was significant from zero dose to 2.5 mg/day (P≤0.001). There were no significant decreases in glucose concentration beyond 2.5 mg/day. The percentage increase in mean insulin from zero dose was 51%, 58%, 44%, and 33% for 2.5, 5, 10, and 20 mg/day respectively. Mean blood insulin increased significantly from zero dose to 2.5 mg/day (P≤0.001). There were no significant increases in mean insulin concentration beyond 2.5 mg/day. CONCLUSION: The results of this study suggest that increasing doses of glibenclamide do not produce a proportional increase in insulin secretion or a proportional decrease in blood glucose concentration.

18.
Case Rep Med ; 2011: 398571, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21966293

RESUMO

A 38-year-old HIV-positive female, recently started on antiretroviral therapy, presented in extremis. She had features suggestive of an HIV-associated cardiomyopathy complicated by the following problems: a four-day-old stroke, extensive deep venous thrombosis, and massive pulmonary embolism. She received intravenous streptokinase with rapid improvement, both haemodynamically and, unexpectedly, neurologically. Our case illustrates that a positive outcome is potentially possible where the two conditions coincide.

20.
South Med J ; 100(11): 1132-6, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17984746

RESUMO

type 2 diabetes mellitus is currently a global health problem. Although the armamentarium of oral hypoglycemic agents is continuously expanding, sulfonylureas (SUs) are still extensively used for the management of type 2 diabetes mellitus. However, despite decades of use, there is controversy as to the dosing of SUs. Despite many dose-response relationship studies indicating that SUs should be prescribed at lower doses, their dose recommendations remain unchanged. Moreover, studies have demonstrated that high doses of SUs may result in a deterioration of glycemic control and increased frequency of protracted hypoglycemic episodes. In view of the controversial dose-response relationship of SUs, it is suggested that the dose of SUs be titrated against glycemic parameters of blood glucose and glycated hemoglobin.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Compostos de Sulfonilureia/administração & dosagem , Administração Oral , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Humanos
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