The Achievement of Glycaemic, Blood Pressure and LDL Cholesterol Targets in Patients with Type 2 Diabetes Attending a South African Tertiary Hospital Outpatient Clinic

Objectives: To determine differences in the control of multiple diabetes control parameters in a select group of subjects with type 2 diabetes (T2DM) after a four-year follow-up period.Design: Cross-sectional study.Setting and subjects: The initial 2009 study population consisted of 666 T2DM patients of whom only 261 (39.2%) were audited at the Charlotte Maxeke Johannesburg Academic Hospital. Outcome measures: Using a public sector database, retrospective data were obtained on the treatment of participants with T2DM attending a tertiary care setting and a descriptive analysis was done.Results: The mean age was 64 (SD 10.6) years, women represented 55% of the cohort and the mean duration of diabetes was 16 years (range 2–40 years) in 2013. Fewer patients achieved an HbA1c goal (of < 7%) in 2013 (15.5%) compared with 2009 (25.4%), whilst an additional 13.7% and 25.0% of the 261 patients reached blood pressure targets (< 140/80 mmHg) and LDL-C targets ( < 2.5 mmol/L), respectively.Conclusion: Overall, more patients in the study reached blood pressure and LDL-C targets but there were difficulties in achieving optimal glycaemic levels over the four-year period. This study highlights the complexities of managing risk factors in T2DM, especially glucose control.Keywords: Diabetes Mellitus, Management, Risk Factors, Target

Hospitalisation of Type 2 diabetes mellitus patients with and without major depressive disorder in a private managed healthcare organisation

Background: The relationship between Type 2 diabetes mellitus (T2DM) and associated co-morbidities, particularly major depressive disorder (MDD), is poorly acknowledged in chronic disease management practices in South Africa. Managed healthcare costs and hospitalisation rates may be influenced by the discrete management of co-morbid conditions. Therefore, the relationship between T2DM and MDD in terms of co-morbidity incidence and hospitalisation resource utilisation was investigated.Method: This retrospective descriptive study analysed the data of 902 adult patients with T2DM from the health system database of a private managed healthcare organisation for 2014.Results: The mean age was 57 ± 15 years and 85% of the identified T2DM patients had at least one recorded co-morbidity. Among this population 17% presented with MDD. A higher percentage of T2DM patients with MDD were admitted to hospital (42%, p = 0.004) compared with those without MDD (30%). The number of overnight admissions was higher among the T2DM with MDD (76%, p = 0.016) compared with T2DM without MDD (66%). The T2DM with MDD group (85%, p = 0.018) had greater non-diabetes related hospital events compared with the T2DM without MDD group (73%). The T2DM patients without MDD were more likely to be hospitalised for diabetes-related events (27%, p = 0.018) at significantly higher admission cost (p = 0.001).Conclusion: Patients with T2DM and MDD present with more co-morbid conditions and had a higher number of hospitalisations than their non-MDD counterparts. However, the hospitalisation costs were significantly higher for diabetes-related admissions in the non-MDD group due to a higher number of macrovascular events. Healthcare organisations need to focus on an integrated approach in the management of chronic conditions with emphasis on active surveillance of T2DM patients, where MDD is identified and treated to lessen the risk of macrovascular complications

Citalopram Enhances the Activity of Chloroquine in Resistant Plasmodium in Vitro and in Vivo 1

ABSTRACT Citalopram, is an extremely potent inhibitor of neuronal serotonin reuptake. It is structurally unrelated to other antidepressants, but it contains the chemical features associated with reversal of drug resistance and exhibits minimal cardiotoxic side effects and fewer of the anticholinergic and adrenolytic side effects associated with other psychotropic agents. Sensitivity tests to citalopram alone and in combination with chloroquine were performed against chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum and Plasmodium chabaudi. Citalopram alone showed intrinsic activity against the chloroquine-resistant strains of P. falciparum (IC 50 ϭ 1.51 Ϯ .6 M) but only limited activity against the chloroquine-sensitive strain (IC 50 ϭ 33.27 Ϯ 5.87 M) and no activity in vivo. The interaction of chloroquine and citalopram in vitro resulted in a synergistic response in the chloroquineresistant strain but there was no interaction between the drugs in the chloroquine-sensitive strain-a pattern found with other reversal agents. Citalopram enhanced chloroquine susceptibility in both strains of P. chabaudi, however, the potentiating effect was seen at lower doses in the chloroquine-resistant strain. The results of this study suggest that citalopram may have potential as a chemosensitizer in Plasmodium infections on the basis of the low toxicity of citalopram at concentrations potentiating chloroquine activity both in vitro and in vivo. Malaria is a significant source of global morbidity and mortality. Despite the development of new antimalarial agents such as mefloquine, halofantrine and the artemisins, chloroquine remains the drug of choice for the treatment of uncomplicated Plasmodium falciparum malaria infections, due to its low cost, rapid onset of action and its low toxicity. However, the efficacy of chloroquine has diminished due to the emergence and prevalence of chloroquine-resistant strains of P. falciparum (Wensdorfer and Payne, 1991). The rapid development and spread of resistance to chloroquine and other antimalarials, and the tremendous cost of drug development has emphasized the necessity to optimize the use of existing antimalarial agents A number of adjunct drugs have been identified from a wide variety of chemical classes including calcium-channel blockers Citalopram,1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3dihydroisobenzofuran-5-carbonite), is an extremely potent inhibitor of neuronal serotonin reuptake The low toxicity coupled with the chemical similarity to chemosensitizers (resistance reversal agents) prompted us to investigate the chemosensitizing effect of citalopram in Plasmodium. In this study, we screened citalopram for chloroquine potentiating activity in chloroquine-resistant and chloroquine sensitive-parasites; both in vitro against P. falciparum and in a rodent malaria model (Plasmodium chabaudi). Methods Effect of Citalopram in Vitro Parasites. Two well-characterized isolates of P. falciparum were used for the drug assays. The chloroquine-resistant FCR-3 strain (IC 50 ϳ 150 nM) (donated by J. Freese, Research in diseases of the Tropical Environment, Durban, South Africa) and the chloroquine

Lithium blocks 45Ca2+ uptake into platelets in bipolar affective disorder and controls.

The basal uptake of radiolabelled 45Ca2+ into platelets and the effect of 1 mM lithium on uptake was measured in manic (n = 13) and depressed (n = 15) patients with bipolar disorder and in controls (n = 13). Lithium was significantly associated with inhibition of uptake of 45Ca2+ into platelets in all three groups. There were no significant intergroup differences in either basal levels of calcium uptake or the effects of lithium on calcium uptake (analysis of variance)

An update on the measurement and management of cholesterol with specific reference to secondary prevention of cardiovascular disease (CVD)

Cardiovascular disease remains the largest contributor to non-communicable adverse disease outcomes. Treatment and prevention of cardiovascular disease have evolved at a dramatic pace in the last 40 years. Serum-cholesterol has emerged as the dominant risk factor for coronary artery disease and events. The link between serum-cholesterol and arterial atherosclerosis is well documented. The attainment of cholesterol goals has historically concentrated on low-density lipoprotein cholesterol (LDL-C) levels. Current evidence and guidelines have shifted to the attainment of non-HDL-C target levels which represent a more thorough inclusion of small dense atherogenic particles. Methods to reduce serum-cholesterol mainly centre around the use of the HMG CoA-reductase inhibitors also known as the statins. High intensity statins like atorvastatin (80 mg) and rosuvastatin (40 mg) are now the preferred starting therapies to lower cholesterol by at least 40–50% in patients with established cardiovascular disease as secondary prevention. In the event of failure of these medications, evidence suggests that the addition of ezetimibe may enhance the total serum-lowering levels to 50–60%. New therapies aimed at inhibiting PCSK9 revealed exciting new targets for LDL-C lowering, but the high cost of these antibodies could preclude access to this therapeutic intervention. Aggressive pursuit of lower LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels may reduce the incidence of secondary myocardial infarctions, strokes and death from cardiovascular disease

Augmented platelet calcium uptake in response to serotonin stimulation in patients with major depression measured using Mn2+ influx and 45Ca2+ uptake.

There is an augmented platelet intracellular calcium response to serotonin stimulation in major depression. The role that calcium influx has in this process is not known. The objective of this study was to determine platelet calcium influx in response to serotonin by two methods, Mn2+ influx and 45Ca2+ uptake, in order to observe if the uptake response to serotonin was augmented in major depression by comparing the response to normal controls. The use of the two methods of calcium influx showed that serotonin stimulates calcium uptake into platelets. Furthermore, patients with major depression have significantly augmented platelet calcium uptake in response to serotonin. The interesting finding was that calcium uptake into platelets is biphasic, occurring immediately and after five minutes. These results may support the two pool model for calcium oscillations within cells whereby extracellular calcium is needed for intracellular calcium release, and for replenishment of depleted stores once intracellular calcium is released