Browsing by Author "Decloedt, Eric"

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    A cross-sectional study of the association between cognitive impairment and haemoglobin levels in HIV-infected South Africans established on antiretroviral therapy
    (2019) Vermaak, John-Randel; Joska, John; Decloedt, Eric
    Background Sub-Saharan Africa, the epicenter of the global population of people living with HIV (PLHIV), is estimated to have more than 25 million PLHIV. In the era before the widespread availability of antiretroviral therapy (ART), anaemia (low serum haemoglobin) was a common clinical finding that was seen as a potential risk factor for HIV-associated neurocognitive impairment. The association between haemoglobin levels and neurocognitive function has not been assessed in a Sub-Saharan study population in the era of ART. Methods A cross-sectional secondary data analysis was performed to assess the association between serum haemoglobin level and neurocognitive function in 129 participants who had both neurocognitive test (global deficit score) and full blood count results performed as part of a randomised placebo controlled trial that evaluated the efficacy of lithium carbonate for the treatment of HIV associated neurocognitive disorders. Results The majority of our participants were female (87%) with a mean age of 37 ±7.78 years. Participants were all established on ART with a median CD4 count of 495 cells/µL (IQR=315- 629). The median haemoglobin level was 12.2 (IQR=11.6-13.00) and anaemia was present in 8.5%. Serum haemoglobin level was not associated with global deficit scores (GDS) and fewer years of education was the only independent risk association for GDS-defined neurocognitive impairment. Conclusion We found that in South Africans, who are established on ART, anaemia is less common than in the pre-ART era and importantly, that low-normal serum Hb levels do not present a risk for GDS-defined neurocognitive impairment. These findings are relevant as they show that aggressive management of low-normal Hb levels is not necessary provided individuals are otherwise clinically well and virally suppressed.
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    Current trends in drug treatment of obsessive–compulsive disorder
    (2010) Decloedt, Eric
    This article aims to highlight current trends in the pharmacologic management of obsessive–compulsive disorder (OCD). A systematic search of the electronic database MEDLINE was conducted. The first case report of clomipramine efficacy in the management OCD more than 40 years ago gave new hope for the treatment of this debilitating disorder. Selective serotonin reuptake inhibitors (SSRIs) proved to have a similar efficacy profile compared with clomipramine but had a superior tolerability profile. While many patients with OCD respond to SSRIs or clomipramine, the treatment of those with refractory OCD remains challenging. Different augmentation agents in treatment-resistant OCD have been explored, with antipsychotic agents having the largest supporting evidence base. Nevertheless, new pharmacologic treatment options are required and are under investigation.
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    Dosage adjustment in medical patients with renal impairment at Groote Schuur Hospital
    (2010) Decloedt, Eric; Leisegang, Rory; Blockman, Marc; Cohen, Karen
    BACKGROUND: Many drugs are eliminated by the kidneys and therefore may require dose adjustment in patients with renal impairment. The need for dose adjustment is frequently neglected by prescribers. METHODS: We reviewed folders of patients admitted to the Groote Schuur Hospital general medical wards between January and March 2008. Patients with renal impairment, defined as an estimated glomerular filtration rate (eGFR) < or = 50 ml per minute per 1.73 m2, were identified. In-patient prescriptions were captured if they were written after clinical notes indicated impaired renal function, or > or = 1 day after renal function tests were performed. We determined what proportion of these prescriptions required dose adjustment and whether drug doses were appropriately adjusted. RESULTS: We found renal impairment in 32% (97/301) of medical admissions. There were 615 prescription entries for the 97 patients with renal impairment. Dose adjustment was required in 19% (117/615) of prescription entries, and only 32% (37/117) of these prescription entries were correctly dose adjusted. Of 97 patients, 69 received one or more drugs that required dose adjustment (median 1, range 1 - 5). All drug doses were correctly adjusted in 12% (8/69) of patients. Importantly, in the majority of patients (59% (41/69)) no doses had been correctly adjusted. CONCLUSION: Consistent with international studies, drug dose adjustment in patients with renal impairment in a South African hospital was frequently neglected. Strategies to alert clinicians of the need for dose adjustment in renal impairment should be considered, including automated eGFR reporting and computerised aids to guide drug dosing, that account for renal impairment.
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    Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial
    (BioMed Central, 2017-06-07) Lesosky, Maia; Joska, John; Decloedt, Eric
    Background: Therapeutic drug monitoring (TDM) is essential practice when dosing drugs with a narrow therapeutic index in order to achieve a plasma drug concentration within a narrow target range above the efficacy concentration but below the toxicity concentration. However, TDM with dose individualisation is challenging during a double-blind clinical trial with laboratory staff and investigators blinded to treatment arm allocation. Methods: Drug concentrations were simulated for participants in the placebo arm by an unblinded independent statistician, utilising the measured values from the treatment arm participants. Simulated and actual concentrations were re-blinded and passed on to a dose-adjusting investigator, who made dose adjustment recommendations but was not directly responsible for clinical care of participants. Results: A total of 257 sham lithium plasma concentrations were simulated utilising 242 true lithium plasma concentrations in real time as the trial progressed. The simulated values had a median (interquartile range) of 0.59 (0.46, 0.72) compared to 0.53 (0.39, 0.72) in the treatment arm. Blinding of the laboratory staff and dose-adjusting investigator was maintained successfully. Conclusions: We succeeded in simulating sham lithium plasma concentrations while maintaining blinding. Our simulated values have a smaller range than the observed data, which can be explained by the challenges with respect to drug adherence and dose timing that were experienced. Trial registration: Pan African Clinical Trials Registry, PACTR201310000635418. Registered on 30 August 2013.