Browsing by Author "Lesosky, Maia"
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- ItemAntibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or re-admission rates(Public Library of Science, 2013-12-09) Boyles, Tom H.; Whitelaw, Andrew; Bamford, Colleen; Moodley, Mischka; Bonorchis, Kim; Morris, Vida; Rawoot, Naazneen; Naicker, Vanishree; Lusakiewicz, Irena; Black, John; Stead, David; Lesosky, Maia; Raubenheimer, Peter; Dlamini, Sipho; Mendelson, MarcBackground Antibiotic consumption is a major driver of bacterial resistance. To address the increasing burden of multi-drug resistant bacterial infections, antibiotic stewardship programmes are promoted worldwide to rationalize antibiotic prescribing and conserve remaining antibiotics. Few studies have been reported from developing countries and none from Africa that report on an intervention based approach with outcomes that include morbidity and mortality. Methods An antibiotic prescription chart and weekly antibiotic stewardship ward round was introduced into two medical wards of an academic teaching hospital in South Africa between January-December 2012. Electronic pharmacy records were used to collect the volume and cost of antibiotics used, the patient database was analysed to determine inpatient mortality and 30-day re-admission rates, and laboratory records to determine use of infection-related tests. Outcomes were compared to a control period, January-December 2011. Results During the intervention period, 475.8 defined daily doses were prescribed per 1000 inpatient days compared to 592.0 defined daily doses/1000 inpatient days during the control period. This represents a 19.6% decrease in volume with a cost reduction of 35% of the pharmacy’s antibiotic budget. There was a concomitant increase in laboratory tests driven by requests for procalcitonin. There was no difference in inpatient mortality or 30-day readmission rate during the control and intervention periods. Conclusions Introduction of antibiotic stewardship ward rounds and a dedicated prescription chart in a developing country setting can achieve reduction in antibiotic consumption without harm to patients. Increased laboratory costs should be anticipated when introducing an antibiotic stewardship program.
- ItemModerate to severe HIV-associated neurocognitive impairment : a randomized placebo-controlled trial of lithium(Wolters Kluwer Health, 2016-11) Decloedt, Eric H.; Freeman, Carla; Howells, Fleur; Casson-Crook, Martine; Lesosky, Maia; Koutsilieri, Eleni; Lovestone, Simon; Maartens, Gary; Joska, John A.Background: HIV-associated neurocognitive disorder (HAND) remains highly prevalent despite effective anti-retroviral therapy (ART). A number of adjunctive pharmacotherapies for HAND have been studied with disappointing results, but preliminary data suggest that lithium may provide clinical benefit. In addition, the low cost of lithium would facilitate access in low- and middle-income countries which carry the greatest burden of HIV. Methods: Our objective was to evaluate the 24-week efficacy and safety of lithium in patients with moderate to severe HAND. Our primary efficacy endpoint was the change in Global Deficit Score (GDS) from baseline to 24 weeks, whereas our secondary endpoint was the change in proton magnetic resonance spectroscopy (1H-MRS) brain metabolite concentrations. We conducted a 24-week randomized placebo-controlled trial of lithium as adjunctive pharmacotherapy. We enrolled participants with moderate to severe HAND, on ART for at least 6 months, with suppressed viral loads and attending public sector primary care clinics in Cape Town, South Africa. We randomized 66 participants to lithium (n = 32) or placebo (n = 34). Lithium or placebo was dosed 12-hourly and titrated to achieve the maintenance target plasma concentration of 0.6 to 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. Results: Totally 61 participants completed the study (lithium arm = 30; placebo arm = 31). Participants at enrolment had a mean age of 40 years and a median CD4+ T-cell count of 500 cells/μL. The median change in GDS between baseline and week 24 for the lithium and placebo arms were –0.57 (95% confidence interval [CI] –0.77, –0.32) and –0.56 (–0.69, –0.34) respectively, with a mean difference of –0.054 (95% CI –0.26, 0.15); P = 0.716. The improvement remained similar when analyzed according to age, severity of impairment, CD4+ count, time on ART, and ART regimen. Standard 1H-MRS metabolite concentrations were similar between the treatment arms. The study drug was well tolerated in both study arms. Six serious adverse events occurred, but none were considered related to the study drug. Conclusion: Adjunctive lithium pharmacotherapy in patients on ART with HAND was well tolerated but had no additional benefit on neurocognitive impairment.
- ItemRenal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy : analysis from a randomized placebo-controlled trial(BioMed Central, 2017-02-04) Decloedt, Eric H.; Lesosky, Maia; Maartens, Gary; Joska, John A.Background: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. Objective: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment. Methods: We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. Results: We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks. Conclusions: We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity.
- ItemSafety of licensed vaccines in HIV-infected persons : a systematic review protocol(BioMed Central, 2014-09) Kagina, Benjamin M.; Wiysonge, Charles S.; Lesosky, Maia; Madhi, Shabir A.; Hussey, Gregory D.Background Safety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons. Methods/Design We will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus. Discussion Globally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be feasible among HIV-infected persons. Systematic review registration PROSPERO CRD42014009794.
- ItemSimulating 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, EricBackground: 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.