ORCID Profile
0000-0003-4188-7755
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Society for Microbiology
Date: 03-2016
DOI: 10.1128/AAC.01605-15
Abstract: Artemether-lumefantrine is a first-line regimen for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy. Previous studies have reported changes in the pharmacokinetics and clinical outcomes following treatment with artemether-lumefantrine in pregnant women compared to nonpregnant adults however, the results are inconclusive. We conducted a study in rural Uganda to compare the pharmacokinetics of artemether-lumefantrine and the treatment responses between 30 pregnant women and 30 nonpregnant adults with uncomplicated Plasmodium falciparum malaria. All participants were uninfected with HIV, treated with a six-dose regimen of artemether-lumefantrine, and monitored clinically for 42 days. The pharmacokinetics of artemether, its metabolite dihydroartemisinin, and lumefantrine were evaluated for 21 days following treatment. We found no significant differences in the overall pharmacokinetics of artemether, dihydroartemisinin, or lumefantrine in a direct comparison of pregnant women to nonpregnant adults, except for a statistically significant but small difference in the terminal elimination half-lives of both dihydroartemisinin and lumefantrine. There were seven PCR-confirmed reinfections (5 pregnant and 2 nonpregnant participants). The observation of a shorter terminal half-life for lumefantrine may have contributed to a higher frequency of reinfection or a shorter posttreatment prophylactic period in pregnant women than in nonpregnant adults. While the comparable overall pharmacokinetic exposure is reassuring, studies are needed to further optimize antimalarial efficacy in pregnant women, particularly in high-transmission settings and because of emerging drug resistance. (This study is registered at ClinicalTrials.gov under registration no. NCT01717885.)
Publisher: Oxford University Press (OUP)
Date: 03-05-2016
DOI: 10.1093/CID/CIW291
Publisher: Springer Science and Business Media LLC
Date: 26-06-2019
Publisher: Oxford University Press (OUP)
Date: 05-08-2020
Publisher: Springer Science and Business Media LLC
Date: 27-04-2018
Publisher: The Endocrine Society
Date: 31-05-2020
Publisher: Wiley
Date: 30-05-2022
DOI: 10.1111/CEN.14757
Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting 8%–13% of reproductive‐aged women. The aetiology of the syndrome is complex, with genetic susceptibility, androgen exposure in early life and adiposity related dysfunction leading to perturbance in hypothalamic–ovarian function. PCOS clinical features are heterogeneous, with manifestations arising even in early adolescence, developing into multisystem reproductive, metabolic and psychological manifestations in adulthood. In this review, we will discuss challenges in the diagnosis of PCOS and understanding of the natural history of PCOS.
Publisher: Wiley
Date: 11-12-2022
DOI: 10.1111/CEN.14647
Abstract: Women with polycystic ovary syndrome (PCOS) have a worsened metabolic profile but the progression of cardiometabolic features over time is unclear. Understanding this natural history is a key priority in PCOS research and vital for guiding the prevention and management of this common condition. We explored cardiometabolic changes that are observed in women with PCOS compared to those without PCOS across the life course. A systematic review of longitudinal cohort studies was conducted across MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews between 15 January 2020 and 11 February 2021. Eligible studies included participants with or without PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) criteria. We included studies that were published from the year 1990 to 2021 with data on cardiometabolic outcomes as per the PCOS core outcomes set. There were 31 longitudinal studies with 28,316 participants from four continents. At the start of follow up, participants were aged between 1 year and 49 years with a follow‐up period ranging from 2 to 32 years. Changes in BMI and the risk of coronary heart disease were similar in adult women with and without PCOS. Women with PCOS had a higher risk of Type 2 diabetes than their non‐PCOS counterparts. Evidence for the majority of all other outcomes was conflicting and with inadequate data. Understanding the natural history of PCOS and particularly changes in cardiometabolic features remains challenging. Existing literature is extensive but heterogeneous and inconsistent. Longitudinal studies in unselected populations are needed to provide high‐quality data in this area.
Publisher: Oxford University Press (OUP)
Date: 27-05-2023
Abstract: The diagnosis of polycystic ovary syndrome (PCOS) remains challenging with international guidelines prioritising accurate cut-offs for in idual diagnostic features. These diagnostic cut-offs are currently based on arbitrary percentiles, often from poorly characterised cohorts, and are dependent on variable laboratory ranges defined by assay manufacturers, limiting diagnostic accuracy. Cluster analysis is the recommended approach for defining normative cut-offs within populations for clinical syndromes. Few PCOS adult studies have applied cluster analysis, with no studies in adolescents. We aimed to define normative cut-offs for in idual PCOS diagnostic features in a community-based population of adolescents using cluster analysis. This analysis utilised data from the Menstruation in Teenagers Study, a subgroup of the Raine Study, which is a population based prospective cohort of 244 adolescents whose mean age at PCOS assessment was 15.2 years. K-means cluster analysis and receiver operating characteristics curves were used to define normative cut-offs for modified Ferriman–Gallwey (mFG) score, free testosterone (free T), free androgen index (FAI), and menstrual cycle length. Normative cut-offs for mFG, free T, FAI, and menstrual cycle lengths were 1.0, 23.4 pmol/L, 3.6, and 29 days, respectively. These corresponded to the 65th, 71st, 70th, and 59th population percentiles, respectively. In this novel study, we define the normative diagnostic criteria cut-offs in this unselected adolescent population and show that these cut-offs correspond to lower percentiles than conventional cut-offs. These findings highlight the pertinent need to re-define PCOS diagnostic cut-offs in adolescents. Validation is required in larger, multi-ethnic, and well-characterised adolescent cohorts.
Publisher: Oxford University Press (OUP)
Date: 10-05-2022
Abstract: What is the natural history of reproductive, psychological and oncological features in women with polycystic ovary syndrome (PCOS) in comparison to those without PCOS across the life course? Existing longitudinal data on changes in reproductive, psychological and oncological features in PCOS are inadequate and conflicting, but the limited evidence suggests that total testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) levels decline more significantly in women with PCOS than in those without PCOS, and the risk of gestational diabetes is higher in pregnant women with PCOS compared to their counterparts without PCOS. The progression of reproductive, psychological and oncological features in PCOS remains unclear, which limits prevention and early diagnosis strategies across the lifespan. Understanding the natural history of PCOS is one of the overarching priorities in PCOS research. This is a systematic review of longitudinal cohort studies with a narrative presentation of findings. Databases MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews were searched between 15 January 2020 and 11 February 2021 with no language restrictions. Only studies published from the year 1990 to February 2021 were included. In line with current guidelines for the assessment and management of PCOS, we included studies where participants were females with PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) consensus criteria. A total of 21 longitudinal studies including 62 123 participants over four continents reported reproductive, psychological and/or oncological outcomes. Participants were females aged between 15 and 49 years at baseline, with follow-up periods ranging from 4 weeks to 32 years. Consistent evidence based on limited studies suggests that total T and DHEAS levels decline to a greater degree in women with PCOS compared to those without PCOS, and the risk gestational diabetes is higher in women with PCOS than in those without PCOS. Evidence reporting changes over time in the majority of the remaining outcomes was unclear due to conflicting and/or insufficient information. There was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches. Understanding the natural history of PCOS and changes in diagnostic, reproductive, psychological and oncological features of PCOS across the lifespan is still a challenge and the existing literature is both limited and conflicting. It is important that future long-term prospective longitudinal studies are conducted in unselected and well-characterized populations. This specific study was not funded. S.K. is supported by scholarships from the Research Training Program of the Commonwealth of Australia and Monash University H.J.T. is supported by an Australian National Health and Medical Research Council fellowship and A.E.J. is supported by the Australian National Health and Medical Research Council's Centre for Research Excellence in Women’s Health in Reproductive Life. R.A. was employed by the American Society for Reproductive Medicine and is a consultant to Spruce Biosciences and Fortress Biotech. The other authors have no conflicts of interest to declare. Prospero registration number: CRD42020165546.
Publisher: Wiley
Date: 20-01-2017
DOI: 10.1111/BJH.14516
Abstract: It is vital to identify people with low recurrence risk of venous thromboembolism (VTE) so as to protect them from dangers of prolonged anticoagulation therapy. Among women who develop VTE following hormone use, the evidence as to whether their risk of recurrence is low if they cease this therapy is conflicting. We investigated whether women whose initial VTE event was hormone-related have a lower risk of VTE recurrence than women whose initial event had no obvious cause (unprovoked). A cohort study utilising the Clinical Practice Research Datalink linked to Hospital Episode Statistics data from England was conducted. We selected 4170 women aged between 15 and 64 years who were diagnosed with a first VTE event between 1997 and 2011. Cox regression models were used to obtain hazard ratios (HR). Hormone users had 29% lower recurrence risk than non-users (adjusted HR = 0·71 95% confidence interval 0·58-0·88), a relationship which existed both in women aged 15-44 years (predominantly oral contraceptive users) and those aged 45-64 years (predominantly hormone replacement therapy users). In conclusion, having a hormone-associated VTE is associated with a lower recurrence risk than one that is unprovoked after discontinuation of the hormone-containing preparation. Prolonged anticoagulation may therefore be unjustified in such women.
Publisher: Wiley
Date: 24-11-2021
DOI: 10.1111/CEN.14640
Abstract: Menstrual cycle regularity underpins the diagnosis of polycystic ovary syndrome (PCOS), which is linked to adverse cardio‐metabolic profile. However, links between menstrual disorders and metabolic conditions are often under‐appreciated and not considered when assessing cardio‐metabolic risk in women. We aimed to assess the risk of diabetes and heart disease in women with irregular menstrual cycles and those whose cycles were regular. This was a community based longitudinal cohort study. We utilized the 1946 to 1951 birth cohort database ( N = 13,714) of the Australian Longitudinal Study on Women's Health (ALSWH) over a 20‐year follow‐up period. Data were analysed using Cox regression models. Women with irregular menstrual cycles had 20% higher risk of developing heart disease [adjusted hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.01–1.43) compared with those with regular menstrual cycles. We also observed 17% higher risk of diabetes (HR: 1.17, 95% CI: 1.00–1.38) in women who had irregular menstrual cycles than in women who had regular menstrual cycles. The diabetes risk was 30% higher (HR: 1.30, 95% CI: 1.09–1.55) if women had irregular cycles and did not use hormone replacement therapy, but this was not significant on adjustment for all covariates. Having irregular menstrual cycles appears to be an early indicator for heart disease and diabetes. These findings suggest that irregular cycles among women in their forties may be linked to adverse cardio‐metabolic outcomes. These women may benefit from screening and prevention strategies as recommended by related guidelines such as the international evidence‐based guideline for the assessment and management of PCOS.
Publisher: Oxford University Press (OUP)
Date: 2016
DOI: 10.1093/OFID/OFW217
Abstract: Artemisinins are primarily responsible for initial parasite clearance. Antimalarial pharmacokinetics (PK), human immunodeficiency virus (HIV) infection, and antiretroviral therapy have been shown to impact treatment outcomes, although their impact on early parasite clearance in children has not been well characterized. Parasite clearance parameters were generated from twice-daily blood smears in HIV-infected and HIV-uninfected Ugandan children treated with artemether-lumefantrine (AL). Artemether and dihydroartemisinin (DHA) area-under-the-curve from 0–8 hours (AUC0-8hr) after the 1st AL dose was compared with AUC0-8hr after the last (6th) dose in a concurrently enrolled cohort. The association between post-1st dose artemisinin AUC0-8hr and parasite clearance was assessed. Parasite clearance was longer in HIV-infected versus HIV-uninfected children (median, 3.5 vs 2.8 hours P = .003). Artemether AUC0-8hr was 3- to 4-fold lower after the 6th dose versus the 1st dose of AL in HIV-infected children on nevirapine- or lopinavir/ritionavir-based regimens and in HIV-uninfected children (P ≤ .002, 1st vs 6th-dose comparisons). Children on efavirenz exhibited combined post-1st dose artemether/DHA exposure that was significantly lower than those on lopinavir/ritonavir and HIV-uninfected children. Multiple regression analysis supported that the effect of artemether/DHA exposure on parasite clearance was significantly moderated by HIV status. Parasite clearance rates remain rapid in Uganda and were not found to associate with PK exposure. However, significant decreases in artemisinin PK with repeated dosing in nearly all children, coupled with small, but significant increase in parasite clearance half-life in those with HIV, may have important implications for AL efficacy, particularly because reports of artemisinin resistance are increasing.
Publisher: Georg Thieme Verlag KG
Date: 07-2021
Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is associated with negative metabolic, reproductive, endocrine, and psychological consequences among women of reproductive age. The diagnosis of PCOS remains challenging due to limited and conflicting evidence regarding definitions for each of the diagnostic features. This review of the recommended PCOS assessment criteria from the international evidence-based guideline highlights the crucial need to reassess, redefine, and optimize the diagnosis of PCOS. Notably, normal values and cut-offs need to be defined for each diagnostic feature across the lifespan and erse ethnic groups. Understanding how these features cluster together and relate to short- and long-term health outcomes in PCOS is also vital. Ultimately, greater knowledge of the natural history of PCOS is needed through well-characterized, community-based longitudinal studies, which will inform future PCOS diagnosis guidelines and optimize women's health in reproductive life.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Dr. Sylvia Kiconco, PhD.