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.

Worldwide, the burden of Sickle Cell disease (SCD) has not been amply addressed. In Africa, Uganda has the 5th highest burden, a situation aggravated by limited and inaccessible formal social support structures to aid patients and families cope better with the psychosocial burden of SCD. In addition, this has been coupled with stigmatization and discrimination of people living with sickle cell disease causing isolation from family and society. This cross sectional study therefore set out to determine the attitudes, perception and level of awareness towards Sickle Cell disease in Ugandan communities. The study used an interviewer administered questionnaires to collect the data. Out of 110 people sampled; 91.2% of the respondents had ever heard of SCD with the highest proportion 38.7% hearing of SCD from friends and family. Close to half of the respondents 48% knew that SCD is inherited, however a large proportion 44.2% did not know the cause of SCD. However, 68.7% of the respondents said they cannot marry a person with SCD. The study results indicate that more effort needs to be done to promote sickle cell awareness in Uganda communities with emphasis on the inclusion of sickle cell in health education campaigns.

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 uncomplicatedPlasmodium falciparummalaria. 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.)

Background. The optimal treatment of malaria in human immunodeficiency virus (HIV)–infected children requires consideration of critical drug–drug interactions in coinfected children, as these may significantly impact drug exposure and clinical outcomes. Methods. We conducted an intensive and sparse pharmacokinetic/pharmacodynamic study in Uganda of the most widely adopted artemisinin-based combination therapy, artemether-lumefantrine. HIV-infected children on 3 different first-line antiretroviral therapy (ART) regimens were compared to HIV-uninfected children not on ART, all of whom required treatment for Plasmodium falciparum malaria. Pharmacokinetic sampling for artemether, dihydroartemisinin, and lumefantrine exposure was conducted through day 21, and associations between drug exposure and outcomes through day 42 were investigated. Results. One hundred forty-five and 225 children were included in the intensive and sparse pharmacokinetic analyses, respectively. Compared with no ART, efavirenz (EFV) reduced exposure to all antimalarial components by 2.1- to 3.4-fold; lopinavir/ritonavir (LPV/r) increased lumefantrine exposure by 2.1-fold; and nevirapine reduced artemether exposure only. Day 7 concentrations of lumefantrine were 10-fold lower in children on EFV vs LPV/r-based ART, changes that were associated with an approximate 4-fold higher odds of recurrent malaria by day 28 in those on EFV vs LPV/r-based ART. Conclusions. The choice of ART in children living in a malaria-endemic region has highly significant impacts on the pharmacokinetics and pharmacodynamics of artemether-lumefantrine treatment. EFV-based ART reduces all antimalarial components and is associated with the highest risk of recurrent malaria following treatment. For those on EFV, close clinical follow-up for recurrent malaria following artemether-lumefantrine treatment, along with the study of modified dosing regimens that provide higher exposure, is warranted.

The diagnosis of polycystic ovary syndrome (PCOS) remains challenging due to limited data regarding normative cut-offs for the diagnostic features in different subpopulations. We aim to conduct a systematic review, build a comprehensive repository of de-identified individual participant data (IPD), and define normative ranges and diagnostic cut-offs for all PCOS diagnostic features. We will conduct a systematic search of MEDLINE and EMBASE databases for studies that assessed PCOS diagnostic features in unselected women. Two reviewers will assess eligibility and perform quality appraisal. Authors of included studies will be invited to contribute IPD. Primary variables include directly assessed modified Ferriman Gallwey (mFG) scores; menstrual cycle lengths; follicle number per ovary (FNPO), ovarian volume (OV), anti-Müllerian hormone (AMH); circulating androgens, including total testosterone (TT), free testosterone, bioavailable testosterone, free androgen index (FAI), androstenedione (A4), and dehydroepiandrosterone sulphate (DHEAS). Normative ranges and cut-offs will be defined using cluster analysis. Monash University Human Research Ethics Committee granted ethical approval (26938/0 1/12/2020), all IPD will be de-identified and primary studies have ethical approval from their institutional ethics committees. Findings will clarify distinction between PCOS and non-PCOS populations, and inform the update of the international evidence-based guidelines for the assessment and management of PCOS.