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Background: Hypertension is the largest contributor to the global burden of disease. Emerging risk factors for cardiovascular disease include blood pressure variability (BPV), but evidence on BPV is lacking among older Nigerians. We reported BPV in a cohort of older persons at the University College Hospital (UCH), Ibadan. Methods: We conducted a retrospective cohort study of respondents aged >50 years within the Ibadan Ambulatory Blood Pressure Registry at the UCH, Ibadan, Nigeria. Socio-demographic characteristics, lifestyle habits and anthropometric measurements were obtained. Results: Among 639 respondents, 332 (52.0%) were female. The blood pressure (BP) variables were strongly associated with age. Compared with younger age groups, mean diastolic BP (DBP) was less at an older age, whereas mean pulse pressure was greater. During the wake-up and sleep periods, mean DBP and mean arterial BP were less with each increasing age category, whereas mean pulse pressure was larger with each increasing age category. BP dipping, systolic, diastolic and mean arterial BP decreased with age. Overall, timed BPV increased significantly with increasing age. The prevalence of white-coat hypertension was greater among older participants than younger participants. Most respondents in the 50-59 years' age group were non-dippers (55.8%), whereas 33.7% of older respondents were reverse-dippers. Conclusion: Older persons experienced a greater abnormal circadian blood variation and greater BPV than younger people. In Nigeria, follow-up data are needed to determine the prognostic significance of these data in this population. [ABSTRACT FROM AUTHOR]

Abstract Background Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance. Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) are efficacious regimens that have been widely adopted in sub-Saharan Africa. However, most study designs ignore the effects of these regimens on peripheral parasitaemia in the first 24 hours of therapy. The study protocol was designed to evaluate more closely the early effects and the standard measures of efficacies of these two regimens. Methods In an open label, randomized controlled clinical trial, children aged 12 months to 132 months were randomized to receive AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days. Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h, and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic identification and quantification of Plasmodium falciparum. Results A total of 193 children were randomized to receive either AL (97) or AA (96). In children that received both medications, early response of peripheral parasitaemia showed that 42% of children who received AL and 36.7% of those who received AA had an immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a rapid fall. The rise in parasitaemia was significant and seems to suggest a mobilization of asexual parasites from the deep tissues to the periphery. Days 3, 7, 14, 28, and 42 cure rates in the per protocol (PP) population were > 90% in both groups of children. Both drug combinations were well tolerated with minimal side effects. Conclusion The study showed the high efficacy of AL and AA in Nigerian children. In addition the study demonstrated the mobilisation of asexual parasites from the deep to the periphery in the early hours of commencing ACT treatment in a subset of patients in both study groups. It is unclear whether the early parasite dynamics discovered in this study play any role in the development of drug resistance and thus it is important to further evaluate this discovery. It may be useful for studies investigating delay in parasite clearance of artemisinin derivatives as a way of monitoring the development of resistance to artemisinin to assess the early effects of the drugs on the parasites.

Abstract Background Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results 1,237 of 2,752 children (45%) had delay in parasite clearance. Overall 211 children (17%) with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P < 0.0001), and enrolment before year 2000 (AOR= 1.55, 95% CI = 1.22-1.96, P < 0.0001). Following treatment, a body temperature ≥ 38°C and parasitaemia > 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P < 0.0001). Conclusion Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.

Introduction: Amodiaquine is a partner drug in the artemisinin-based combination therapy artesunate-amodiaquine. Reports of the adverse drug reaction known as amodiaquine-associated asthenia are scarce, and this adverse reaction needs to be investigated in detail. This article presents and reviews a case of amodiaquine-associated asthenia. A literature search for the characteristics of this adverse reaction highlighted gaps in the literature. Methods: A case of probable amodiaquine asthenia was described and discussed under the sub-headings of epidemiology, clinical features, laboratory features, aetiopathogenesis, and management. A literature search limited to Medline Health Databases (Medline and PubMed Central, PMC) using the search terms and was conducted on 10 March 2015. Retrieved literature on the subject was closely scrutinized for relevant details of adverse drug reactions to amodiaquine when used in the management or prophylaxis of malaria. Cited literature within retrieved manuscripts was examined manually for other relevant literature. Papers retrieved from the search were used to describe the existing knowledge and gaps in it of the adverse drug reaction under sub-categories of incidence, clinical features, laboratory features, aetiopathogenesis, and management. Results: Thirty-nine manuscripts were retrieved; 20 had content relevant to the objectives of this review. The frequency of amodiaquine-associated asthenia in different populations ranged from 12-36%. There is a paucity of reports, and no detailed study of this adverse reaction has been published in popular English medical literature. Conclusion: With the use of amodiaquine as a partner drug in antimalarial combination therapies being scaled up, well-structured studies are needed on adverse reactions to amodiaquine and to investigate amodiaquine-associated asthenia. In addition, approaches to elucidating this adverse reaction more effectively in children need to be developed. [ABSTRACT FROM AUTHOR]

Background: Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance. Artemether-lumefantrine (AL) and artesunateamodiaquine (AA) are efficacious regimens that have been widely adopted in sub-Saharan Africa. However, most study designs ignore the effects of these regimens on peripheral parasitaemia in the first 24 hours of therapy. The study protocol was designed to evaluate more closely the early effects and the standard measures of efficacies of these two regimens. Methods: In an open label, randomized controlled clinical trial, children aged 12 months to 132 months were randomized to receive AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days. Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h, and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic identification and quantification of Plasmodium falciparum. Results: A total of 193 children were randomized to receive either AL (97) or AA (96). In children that received both medications, early response of peripheral parasitaemia showed that 42% of children who received AL and 36.7% of those who received AA had an immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a rapid fall. The rise in parasitaemia was significant and seems to suggest a mobilization of asexual parasites from the deep tissues to the periphery. Days 3, 7, 14, 28, and 42 cure rates in the per protocol (PP) population were >90% in both groups of children. Both drug combinations were well tolerated with minimal side effects. Conclusion: The study showed the high efficacy of AL and AA in Nigerian children. In addition the study demonstrated the mobilisation of asexual parasites from the deep to the periphery in the early hours of commencing ACT treatment in a subset of patients in both study groups. It is unclear whether the early parasite dynamics discovered in this study play any role in the development of drug resistance and thus it is important to further evaluate this discovery. It may be useful for studies investigating delay in parasite clearance of artemisinin derivatives as a way of monitoring the development of resistance to artemisinin to assess the early effects of the drugs on the parasites. [ABSTRACT FROM AUTHOR]