Lumefantrine plasma concentrations in uncontrolled conditions among patients treated with artemether-lumefantrine for uncomplicated plasmodium falciparum malaria in Mwanza, Tanzania.

BACKGROUND: Therapeutic efficacy of artemether-lumefantrine is highly dependent on adequate systemic exposure to the partner drug lumefantrine particularly day 7 lumefantrine plasma concentration. There has been contradicting findings on the role of the cut-off values in predicting treatment outcomes among malaria patients in malaria endemic regions. This study assesses the day 3 and 7 lumefantrine plasma concentrations including related determinant factors and their influence on treatment outcomes among treated Tanzanian children and adults in uncontrolled conditions (real life condition). METHODS: Data was nested from an efficacy study employing the WHO protocol, 2015 for monitoring antimalarial drug efficacy. Lumefantrine plasma concentration was measured by high performance liquid chromatography with ultraviolet (HPLC-UV). RESULTS: Lumefantrine plasma concentrations below 175ng/ml and 200ng/ml on day 3 and 7 did not affect adequate clinical and parasitological response (ACPR) and recurrence of infection (p = 0.428 and 0.239 respectively). Age and baseline parasitemia were not associated to day 3 median lumefantrine plasma concentrations (p = 0.08 and 0.31 respectively) and day 7 lumefantrine plasma concentrations (p = 0.07 and 0.41 respectively). However, the day 3 and day 7 lumefantrine plasma concentrations were significantly higher in males compared to females (p = 0.03 and 0.042 respectively). CONCLUSION: Lumefantrine plasma concentrations below cut-off points (175ng/ml and 200ng/ml) on day 3 and 7 did not influence treatment outcomes.

Cyclooxygenase inhibitors for treating preterm labour: What is the molecular evidence? 1.

Preterm birth (<37 weeks of gestation) significantly increases the risk of neonatal mortality and morbidity. As many as half of all preterm births occur following spontaneous preterm labour. Since in such cases there are no known reasons for the initiation of labour, treatment of preterm labour (tocolysis) has sought to stop labour contractions and delay delivery. Despite some success, the use of cyclooxygenase (COX) inhibitors is associated with maternal/fetal side effects, and possibly increased risk of preterm birth. Clinical use of these drugs predates the collection of molecular and biochemical evidence in vitro, examining the expression and activity of COX enzymes in pregnant uterine tissues with and without labour. Such evidence is important to the rationale that COX enzymes are, or are not, appropriate targets for the tocolysis. The current study systematically searched existing scientific evidence to address the hypothesis that COX expression/activity is increased with the onset of human labour, in an effort to determine whether there is a rationale for the use of COX inhibitors as tocolytics. Our review identified 44 studies, but determined that there is insufficient evidence to support or refute a role of COX-1/-2 in the onset of preterm labour that supports COX-targeted tocolysis.

Traditional herbal medicine use among hypertensive patients in sub-Saharan Africa: a systematic review.

Hypertension is increasingly common in sub-Saharan Africa, and rates of hypertension control are low. Use of traditional herbal medicines (THM) is common among adults in sub-Saharan Africa and may affect hypertension therapy. We searched Ovid MEDLINE, Ovid EMBASE, and Web of Knowledge in June 2013 to find studies about THM use among hypertensive patients living in sub-Saharan Africa. Two independent reviewers evaluated titles and abstracts. Qualifying references were reviewed in full text. Data were extracted using a standardized questionnaire. Four hundred and eighty-one references were retrieved, and four articles from two countries met criteria for inclusion. The prevalence of THM use was 25-65% (average 38.6%). THM was the most common type of complementary and alternative medicines used by patients (86.7-96.6%). Among THM users, 47.5% concomitantly used both allopathic medicine and THM. Increased age (p<0.001), male sex (RR 2.58), belief in a supernatural cause of hypertension (RR 2.11), and family history of hypertension (OR 1.78) were positively associated with THM use, while belief that hypertension is preventable was negatively associated with THM use (OR 0.57). More than one-third of adults with hypertension in sub-Saharan Africa use THM. Half of these patients use THM concurrently with allopathic medicine. Healthcare workers in sub-Saharan Africa must discuss THM use with their hypertensive patients. More research is urgently needed to define the impact of THM use on hypertension control and outcomes in sub-Saharan Africa.

Difference in blood pressure response to ACE-Inhibitor monotherapy between black and white adults with arterial hypertension: a meta-analysis of 13 clinical trials.

BACKGROUND: Among African-Americans adults, arterial hypertension is both more prevalent and associated with more complications than among white adults. Hypertension is also epidemic among black adults in sub-Saharan Africa. The treatment of hypertension among black adults may be complicated by lesser response to certain classes of anti-hypertensive agents. METHODS: We systematically searched literature for clinical trials of ACE-inhibitors among hypertensive adults comparing blood pressure response between whites and blacks. Meta-analysis was performed to determine the difference in systolic and diastolic blood pressure response. Further analysis including meta-regressions, funnel plots, and one-study-removed analyses were performed to investigate possible sources of heterogeneity or bias. RESULTS: In a meta-analysis of 13 trials providing 17 different patient groups for evaluation, black race was associated with a lesser reduction in systolic (mean difference: 4.6 mmHg (95% CI 3.5-5.7)) and diastolic (mean difference: 2.8 mmHg (95% CI 2.2-3.5)) blood pressure response to ACE-inhibitors, with little heterogeneity. Meta-regression revealed only ACE-inhibitor dosage as a significant source of heterogeneity. There was little evidence of publication bias. CONCLUSIONS: Black race is consistently associated with a clinically significant lesser reduction in both systolic and diastolic blood pressure to ACE-inhibitor therapy in clinical trials in the USA and Europe. In black adults requiring monotherapy for uncomplicated hypertension, drugs other than ACE-inhibitors may be preferred, though the proven benefits of ACE-inhibitors in some sub-groups and the large overlap of response between blacks and whites must be remembered. These data are particularly important for interpretation of clinical drug trials for hypertensive black adults in sub-Saharan Africa and for the development of treatment recommendations in this population.