Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine

How to screen for non-adherence to antihypertensive therapy

The quality of assessment of non-adherence to treatment in hypertensive is poor. Within this review, we discuss the different methods used to assess adherence to blood-pressure-lowering medications in hypertension patients. Subjective reports such as physicians’ perceptions are inaccurate, and questionnaires completed by patients tend to overreport adherence and show a low diagnostic specificity. Indirect objective methods such as pharmacy database records can be useful, but they are limited by the robustness of the recorded data. Electronic medication monitoring devices are accurate but usually track adherence to only a single medication and can be expensive. Overall, the fundamental issue with indirect objective measures is that they do not fully confirm ingestion of antihypertensive medications. Detection of antihypertensive medications in body fluids using liquid chromatography–tandem mass spectrometry is currently, in our view, the most robust and clinically useful method to assess non-adherence to blood-pressure-lowering treatment. It is particularly helpful in patients presenting with resistant, refractory or uncontrolled hypertension despite the optimal therapy. We recommend using this diagnostic strategy to detect non-adherence alongside a no-blame approach tailoring support to address the perceptions (e.g. beliefs about the illness and treatment) and practicalities (e.g. capability and resources) influencing motivation and ability to adhere

Prevalence and under-detection of gambiense human African trypanosomiasis during mass screening sessions in Uganda and Sudan.

BACKGROUND: Active case detection through mass community screening is a major control strategy against human African trypanosomiasis (HAT, sleeping sickness) caused by T. brucei gambiense. However, its impact can be limited by incomplete attendance at screening sessions (screening coverage) and diagnostic inaccuracy. METHODS: We developed a model-based approach to estimate the true prevalence and the fraction of cases detected during mass screening, based on observed prevalence, and adjusting for incomplete screening coverage and inaccuracy of diagnostic algorithms for screening, confirmation and HAT stage classification. We applied the model to data from three Médecins Sans Frontières projects in Uganda (Adjumani, Arua-Yumbe) and Southern Sudan (Kiri). RESULTS: We analysed 604 screening sessions, targeting about 710,000 people. Cases were about twice as likely to attend screening as non-cases, with no apparent difference by stage. Past incidence, population size and repeat screening rounds were strongly associated with observed prevalence. The estimated true prevalence was 0.46% to 0.90% in Kiri depending on the analysis approach, compared to an observed prevalence of 0.45%; 0.59% to 0.87% in Adjumani, compared to 0.92%; and 0.18% to 0.24% in Arua-Yumbe, compared to 0.21%. The true ratio of stage 1 to stage 2 cases was around two-three times higher than that observed, due to stage misclassification. The estimated detected fraction was between 42.2% and 84.0% in Kiri, 52.5% to 79.9% in Adjumani and 59.3% to 88.0% in Arua-Yumbe. CONCLUSIONS: In these well-resourced projects, a moderate to high fraction of cases appeared to be detected through mass screening. True prevalence differed little from observed prevalence for monitoring purposes. We discuss some limitations to our model that illustrate several difficulties of estimating the unseen burden of neglected tropical diseases

Effect of toothbrushing with different manual toothbrushes on the shear bond strength of orthodontic brackets

The aim of this study was to evaluate the effect of brushing with a Colgate 360º or Oral B Indicator 35 toothbrush on the shear bond strength of orthodontic brackets bonded to extracted human teeth. The bristle wear and bristle tip morphology were also examined after simulated tooth-brushing. Orthodontic brackets (Roth-P/1st and 2nd premolar S/D- Slot 0.18") were bonded (Transbond XT®) to the smoothest surface of each of 45 extracted human molar and premolar teeth. Test specimens were randomly divided into three groups: Group 1, control group with no brushing; Group 2, brushing with the Oral B Indicator 35; Group 3, brushing with the Colgate 360º. Samples were adapted to a machine that simulated tooth-brushing. The bond strength of each bracket to each tooth was assessed with a mechanical testing machine. The bristle wear and bristle tip morphology indices were also assessed. Statistically significant differences were defined for p < 0.05. The average bond strengths (range: 90.18-90.89 kgf/cm²) did not differ among the three groups. The Colgate 360º showed less bristle wear and a better bristle tip morphology than the Oral B Indicator 35 toothbrush. However, use of either toothbrush did not decrease the bond strength of the orthodontic brackets. Therefore, patients undergoing orthodontic therapy can safely use either toothbrush

Income distribution, economic growth and European integration

Growth, Inequality,