| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Bowman, L. R., et al.
(författare)
-
Alarm Variables for Dengue Outbreaks: A Multi-Centre Study in Asia and Latin America
- 2016
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background Worldwide, dengue is an unrelenting economic and health burden. Dengue outbreaks have become increasingly common, which place great strain on health infrastructure and services. Early warning models could allow health systems and vector control programmes to respond more cost-effectively and efficiently. The Shewhart method and Endemic Channel were used to identify alarm variables that may predict dengue outbreaks. Five country datasets were compiled by epidemiological week over the years 2007-2013. These data were split between the years 2007-2011 (historic period) and 2012-2013 (evaluation period). Associations between alarm/outbreak variables were analysed using logistic regression during the historic period while alarm and outbreak signals were captured during the evaluation period. These signals were combined to form alarm/outbreak periods, where 2 signals were equal to 1 period. Alarm periods were quantified and used to predict subsequent outbreak periods. Across Mexico and Dominican Republic, an increase in probable cases predicted outbreaks of hospitalised cases with sensitivities and positive predictive values (PPV) of 93%/83% and 97%/86% respectively, at a lag of 1-12 weeks. An increase in mean temperature ably predicted outbreaks of hospitalised cases in Mexico and Brazil, with sensitivities and PPVs of 79%/73% and 81%/46% respectively, also at a lag of 1-12 weeks. Mean age was predictive of hospitalised cases at sensitivities and PPVs of 72%/74% and 96%/45% in Mexico and Malaysia respectively, at a lag of 4-16 weeks. An increase in probable cases was predictive of outbreaks, while meteorological variables, particularly mean temperature, demonstrated predictive potential in some countries, but not all. While it is difficult to define uniform variables applicable in every country context, the use of probable cases and meteorological variables in tailored early warning systems could be used to highlight the occurrence of dengue outbreaks or indicate increased risk of dengue transmission.
|
|
| 5. |
- Hennig, Stefanie, et al.
(författare)
-
Population pharmacokinetic drug-drug interaction pooled analysis of existing data for rifabutin and HIV PIs
- 2016
-
Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 71:5, s. 1330-1340
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Extensive but fragmented data from existing studies were used to describe the drug-drug interaction between rifabutin and HIV PIs and predict doses achieving recommended therapeutic exposure for rifabutin in patients with HIV-associated TB, with concurrently administered PIs.METHODS: Individual-level data from 13 published studies were pooled and a population analysis approach was used to develop a pharmacokinetic model for rifabutin, its main active metabolite 25-O-desacetyl rifabutin (des-rifabutin) and drug-drug interaction with PIs in healthy volunteers and patients who had HIV and TB (TB/HIV).RESULTS: Key parameters of rifabutin affected by drug-drug interaction in TB/HIV were clearance to routes other than des-rifabutin (reduced by 76%-100%), formation of the metabolite (increased by 224% in patients), volume of distribution (increased by 606%) and distribution to the peripheral compartment (reduced by 47%). For des-rifabutin, clearance was reduced by 35%-76% and volume of distribution increased by 67%-240% in TB/HIV. These changes resulted in overall increased exposure to rifabutin in TB/HIV patients by 210% because of the effects of PIs and 280% with ritonavir-boosted PIs.CONCLUSIONS: Given together with non-boosted or ritonavir-boosted PIs, rifabutin at 150 mg once daily results in similar or higher exposure compared with rifabutin at 300 mg once daily without concomitant PIs and may achieve peak concentrations within an acceptable therapeutic range. Although 300 mg of rifabutin every 3 days with boosted PI achieves an average equivalent exposure, intermittent doses of rifamycins are not supported by current guidelines.
|
|
