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Biomedical subjects

L Orton

Publications and source records attributed to L Orton.

5 recordsLinked to original sources

Atovaquone-proguanil for treating uncomplicated malaria.

BACKGROUND: Many conventional treatments for uncomplicated malaria are failing because malaria parasites develop resistance to them. One way to combat this resistance is to treat people with a combination of drugs, such as atovaquone-proguanil. OBJECTIVES: To compare atovaquone-proguanil with other antimalarial drugs (alone or in combination) for treating children and adults with uncomplicated Plasmodium falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (June 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), LILACS (1982 to June 2005), reference lists, and conference abstracts. We also contacted relevant pharmaceutical manufacturers and researchers. SELECTION CRITERIA: Randomized controlled trials comparing atovaquone-proguanil with other antimalarial drugs for treating children and adults confirmed to have uncomplicated P. falciparum malaria. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trial eligibility and methodological quality, and extracted data for an intention-to-treat analysis (where possible). We used relative risk (RR) and 95% confidence intervals (CI) for dichotomous data. We contacted trial authors for additional information where needed. MAIN RESULTS: Ten trials, with a total of 2345 participants, met the inclusion criteria. The trials were conducted in four geographical regions and were often small, but they included comparisons across eight drugs. Nine trials were funded by a pharmaceutical company, only three carried out an intention-to-treat analysis, and allocation concealment was unclear in seven. Atovaquone-proguanil had fewer treatment failures by day 28 than chloroquine (RR 0.04, 95% CI 0.00 to 0.57; 27 participants, 1 trial), amodiaquine (RR 0.22, 95% CI 0.13 to 0.36; 342 participants, 2 trials), and mefloquine (RR 0.04, 95% CI 0.00 to 0.73; 158 participants, 1 trial). There were insufficient data to draw a conclusion for this outcome from comparisons with sulfadoxine-pyrimethamine (172 participants, 2 trials), halofantrine (205 participants, 1 trial), artesunate plus mefloquine (1063 participants, 1 trial), quinine plus tetracycline (154 participants, 1 trial), and dihydroartemisinin-piperaquine-trimethoprim-primaquine (161 participants, 1 trial). Adverse events were mainly common symptoms of malaria and did not differ in frequency between groups. AUTHORS' CONCLUSIONS: Data are limited but appear to suggest that atovaquone-proguanil is more effective than chloroquine, amodiaquine, and mefloquine. There are insufficient data for comparisons against sulfadoxine-pyrimethamine, halofantrine, artesunate plus mefloquine, quinine plus tetracycline, and dihydroartemisinin-piperaquine-trimethoprim-primaquine in treating malaria. There are not enough data to assess safety, but a number of adverse events were identified with all drugs. Large trials comparing atovaquone-proguanil with other new combination therapies are needed.

Antimalarials↗

Artesunate plus mefloquine versus mefloquine for treating uncomplicated malaria.

BACKGROUND: Multiple-drug-resistant malaria is widespread, and in South-East Asia resistance is high against nearly all single therapy antimalarial drugs. Here, and in other areas with low malaria transmission, the combination of artesunate and mefloquine may provide an effective alternative. OBJECTIVES: To compare artesunate plus mefloquine with mefloquine alone for treating uncomplicated Plasmodium falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (May 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1988 to May 2005), LILACS (May 2005), BIOSIS (1985 to June 2005), conference proceedings, and reference lists. We also contacted researchers, organizations, and pharmaceutical companies. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing artesunate plus mefloquine with mefloquine alone for treating uncomplicated malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria, extracted data, and assessed methodological quality. The primary outcome was treatment failure by day 28, defined as evidence of parasitaemia with or without clinical failure between days zero (start of treatment) and 28. For dichotomous data we calculated relative risks (RR) and 95% confidence intervals (CI). MAIN RESULTS: Eight trials involving 1996 participants met the inclusion criteria. All were conducted in areas with low malaria transmission, seven in South-East Asia and one in the Peruvian Amazon. The doses and dosing regimens of artesunate and mefloquine varied across trials. The trials using a total dose of 25 mg/kg mefloquine and 10 mg artesunate reported fewer treatment failures with the combination at all time points: day 28 (RR 0.17, 95% CI 0.06 to 0.47; 824 participants, 4 trials), day 42 (RR 0.23, 95% CI 0.14 to 0.39; 298 participants, 1 trial), and day 63 (RR 0.26, 95% CI 0.09 to 0.77; 501 participants, 2 trials). The results for parasitaemia showed a similar trend. Trials using a lower dose of artesunate tended to favour the artesunate plus mefloquine combination. Overall, adverse events were similar across treatment arms. AUTHORS' CONCLUSIONS: Artesunate plus mefloquine performs better than mefloquine alone for treating uncomplicated falciparum malaria in areas with low malaria transmission. A total dose of 25 mg/kg mefloquine and at least 10 mg artesunate leads to higher cure rates. Better reporting of methods and standardisation of outcomes would help the interpretation of future trials.

Antimalarials↗

Drugs for treating uncomplicated malaria in pregnant women.

BACKGROUND: Women are more vulnerable to malaria during pregnancy, and malaria infection may have adverse consequences for the fetus. Identifying safe and effective treatments is important. OBJECTIVES: To compare the effects of drug regimens for treating uncomplicated falciparum malaria in pregnant women. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (May 2005), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1974 to May 2005), LILACS (May 2005), reference lists, and conference abstracts. We also contacted researchers in the field, organizations, and pharmaceutical companies. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of antimalarial drugs for treating uncomplicated malaria in pregnant women. DATA COLLECTION AND ANALYSIS: Both authors assessed trial eligibility and methodological quality, and extracted data. We performed a quantitative analysis only where we could combine the data. We combined dichotomous data using relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Six trials (513 participants) met the inclusion criteria. Two were quasi-randomized, and none described allocation concealment. Data were scarce for the primary outcome, treatment failure. One trial compared artesunate plus mefloquine with quinine and reported fewer treatment failures at day 63 with the combination (RR 0.09, 95% CI 0.02 to 0.38; 106 participants). AUTHORS' CONCLUSIONS: There is insufficient reliable research on malaria treatment options in pregnancy.

Antimalarials↗

Unit-dose packaged drugs for treating malaria.

BACKGROUND: Unit-dose packaging of antimalarial drugs may improve malaria cure by making it easier for patients to take their treatment correctly. OBJECTIVES: To summarize the effects of unit-dose packaged treatment on cure and treatment adherence in people with uncomplicated malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (November 2004), CENTRAL (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), LILACS (November 2004), conference proceedings, and reference lists of articles. We also contacted pharmaceutical companies, organizations, and researchers in the field. SELECTION CRITERIA: Randomized controlled trials (RCTs), cluster-RCTs, quasi-RCTs, and controlled before-and-after studies of unit-dose packaged drugs for treating uncomplicated malaria. DATA COLLECTION AND ANALYSIS: We independently assessed study eligibility and methodological quality, and extracted data for an intention to treat analysis, where possible. We combined binary data using relative risk (RR) and the fixed-effect model, and presented them with 95% confidence intervals (CI). We attempted to contact study authors for additional information. MAIN RESULTS: Three quasi-RCTs (895 participants) and one cluster-RCT (6 health facilities) met the inclusion criteria. Trials were of poor methodological quality, and none adequately assessed treatment failure. Unit-dose packaged drugs (in conjunction with prescriber training and patient information) appeared to be associated with higher participant-reported treatment adherence in all trials.A meta-analysis of two trials (596 participants) showed that participant-reported treatment adherence was higher with blister-packed tablets compared with tablets in paper envelopes (RR 1.18, 1.12 to 1.25). Two trials using tablets in sectioned polythene bags as the intervention also noted an increase in participant-reported treatment adherence: the cluster-RCT (6 clusters) compared it with tablets in paper envelopes, and the other trial compared it with syrup in bottles (RR 2.15, 1.76 to 2.61; 299 participants). AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effect of unit-dose packaged antimalarial drugs on treatment failure. Unit-dose packaging supported by prescriber training and patient information appears to improve participant-reported treatment adherence, but these data come from trials with methodological limitations.

Antimalarials↗

VSO policy.

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Anti-HIV Agents↗