Publications

BACKGROUND

Approximately 150 women annually become pregnant while taking isotretinoin despite participation in the iPLEDGE program. Noncompliance with the requirement to be abstinent or use 2 contraceptive methods may be a contributing factor.

OBJECTIVE

We sought to determine the degree of adherence to contraception or abstinence among women taking isotretinoin.

METHODS

We conducted an anonymous survey of women of childbearing potential taking isotretinoin for at least 2 months.

RESULTS

Among 75 participants, 21 (28%) chose abstinence as their primary means of pregnancy prevention, of whom 4 (19%) were sexually active during treatment. The most commonly chosen contraceptive methods among the 39 women who were sexually active were condoms (35, 90%) and oral contraceptive pills (18, 46%). Twelve women (31%) admitted to having intercourse at least once using 1 or fewer forms of contraception; 10 failed to use condoms, and 1 reported completely unprotected intercourse. Among sexually active oral contraceptive pill users, 7 (39%) reported missing 1 or more pills in the previous month.

LIMITATIONS

Data were self-reported, thus participants may have inaccurately reported contraception use.

CONCLUSIONS

Encouraging the use of highly effective, patient-independent contraception and limiting abstinence to women who have never been sexually active may further reduce the rate of isotretinoin-exposed pregnancies.

The increasing prevalence in Southeast Asia of Plasmodium falciparum infections with delayed parasite clearance rates, following treatment of malaria patients with the artemisinin derivative artesunate, highlights an urgent need to identify which of the currently available artemisinin-based combination therapies (ACTs) are most suitable to treat populations with emerging artemisinin resistance. Here, we demonstrate that the rodent Plasmodium berghei SANA strain has acquired artemisinin resistance following drug pressure, as defined by reduced parasite clearance and early recrudescence following daily exposure to high doses of artesunate or the active metabolite dihydroartemisinin. Using the SANA strain and the parental drug-sensitive N strain, we have interrogated the antimalarial activity of five ACTs, namely, artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine, and the newest combination artesunate-pyronaridine. By monitoring parasitemia and outcome for 30 days following initiation of treatment, we found that infections with artemisinin-resistant P. berghei SANA parasites can be successfully treated with artesunate-pyronaridine used at doses that are curative for the parental drug-sensitive N strain. No other partner drug combination was as effective in resolving SANA infections. Of the five partner drugs tested, pyronaridine was also the most effective at suppressing the recrudescence of SANA parasites. These data support the potential benefit of implementing ACTs with pyronaridine in regions affected by artemisinin-resistant malaria.

Fluorescence optical detection in sedimentation velocity analytical ultracentrifugation allows the study of macromolecules at nanomolar concentrations and below. This has significant promise, for example, for the study of systems of high-affinity protein interactions. Here we describe adaptations of the direct boundary modeling analysis approach implemented in the software SEDFIT that were developed to accommodate unique characteristics of the confocal fluorescence detection system. These include spatial gradients of signal intensity due to scanner movements out of the plane of rotation, temporal intensity drifts due to instability of the laser and fluorophores, and masking of the finite excitation and detection cone by the sample holder. In an extensive series of experiments with enhanced green fluorescent protein ranging from low nanomolar to low micromolar concentrations, we show that the experimental data provide sufficient information to determine the parameters required for first-order approximation of the impact of these effects on the recorded data. Systematic deviations of fluorescence optical sedimentation velocity data analyzed using conventional sedimentation models developed for absorbance and interference optics are largely removed after these adaptations, resulting in excellent fits that highlight the high precision of fluorescence sedimentation velocity data, thus allowing a more detailed quantitative interpretation of the signal boundaries that is otherwise not possible for this system.