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- Lohy Das, Jesmin, 1979-, et al.
(författare)
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Population Pharmacokinetics of Artemether, Dihydroartemisinin, and Lumefantrine in Rwandese Pregnant Women Treated for Uncomplicated Plasmodium falciparum Malaria
- 2018
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 62:10
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Tidskriftsartikel (refereegranskat)abstract
- The artemisinin-based combination therapy artemether-lumefantrine is commonly used in pregnant malaria patients. However, the effect of pregnancy-related changes on exposure is unclear, and pregnancy has been associated with decreased efficacy in previous studies. This study aimed to characterize the population pharmacokinetics of artemether, its active metabolite dihydroartemisinin, and lumefantrine in 22 Rwandese pregnant women in their second (n = 11) or third (n = 11) trimester with uncomplicated Plasmodium falciparum malaria. These patients were enrolled from Rwamagana district hospital and received the standard fixed oral dose combination of 80 mg of artemether and 480 mg of lumefantrine twice daily for 3 days. Venous plasma concentrations were quantified for all three analytes using liquid chromatography coupled with tandem mass spectroscopy, and data were analyzed using nonlinear mixed-effects modeling. Lumefantrine pharmacokinetics was described by a flexible but highly variable absorption, with a mean absorption time of 4.04 h, followed by a biphasic disposition model. The median area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) for lumefantrine was 641 h . mg/liter. Model-based simulations indicated that 11.7% of the study population did not attain the target day 7 plasma concentration (280 ng/ml), a threshold associated with increased risk of recrudescence. The pharmacokinetics of artemether was time dependent, and the autoinduction of its clearance was described using an enzyme turnover model. The turnover half-life was predicted to be 30.4 h. The typical oral clearance, which started at 467 liters/h, increased 1.43-fold at the end of treatment. Simulations suggested that lumefantrine pharmacokinetic target attainment appeared to be reassuring in Rwandese pregnant women, particularly compared to target attainment in Southeast Asia. Larger cohorts will be required to confirm this finding.
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| 2. |
- Påfs, Jessica, 1984-, et al.
(författare)
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Beyond the numbers of maternal near-miss in Rwanda - a qualitative study on women's perspectives on access and experiences of care in early and late stage of pregnancy.
- 2016
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Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rwanda has made remarkable progress in decreasing the number of maternal deaths, yet women still face morbidities and mortalities during pregnancy. We explored care-seeking and experiences of maternity care among women who suffered a near-miss event during either the early or late stage of pregnancy, and identified potential health system limitations or barriers to maternal survival in this setting.METHODS: A framework of Naturalistic Inquiry guided the study design and analysis, and the 'three delays' model facilitated data sorting. Participants included 47 women, who were interviewed at three hospitals in Kigali, and 14 of these were revisited in their homes, from March 2013 to April 2014.RESULTS: The women confronted various care-seeking barriers depending on whether the pregnancy was wanted, the gestational age, insurance coverage, and marital status. Poor communication between the women and healthcare providers seemed to result in inadequate or inappropriate treatment, leading some to seek either traditional medicine or care repeatedly at biomedical facilities.CONCLUSION: Improved service provision routines, information, and amendments to the insurance system are suggested to enhance prompt care-seeking. Additionally, we strongly recommend a health system that considers the needs of all pregnant women, especially those facing unintended pregnancies or complications in the early stages of pregnancy.
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| 4. |
- Påfs, Jessica, 1984-, et al.
(författare)
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'They would never receive you without a husband' : Paradoxical barriers to antenatal care scale-up in Rwanda
- 2015
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Ingår i: Midwifery. - : Elsevier. - 0266-6138 .- 1532-3099. ; 31:12, s. 1149-1156
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: to explore perspectives and experiences of antenatal care and partner involvement among women who nearly died during pregnancy ('near-miss').DESIGN: a study guided by naturalistic inquiry was conducted, and included extended in-community participant observation, semi-structured interviews, and focus group discussions. Qualitative data were collected between March 2013 and April 2014 in Kigali, Rwanda.FINDINGS: all informants were aware of the recommendations of male involvement for HIV-testing at the first antenatal care visit. However, this recommendation was seen as a clear link in the chain of delays and led to severe consequences, especially for women without engaged partners. The overall quality of antenatal services was experienced as suboptimal, potentially missing the opportunity to provide preventive measures and essential health education intended for both parents. This seemed to contribute to women's disincentive to complete all four recommended visits and men's interest in attending to ensure their partners' reception of care. However, the participants experienced a restriction of men's access during subsequent antenatal visits, which made men feel denied to their increased involvement during pregnancy.CONCLUSIONS: 'near-miss' women and their partners face paradoxical barriers to actualise the recommended antenatal care visits. The well-intended initiative of male partner involvement counterproductively causes delays or excludes women whereas supportive men are turned away from further health consultations. Currently, the suboptimal quality of antenatal care misses the opportunity to provide health education for the expectant couple or to identify and address early signs of complications IMPLICATIONS FOR PRACTICE: these findings suggest a need for increased flexibility in the antenatal care recommendations to encourage women to attend care with or without their partner, and to create open health communication about women's and men's real needs within the context of their social situations. Supportive partners should not be denied involvement at any stage of pregnancy, but should be received only upon consent of the expectant mother.
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| 5. |
- Påfs, Jessica, 1984-, et al.
(författare)
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'You try to play a role in her pregnancy' - a qualitative study on recent fathers' perspectives about childbearing and encounter with the maternal health system in Kigali, Rwanda
- 2016
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rwanda has raised gender equality on the political agenda and is, among other things, striving for involving men in reproductive health matters. With these structural changes taking place, traditional gender norms in this setting are challenged. Deeper understanding is needed of men's perceptions about their gendered roles in the maternal health system.OBJECTIVE: To explore recent fathers' perspectives about their roles during childbearing and maternal care-seeking within the context of Rwanda's political agenda for gender equality.DESIGN: Semi-structured interviews were conducted with 32 men in Kigali, Rwanda, between March 2013 and April 2014. A framework of naturalistic inquiry guided the overall study design and analysis. In order to conceptualize male involvement and understand any gendered social mechanisms, the analysis is inspired by the central principles from relational gender theory.RESULTS: The participants in this study appeared to disrupt traditional masculinities and presented ideals of an engaged and caring partner during pregnancy and maternal care-seeking. They wished to carry responsibilities beyond the traditional aspects of being the financial provider. They also demonstrated willingness to negotiate their involvement according to their partners' wishes, external expectations, and perceived cultural norms. While the men perceived themselves as obliged to accompany their partner at first antenatal care (ANC) visit, they experienced several points of resistance from the maternal health system for becoming further engaged.CONCLUSIONS: These men perceived both maternal health system policy and care providers as resistant toward their increased engagement in childbearing. Importantly, perceiving themselves as estranged may consequently limit their engagement with the expectant partner. Our findings therefore recommend maternity care to be more responsive to male partners. Given the number of men already taking part in ANC, this is an opportunity to embrace men's presence and promote behavior in favor of women's health during pregnancy and childbirth - and may also function as a cornerstone in promoting gender-equitable attitudes.
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| 6. |
- Saito, Makoto, et al.
(författare)
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Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis
- 2023
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 401:10371, s. 118-130
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. Methods: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. Findings: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49–1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47–1·17), stillbirth (aHR=0·71, 0·32–1·57), and major congenital anomalies (aHR=0·60, 0·13–2·87). The risk of adverse pregnancy outcomes was lower with artemether–lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36–0·92). Interpretation: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether–lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether–lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether–lumefantrine is unavailable, other ACTs (except artesunate–sulfadoxine–pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.
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