Misoprostol as an Adjunct to Standard Uterotonics for Treatment of Post-Partum Haemorrhage : A Multicentre, Double-Blind Randomised Trial

BACKGROUND: Post-partum haemorrhage is a leading cause of global maternal morbidity and mortality. Misoprostol, a prostaglandin analogue with uterotonic activity, is an attractive option for treatment because it is stable, active orally, and inexpensive. We aimed to assess the effectiveness of misoprostol as an adjunct to standard uterotonics compared with standard uterotonics alone for treatment of post-partum haemorrhage. METHODS: Women delivering vaginally who had clinically diagnosed post-partum haemorrhage due to uterine atony were enrolled from participating hospitals in Argentina, Egypt, South Africa, Thailand, and Vietnam between July, 2005, and August, 2008. Computer-generated randomisation was used to assign women to receive 600 microg misoprostol or matching placebo sublingually; both groups were also given routine injectable uterotonics. Allocation was concealed by distribution of sealed and sequentially numbered treatment packs in the order that women were enrolled. Providers and women were masked to treatment assignment. The primary outcome was blood loss of 500 mL or more within 60 min after randomisation. Analysis was by intention to treat. This study is registered, number ISRCTN34455240. FINDINGS: 1422 women were assigned to receive misoprostol (n=705) or placebo (n=717). The proportion of women with blood loss of 500 mL or more within 60 min was similar between the misoprostol group (100 [14%]) and the placebo group (100 [14%]; relative risk 1.02, 95% CI 0.79-1.32). In the first 60 min, an increased proportion of women on misoprostol versus placebo, had shivering (455/704 [65%] vs 230/717 [32%]; 2.01, 1.79-2.27) and body temperature of 38 degrees C or higher (303/704 [43%] vs 107/717 [15%]; 2.88, 2.37-2.50). INTERPRETATION: Findings from this study do not support clinical use of 600 microg sublingual misoprostol in addition to standard injectable uterotonics for treatment of post-partum haemorrhage. FUNDING: Bill & Melinda Gates Foundation, and UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

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Impact of Intermittent Screening and Treatment for Malaria among School Children in Kenya : A Cluster Randomized Trial
(World Bank, Washington, DC, 2014-02) Halliday, Katherine E.; Okello, George; Turner, Elizabeth L.; Njagi, Kiambo; Mcharo, Carlos; Kengo, Juddy; Allen, Elizabeth; Dubeck, Margaret M.; Jukes, Matthew C.H.; Brooker, Simon J.
This paper investigates the effects of intermittent screening and treatment of malaria on the health and education of school children in an area of low-to-moderate malaria transmission. A cluster randomized trial was implemented with 5,233 children in 101 government primary schools on the south coast of Kenya in 2010-12. The intervention was delivered to children randomly selected from classes 1 and 5 who were followed up twice across 24 months. Once during each school term, public health workers used malaria rapid diagnostic tests to screen the children. Children who tested positive were treated with a six-dose regimen of artemether-lumefantrine. Given the nature of the intervention, the trial was not blinded. The primary outcomes were anemia and sustained attention and the secondary outcomes were malaria parasitaemia and educational achievement. The data were analyzed on an intention-to-treat basis. Anemia in this setting in Kenya, intermittent screening and treatment, as implemented in this study, is not effective in improving the health or education of school children. Possible reasons for the absence of an impact are the marked geographical heterogeneity in transmission, the rapid rate of reinfection following artemether-lumefantrine treatment, the variable reliability of malaria rapid diagnostic tests, and the relative contribution of malaria to the etiology of anemia in this setting.
Timor-Leste Health Sector Review : Meeting Challenges and Improving Health Outcomes
(Washington, DC, 2006-10-06) World Bank
The Timor-Leste health sector review describes the accomplishments made by the government of Timore-Leste in the health sector since it separated from Indonesia, and analyzes the challenges still facing the government moving forward. Infant and maternal mortality, and malnutrition, are still important battles. Underutilization of services, and poor quality of services when available, are also reasons for the poor health quality indicators. Improving the quality or effectiveness of health services is difficult. However, now that most of the basic health care infrastructure is in place, the time is right for the Ministry of Health (MOH) to develop a system to monitor and upgrade the quality of health care services, starting with public sector services. One initiative put forth is health education delivered through various channels, which would make households better aware of the risks associated with certain health conditions or symptoms and the importance of using the available health services from government and NGO facilities. A second type of potential intervention is the introduction of conditional cash transfers, whereby the Government pays a subsidy to households in exchange for certain behaviors beneficial to society, such as having their children immunized. Carrying out the various interventions described above would require that the Government increased its spending on health services further.
Can Midlevel Health-Care Providers Administer Early Medical Abortion as Safely and Effectively as Doctors? A Randomised Controlled Equivalence Trial in Nepal
(2011) Warriner, I. K.; Wang, D.; Huong, N. T.; Thapa, K.; Tamang, A.; Shah, I.; Baird, D. T.; Meirik, O.
BACKGROUND: Medical abortion is under-used in developing countries. We assessed whether early fi rst-trimester medical abortion provided by midlevel providers (government-trained, certified nurses and auxiliary nurse midwives) was as safe and effective as that provided by doctors in Nepal. METHODS: This multicentre randomised controlled equivalence trial was done in fi ve rural district hospitals in Nepal. Women were eligible for medical abortion if their pregnancy was of less than 9 weeks (63 days) and if they resided less than 90 min journey away from the study clinic. Women were ineligible if they had any contraindication to medical abortion. We used a computer-generated randomisation scheme stratified by study centre with a block size of six. Women were randomly assigned to a doctor or a midlevel provider for oral administration of 200 mg mifepristone followed by 800 mug misoprostol vaginally 2 days later, and followed up 10-4 days later. The primary endpoint was complete abortion without manual vacuum aspiration within 30 days of treatment. The study was not masked. Abortions were recorded as complete, incomplete, or failed (continuing pregnancy). Analyses for primary and secondary endpoints were by intention to treat, supplemented by per-protocol analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT01186302. FINDINGS: Of 1295 women screened, 535 were randomly assigned to a doctor and 542 to a midlevel provider. 514 and 518, respectively, were included in the analyses of the primary endpoint. Abortions were judged complete in 504 (97.3%) women assigned to midlevel providers and in 494 (96.1%) assigned to physicians. The risk difference for complete abortion was 1.24% (95% CI -0.53 to 3.02), which falls within the predefined equivalence range (-5% to 5%). Five cases (1%) were recorded as failed abortion in the doctor cohort and none in the midlevel provider cohort; the remaining cases were recorded as incomplete abortions. No serious complications were noted. INTERPRETATION: The provision of medical abortion up to 9 weeks' gestation by midlevel providers and doctors was similar in safety and effectiveness. Where permitted by law, appropriately trained midlevel health-care providers can provide safe, low-technology medical abortion services for women independently from doctors. FUNDING: UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), World Health Organization.
Two Mifepristone Doses and Two Intervals of Misoprostol Administration for Termination of Early Pregnancy : A Randomised Factorial Controlled Equivalence Trial
(2009) von Hertzen, H.; Piaggio, G.; Wojdyla, D.; Marions, L.; My Huong, N. T.; Tang, O. S.; Fang, A. H.; Wu, S. C.; Kalmar, L.; Mittal, S.; Erdenetungalag, R.; Horga, M.; Pretnar-Darovec, A.; Kapamadzija, A.; Dickson, K.; Anh, N. D.; Tai, N. V.; Tuyet, H. T.; Peregoudov, A.
OBJECTIVE: To compare the efficacy of 100 mg and 200 mg of mifepristone and 24- and 48-hour intervals to administration of 800 microg vaginal misoprostol for termination of early pregnancy. DESIGN: Placebo-controlled, randomized, equivalence trial, stratified by centre. SETTING: 13 departments of obstetrics and gynecology in nine countries. POPULATION: 2,181 women with 63 days or less gestation requesting medical abortion. METHODS: Two-sided 95% CI for the risk differences of failure to complete abortion were calculated and compared with 5% equivalence margin between two doses of mifepristone and two intervals to misoprostol administration. Proportions of women with adverse effects were compared between the regimens using standard testes for proportions. OUTCOME MEASURES: Rates of complete abortion without surgical intervention and adverse effects associated with the regimens. RESULTS: Efficacy outcome was analysed for 2,126 women (97.5%) excluding 55 lost to follow up. Both mifepristone doses were found to be similar in efficacy. The rate of complete abortion was 92.0% for women assigned 100 mg of mifepristone and 93.2% for women assigned 200 mg of mifepristone (difference 1.2%, 95% CI: -1.0 to 3.5). Equivalence was also evident for the two intervals of administration: the rate of complete abortion was 93.5% for 24-hour interval and 91.7% for the 48-hour interval (difference -1.8%, 95% CI: -4.0 to 0.5). Interaction between doses and interval to misoprostol administration was not significant (P = 0.92). Adverse effects related to treatments did not differ between the groups. CONCLUSIONS: Both the 100 and 200 mg doses of mifepristone and the 24- and 48-hour intervals have a similar efficacy to achieve complete abortion in early pregnancy when mifepristone is followed by 800 micrograms of vaginally administered misoprostol.
Population Health and Economic Growth
(World Bank, Washington, DC, 2008) Bloom, David E.; Canning, David
Health is a direct source of human welfare and also an instrument for raising income levels. The authors discuss a number of mechanisms through which health can affect income, focusing on worker productivity, children's education, savings and investment, and demographic structure. As well as the impact of current illness, health may have large effects on prospective life spans and life cycle behavior. Studies suggest there may be a large effect of health and nutrition in uteri, and in the first few years of life, on physical and cognitive development and economic success as an adult. Macroeconomic evidence for an effect on growth is mixed, with evidence of a large effect in some studies. However, there is a possibility that gains from health may be outweighed by the effect of increased survival on population growth, until a fertility transition occurs. The low cost of some health interventions that have large-scale effects on population health makes health investments a promising policy tool for growth in developing countries. In addition, higher priority could be given to tackling widespread 'neglected' diseases that is, diseases with low mortality burdens that are not priorities from a pure health perspective, but that do have substantial effects on productivity.

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