How to assess success of treatment when using multiple doses: the case of misoprostol for medical abortion.

Background: The assessment of treatment success in clinical trials when multiple (repeated) doses (courses) are involved is quite common, for example, in the case of infertility treatment with assisted reproductive technology (ART), and medical abortion using misoprostol alone or in combination with mifepristone. Under these or similar circumstances, most researchers assess success using binomial proportions after a certain number of consecutive doses, and some have used survival analysis. In this paper we discuss the main problems in using binomial proportions to summarize (the overall) efficacy after two or more consecutive doses of the relevant treatment, particularly for the case of misoprostol in medical abortion studies. We later discuss why the survival analysis is best suited under these circumstances, and illustrate this by using simulated data. Methods: The formulas required for the binomial proportion and survival analysis (without and with competing risks) approaches are summarized and analytically compared. Additionally, numerical results are computed and compared between the two approaches, for several theoretical scenarios. Results: The main conceptual limitations of the binomial proportion approach are identified and discussed, caused mainly by the presence of censoring and competing risks, and it is demonstrated how survival analysis can solve these problems. In general, the binomial proportion approach tends to underestimate the “real” success rate, and tends to overestimate the corresponding standard error. Conclusions: Depending on the rates of censored observations or competing events between repeated doses of the treatment, the bias of the binomial proportion approach as compared to the survival analysis approaches varies; however, the use of the binomial approach is unjustified as the survival analysis options are well known and available in multiple statistical packages. Our conclusions also apply to other situations where success is estimated after multiple (repeated) doses (courses) of the treatment

Age at natural menopause among patients with systemic lupus erythematosus

Objective. The aim of this study was to estimate the age at natural menopause in women with SLE. Methods. One thousand and thirty-nine consecutive SLE patients <60 years of age were surveyed. Demographic and clinical data were queried by a single investigator. SLE characteristics and co-morbidities were retrieved from their medical records. Natural menopause was defined as amenorrhoea ≥12 months in the absence of previous hysterectomy, CYC exposure and severe chronic kidney disease (SCKD). Pregnant women and those with menses during the 12 months prior to interview were considered premenopausal. Median age at menopause was estimated by both logit and survival analyses. In addition, mean age at menopause was calculated for patients aged ≥40 years. Factors associated with age at natural menopause were assessed by Cox regression analysis. Results. A total of 961 SLE women were analysed. At interview, most patients (81.6%) were premenopausal, 7.9% had natural menopause, 6.3% were postmenopausal previously exposed to CYC, 4.1% had undergone hysterectomy before menopause and 0.1% presented with SCKD and amenorrhoea. The mean age at interview was 35.2 years (s.d. 10.1), the mean age at SLE diagnosis was 26.9 years (s.d. 8.6) and the mean duration of disease was 8.2 years (s.d. 7.1). The mean recalled age at menopause was 46.4 years (s.d. 4.7). Median age at menopause estimated by logit and survival analyses were 50.7 and 50.8 years, respectively. Only the age at SLE diagnosis was associated with age at natural menopause. Conclusion. Median age at natural menopause in women with lupus is 50 years. This is consistent with the age at menopause reported in the general populatio

Maternal and Perinatal Outcomes of Twin Pregnancy in 23 Low- and Middle-Income Countries

Background: Twin pregnancies in low- and middle-income countries (LMICs) pose a high risk to mothers and newborns due to inherent biological risks and scarcity of health resources. We conducted a secondary analysis of the WHO Global Survey dataset to analyze maternal and perinatal outcomes in twin pregnancies and factors associated with perinatal morbidity and mortality in twins.Methods: We examined maternal and neonatal characteristics in twin deliveries in 23 LMICs and conducted multi-level logistic regression to determine the association between twins and adverse maternal and perinatal outcomes.Results: 279,425 mothers gave birth to 276,187 (98.8%) singletons and 6,476 (1.2%) twins. Odds of severe adverse maternal outcomes (death, blood transfusion, ICU admission or hysterectomy) (AOR 1.85, 95% CI 1.60-2.14) and perinatal mortality (AOR 2.46, 95% CI 1.40-4.35) in twin pregnancies were higher, however early neonatal death (AOR 2.50, 95% CI 0.95-6.62) and stillbirth (AOR 1.22, 95% CI 0.58-2.57) did not reach significance. Amongst twins alone, maternal age 15%, born second, preterm birth and low birthweight were associated with perinatal mortality. Marriage and caesarean section were protective.Conclusions: Twin pregnancy is a significant risk factor for maternal and perinatal morbidity and mortality in low- resource settings; maternal risk and access to safe caesarean section may determine safest mode of delivery in LMICs. Improving obstetric care in twin pregnancies, particularly timely access to safe caesarean section, is required to reduce risk to mother and baby.Australian Postgraduate AwardA & A Saw ScholarshipUniv Western Australia, Sch Populat Hlth, Fac Med Dent & Hlth Sci, Perth, WA 6009, AustraliaUNDP UNFPA UNICEF WHO World Bank Special Programm, Dept Reprod Hlth & Res, World Hlth Org, Geneva, SwitzerlandUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilBrazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilWeb of Scienc

The Effect of Calcium Supplementation on Body Weight Before and During Pregnancy in Women Enrolled in the WHO Calcium and Preeclampsia Trial

Introduction: Obesity is a major and challenging public health problem. The aim of this substudy is to evaluate the effect of calcium supplementation on body weight in women recruited in the Calcium and Preeclampsia trial. Methods: Women were recruited before pregnancy and randomized to receive a calcium supplement containing 500 mg of elemental calcium or placebo until 20 weeks’ gestation; all women received 1.5 g from 20 weeks until delivery. Results: A total of 630 women conceived during the study, 322 allocated to calcium and 308 to placebo. Among these, 230 allocated to calcium and 227 allocated to placebo had information on body weight at baseline and at 8 weeks' gestation. During the study period, women allocated to calcium had a mean weight increase of 1.1 (SD ±5.5) kg, whereas those allocated to placebo had a mean increase of 1.5 (SD ±6.1) kg, a mean difference of 0.4 kg (95% −0.4 (−1.4 to 0.6); P =.408). Women classified as obese at the start of the trial had a lower body weight gain at 8 weeks’ gestation (1.0 kg; 95% CI: −3.2 to 1.2; P =.330) and at 32 weeks’ gestation (2.1 kg; 95% CI: 5.6-1.3; P =.225) if they received calcium as compared to placebo. However, none of these differences were statistically significant. Conclusion: The smaller increase in body weight found in women supplemented with 500 mg elemental calcium daily is quantitatively consistent with previous studies. However, in this study, the difference was not statistically significant.Fil: Cormick, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Universidad Nacional de La Matanza; Argentina. University of Cape Town; SudáfricaFil: Betrán, Ana Pilar. Organizacion Mundial de la Salud; ArgentinaFil: Harbron, Janetta. University of Cape Town; SudáfricaFil: Seuc, Armando. Instituto Nacional de Higiene; CubaFil: White, Cintia. Universidad Nacional de La Matanza; ArgentinaFil: Roberts, James M.. University of Pittsburgh; Estados UnidosFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Hofmeyr, G. Justus. University of the Witwatersrand; Sudáfric

Do Italian women prefer cesarean section? Results from a survey on mode of delivery preferences

Background: About 20 million cesareans occur each year in the world and rates have steadily increased in almost all middle- and high-income countries over the last decades. Maternal request is often argued as one of the key forces driving this increase. Italy has the highest cesarean rate of Europe, yet there are no national surveys on the views of Italian women about their preferences on route of delivery. This study aimed to assess Italian women's preference for mode of delivery, as well as reasons and factors associated with this preference, in a nationally representative sample of women.Methods: This cross sectional survey was conducted between December 2010-March 2011. An anonymous structured questionnaire asked participants what was their preferred mode of delivery and explored the reasons for this preference by assessing their agreement to a series of statements. Participants were also asked to what extent their preference was influenced by a series of possible sources. the 1st phase of the study was carried out among readers of a popular Italian women's magazine (Io Donna). in a 2nd phase, the study was complemented by a structured telephone interview.Results: A total of 1000 Italian women participated in the survey and 80% declared they would prefer to deliver vaginally if they could opt. the preference for vaginal delivery was significantly higher among older (84.7%), more educated (87.6%), multiparous women (82.3%) and especially among those without any previous cesareans (94.2%). the main reasons for preferring a vaginal delivery were not wanting to be separated from the baby during the first hours of life, a shorter hospital stay and a faster postpartum recovery. the main reasons for preferring a cesarean were fear of pain, convenience to schedule the delivery and because it was perceived as being less traumatic for the baby. the source which most influenced the preference of these Italian women was their obstetrician, followed by friends or relatives.Conclusion: Four in five Italian women would prefer to deliver vaginally if they could opt. Factors associated with a higher preference for cesarean delivery were youth, nulliparity, lower education and a previous cesarean.Universidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilWHO, Dept Reprod Hlth & Res, CH-1211 Geneva, SwitzerlandOsservatorio Nazl Salute Donna, ONDa, Milan, ItalyInst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, ArgentinaUniv Florence, Meyer Children Hosp, I-50121 Florence, ItalyUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilWeb of Scienc

Health systems analysis and evaluation of the barriers to availability, utilisation and readiness of sexual and reproductive health services in COVID-19-affected areas: a WHO mixed-methods study protocol.

Introduction COVID-19 has led to an unprecedented increase in demand on health systems to care for people infected, necessitating the allocation of significant resources, especially medical resources, towards the response. This, compounded by the restrictions on movement instituted may have led to disruptions in the provision of essential services, including sexual and reproductive health (SRH) services. This study aims to assess the availability of contraception, comprehensive abortion care, sexually transmitted infection prevention and treatment and sexual and gender-based violence care and support services in local health facilities during COVID-19 pandemic. This is a standardised generic protocol designed for use across different global settings. Methods and analysis This study adopts both quantitative and qualitative methods to assess health facilities’ SRH service availability and readiness, and clients’ and providers’ perceptions of the availability and readiness of these services in COVID-19-affected areas. The study has two levels: (1) perceptions of clients (and the partners) and healthcare providers, using qualitative methods, and (2) assessment of infrastructure availability and readiness to provide SRH services through reviews, facility service statistics for clients and a qualitative survey for healthcare provider perspectives. The health system assessment will use a cross-sectional panel survey design with two data collection points to capture changes in SRH services availability as a result of the COVID-19 epidemic. Data will be collected using focus group discussions, in-depth interviews and a health facility assessment survey. Ethics and dissemination Ethical approval for this study was obtained from the WHO Scientific and Ethics Review Committee (protocol ID CERC.0103). Each study site is required to obtain the necessary ethical and regulatory approvals that are required in each specific country

Therapeutic angiogenesis following intramuscular gene transfer of vascular endothelial growth factor 121 in a dog model of hindlimb ischemia

Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, has been shown to promote therapeutic angiogenesis in animal models of critical limb ischemia. Ischemic skeletal muscle is advantageous for taking up and expressing foreign genes transferred as naked plasmid DNA. Accordingly, we investigated the hypothesis that intramuscular administration of naked plasmid DNA encoding the 121-amino acid isoform of VEGF could augment collateral development and tissue perfusion in a dog hindlimb ischemia model. Unilateral hindlimb ischemia was surgically induced in Beagle dogs. Ten days later, animals received intramuscular injections of pVEGF121 plasmid directly in the ischemic muscles. Angiogenic effects were evaluated by angiography, calf blood pressure ratio and vasomotor reserve analyses. Thirty days after gene transfer, angiographically recognizable collateral vessels were increased in pVEGF121-treated animals compared with controls. Improvement in perfusion to the ischemic limb was documented by a significantly higher calf blood pressure ratio for pVEGF121 (0.79 \ub1 0.05) versus controls (0.56 \ub1 0.14, P&lt;0.01). Vasomotor reserve assay suggested amelioration in blood availability at the microcirculation level in pVEGF121-treated animals. Hematological variables showed no significant modification due to the treatment. Our results suggest that intramuscular gene transfer of VEGF121 may promote therapeutic angiogenesis in critical limb vascular insufficiency