Underuse of modern methods of contraception: underlying causes and consequent undesired pregnancies in 35 low- and middle-income countries

Study question: What is the contribution of the underuse of modern methods (MM) of contraception to the annual undesired pregnancies in 35 low- and middle-income countries? Summary answer: Fifteen million out of 16.7 million undesired pregnancies occurring annually in 35 countries could have been prevented with the optimal use of MM of contraception. What is known already: Every year, 87 million women worldwide become pregnant unintentionally because of the underuse of MM of contraception. Study design, size, duration: Demographic and health surveys (DHS) of 35 countries, conducted between 2005 and 2012, were analysed. Participants/materials, setting, methods: Contraceptive use of 12 874 unintentionally pregnant women was compared with 111 301 sexually active women who were neither pregnant nor desiring pregnancy. Main results and the role of chance: An average of 96% of 15- to 49-year-old eligible women took part in the survey. When adjusted for covariates and compared with the use of MM of contraception, the use of traditional methods was associated with a 2.7 [95% confidence interval (CI): 2.3-3.4] times increase in odds of an undesired pregnancy, while non-use of any method was associated with a 14.3 (95% CI, 12.3-16.7) times increase. This corresponded to an estimated 16.7 million undesired pregnancies occurring annually in the 35 countries, of which 15.0 million could have been prevented with the optimal use of MM of contraception (13.5 million women did not use MM whilst 1.5 million women utilized MM incorrectly). Women with the lowest educational attainment and wealth quintile were 8.6 (95% CI: 8.2-9.1) and 2.6 (95% CI: 2.4-2.9) times less likely to use contraceptives compared with those with the highest level of each, respectively. Of the 14 893 women who neither desired pregnancy nor used contraception, 5559 (37.3%) cited fear of side effects and health concerns as the reason for non-use, 3331 (22.4%) cited they or their partner\u27s opposition to contraception or religious prohibition and 2620 (17.6%) underestimated the risk of pregnancy. Limitations, reasons for caution: Despite the fact that DHS are considered high-quality studies, we should not underestimate the role played by recall bias for past pregnancies. Few women report a current pregnancy in the first trimester and undesired pregnancies at that time are probably prone to under-reporting. Some terminated pregnancies may not be included in the current pregnancy group. Furthermore, covariates measured at the time of the survey may not have reflected the same covariates at the time the currently pregnant women became pregnant. Wider implications of the findings: Underuse of MM of contraception burdens especially the poor and the less educated. National strategies should address unfounded health concerns, fear of side effects, opposition and underestimated risk of pregnancy, which are major contributors to undesired pregnancies. Funding/conflicts of interest: No external funding was utilized for this report. There are no conflicts of interest to declare

Inadequate Folic Acid Intake Among Women Taking Antiepileptic Drugs During Pregnancy in Japan: A Cross-Sectional Study

This study aimed to assess characteristics of pregnant women taking antiepileptic drugs with inadequate folic acid intake. This cross-sectional study examined pregnant women taking antiepileptic drugs who were registered in the Japanese Drug Information Institute in Pregnancy (JDIIP) database between October 2005 and December 2016. Participants were classified into two groups according to when they started folic acid supplementation (before pregnancy: ‘adequate’, after pregnancy or never: ‘inadequate’). Logistic regression analysis was performed to investigate factors associated with inadequate folic acid intake. Of 12,794 registrants, 468 pregnant women were taking antiepileptics during the first trimester. Of these, we analysed data from 456 women who had no missing data. As a result, inadequate folic acid intake was noted among 83.3% of them, suggesting that the current level of folic acid intake is insufficient overall. Younger age, smoking, alcohol drinking, multiparity, unplanned pregnancy, and being prescribed AEDs by paediatric or psychiatric departments were independent factors associated with inadequate folic acid intake. As planned pregnancy was the strongest factor, healthcare professionals should ensure that childbearing women taking antiepileptics are informed of the importance of planned pregnancy. In addition, healthcare professionals must gain a better understanding of folic acid intake, as the prevalence of adequate intake differed according to which departments prescribed antiepileptic drugs

Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model.

The recent clinical application of perfusion technology for the machine preservation of donation after cardiac death (DCD) grafts has some advantages. Oxygenation has been proposed for the preservation of DCD liver grafts. The aim of this study is to clarify whether the use of HbV-containing preservation solution during the subnormothermic machine perfusion (SNMP) of the liver graft improves the graft function of DCD porcine livers in an ex vivo reperfusion model. Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: 4°C cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) with UW gluconate solution (HMP group; N = 5), SNMP (21°C) with UW gluconate solution (SNMP group; N = 5), SNMP (21°C) with HbVs (Hb; 1.8 mg/dl) perfusate (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model (IRM). The oxygen consumption of the SNMP and SNMP+HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, the AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH after reperfusion was significantly lower in SNMP+HbV group than CS and HMP groups. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained in comparison to the CS, HMP and SNMP groups. The SNMP+HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver

Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I–II essential hypertension: a randomized, double-blind clinical study

Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20–40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8–12 mg once daily by forced titration) in 622 Japanese patients with grade I–II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was −12.4 mm Hg in the azilsartan group and −9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: −2.6 mm Hg, 95% confidence interval (CI): −4.08 to −1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was −21.8 mm Hg and −17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: −4.4 mm Hg, 95% CI: −6.53 to −2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety

Maternal and perinatal health research priorities beyond 2015 : an international survey and prioritization exercise

Background: Maternal mortality has declined by nearly half since 1990, but over a quarter million women still die every year of causes related to pregnancy and childbirth. Maternal-health related targets are falling short of the 2015 Millennium Development Goals and a post-2015 Development Agenda is emerging. In connection with this, setting global research priorities for the next decade is now required. Methods. We adapted the methods of the Child Health and Nutrition Research Initiative (CHNRI) to identify and set global research priorities for maternal and perinatal health for the period 2015 to 2025. Priority research questions were received from various international stakeholders constituting a large reference group, and consolidated into a final list of research questions by a technical working group. Questions on this list were then scored by the reference working group according to five independent and equally weighted criteria. Normalized research priority scores (NRPS) were calculated, and research priority questions were ranked accordingly. Results: A list of 190 priority research questions for improving maternal and perinatal health was scored by 140 stakeholders. Most priority research questions (89%) were concerned with the evaluation of implementation and delivery of existing interventions, with research subthemes frequently concerned with training and/or awareness interventions (11%), and access to interventions and/or services (14%). Twenty-one questions (11%) involved the discovery of new interventions or technologies. Conclusions: Key research priorities in maternal and perinatal health were identified. The resulting ranked list of research questions provides a valuable resource for health research investors, researchers and other stakeholders. We are hopeful that this exercise will inform the post-2015 Development Agenda and assist donors, research-policy decision makers and researchers to invest in research that will ultimately make the most significant difference in the lives of mothers and babies.</p

Maternal and perinatal health research priorities beyond 2015 : an international survey and prioritization exercise

Abstract Background: Maternal mortality has declined by nearly half since 1990, but over a quarter million women still die every year of causes related to pregnancy and childbirth. Maternal-health related targets are falling short of the 2015 Millennium Development Goals and a post-2015 Development Agenda is emerging. In connection with this, setting global research priorities for the next decade is now required. Methods: We adapted the methods of the Child Health and Nutrition Research Initiative (CHNRI) to identify and set global research priorities for maternal and perinatal health for the period 2015 to 2025. Priority research questions were received from various international stakeholders constituting a large reference group, and consolidated into a final list of research questions by a technical working group. Questions on this list were then scored by the reference working group according to five independent and equally weighted criteria. Normalized research priority scores (NRPS) were calculated, and research priority questions were ranked accordingly. Results: A list of 190 priority research questions for improving maternal and perinatal health was scored by 140 stakeholders. Most priority research questions (89%) were concerned with the evaluation of implementation and delivery of existing interventions, with research subthemes frequently concerned with training and/or awareness interventions (11%), and access to interventions and/or services (14%). Twenty-one questions (11%) involved the discovery of new interventions or technologies

A Review of the Implementation Status of and National Plans on HPV Vaccination in 17 Middle-Income Countries of the WHO Western Pacific Region

The World Health Organization’s Western Pacific Region is responsible for one-fourth of the global cervical cancer burden, and nearly 90% of that burden is concentrated in middle-income countries (MICs). Applying a conceptual model of implementation of population-based interventions, we synthesized the current implementation status of human papillomavirus (HPV) vaccination and national plans that form the basis of its implementation in 17 MICs. We gathered information from a range of governmental documents, published studies, and global databases. For all available national cancer-related plans and immunization plans, we examined the description of HPV vaccination. We found that, as of July 2021, only four countries (24%) had a mature HPV vaccination program with a high first-dose coverage; three (18%) had introduced HPV vaccination, but needed further efforts to scale it up, seven (41%) had not been able to introduce it after conducting demonstration projects, and three (18%) did not have any experience in HPV vaccination. In the national plans, most of the countries recognized the importance of HPV vaccination, but only 10 (59%) provided an implementation strategy on how it would be introduced or scaled up. Countries with a mature program were more likely to have their implementation strategy detailed in their national cancer control plan. Successful implementation of HPV vaccination requires overcoming known challenges and having a clear national plan. Positioning HPV vaccination clearly in the overall national cancer control plan may be key to accelerating its nationwide implementation

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma

(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment

A rapid landscape review of postpartum anaemia measurement: challenges and opportunities

Abstract Background Anaemia is a reduction in haemoglobin concentration below a threshold, resulting from various factors including severe blood loss during and after childbirth. Symptoms of anaemia include fatigue and weakness, among others, affecting health and quality of life. Anaemic pregnant women have an increased risk of premature delivery, a low-birthweight infant, and postpartum depression. They are also more likely to have anaemia in the postpartum period which can lead to an ongoing condition and affect subsequent pregnancies. In 2019 nearly 37% of pregnant women globally had anaemia, and estimates suggest that 50–80% of postpartum women in low- and middle-income countries have anaemia, but currently there is no standard measurement or classification for postpartum anaemia. Methods A rapid landscape review was conducted to identify and characterize postpartum anaemia measurement searching references within three published systematic reviews of anaemia, including studies published between 2012 and 2021. We then conducted a new search for relevant literature from February 2021 to April 2022 in EMBASE and MEDLINE using a similar search strategy as used in the published reviews. Results In total, we identified 53 relevant studies. The timing of haemoglobin measurement ranged from within the immediate postpartum period to over 6 weeks. The thresholds used to diagnose anaemia in postpartum women varied considerably, with < 120, < 110, < 100 and < 80 g/L the most frequently reported. Other laboratory results frequently reported included ferritin and transferrin receptor. Clinical outcomes reported in 32 out of 53 studies included postpartum depression, quality of life, and fatigue. Haemoglobin measurements were performed in a laboratory, although it is unclear from the studies if venous samples and automatic analysers were used in all cases. Conclusions This review demonstrates the need for improving postpartum anaemia measurement given the variability observed in published measures. With the high prevalence of anaemia, the relatively simple treatment for non-severe cases of iron deficiency anaemia, and its importance to public health with multi-generational effects, it is crucial to develop common measures for women in the postpartum period and promote rapid uptake and reporting