Neddylation inhibition upregulates PD‐L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/1/ijc32379_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/2/ijc32379-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/3/ijc32379.pd

Antenatal care as a means to increase participation in the continuum of maternal and child healthcare: an analysis of the poorest regions of four Mesoamérican countries

Abstract Background Antenatal care (ANC) is a means to identify high-risk pregnancies and educate women so that they might experience a healthier delivery and outcome. There is a lack of evidence about whether receipt of ANC is an effective strategy for keeping women in the system so they partake in other maternal and child interventions, particularly for poor women. The present analysis examines whether ANC uptake is associated with other maternal and child health behaviors in poor mothers in Guatemala, Honduras, Nicaragua, and Mexico (Chiapas). Methods We conducted a cross-sectional survey of women regarding their uptake of ANC for their most recent delivery in the last two years and their uptake of selected services and healthy behaviors along a continuity of maternal and child healthcare. We conducted logistic regressions on a sample of 4844 births, controlling for demographic, household, and maternal characteristics to understand the relationship between uptake of ANC and later participation in the continuum of care. Results Uptake of four ANC visits varied by country from 17.0% uptake in Guatemala to 81.4% in Nicaragua. In all countries but Nicaragua, ANC was significantly associated with in-facility delivery (IFD) (Guatemala odds ratio [OR] = 5.28 [95% confidence interval [CI] 3.62–7.69]; Mexico OR = 5.00 [95% CI: 3.41–7.32]; Honduras OR = 2.60 [95% CI: 1.42–4.78]) and postnatal care (Guatemala OR = 4.82 [95% CI: 3.21–7.23]; Mexico OR = 4.02 [95% CI: 2.77–5.82]; Honduras OR = 2.14 [95% CI: 1.26–3.64]), but did not appear to have any positive relationship with exclusive breastfeeding habits or family planning methods, which may be more strongly determined by cultural influences. Conclusions Our results demonstrate that uptake of the WHO-recommended four ANC visits has limited effectiveness on uptake of services in some poor populations in Mesoamérica. Our study highlights the need for continued and varied efforts in these populations to increase both the uptake and the effectiveness of ANC in encouraging positive and lasting effects on women’s uptake of health care services

Coverage and timing of antenatal care among poor women in 6 Mesoamerican countries

Background: Poor women in the developing world have a heightened need for antenatal care (ANC) but are often the least likely to attend it. This study examines factors associated with the number and timing of ANC visits for poor women in Guatemala, Honduras, Mexico, Nicaragua, Panama, and El Salvador. Methods: We surveyed 8366 women regarding the ANC they attended for their most recent birth in the past two years. We conducted logistic regressions to examine demographic, household, and health characteristics associated with attending at least one skilled ANC visit, four skilled visits, and a skilled visit in the first trimester. Results: Across countries, 78 % of women attended at least one skilled ANC visit, 62 % attended at least four skilled visits, and 56 % attended a skilled visit in the first trimester. The proportion of women attending four skilled visits was highest in Nicaragua (81 %) and lowest in Guatemala (18 %) and Panama (38 %). In multiple countries, women who were unmarried, less-educated, adolescent, indigenous, had not wanted to conceive, and lacked media exposure were less likely to meet international ANC guidelines. In countries with health insurance programs, coverage was associated with attending skilled ANC, but not the timeliness. Conclusions: Despite significant policy reforms and initiatives targeting the poor, many women living in the poorest regions of Mesoamérica are not meeting ANC guidelines. Both supply and demand interventions are needed to prioritize vulnerable groups, reduce unplanned pregnancies, and reach populations not exposed to common forms of media. Top performing municipalities can inform effective practices across the region

Missed Opportunities for Measles, Mumps, and Rubella (MMR) Immunization in Mesoamerica: Potential Impact on Coverage and Days at Risk

<div><p>Background</p><p>Recent outbreaks of measles in the Americas have received news and popular attention, noting the importance of vaccination to population health. To estimate the potential increase in immunization coverage and reduction in days at risk if every opportunity to vaccinate a child was used, we analyzed vaccination histories of children 11–59 months of age from large household surveys in Mesoamerica.</p><p>Methods</p><p>Our study included 22,234 children aged less than 59 months in El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama. Child vaccination cards were used to calculate coverage of measles, mumps, and rubella (MMR) and to compute the number of days lived at risk. A child had a missed opportunity for vaccination if their card indicated a visit for vaccinations at which the child was not caught up to schedule for MMR. A Cox proportional hazards model was used to compute the hazard ratio associated with the reduction in days at risk, accounting for missed opportunities.</p><p>Results</p><p>El Salvador had the highest proportion of children with a vaccine card (91.2%) while Nicaragua had the lowest (76.5%). Card MMR coverage ranged from 44.6% in Mexico to 79.6% in Honduras while potential coverage accounting for missed opportunities ranged from 70.8% in Nicaragua to 96.4% in El Salvador. Younger children were less likely to have a missed opportunity. In Panama, children from households with higher expenditure were more likely to have a missed opportunity for MMR vaccination compared to the poorest (OR 1.62, 95% CI: 1.06–2.47). In Nicaragua, compared to children of mothers with no education, children of mothers with primary education and secondary education were less likely to have a missed opportunity (OR 0.46, 95% CI: 0.24–0.88 and OR 0.25, 95% CI: 0.096–0.65, respectively). Mean days at risk for MMR ranged from 158 in Panama to 483 in Mexico while potential days at risk ranged from 92 in Panama to 239 in El Salvador.</p><p>Conclusions</p><p>Our study found high levels of missed opportunities for immunizing children in Mesoamerica. Our findings cause great concern, as they indicate that families are bringing their children to health facilities, but these children are not receiving all appropriate vaccinations during visits. This points to serious problems in current immunization practices and protocols in poor areas in Mesoamerica. Our study calls for programs to ensure that vaccines are available and that health professionals use every opportunity to vaccinate a child.</p></div

Descriptive characteristics comparing children with and without a vaccine card (% unless otherwise noted).

<p>† N varies by variable due to missing values.</p><p>* p<0.05</p><p>** p<0.01</p><p>*** p<0.001</p><p>Descriptive characteristics comparing children with and without a vaccine card (% unless otherwise noted).</p

Child, maternal, and household characteristics associated with a child having a vaccine card^†.

<p>OR: odds ratio. CI: confidence interval.</p><p>Exponentiated coefficients; 95% confidence intervals in brackets</p><p>* p<0.05</p><p>** p<0.01</p><p>*** p<0.001</p><p>†Models adjusted for all variables in the table</p><p>Child, maternal, and household characteristics associated with a child having a vaccine card<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139680#t002fn006" target="_blank">^†</a>.</p

Child, maternal, and household characteristics associated with a child having a missed opportunity for MMR vaccine^†.

<p>OR: odds ratio. CI: confidence interval.</p><p>Exponentiated coefficients; 95% confidence intervals in brackets</p><p>†Models adjusted for all variables in the table</p><p>* p<0.05</p><p>** p<0.01</p><p>*** p<0.001</p><p>Child, maternal, and household characteristics associated with a child having a missed opportunity for MMR vaccine<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139680#t007fn003" target="_blank">^†</a>.</p

Descriptive characteristics comparing children with and without coverage for MMR at the time of the survey (% unless otherwise noted).

<p>† N varies by variable due to missing values.</p><p>* p<0.05</p><p>** p<0.01</p><p>*** p<0.001</p><p>Descriptive characteristics comparing children with and without coverage for MMR at the time of the survey (% unless otherwise noted).</p

Cox proportional hazard model for MMR coverage^†.

<p>CI: confidence interval.</p><p>95% confidence intervals in brackets</p><p>†Models adjusted for all variables indicated in the column</p><p>* p<0.05</p><p>*** p<0.001</p><p>Cox proportional hazard model for MMR coverage<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139680#t008fn003" target="_blank">^†</a>.</p

Coverage cascade of MMR by country.

<p>* Coverage for children 13.5–59 months.</p><p>† Excluding children without vaccination cards. If the child has completed the number of required doses for age, they are considered compliant.</p><p>‡ Excluding children without vaccination cards. If the child has completed the number of required doses for age and not before the eligibility window, they are considered compliant.</p><p>Coverage cascade of MMR by country.</p