Long-term open-label vebicorvir for chronic HBV infection: Safety and off-treatment responses.

Background & Aims: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs). Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR + NrtI, discontinued VBR only, or continued both VBR + NrtI. The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at 24 weeks off treatment. Results: Ninety-two patients entered the extension study and received VBR + NrtI. Long-term VBR + NrtI treatment led to continued suppression of HBV nucleic acids and, to a lesser extent, HBV antigens. Forty-three patients met criteria to discontinue VBR + NrtI, with no patients achieving the primary endpoint; the majority of virologic rebound occurred ≥4 weeks off treatment. Treatment was generally well tolerated, with few discontinuations due to adverse events (AEs). There were no deaths. Most AEs and laboratory abnormalities were related to elevations in alanine aminotransferase and occurred during the off-treatment or NrtI-restart phases. No drug-drug interactions between VBR + NrtI and no cases of treatment-emergent resistance among patients who adhered to treatment were observed. Conclusions: Long-term VBR + NrtI was safe and resulted in continued reductions in HBV nucleic acids following completion of the 24-week parent studies. Following treatment discontinuation, virologic relapse was observed in all patients. This first-generation core inhibitor administered with NrtI for at least 52 weeks was not sufficient for HBV cure. Clinical trial number: NCT03780543. Impact and implications: Approved treatments for chronic hepatitis B virus infection (cHBV) suppress viral replication, but viral rebound is almost always observed after treatment discontinuation, highlighting an unmet need for improved therapies with finite treatment duration producing greater therapeutic responses that can be sustained off treatment. First-generation core inhibitors, such as vebicorvir, have mechanisms of action orthogonal to standard-of-care therapies that deeply suppress HBV viral replication during treatment; however, to date, durable virologic responses have not been observed after treatment discontinuation. The results reported here will help researchers with the design and interpretation of future studies investigating core inhibitors as possible components of finite treatment regimens for patients with cHBV. It is possible that next-generation core inhibitors with enhanced potency may produce deeper and more durable antiviral activity than first-generation agents, including vebicorvir.

Maternity protection policies and the enabling environment for breastfeeding in the Philippines: a qualitative study.

BACKGROUND: The Philippines has enacted maternity protection policies, such as the 105-Day Expanded Maternity Leave Law and the Expanded Breastfeeding Promotion Act of 2009, to protect, promote, and support breastfeeding. This study aimed to review the content and implementation of maternity protection policies in the Philippines and assess their role in enabling recommended breastfeeding practices. It also identified bottlenecks to successful implementation from the perspectives of mothers and their partners, employers, and authorities from the government and non-government organizations involved in developing, implementing, monitoring, and enforcing maternity protection policies. METHODS: This study employed a desk review of policies, guidelines, and related documents on maternity protection, and in-depth interviews. Of the 87 in-depth interviews, there were 12 employed pregnant women, 29 mothers of infants, 15 partners of the mothers, 12 employers and 19 key informants from the government and non-government organizations. Respondents for the in-depth interviews were from the Greater Manila Area and were recruited using purposive snowball sampling. Data were collected from December 2020 to April 2021. RESULTS: The study shows that maternity protection policies in the Philippines are mostly aligned with the maternity protection standards set by the International Labour Organization. However, their role in improving breastfeeding practices is limited because: (1) not all working women have access to maternity protection entitlements; (2) the duration of maternity leave entitlements is inconsistent with the World Health Organization's recommended duration of exclusive breastfeeding; (3) there are gaps in policy implementation including: a lack of monitoring systems to measure the availability, functionality, and usage of lactation spaces; limited workplace support for breastfeeding; poor communication of maternity and paternity entitlements; and limited breastfeeding advocacy and promotion; and (4) there is limited integration between maternity protection and breastfeeding promotion interventions. CONCLUSIONS: There is a need to (1) strengthen communication about and promotion of maternity and paternity entitlements for mothers, fathers and employers, (2) improve monitoring and enforcement mechanisms to ensure utilization of entitlements among mothers, (3) develop modalities to extend the coverage of maternity entitlements to the informal sector, (4) fully cover paid leave entitlements from social insurance or public funding sources in line with International Labour Organization recommendations, and (5) revisit the limitations on the coverage of paternity entitlement.

Minimal conditions for solidification and thermal processing of colloidal gels.

Colloidal gelation is used to form processable soft solids from a wide range of functional materials. Although multiple gelation routes are known to create gels of different types, the microscopic processes during gelation that differentiate them remain murky. A fundamental question is how the thermodynamic quench influences the microscopic driving forces of gelation, and determines the threshold or minimal conditions where gels form. We present a method that predicts these conditions on a colloidal phase diagram, and mechanistically connects the quench path of attractive and thermal forces to the emergence of gelled states. Our method employs systematically varied quenches of a colloidal fluid over a range of volume fractions to identify minimal conditions for gel solidification. The method is applied to experimental and simulated systems to test its generality toward attractions with varied shapes. Using structural and rheological characterization, we show that all gels incorporate elements of percolation, phase separation, and glassy arrest, where the quench path sets their interplay and determines the shape of the gelation boundary. We find that the slope of the gelation boundary corresponds to the dominant gelation mechanism, and its location approximately scales with the equilibrium fluid critical point. These results are insensitive to potential shape, suggesting that this interplay of mechanisms is applicable to a wide range of colloidal systems. By resolving regions of the phase diagram where this interplay evolves in time, we elucidate how programmed quenches to the gelled state could be used to effectively tailor gel structure and mechanics.

The volume and monetary value of human milk produced by the world's breastfeeding mothers: Results from a new tool.

The Mothers' Milk Tool was developed to make more visible the economic value contributed to society by women's unpaid care work through breastfeeding infants and young children. This manuscript describes the development and display key features of the tool, and reports results for selected countries. For the development, we used five steps: (1) defining the tool by reviewing existing tools and scholarly literature to identify uses, approaches, design features, and required data characteristics for a suitable product; (2) specifying the best open-access data available for measurement and easy updating; (3) analyzing development options; (4) testing predictive models to fill identified breastfeeding data gaps; and (5) validating the tool with prospective users and against previous research. We developed an Excel-based tool that allows working offline, displaying preloaded data, imputing data, and inputting users' data. It calculates annual quantities of milk produced by breastfeeding women for children aged 0-35.9 months, and the quantities lost compared to a defined biologically feasible level. It supports calculations for an individual mother, for countries, and global level. Breastfeeding women globally produce around 35.6 billion liters of milk annually, but 38.2% is currently "lost" due to cultural barriers and structural impediments to breastfeeding. The tool can also attribute a monetary value to the production. In conclusion, the Mothers' Milk Tool shows what is at risk economically if women's important capacity for breastfeeding is not protected, promoted, and supported by effective national policies, programs, and investments. The tool is of value to food and health policymakers, public officials, advocates, researchers, national accountants and statisticians, and individual mother/baby dyads, and will assist consideration of breastfeeding in food balance sheets and economic production statistics. The tool supports the 2015 Call to Action by the Global Breastfeeding Collective by facilitating the tracking of progress on breastfeeding targets.

Cross-sectional multimedia audit reveals a multinational commercial milk formula industry circumventing the Philippine Milk Code with misinformation, manipulation, and cross-promotion campaigns.

The Philippine Milk Code was enacted in 1986 to protect breastfeeding and reduce inappropriate marketing of breastmilk substitutes (BMS). The Philippine Milk Code is categorized as "substantially aligned" with the International Code of Marketing of Breast-milk Substitutes ("the Code"), but its provisions are assessed as relatively weak in prohibiting promotion to the general public. The extent to which violations of the Philippine Milk Code persist in traditional media platforms and in the digital space has not been systematically explored. This study employed a cross-sectional multimedia audit to examine the marketing and promotion of products under the scope of the Code, as well as those regulated by the Philippine Milk Code. Through a media monitoring conducted from March to September 2018, a total of 430 unique television (n = 32), printed (n = 87) and online (n = 311) promotional materials were identified. A coding tool was used to analyze the content, including the marketing elements used in the materials. Our findings show that commercial milk formula (CMF) for children ≥36 months old was the most promoted type of product (n = 251); and staging of events (n = 211), provision of special discounts or financial inducements (n = 115) and the use of taglines (n = 112) were the most used marketing elements. Promotion of CMF for children <36 months old was uncommon, which supports the conclusion that there is broad compliance with the Philippine Milk Code in terms of the types of products promoted. However, analysis of marketing elements reveals that the CMF industry circumvents the Philippine Milk Code through the use of false and misleading health and nutrition claims, emotionally manipulative language in promotional materials, and cross-promotion. The findings indicate gaps in enforcement and regulatory measures that require urgent attention.

Oral testosterone therapy: past, present, and future.

INTRODUCTION: Testosterone replacement therapy (TRT) remains a commonly utilized treatment for men with testosterone deficiency (TD). Despite the recent FDA approval of new oral TRT medications, concerns remain regarding their efficacy and safety, and prescription rates for these medications have decreased compared to those for TD medications with other routes of administration. OBJECTIVE: In this study we sought to investigate the efficacy and safety of oral testosterone undecanoate (oTU), a new oral TRT medication. METHODS: A comprehensive review of the literature was performed using the Medline, EMBASE, and Cochrane Library databases; 1269 articles were identified, with 44 articles included in the final review and 12 used to perform meta-analyses to investigate the change in serum total testosterone (TT) and risk of adverse effects following oral testosterone undecanoate (oTU) use. Articles were also reviewed to investigate the reported effects of oTU on body composition, liver function, hematologic assays, lipid profiles, hormone assays, prostate growth, hypertension, and symptoms of TD. RESULTS: Across placebo-controlled randomized trials, there was no significant increase in TT for those receiving oTU vs placebo (mean difference, -0.26 [95% CI, -1.26 to 0.73]). On subanalysis, when eugonadal participants received oTU, a significant decrease in TT was demonstrated (mean difference -0.86 [95% CI, -1.28 to 0.43]). When participants who were hypogonadal at baseline received oTU, a significant increase in TT compared to placebo was seen (mean difference 1.25 [95% CI, 0.22-2.29]). There was no significant risk of adverse effects (RR, -0.03 [95% CI, -0.08 to 0.03]) or serious adverse effects (RR, 0.15 [95% CI, -0.66 to 0.96]) in the oTU groups compared to placebo. CONCLUSION: oTU was found to be well tolerated in hypogonadal patients, resulting in improved testosterone levels, height velocity, and sexual symptoms, without significant hepatotoxicity, prostatic enlargement, or worsening hypertension. There was no consensus regarding the effect of oTU on lean and fat mass percentages, hematologic assays, lipid profiles, mood, and general well-being.

Safety, pharmacokinetics and antiviral activity of ABI-H2158, a hepatitis B virus core inhibitor: A randomized, placebo-controlled phase 1 study.

Treatment for chronic hepatitis B virus infection (cHBV) is mostly indefinite, with new finite-duration therapies needed. We report safety, pharmacokinetics and antiviral activity of the investigational HBV core inhibitor ABI-H2158. This Phase 1a/b study (NCT03714152) had three parts: Part A, participants received a single ascending oral dose of ABI-H2158 (5-500 mg) or placebo; Part B, participants received multiple doses of ABI-H2158 300 mg once (QD) or twice (BID) daily or placebo, for 10 days; Part C, cHBV patients received ABI-H2158 (100, 300, or 500 mg QD or 300 mg BID) or placebo, for 14 days. Ninety-three participants enrolled. In Parts A/B, there were no serious adverse events (SAEs) or deaths, and all treatment-emergent AEs (TEAEs) were Grade 1. In Part C, two patients had Grade 3 TEAEs unrelated to ABI-H2158; there were no deaths, SAEs or Grade 4 TEAEs. In Part A, median time to maximum ABI-H2158 plasma concentration (Tmax ) and mean terminal elimination half-life (t½ ) were 1-4 and 9.8-20.7 h, and area under the plasma concentration-time curve increased dose proportionally. In Part B, Day 10 Tmax was 2 h, mean t½ was 15.5-18.4 h, and exposure accumulated 1.7- to 3.1-fold. In Part C, Day 14 Tmax was 1 h, exposure accumulated 1.4- to 1.8-fold, and ABI-H2158 was associated with >2 log10 declines in HBV nucleic acids. In conclusion, ABI-H2158 in cHBV patients following 14 days of dosing was well tolerated and demonstrated potent antiviral activity. Safety and pharmacokinetics supported future QD dosing.

The Financial Costs of Mass Media Interventions Used for Improving Breastfeeding Practices in Bangladesh, Burkina Faso, Nigeria, and Vietnam.

Breastfeeding is essential for child survival but globally less than fifty percent of infants receive adequate breastfeeding. Gaps in breastfeeding knowledge and misinformation are widespread. Mass media aims to motivate mothers and families, encourage care-seeking, improve social norms, and counteract misleading advertising. However, the costs and coverage of mass media are not well documented. Our study provides a cost-accounting of four large-scale mass media interventions and coverage obtained through mass media. We retrospectively calculated annual costs and costs per beneficiary of mass media interventions based on expenditure records in four countries. The interventions were a part of multi-component breastfeeding strategies in Bangladesh, Burkina Faso, Nigeria, and Vietnam. Annual costs ranged from 566,366 USD in Nigeria to 1,210,286 USD in Vietnam. The number of mothers of children under two years and pregnant women ranged from 685,257 to 5,566,882, and all designated recipients reached during the life of programs ranged from 1,439,040 to 11,690,453 in Burkina Faso and Bangladesh, respectively. The cost per mother varied from USD 0.13 USD in Bangladesh to 0.85 USD in Burkina Faso. Evaluations showed that mass media interventions reached high coverage and frequent exposure. This analysis documents the financial costs and budgetary needs for implementing mass media components of large-scale breastfeeding programs. It provides annual costs, cost structures, and coverage achieved through mass media interventions in four low- and middle-income countries.

Birth and newborn care policies and practices limit breastfeeding at maternity facilities in Vietnam.

The prevalence of early and exclusive breastfeeding in Vietnam remains sub-optimal. The objective of this study was to determine factors associated with early initiation of breastfeeding (EIBF) and exclusive breastfeeding for the first 3 days after birth (EBF3D). We conducted a population-based, cross-sectional survey of 726 mothers with children aged 0-11 months in two provinces and one municipality from May to July 2020. Multinomial logistic regression was used to examine factors associated with EIBF and EBF3D. The prevalence of EIBF was 39.7% and EBF3D 18.0%. The EIBF prevalence is positively associated with immediate and uninterrupted skin-to-skin contact (SSC) for 10-29 min (aOR: 2.55; 95% CI: 1.49, 4.37), 30-59 min (aOR: 4.15; 95% CI: 2.08, 8.27), 60-80 min (aOR: 4.35; 95% CI: 1.50, 12.6), or ≥90 min (aOR: 5.87; 95% CI: 3.14, 10.98). EIBF was negatively associated with cesarean birth (aOR: 0.24; 95% CI: 0.11, 0.51), bringing infant formula to the birth facility (aOR: 0.49; 95% CI: 0.30, 0.78), purchased it after arrival (aOR: 0.37; 95% CI: 0.24, 0.60), or did both (aOR: 0.43; 95% CI: 0.21, 0.89). EBF3D was negatively associated with cesarean section birth (aOR: 0.15; 95% CI: 0.06, 0.39), vaginal birth with episiotomy (aOR: 0.40; 95% CI: 0.18, 0.88), bringing formula to the maternity facility (aOR: 0.03; 95% CI: 0.01, 0.07), purchased it after arrival (aOR: 0.02; 95% CI: 0.01, 0.06) or did both (aOR: 0.04; 95% CI: 0.02, 0.10). Receiving counseling from any source was not significantly associated with early breastfeeding practices. Policy and health service delivery interventions should be directed at eliminating infant formula from birthing environments, reducing unnecessary cesarean sections and episiotomies, providing immediate and uninterrupted SSC for all births, and improving breastfeeding counseling and support.

Implementation and Effectiveness of Policies Adopted to Enable Breastfeeding in the Philippines Are Limited by Structural and Individual Barriers.

The Philippines has adopted policies to protect, promote, and support breastfeeding on par with global standards, yet the impact of these policies is not well understood. This study assesses the adequacy and potential impact of breastfeeding policies, as well as the perceptions of stakeholders of their effectiveness and how to address implementation barriers. This mixed methods study entailed a desk review of policies and documents and in-depth interviews with 100 caregivers, employees, employers, health workers, and policymakers in the Greater Manila Area. Although the Philippines has a comprehensive breastfeeding policy framework, its effectiveness was limited by structural and individual barriers. Structural barriers included inconsistent breastfeeding promotion, limited access of mothers to skilled counseling, limited workplace breastfeeding support, gaps in legal provisions, weak monitoring and enforcement of the Philippine Milk Code, and the short duration and limited coverage of maternity leave. Individual barriers included knowledge and skills gaps, misconceptions, and low self-confidence among mothers due to insufficient support to address breastfeeding problems, misconceptions in the community that undermine breastfeeding, limited knowledge and skills of health workers, and insufficient support extended to mothers by household members. Breastfeeding policies in the Philippines are consistent with global standards, but actions to address structural and individual barriers are needed to enhance their effectiveness for improving breastfeeding practices.

Modeling colloidal interactions that predict equilibrium and non-equilibrium states.

Modulating the interaction potential between colloids suspended in a fluid can trigger equilibrium phase transitions as well as the formation of non-equilibrium "arrested states," such as gels and glasses. Faithful representation of such interactions is essential for using simulation to interrogate the microscopic details of non-equilibrium behavior and for extrapolating observations to new regions of phase space that are difficult to explore in experiments. Although the extended law of corresponding states predicts equilibrium phases for systems with short-ranged interactions, it proves inadequate for equilibrium predictions of systems with longer-ranged interactions and for predicting non-equilibrium phenomena in systems with either short- or long-ranged interactions. These shortcomings highlight the need for new approaches to represent and disambiguate interaction potentials that replicate both equilibrium and non-equilibrium phase behavior. In this work, we use experiments and simulations to study a system with long-ranged thermoresponsive colloidal interactions and explore whether a resolution to this challenge can be found in regions of the phase diagram where temporal effects influence material state. We demonstrate that the conditions for non-equilibrium arrest by colloidal gelation are sensitive to both the shape of the interaction potential and the thermal quench rate. We exploit this sensitivity to propose a kinetics-based algorithm to extract distinct arrest conditions for candidate potentials that accurately selects between potentials that differ in shape but share the same predicted equilibrium structure. The algorithm selects the candidate that best matches the non-equilibrium behavior between simulation and experiments. Because non-equilibrium behavior in simulation is encoded entirely by the interparticle potential, the results are agnostic to the particular mechanism(s) by which arrest occurs, and so we expect our method to apply to a range of arrested states, including gels and glasses. Beyond its utility in constructing models, the method reveals that each potential has a quantitatively distinct arrest line, providing insight into how the shape of longer-ranged potentials influences the conditions for colloidal gelation.

Safety and efficacy of vebicorvir administered with entecavir in treatment-naïve patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress HBV DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core inhibitor that interferes with multiple aspects of HBV replication. This phase II trial evaluated the safety and efficacy of VBR in combination with entecavir (ETV) in treatment-naïve patients with cHBV. METHODS: HBeAg-positive, treatment-naïve patients without cirrhosis were randomised 1:1 in a double-blind manner to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV 0.5 mg for 24 weeks. The primary endpoint was change in mean log10 HBV DNA from Baseline to Week 12 and 24. RESULTS: All patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At Week 12, VBR+ETV led to a greater mean (SD) reduction from Baseline in log10 IU/ml HBV DNA (-4.45 [1.03]) vs. PBO+ETV (-3.30 [1.18]; p = 0.0077). At Week 24, VBR+ETV led to a greater reduction from Baseline in log10 IU/ml HBV DNA (-5.33 [1.59]) vs. PBO+ETV (-4.20 [0.98]; p = 0.0084). Greater mean reductions in pregenomic RNA were observed at Week 12 and 24 in patients receiving VBR+ETV vs. PBO+ETV (p <0.0001 and p <0.0001). Changes in viral antigens were similar in both groups. No drug interaction between VBR and ETV was observed. Two patients experienced HBV DNA rebound during treatment, with no resistance breakthrough detected. The safety of VBR+ETV was similar to PBO+ETV. All treatment-emergent adverse events and laboratory abnormalities were Grade 1/2. There were no deaths, serious adverse events, or evidence of drug-induced liver injury. CONCLUSIONS: In this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naïve patients with cHBV, with a favourable safety and tolerability profile. CLINICAL TRIAL NUMBER: NCT03577171 LAY SUMMARY: Hepatitis B is a long-lasting viral infection of the liver. Current treatments can suppress hepatitis B virus but do not offer the opportunity of cure, hence, new treatment approaches are required. Herein, we show that the combination of the novel core inhibitor vebicorvir with an existing antiviral (entecavir) in treatment-naïve patients chronically infected with hepatitis B virus demonstrated greater antiviral activity than entecavir alone. Additionally, vebicorvir was safe and well tolerated. Thus, further studies evaluating its potential role in the treatment of chronic hepatitis B are warranted.

Safety and efficacy of vebicorvir in virologically suppressed patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs. METHODS: Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks. RESULTS: Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported. CONCLUSIONS: In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone. CLINICAL TRIALS NUMBER: NCT03576066. LAY SUMMARY: Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated.

Awareness, Perceptions, Gaps, and Uptake of Maternity Protection among Formally Employed Women in Vietnam.

Maternity protection is a normative fundamental human right that enables women to combine their productive and reproductive roles, including breastfeeding. The aim of this study is to examine the uptake of Vietnam's maternity protection policy in terms of entitlements and awareness, perceptions, and gaps in implementation through the lens of formally employed women. In this mixed methods study, we interviewed 494 formally employed female workers, among whom 107 were pregnant and 387 were mothers of infants and conducted in-depth interviews with a subset of these women (n = 39). Of the 494 women interviewed, 268 (54.3%) were working in blue-collar jobs and more than 90% were contributing to the public social insurance fund. Among the 387 mothers on paid maternity leave, 51 (13.2%) did not receive cash entitlements during their leave. Among the 182 mothers with infants aged 6-11 months, 30 (16.5%) returned to work before accruing 180 days of maternity leave. Of 121 women who had returned to work, 26 (21.5%) did not receive a one-hour paid break every day to express breastmilk, relax, or breastfeed, and 46 (38.0%) worked the same or more hours per day than before maternity leave. Although most women perceived maternity leave as beneficial for the child's health (92.5%), mother's health (91.5%), family (86.2%), and society (90.7%), fewer women perceived it as beneficial for their income (59.5%), career (46.4%), and employers (30.4%). Not all formally employed women were aware of their maternity protection rights: women were more likely to mention the six-month paid maternity leave (78.7%) and one-hour nursing break (62.3%) than the other nine entitlements (2.0-35.0%). In-depth interviews with pregnant women and mothers of infants supported findings from the quantitative survey. In conclusion, although Vietnam's maternity protection policy helps protect the rights of women and children, our study identified implementation gaps that limit its effectiveness. To ensure that all women and their families can fully benefit from maternity protection, there is a need to increase awareness of the full set of maternity entitlements, strengthen enforcement of existing policies, and expand entitlements to the informal sector.

Beliefs and Norms Associated with the Use of Ultra-Processed Commercial Milk Formulas for Pregnant Women in Vietnam.

Commercial milk formula for pregnant women (CMF-PW) is an expensive, ultra-processed food with a high concentration of sugar, the consumption of which may be linked to negative health outcomes. However, CMF-PWs are promoted as beneficial for pregnant women and lactating mothers as well as their children. To date, little is known about the factors associated with the use of CMF-PW among pregnant women. We performed this analysis to examine the association between the use of CMF-PW and related beliefs and norms among pregnant women in Vietnam. We interviewed 268 pregnant women in their second and third trimesters from two provinces and one municipality representing diverse communities in Vietnam. Multinomial (polytomous) logistic regression, structural equation modeling (SEM), and propensity score matching (PSM) analysis were used to examine associations between beliefs and social norms related to CMF-PW and reported consumption, characterized as occasional, recent, and never during the current pregnancy. Overall, 64.6% of pregnant women reported using CMF-PW during the current pregnancy and 34.7% consumed CMF-PW on the day prior to the interview. Strong beliefs that CMF-PW will make a child smart and healthy (53.7%) and the perception that use of CMF-PW is common (70.9%) were associated with increased use on the previous day (beliefs: aOR: 3.56; 95% Confidence Interval (95% CI): 1.65, 7.71; p < 0.01 and social norms aOR: 2.29; 95% CI: 1.13, 4.66; p < 0.05). SEM and PSM analyses confirmed these findings for both occasional and regular CMF-PW use. Results are consistent with observations of CMF-PW product labels and marketing tactics in Vietnam. The prevalent use of CMF-PW in Vietnam is associated with the belief that these products make children smart and healthy and the perceived social norm that most mothers use these products, which mirrors marketing messages and approaches employed by the CMF industry.

Implementation of the Code of Marketing of Breast-Milk Substitutes in Vietnam: Marketing Practices by the Industry and Perceptions of Caregivers and Health Workers.

BACKGROUND: The promotion of breastmilk substitutes (BMS) is an important barrier to successful breastfeeding. OBJECTIVE: To examine the enactment and implementation of the Code of Marketing of Breast-Milk Substitutes (the Code) in Vietnam with a focus on marketing practices by the baby food industry and perceptions of caregivers, health workers, and policy makers. METHODS: From May to July 2020, we conducted a mixed-method, cross-sectional study including a survey of 268 pregnant women and 726 mothers of infants aged 0-11 months and in-depth interviews with a subset of interviewed women (n = 39), policy makers, media executives, and health workers (n = 31). RESULTS: In the previous 30 days, two mothers (out of 726) participating in the quantitative survey reported that health workers had recommended BMS, at private hospitals in both cases. In-depth interviews with health workers showed that hospitals have internal procedures to prevent the promotion of BMS by health workers. However, companies employed representatives to promote products not covered under the Code (e.g., commercial milk formula for pregnant women) at antenatal care visits and by gaining contact information from women and using this information to promote BMS outside the hospital, often on social media. In the 30 days preceding the survey, one-fifth of pregnant women were exposed to promotions of commercial milk formula for pregnant women and 7.1% to promotions of BMS. Among mothers of infants, 7.3% and 10.7% of respondents with infants aged 0-5 and 6-11 months, respectively, were exposed to some form of BMS promotion in the past 30 days. Around the time of birth, parents commonly brought BMS to maternity facilities (52.5%) or purchased it nearby (35.4%). CONCLUSIONS: Although Vietnam has a strong regulatory environment for the protection, promotion, and support of breastfeeding, there are implementation, monitoring, and enforcement gaps. Stronger enforcement of national policies to regulate the presence of BMS industry representatives in health facilities-both public and private-and the promotion of BMS products on digital platforms are needed.

Community support model on breastfeeding and complementary feeding practices in remote areas in Vietnam: implementation, cost, and effectiveness.

BACKGROUND: Poor access to healthcare facilities and consequently nutrition counseling services hinders the uptake of recommended infant and young child feeding (IYCF) practices. To address these barriers and improve IYCF practices, Alive & Thrive (A&T) initiated community support groups in remote villages across nine provinces in Vietnam. OBJECTIVE: This study examines the effectiveness of the support group model and related project costs for reaching underserved areas to improve IYCF practices. METHODS: To evaluate the model's implementation and project costs, we reviewed implementation guidelines, expenditure and coverage reports, monitoring data, and budgets for the nine provinces. To evaluate the model's effectiveness, we used a 3-stage sampling method to conduct a cross-sectional survey from April to May 2014 in three provinces entailing interviewing mothers of children aged 0-23 months in communes with (intervention; n = 551) and without support groups (comparison; n = 559). FINDINGS: Coverage: From November 2011 to November 2014, in partnership with the government, A&T supported training for 1513 facilitators and the establishing 801 IYCF support groups in 267 villages across nine provinces. During this period, facilitators provided ~ 166,000 meeting/support contacts with ~ 33,000 pregnant women and mothers with children aged 0-23 months in intervention villages. COSTS: The average project costs for supporting the meetings, compensating village collaborators, and providing supportive supervision through staff in commune health stations were USD 5 per client and USD 1 per contact. After adding expenditures for training, supportive supervision, and additional administrative costs at central and provincial levels, the average project cost was USD 15 per client and USD 3 per contact. Effectiveness: Survey participants in intervention and comparison communes had similar maternal, child, and household characteristics. Multiple logistic regression models showed that living in intervention communes was associated with higher odds of early initiation of breastfeeding (OR: 1.7; 95% CI: 1.1, 2.7), exclusive breastfeeding from 0 to 5 months (OR: 12.5; 95% CI: 6.7, 23.4), no bottle feeding (OR: 2.69; 95% CI: 1.82, 3.99), and minimum acceptable diet (OR: 1.51; 95% CI: 0.98, 2.33) compared to those living in comparison communes. CONCLUSION: The IYCF support group model was effective in reaching populations residing in remote areas and likely contributed to improved IYCF practices. The study suggests that the model could be scaled up to promote equity in breastfeeding support.

Human cardiac fibroblasts produce pro-inflammatory cytokines upon TLRs and RLRs stimulation.

Heart inflammation is one of the major causes of heart damage that leads to dilated cardiomyopathy and often progresses to end-stage heart failure. In the present study, we aimed to assess whether human cardiac cells could release immune mediators upon stimulation of Toll-like receptors (TLRs) and Retinoic acid-inducible gene (RIG)-I-like receptors (RLRs).Commercially available human cardiac fibroblasts and an immortalized human cardiomyocyte cell line were stimulated in vitro with TLR2, TLR3, and TLR4 agonists. In addition, cytosolic RLRs were activated in cardiac cells after transfection of polyinosinic-polycytidylic acid (PolyIC). Upon stimulation of TLR3, TLR4, MDA5, and RIG-I, but not upon stimulation of TLR2, human cardiac fibroblasts produced high amounts of the pro-inflammatory cytokines IL-6 and IL-8. On the contrary, the immortalized human cardiomyocyte cell line was unresponsive to the tested TLRs agonists. Upon RLRs stimulation, cardiac fibroblasts, and to a lesser extent the cardiomyocyte cell line, induced anti-viral IFN-ß expression.These data demonstrate that human cardiac fibroblasts and an immortalized human cardiomyocyte cell line differently respond to various TLRs and RLRs ligands. In particular, human cardiac fibroblasts were able to induce pro-inflammatory and anti-viral cytokines on their own. These aspects will contribute to better understand the immunological function of the different cell populations that make up the cardiac tissue.

Old Tricks, New Opportunities: How Companies Violate the International Code of Marketing of Breast-Milk Substitutes and Undermine Maternal and Child Health during the COVID-19 Pandemic.

Breastfeeding is critical to maternal and child health and survival, and the benefits persist until later in life. Inappropriate marketing of breastmilk substitutes (BMS), feeding bottles, and teats threatens the enabling environment of breastfeeding, and exacerbates child mortality, morbidity, and malnutrition, especially in the context of COVID-19. These tactics also violate the International Code of Marketing of Breast-Milk Substitutes. This study identified marketing tactics of BMS companies since the start of the COVID-19 pandemic by reviewing promotional materials and activities from 9 companies in 14 countries, and the official Code reporting data from the Philippines. Eight qualitative themes emerged that indicate companies are capitalizing on fear related to COVID-19 by using health claims and misinformation about breastfeeding. Other promotional tactics such as donations and services were used to harness the public sentiment of hope and solidarity. Past studies show that these tactics are not new, but the pandemic has provided a new entry point, helped along by the unprecedented boom in digital marketing. There was a sharp increase of reported violations in the Philippines since the pandemic: 291 during the first months of the outbreak compared with 70 in all of 2019, corroborating the thematic findings. A lack of public awareness about the harm of donations and inadequate Code implementation and enforcement have exacerbated these problems. Proposed immediate action includes using monitoring findings to inform World Health Assembly (WHA) actions, targeted enforcement, and addressing misinformation about breastfeeding in the context of COVID-19. Longer-term action includes holding social media platforms accountable, raising public awareness on the Code, and mobilizing community monitoring.