Human rights and the COVID-19 pandemic: a retrospective and prospective analysis.

When the history of the COVID-19 pandemic is written, the failure of many states to live up to their human rights obligations should be a central narrative. The pandemic began with Wuhan officials in China suppressing information, silencing whistleblowers, and violating the freedom of expression and the right to health. Since then, COVID-19's effects have been profoundly unequal, both nationally and globally. These inequalities have emphatically highlighted how far countries are from meeting the supreme human rights command of non-discrimination, from achieving the highest attainable standard of health that is equally the right of all people everywhere, and from taking the human rights obligation of international assistance and cooperation seriously. We propose embedding human rights and equity within a transformed global health architecture as the necessary response to COVID-19's rights violations. This means vastly more funding from high-income countries to support low-income and middle-income countries in rights-based recoveries, plus implementing measures to ensure equitable distribution of COVID-19 medical technologies. We also emphasise structured approaches to funding and equitable distribution going forward, which includes embedding human rights into a new pandemic treaty. Above all, new legal instruments and mechanisms, from a right to health treaty to a fund for civil society right to health advocacy, are required so that the narratives of future health emergencies-and people's daily lives-are ones of equality and human rights.

Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA.

Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.

Non-targeted urinary metabolomics in pregnancy and associations with fetal growth restriction.

Our objective was to identify metabolites associated with fetal growth restriction (FGR) by examining early and late pregnancy differences in non-targeted urinary metabolites among FGR cases and non-FGR controls. An exploratory case-control study within LIFECODES birth cohort was performed. FGR cases (N = 30), defined as birthweight below the 10th percentile, were matched with controls (N = 30) based on maternal age, race, pre-pregnancy body mass index, and gestational age at delivery. Gas chromatography/electron-ionization mass spectrometry was performed on urine samples collected at 10 and 26 weeks of gestation. Differences in urinary metabolite levels in cases and controls at each time point and between the two time points were calculated and then changes compared across pregnancy. 137 unique urinary metabolites were annotated, and several identified that were higher in cases compared to controls. For example, urinary concentrations of benzoic acid were higher in cases compared to controls at both study visits (3.01-fold higher in cases at visit 1, p < 0.01; 3.10-fold higher in cases at visit 3, p = 0.05). However, these findings from our exploratory analysis were not robust to false-discovery-rate adjustment. In conclusion, using a high-resolution, non-targeted approach, we found specific urinary organic acids differed over pregnancy by FGR case status.

Assessing patient perceptions of cytomegalovirus infection in pregnancy.

Pregnant women impacted by cytomegalovirus (CMV) make clinical decisions despite uncertain outcomes. Intolerance of uncertainty score (IUS) is a validated measure of tendency for individuals to find unacceptable that a negative event might occur. We investigated patient perceptions of CMV infection during pregnancy and correlated IUS and knowledge with decision-making. Electronic questionnaire was sent to women from July to August 2017. The questionnaire evaluated knowledge of CMV, IUS, and responses regarding management to three clinical scenarios with escalating risk of CMV including choices for no further testing, ultrasound, amniocentesis, or abortion. For each scenario, logistic regression was used to model IUS on responses. A total of 815 women were included. The majority of participants was white (63.1%) and 42% had a postgraduate degree. Over 70% reported that they had not previously heard of CMV. In the scenario with only CMV exposure, participants with increasing IUS were more likely to choose abortion (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.01, 1.06) and no further testing (OR = 0.97; 95% CI: 0.95, 0.99). In the scenario with mild ultrasound findings in setting of CMV exposure, increasing IUS was associated with higher odds of choosing no further testing (OR = 0.97; 95% CI, 0.94, 0.99). No significant association was observed between IUS and responses in the scenario with severe ultrasound abnormalities in setting of CMV exposure. The majority of patients had no knowledge of CMV. Higher IUS was associated more intervention in low severity scenarios, but in severe scenarios, IUS was not associated with participants' choices.

Prevention of Postpartum Venous Thromboembolism.

IMPORTANCE: Postpartum venous thromboembolism (VTE) results in significant morbidity and mortality. The practicing obstetrician-gynecologist should have a plan for management and prevention. OBJECTIVE: The objective of this review is to familiarize obstetric providers with available evidence regarding postpartum VTE prevention and suggest a clinical practice guideline. EVIDENCE ACQUISITION: Published literature was retrieved through a search of PubMed and relevant review articles, original research articles, systematic reviews, and practice guidelines. RESULTS: Thromboembolic disease is one of the leading causes of maternal death in developed nations. Current evidence does not support universal postpartum VTE prophylaxis. Risk factor stratification is suggested to identify patients at high risk of VTE. Recent guidelines have recommended complex algorithms that are difficult to put into practice and have not been validated in the postpartum state. The American College of Obstetricians and Gynecologists has recommended that each institution develop a protocol to identify and treat women at high risk of postpartum VTE. CONCLUSIONS AND RELEVANCE: Obstetric providers should be familiar with available evidence and best practice regarding postpartum VTE prevention. A suggested clinical practice guideline for the prevention of postpartum VTE is provided.

Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines.

BACKGROUND: Investigators have hypothesized that omega-3 fatty acid supplementation may modulate the immune response. However, available evidence is conflicting. We performed this study to investigate the effect of prenatal eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil supplementation on maternal and fetal cytokine production. METHODS: This study is a secondary analysis of a randomized controlled trial designed to assess whether prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal depressive symptoms among women at risk. Enrolled participants received EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12-20 weeks gestation) and after supplementation (34-36 weeks gestation). Umbilical cord blood was collected at delivery. We analyzed stored plasma specimens for 16 human cytokines using multiplex immunoassays. Maternal and cord blood cytokine levels were compared among the treatment groups. Associations of serum DHA and EPA with maternal and cord blood cytokines were explored via regression analysis. RESULTS: We enrolled 126 women, of whom 118 completed the trial. Prenatal supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15, and TNFα concentrations. However, supplementation with DHA-rich fish oil had no significant effect on maternal cytokine profiles. Maternal serum DHA fraction was significantly associated with IL1α, and maternal serum DHA and EPA fractions were significantly associated with IL 10 concentrations after supplementation. Compared with placebo, supplementation with EPA- or DHA-rich fish oils had no significant effect on cord blood cytokine concentrations. CONCLUSIONS: Prenatal supplementation with EPA-rich fish oil significantly reduced levels of several inflammatory cytokines in maternal plasma, while prenatal DHA-rich fish oil had no significant effect on cytokine concentrations. Supplementation with EPA- and DHA- rich fish oil had no significant effect on umbilical cord blood cytokine concentrations. TRIAL REGISTRATION: Clinical Trial Registration: registration number NCT00711971 7/7/2008.

Who pays for cooperation in global health? A comparative analysis of WHO, the World Bank, the Global Fund to Fight HIV/AIDS, Tuberculosis and Malaria, and Gavi, the Vaccine Alliance.

In this report we assess who pays for cooperation in global health through an analysis of the financial flows of WHO, the World Bank, the Global Fund to Fight HIV/AIDS, TB and Malaria, and Gavi, the Vaccine Alliance. The past few decades have seen the consolidation of influence in the disproportionate roles the USA, UK, and the Bill & Melinda Gates Foundation have had in financing three of these four institutions. Current financing flows in all four case study institutions allow donors to finance and deliver assistance in ways that they can more closely control and monitor at every stage. We highlight three major trends in global health governance more broadly that relate to this development: towards more discretionary funding and away from core or longer-term funding; towards defined multi-stakeholder governance and away from traditional government-centred representation and decision-making; and towards narrower mandates or problem-focused vertical initiatives and away from broader systemic goals.

Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study.

The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors to immune regulatory and specialized pro-resolving mediators (SPM) of inflammation termed resolvins, maresins, and protectins. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX) and 15-LOX metabolic pathway precursors and downstream metabolites. We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA-rich fish oil supplementation increased SPM precursor 17-hydroxy docosahexaenoic acid (17-HDHA) concentrations in maternal and umbilical cord blood (P = 0.02). We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P = 0.049). Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P < 0.001, both).

Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study.

BACKGROUND: Vitamin D insufficiency may be associated with depressive symptoms in non-pregnant adults. We performed this study to evaluate whether low maternal vitamin D levels are associated with depressive symptoms in pregnancy. METHODS: This study was a secondary analysis of a randomized trial designed to assess whether prenatal omega-3 fatty acid supplementation would prevent depressive symptoms. Pregnant women from Michigan who were at risk for depression based on Edinburgh Postnatal Depression Scale Score or history of depression were enrolled. Participants completed the Beck Depression Inventory (BDI) and Mini International Neuropsychiatric Interview at 12-20 weeks, 26-28 weeks, 34-36 weeks, and 6-8 weeks postpartum. Vitamin D levels were measured at 12-20 weeks (N = 117) and 34-36 weeks (N = 112). Complete datasets were available on 105 subjects. Using regression analyses, we evaluated the relationship between vitamin D levels with BDI scores as well as with MINI diagnoses of major depressive disorder and generalized anxiety disorder. Our primary outcome measure was the association of maternal vitamin D levels with BDI scores during early and late pregnancy and postpartum. RESULTS: We found that vitamin D levels at 12-20 weeks were inversely associated with BDI scores both at 12-20 and at 34-36 weeks' gestation (P < 0.05, both). For every one unit increase in vitamin D in early pregnancy, the average decrease in the mean BDI score was .14 units. Vitamin D levels were not associated with diagnoses of major depressive disorder or generalized anxiety disorder. CONCLUSIONS: In women at risk for depression, early pregnancy low vitamin D levels are associated with higher depressive symptom scores in early and late pregnancy. Future investigations should study whether vitamin D supplementation in early pregnancy may prevent perinatal depressive symptoms. TRIAL REGISTRATION: https://clinicaltrials.gov/ REGISTRATION NUMBER: NCT00711971.

Unilateral Fetal Renal Abnormalities: Are They Really Isolated?

OBJECTIVES: Our objective was to describe the association between unilateral fetal renal abnormalities and other major anomalies that were not apparent in the second trimester. METHODS: A review of the ultrasound database identified fetuses with suspected unilateral renal agenesis, unilateral multicystic dysplastic kidney, and renal ectopia from 2005 to 2014. Neonatal records were reviewed to identify anomalies not suspected in the second trimester, and postnatal imaging studies were reviewed. Categorical data were compared by &x003C7;(2) analysis and the Fisher exact test. RESULTS: We identified 102 cases, including 36 with suspected renal agenesis, 28 with suspected multicystic dysplastic kidney, and 38 with suspected renal ectopia. There were 8 cases (7.8%) with major anomalies not suspected in the second trimester. In 5 cases (4.9%), there were no associated findings in the second trimester. There were no significant differences in the rates of unsuspected abnormalities between the 3 groups. There was a trend toward a higher rate of unsuspected anomalies in the cases with a single umbilical artery compared to those with a 3-vessel cord (28.6% vs 6.3%; P= .09). CONCLUSIONS: In fetuses with unilateral renal abnormalities, major anomalies that were not suspected in the second trimester were uncommon. However, patients should be aware of the possibility that other major anomalies could subsequently be identified, and the outcome may depend on more than postnatal renal function.

Whole-foods, plant-based diet alleviates the symptoms of osteoarthritis.

Objective. To evaluate the effectiveness of a whole-foods, plant-based diet (WFPB) to reduce symptoms of osteoarthritis. Methods. Six-week, prospective randomized open-label study of patients aged 19-70 with osteoarthritis. Participants were randomized to a WFPB (intervention) or continuing current diet (control). Outcomes were assessed by mixed models analysis of participant self-assessed weekly SF-36v2 domain t scores, weekly Patient Global Impression of Change (PGIC) scales, and mean weekly Visual Analog Scale (VAS) pain assessment. Mixed models analysis also evaluated pre-post change from baseline level for standard clinical measures: weight, BMI, body temperature, pulse, and blood pressure. Results. Forty participants were randomized. Thirty-seven of them, 18 control and 19 intervention, completed the study. The intervention group reported a significantly greater improvement than the control group in SF-36v2 energy/vitality, physical functioning, role physical, and the physical component summary scale. The differences between the intervention and control PGIC scales were statistically significant over time. Intervention group improvement in VAS weekly mean was also significantly greater than that of the control group from week 2 onward. Conclusion. Study results suggest that a whole-foods, plant-based diet significantly improves self-assessed measures of functional status among osteoarthritis patients.

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial.

OBJECTIVES: Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid (DHA), has been associated with perinatal depression, but there is evidence that supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA in treating depressive symptoms. This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression. STUDY DESIGN: We enrolled 126 pregnant women at risk for depression (Edinburgh Postnatal Depression Scale score 9-19 or a history of depression) in early pregnancy and randomly assigned them to receive EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA), or soy oil placebo. Subjects completed the Beck Depression Inventory (BDI) and Mini-International Neuropsychiatric Interview at enrollment, 26-28 weeks, 34-36 weeks, and at 6-8 weeks' postpartum. Serum fatty acids were analyzed at entry and at 34-36 weeks' gestation. RESULTS: One hundred eighteen women completed the trial. There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation. The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively. Serum DHA- concentrations at 34-36 weeks were inversely related to BDI scores in late pregnancy. CONCLUSION: EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum.

Developmental programming for allergy: a secondary analysis of the Mothers, Omega-3, and Mental Health Study.

OBJECTIVE: Fetal dysregulation of T helper cell pathways may predispose to allergy, as high cord blood T helper 2/T helper 1 ratios have been shown to precede development of allergic diseases. We aimed to determine whether prenatal eicosapentaenoic acid and docosahexaenoic acid supplementation reduces T helper 2 to T helper 1-associated chemokine ratios. We also explored the effect of mode of delivery on T helper 2/T helper 1 ratios. STUDY DESIGN: We conducted a secondary analysis of a randomized placebo controlled trial initially performed to assess the effects of docosahexaenoic acid or eicosapentaenoic acid supplementation on pregnancy-related depressive symptoms among 126 participants. Cord plasma specimens from 98 newborns were assayed for chemokines associated with T helper 2 (thymus and activation-regulated chemokine [CCL17], macrophage-derived chemokine [CCL22], eotaxin [CCL 11]) and T helper 1 (interferon-inducible protein-10 [CXCL 10]) by enzyme-linked immunosorbent assay and Multiplex immunoassays. Ratios of log-transformed chemokines macrophage-derived chemokine/interferon-inducible protein-10 and thymus and activation-regulated chemokine/interferon-inducible protein-10 were compared between groups by analyses of variance. Multiple linear regression was performed to examine associations between treatments and chemokine ratios, adjusting for covariates. RESULTS: After adjusting for gestational age at delivery, birthweight, and mode of delivery, both omega-3 supplementation groups were associated with lower macrophage-derived chemokine/interferon-inducible protein-10 ratios than placebo (eicosapentaenoic acid: coefficient -1.8; 95% confidence interval [CI], -3.6 to -0.05; P = .04; docosahexaenoic acid: -2.0; 95% CI, -3.9 to -0.07; P = .04). Similar associations were found for thymus and activation-regulated chemokine/interferon-inducible protein-10 (eicosapentaenoic acid: -1.5; 95% CI, -3.0 to 0.06; P = .06; docosahexaenoic acid -2.2; 95% CI, -3.8 to -0.52; P = .01). Cesarean delivery was associated with higher macrophage-derived chemokine/interferon-inducible protein-10 (1.6; 95% CI, 0.01-3.3; P = .049) and thymus and activation-regulated chemokine/interferon-inducible protein-10 (1.5; 95% CI, 0.1-2.9; P = .042) ratios than vaginal delivery. CONCLUSION: Prenatal supplementation with eicosapentaenoic acid and docosahexaenoic acid resulted in decreased cord blood T helper 2/T helper 1 chemokine ratios. Cesarean delivery was associated with a pronounced T helper 2 deviation at birth.

Inching toward incrementalism: federalism, devolution, and health policy in the United States and the United Kingdom.

In the United States, the recently enacted Patient Protection and Affordable Care Act of 2010 envisions a significant increase in federal oversight over the nation's health care system. At the same time, however, the legislation requires the states to play key roles in every aspect of the reform agenda (such as expanding Medicaid programs, creating insurance exchanges, and working with providers on delivery system reforms). The complicated intergovernmental partnerships that govern the nation's fragmented and decentralized system are likely to continue, albeit with greater federal oversight and control. But what about intergovernmental relations in the United Kingdom? What impact did the formal devolution of power in 1999 to Scotland, Wales, and Northern Ireland have on health policy in those nations, and in the United Kingdom more generally? Has devolution begun a political process in which health policy in the United Kingdom will, over time, become increasingly decentralized and fragmented, or will this "state of unions" retain its long-standing reputation as perhaps the most centralized of the European nations? In this article, we explore the federalist and intergovernmental implications of recent reforms in the United States and the United Kingdom, and we put forward the argument that political fragmentation (long-standing in the United States and just emerging in the United Kingdom) produces new intergovernmental partnerships that, in turn, produce incremental growth in overall government involvement in the health care arena. This is the impact of what can be called catalytic federalism.