MiRNAs related in signaling pathways of women's reproductive diseases: an overview.

BACKGROUND: One of the main health issues that can affect women's health is reproductive diseases, such as polycystic ovary syndrome (PCOS), endometriosis (EMs), uterine leiomyomas (ULs), and ovarian cancer (OC). Although these diseases are very common, we do not have a complete understanding of their underlying cellular and molecular mechanisms. It is important to mention that the majority of patients are diagnosed with these diseases at later stages because of the absence of early diagnostic techniques and dependable molecular indicators. Hence, it is crucial to discover novel and non-invasive biomarkers that have prognostic, diagnostic and therapeutic capabilities. MiRNAs, also known as microRNAs, are small non-coding RNAs that play a crucial role in regulating gene expression at the post-transcriptional level. They are short in length, typically consisting of around 22 nucleotides, and are highly conserved across species. Numerous studies have shown that miRNAs are expressed differently in various diseases and can act as either oncogenes or tumor suppressors. METHODS: The author conducted a comprehensive review of all the pertinent papers available in web of science, PubMed, Google Scholar, and Scopus databases. RESULTS: We achieved three goals: providing readers with better information, enhancing search results, and making peer review easier. CONCLUSIONS: This review focuses on the investigation of miRNAs and their involvement in various reproductive disorders in women, including their molecular targets. Additionally, it explores the role of miRNAs in the development and progression of these disorders.

Neurological outcome in long-chain hydroxy fatty acid oxidation disorders.

OBJECTIVE: This study aims to elucidate the long-term benefit of newborn screening (NBS) for individuals with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide. METHODS: German national multicenter study of individuals with confirmed LCHAD/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long-term clinical outcomes. RESULTS: Sixty-seven individuals with LCHAD/MTP deficiency were included in the study, thereof 54 identified by NBS. All screened individuals with LCHAD deficiency survived, but four with MTP deficiency (14.8%) died during the study period. Despite NBS and early treatment neonatal decompensations (28%), symptomatic disease course (94%), later metabolic decompensations (80%), cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and/or neuropathy (22%) occurred. Hospitalization rates were high (up to a mean of 2.4 times/year). Disease courses in screened individuals with LCHAD and MTP deficiency were similar except for neuropathy, occurring earlier in individuals with MTP deficiency (median 3.9 vs. 11.4 years; p = 0.0447). Achievement of dietary goals decreased with age, from 75% in the first year of life to 12% at age 10, and consensus group recommendations on dietary management were often not achieved. INTERPRETATION: While NBS and early treatment result in improved (neonatal) survival, they cannot reliably prevent long-term morbidity in screened individuals with LCHAD/MTP deficiency, highlighting the urgent need of better therapeutic strategies and the development of disease course-altering treatment.

A systematic scoping review of medicine availability and affordability in Africa.

BACKGROUND: The most recent World Medicines Situation Report published in 2011 found substantial medicine availability and affordability challenges across WHO regions, including Africa. Since publication of the 2011 report, medicine availability and affordability has risen on the international agenda and was included in the Sustainable Development Goals as Target 3.8. While numerous medicine availability and affordability studies have been conducted in Africa since the last World Medicines Situation Report, there has not been a systematic analysis of the methods used in these studies, measures of medicine availability and affordability, categories of medicines studied, or geographic distribution. Filling this knowledge gap can help inform future medicine availability and affordability studies, design systems to monitor progress toward Sustainable Development Goal Target 3.8 in Africa and beyond, and inform policy and program decisions to improve medicine availability and affordability. METHODS: We conducted a systematic scoping review of studies assessing medicine availability or affordability conducted in the WHO Africa region published from 2009-2021. RESULTS: Two hundred forty one articles met our eligibility criteria. 88% of the articles (213/241) reported descriptive studies, while 12% (28/241) reported interventional studies. Of the 198 studies measuring medicine availability, the most commonly used measure of medicine availability was whether a medicine was in stock on the date of a survey (124/198, 63%). We also identified multiple other availability methods and measures, including retrospective stock record reviews and self-reported medicine availability surveys. Of the 59 articles that included affordability measures, 32 (54%) compared the price of the medicine to the daily wage of the lowest paid government worker. Other affordability measures were patient self-reported affordability, capacity to pay measures, and comparing medicines prices with a population-level income standard (such as minimum wage, poverty line, or per capita income). The most commonly studied medicines were antiparasitic and anti-bacterial medicines. We did not identify studies in 22 out of 48 (46%) countries in the WHO Africa Region and more than half of the studies identified were conducted in Ethiopia, Kenya, Tanzania, and/or Uganda. CONCLUSION: Our results revealed a wide range of medicine availability and affordability assessment methodologies and measures, including cross-sectional facility surveys, population surveys, and retrospective data analyses. Our review also indicated a need for greater focus on medicines for certain non-communicable diseases, greater geographic diversity of studies, and the need for more intervention studies to identify approaches to improve access to medicines in the region.

Efecto de la igualdad de género en la mortalidad por enfermedades no transmisibles / Effect of gender equality on mortality from non-communicable diseases

Objetivo: Relacionar las desigualdades de género con la probabilidad de mortalidad por enfermedades no transmisibles (ENT) en los países del mundo desde 2000 hasta 2019, para detectar el progreso de la Meta 3.4 del Objetivo de Desarrollo Sostenible 3, de reducir en un tercio las ENT entre los 30 y los 70 años para 2030. Método: Estudio ecológico exploratorio sobre la asociación entre la probabilidad de fallecimiento por ENT y el índice de desigualdad de género (IDG) en el mundo en 2000, 2015 y 2019. Estimación mediante regresión logística del riesgo de no estar en proceso de cumplir la Meta 3.4 en 2019 según desigualdad de género. Resultados: La probabilidad media de fallecimiento por ENT descendió progresivamente en todos los países. Medianas 2000/2015/2019: mujeres 20,20/16,58/16; hombres 26,59/22,45/21,88; total 23,14/20,10/19,23. El riesgo de no estar logrando la meta en 2019 es mayor en los países con menor IDG que en los países con mayor IDG (OR: 2,13; IC95%: 1,14-3,99; p = 0,018), siendo el riesgo mayor en las mujeres (OR: 2,64; IC95%: 1,40-5,06; p = 0,003) que en los hombres (OR: 2,12; IC95%: 1,44-3,98; p = 0,017). Conclusiones: El riesgo de fallecimiento por ENT descendió en ambos sexos en todos los países del mundo desde el año 2000, pero el progreso es lento y, a mayor desigualdad de género en los países, mayor riesgo de no estar logrando el descenso necesitado para cumplir con el acuerdo de reducir un tercio la mortalidad por ENT en 2030, siendo este riesgo mayor en las mujeres que en los hombres.(AU)

Objective: Relate gender inequalities with the probability of mortality from non-communicable diseases (NCD), in the countries of the world from the year 2000 to 2019, to detect the progress of Target 3.4 of the Sustainable Development Goal 3, to reduce NCD by one third between the ages of 30 and 70 by 2030. Method: Exploratory ecological study on the association between the probability of death from NCD and the gender inequality index (GII) at the global level in 2000, 2015 and 2019. Logistic regression estimation of the risk of not being on track to meet Target 3.4 by 2019 by gender inequality. Results: The mean probability of death from NCD decreased progressively in all countries. Median 2000/2015/2019: women 20.20/16.58/16; men 26.59/22.45/21.88; total 23.14/20.10/19.23. The risk of not achieving the goal in 2019 is greater in countries with a lower GII than in countries with a higher GII (OR: 2.13; 95% CI: 1.14–3.99; p = 0.018), being the higher risk in women (OR: 2.64; 95% CI: 1.40–5.06; p = 0.003) than in men (OR: 2.12; 95% CI: 1.44–3.98; p = 0.017). Conclusions: The risk of deaths from NCD has decreased in both sexes in all countries of the world since the year 2000; but progress is slow, so the greater gender inequality in the countries, there is a greater risk of not achieving the reduction needed to comply with the agreement to reduce mortality from NCD by one third in 2030; this risk being greater in women than in men.(AU)

INDIVIDUAL ARTICLE: Management of Prurigo Nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic disease characterized by intense pruritus and nodular lesions associated with reduced quality of life. Until recently, no US Food and Drug Administration (FDA)-approved therapies have been available for the management of PN. Treatment regimens have been highly variable and clinical management guidelines are lacking overall; formal treatment guidelines do not exist within the US. In 2022, dupilumab became the first FDA-approved medication for PN. Multiple novel agents that target the neuroimmune underpinnings of the disease are currently in development and show promise for this challenging disorder. OBJECTIVE: To review current treatments and emerging therapies for effective management of patients with PN. METHODS: We reviewed publications on PN management identified from PubMed, Embase, Web of Science, and the Cochrane Library. We also included publicly available data on clinical trials for PN therapies reported on the US National Library of Medicine ClinicalTrials.gov, the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) Database, and the European Clinical Trials (EudraCT) Database. RESULTS: The recommended management of PN begins with an assessment of disease severity, including disease burden and pruritus intensity, and evaluation of comorbid medical disorders. Treatment goals include resolution of itch, improvement in nodules or cutaneous lesions, and improvement in quality of life. Therapies should be selected based on a patient’s clinical presentation and comorbidities. Treatment should simultaneously address the neural and immunologic components of PN. Combination therapy, particularly with conventional agents, may be beneficial. LIMITATIONS: Data on most conventional PN treatments are limited to anecdotal reports, small clinical trials, or expert consensus recommendations. No head-to-head comparative trials have evaluated the relative efficacy of conventional and/or emerging agents, or combination therapy. CONCLUSION: An effective treatment approach for patients with PN should reduce pruritus, allow nodular lesions to heal, and improve individual quality of life. The treatment landscape for PN is rapidly evolving with one FDA-approved agent and several new promising therapies on the horizon. J Drugs Dermatol. 2023;22:12(Suppl 2):s15-22.

Adapting to a global pandemic: a qualitative assessment of programmatic responses to COVID-19 in the multi-country Women's Integrated Sexual Health (WISH) programme.

The COVID-19 pandemic caused significant disruption to sexual and reproductive health and rights (SRHR) globally but there is little published evidence on the COVID-19 response of SRHR programmes, or lessons learned through their adaptations. To document the COVID-19 response of a global SRHR programme (the Women's Integrated Sexual Health programme), in-depth interviews were conducted between April and July 2021 with 22 key informants from implementing partners in Sierra Leone, Ethiopia and central or regional offices, the UK Foreign, Commonwealth and Development Office and the third-party monitoring partner. Framework analysis methods were used. Several rapid COVID-19 adaptations were identified: the development of crisis management and communication teams; increased partnership and engagement with government; reduced contact and risk in service delivery; reformulated community mobilisation; flexible performance management and remote methods of quality assurance; and sharing of learnings alongside the development of new guidance and tools. Throughout the pandemic, the programme was able to continue high-quality service delivery, though equity goals proved more difficult to reach. Challenges included the continually changing environment, competing pressures on governments, burdensome reporting, and staff burnout. The pandemic response was facilitated by prior experience of health emergencies, strong government relationships, a supportive workforce and some pre-existing approaches, tools, and systems. This study has identified important lessons that can inform programming in future crises, including the need for immediate recognition of SRHR as essential, sustained support for staff, use of multiple mechanisms to reach marginalised groups, adequate funding for equity goals, and a better balance between the burden of reporting and accountability needs.

Health and well-being key performance indicators in corporate sustainability disclosure. A review of sustainability reports from a sample of major European companies.

BACKGROUND AND AIM: Health and Well-Being (HWB) measurement represents a key issue for companies in all sectors and a core element of social sustainability, according to the Sustainable Development Goals (SDGs). Despite its importance for companies and in sustainability reporting, the topic has not been investigated yet from a cross-sectoral perspective. Therefore, this research aims to assess if health and well-being are disclosed in sustainability reports of the largest European companies. METHODS: The disclosure of Key Performance Indicators (KPIs) has been investigated and compared according to the main international frameworks of sustainability. The research focused on sustainability reporting from a sample of the 30 largest companies in three methodological steps. First, the inclusion of HWB issues has been analyzed, identifying references to the SDGs and ISO 45001 within the documents. A second level of analysis considered the adoption of the Global Reporting Initiatives (GRI) Standards, with particular attention to Health metrics (GRI:403). The third level of analysis aimed at researching health and well-being performances, linked to specific KPIs from two selected case studies. RESULTS: The review highlighted that all 30 companies generally refer to SDG 3 and SDG 8 in their sustainability reporting while 83%(n=25) of them also apply either Occupational Health and Safety ISO 45001 or Health metrics in GRI Standards; 22 (73%) companies adopted both GRI as the sustainability reporting standard and disclosed the adoption of ISO 45001 management system. Only in two cases, an additional structured framework for HWB is reported highlighting the need for more comprehensive KPIs, especially for employee's well-being. CONCLUSIONS: The study highlighted that health indicators disclosure is generally limited to GRI Standards disclosure. To achieve greater transparency in sustainability reporting, there is a need to further investigate the issue. (www.actabiomedica.it).

Consensus recommendations on holistic care in hereditary ATTR amyloidosis: an international Delphi survey of patient advocates and multidisciplinary healthcare professionals.

BACKGROUND: Hereditary transthyretin-mediated amyloidosis is a rare, progressive and potentially life-limiting multisystem disease, affecting every aspect of a patient's life. OBJECTIVES: This online international Delphi survey aimed to evolve clinical-patient-led practical guidance, to inspire and encourage a holistic approach to care that is managed in specialist settings by multidisciplinary teams and supported by allied healthcare professionals (HCPs) and patient advocacy groups (PAGs). DESIGN: A 14-member joint patient advocate-HCP primary panel was convened including representation from PAGs and key clinical specialties (neurology, cardiology, internal medicine, physiotherapy, clinical psychology, dietetics and specialist nursing). Guidance evolved on the care provision needed to support seven core goals: early diagnosis and treatment; disease monitoring and organisation of care; maintenance of physical and mental health; family-centred care and caregiver support; patient-doctor dialogue; access to social support and social networking. PARTICIPANTS: From June to October 2022, 252 HCPs and 51 PAG representatives from 27 countries were invited to participate in a Delphi survey. Of the 122 respondents who answered at least one survey question, most were HCPs (100, 82%) from specialist centres; the remainder were PAG representatives (22, 18%). MAIN OUTCOME MEASURE: Both level of agreement and feasibility in practice of each recommendation was tested by two anonymised online Delphi voting rounds. RESULTS: Based on an a priori threshold for consensus of ≥75% agreement, the clinical-patient community endorsed all but one recommendation. However, only 17/49 (35%) recommendations were identified by most HCPs as a core part of routine care; the remainder (32/49 (65%)) were identified as part of core care by <50% of HCPs respondents, or as largely achievable by 30%-45% of HCPs. By comparison, PAGs recorded lower implementation levels. CONCLUSIONS: Further consideration is needed on how to evolve multidisciplinary services (supported by allied HCPs and PAGs) to address the complex needs of those affected by this disease.

Reframing human trafficking awareness campaigns in the United States: goals, audience, and content.

Introduction: Human trafficking (HT) awareness campaigns can educate the public and specific professional figures about this crime and ways to prevent it. However, there currently remains a gap in terms of how to best frame such campaigns without stigmatizing groups of individuals or portraying victims in unrealistic ways. Methods: We conducted four focus groups with 22 experts in HT to explore their perspectives and opinions on current challenges in the framing of HT awareness campaigns in the United States. Focus groups were conducted via Zoom and transcribed verbatim. Two independent reviewers analyzed the transcripts to identify themes using an inductive approach. The results of the focus groups analysis were used to structure the guiding questions of a brainstorming technique named Nominal Group Technique (NGT). Fifteen of 22 experts that participated in the focus groups joined the in-person NGT with the intent of generating ideas and achieving consensus on target audiences, goals, and content of human trafficking awareness campaigns. At the end of the NGT participants ranked priority for actions in the development of HT awareness efforts in the United States. Results: During the NGT the experts provided a number of recommendations to improve HT awareness and to empower victims to reach for help. They pointed to the need for: awareness efforts that describe HT on a spectrum of human abuse and exploitation; training for professional figures about trauma-informed care and communication; and efforts that empower trafficked victims to seek support. They also pointed to the need to develop awareness efforts tailored to local needs in close collaborations with the community-based organizations that can champion their dissemination and be the primary point of access for victims seeking help.

Comparing the reasons for contraceptive discontinuation between parenting adolescents and young women in sub-Saharan Africa: a multilevel analysis.

BACKGROUND: Adolescent sexual and reproductive health remains a major public health and development issue of global importance. Given that adolescents and young people are heterogenous groups in terms of many characteristics, this study expands the literature by comparing the reasons for contraceptive discontinuation between parenting adolescents (aged 15-19) and parenting young women (aged 20-24) in sub-Saharan Africa (SSA). METHODS: Data for the study came from Demographic and Health Surveys of 22 SSA countries. The outcome variable was reasons for discontinuation. We performed multilevel binary logistic regression on analytic samples comprising 1485 parenting adolescents and 10,287 parenting young women across the selected SSA countries. RESULTS: Findings show that the proportion of respondents who used modern contraceptives was lower among parenting adolescents (35%) relative to their 20-24-year-old counterparts (43%). Higher percentages of parenting adolescents than young women discontinued contraceptives because of reasons such as pregnancy or method failure (i.e., 9.9% and 8.17% accordingly), husband disapproval, access or availability issues, wanting more effective methods, and inconvenience in using methods. The multilevel analysis further highlighted disparities between parenting adolescents and parenting young women who discontinued contraceptives. For instance, parenting young women had 30% lower odds of discontinuing contraceptives due to pregnancy or method failure than parenting adolescents. CONCLUSION: The study established disparities in the reasons for contraceptive discontinuation between parenting adolescents and parenting young women, with adolescents demonstrating greater vulnerabilities and higher risks. Considerable attention must be given to parenting adolescents in the efforts to achieve equity goals such as the Sustainable Development Goals and universal health coverage in SSA.

Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study.

BACKGROUND: Orforglipron, an oral, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist, is in development for type 2 diabetes and obesity. We assessed the efficacy and safety of orforglipron versus placebo or dulaglutide in participants with type 2 diabetes. METHODS: In this 26-week, phase 2, double-blind, randomised, multicentre study, participants were recruited from 45 centres (private clinics, hospitals, and research centers) in the USA, Hungary, Poland, and Slovakia. Adult participants aged 18 years or older with type 2 diabetes treated with diet and exercise, with or without metformin, and with a glycated haemoglobin (HbA1c) of 7·0-10·5%, and stable BMI of 23 kg/m2 or more, were randomly assigned (5:5:5:5:5:3:3:3:3) via an interactive web-response system to placebo, dulaglutide 1·5 mg once per week, or orforglipron 3 mg, 12 mg, 24 mg, 36 mg (group 1), 36 mg (group 2), 45 mg (group 1), or 45 mg (group 2) once per day with no food or water restrictions. Two different dose escalation regimens were evaluated for each of the 36 mg and 45 mg cohorts. Participants were masked to the study drug, dulaglutide, and placebo. The primary efficacy outcome The primary efficacy outcome was mean change in HbA1c from baseline with orforglipron versus placebo at week 26. Efficacy was analysed in all randomly assigned participants who received at least one dose of study drug and excluded data after the permanent discontinuation of study drug or initiation of rescue medication. Safety was analysed in all participants who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT05048719) and is completed. FINDINGS: Between Sept 15, 2021, and Sept 30, 2022, 569 participants were screened and 383 were enrolled and randomly assigned to a group. 352 (92%) completed the study and 303 (79%) completed 26 weeks of treatment. At baseline, the mean age was 58·9 years, HbA1c was 8·1%, BMI was 35·2 kg/m2, 226 (59%) were men, and 157 (41%) were women. At week 26, mean change in HbA1c with orforglipron was up to -2·10% (-1·67% placebo adjusted), versus -0·43% with placebo and -1·10% with dulaglutide. HbA1c reduction was statistically superior with orforglipron versus placebo (estimated treatment difference -0·8% to -1·7%). Change in mean bodyweight at week 26 was up to -10·1 kg (95% CI -11·5 to -8·7; 7·9 kg placebo adjusted [-9·9 to -5·9]) with orforglipron versus -2·2 kg (-3·6 to -0·7) for placebo and -3·9 kg (-5·3 to -2·4) for dulaglutide. The incidence of treatment-emergent adverse events ranged from 61·8% to 88·9% in orforglipron-treated participants, compared with 61·8% with placebo and 56·0% with dulaglutide. The majority were gastrointestinal events (44·1% to 70·4% with orforglipron, 18·2% with placebo, and 34·0% with dulaglutide) of mild to moderate severity. Three participants receiving orforglipron and one participant receiving dulaglutide had clinically significant (<54 mg/dL [<3 mmol/L]) hypoglycaemia and no participants had severe hypoglycaemia. One death occurred in the placebo group and was not related to study treatment. INTERPRETATION: In this phase 2 trial the novel, oral, non-peptide GLP-1 receptor agonist orforglipron at doses of 12 mg or greater showed significant reductions in HbA1c and bodyweight compared with placebo or dulaglutide. The adverse event profile was similar to other GLP-1 receptor agonists in similar stage of development. Orforglipron might provide an alternative to injectable GLP-1 receptor agonists and oral semaglutide, with the prospect of less burdensome administration to achieve treatment goals in people with type 2 diabetes. FUNDING: Eli Lilly and Company.

Factors influencing the free maternal health care policy under the national health insurance scheme's provision for skilled delivery services in Ghana: a narrative literature review.

BACKGROUND: Skilled Birth Attendance (SBA) is important in achieving the Sustainable Development Goals (SDGs) targets 3.1, 3.2 and 3.3.1. Ghana has made steady progress in SBA, yet, unsupervised deliveries still occur. The introduction of the Free Maternal Health Care Policy under the National Health Insurance Scheme (FMHCP under the NHIS) has improved the uptake of SBA but with some implementation challenges. This narrative review sought to explore the factors influencing the FMHCP under the NHIS provision for skilled delivery services in Ghana. METHODS: Electronic searches were conducted of databases including PubMed, Popline, Science direct, BioMed Central, Scopus and Google scholar for peer reviewed articles as well as grey articles from other relevant sources, published between 2003 and 2021 on factors influencing FMHCP/NHIS provision for skilled delivery services in Ghana. Keywords used in the literature search were in various combinations for the different databases. The articles were screened to determine the inclusion and exclusion criteria and quality was assessed using a published critical appraisal checklist. A total of 516 articles were retrieved for initial screening based on their titles, of which 61 of them, were further screened by reading their abstracts and full text. Of this number, 22 peer-reviewed and 4 grey articles were selected for the final review based on their relevance. RESULTS: The study revealed that the FMHCP under the NHIS does not cover the full costs associated with skilled delivery and low socioeconomic status of households affects SBA. Also, funding and sustainability, hinders the quality-of-service delivery offered by the policy. CONCLUSION: For Ghana to achieve the SDGs above and further improve SBA, the cost associated with skilled delivery should be fully covered by the NHIS. Also, the government and the key stakeholders involved in the policy implementation, must put in place measures that will enhance the operation and the financial sustainability of the policy.

Disability and intimate partner violence in fragile states: A multi-country analysis.

The 2030 Sustainable Development Goals call for both the elimination of violence against women and girls and disability-disaggregated data. However, few population-based, multi-country studies have examined how disability impacts intimate partner violence (IPV) in fragile settings. Demographic and Health Survey data from five countries (Pakistan, Timor-Leste, Mali, Uganda, and Haiti) were pooled and analyzed to assess the relationship between disability and IPV (N = 22,984). Pooled analysis revealed an overall disability prevalence of 18.45%, with 42.35% lifetime IPV (physical, sexual and/or emotional), and 31.43% past-year IPV. Women with disabilities reported higher levels of past-year and lifetime IPV compared to those without disabilities (AOR 1.18; 95% CI 1.07, 1.30; AOR 1.31; 95% CI 1.19, 1.44, respectively). Women and girls with disabilities may be disproportionately impacted by IPV in fragile settings. More global attention is needed to address IPV and disability in these settings.

The Minderoo-Monaco Commission on Plastics and Human Health.

Background: Plastics have conveyed great benefits to humanity and made possible some of the most significant advances of modern civilization in fields as diverse as medicine, electronics, aerospace, construction, food packaging, and sports. It is now clear, however, that plastics are also responsible for significant harms to human health, the economy, and the earth's environment. These harms occur at every stage of the plastic life cycle, from extraction of the coal, oil, and gas that are its main feedstocks through to ultimate disposal into the environment. The extent of these harms not been systematically assessed, their magnitude not fully quantified, and their economic costs not comprehensively counted. Goals: The goals of this Minderoo-Monaco Commission on Plastics and Human Health are to comprehensively examine plastics' impacts across their life cycle on: (1) human health and well-being; (2) the global environment, especially the ocean; (3) the economy; and (4) vulnerable populations-the poor, minorities, and the world's children. On the basis of this examination, the Commission offers science-based recommendations designed to support development of a Global Plastics Treaty, protect human health, and save lives. Report Structure: This Commission report contains seven Sections. Following an Introduction, Section 2 presents a narrative review of the processes involved in plastic production, use, and disposal and notes the hazards to human health and the environment associated with each of these stages. Section 3 describes plastics' impacts on the ocean and notes the potential for plastic in the ocean to enter the marine food web and result in human exposure. Section 4 details plastics' impacts on human health. Section 5 presents a first-order estimate of plastics' health-related economic costs. Section 6 examines the intersection between plastic, social inequity, and environmental injustice. Section 7 presents the Commission's findings and recommendations. Plastics: Plastics are complex, highly heterogeneous, synthetic chemical materials. Over 98% of plastics are produced from fossil carbon- coal, oil and gas. Plastics are comprised of a carbon-based polymer backbone and thousands of additional chemicals that are incorporated into polymers to convey specific properties such as color, flexibility, stability, water repellence, flame retardation, and ultraviolet resistance. Many of these added chemicals are highly toxic. They include carcinogens, neurotoxicants and endocrine disruptors such as phthalates, bisphenols, per- and poly-fluoroalkyl substances (PFAS), brominated flame retardants, and organophosphate flame retardants. They are integral components of plastic and are responsible for many of plastics' harms to human health and the environment.Global plastic production has increased almost exponentially since World War II, and in this time more than 8,300 megatons (Mt) of plastic have been manufactured. Annual production volume has grown from under 2 Mt in 1950 to 460 Mt in 2019, a 230-fold increase, and is on track to triple by 2060. More than half of all plastic ever made has been produced since 2002. Single-use plastics account for 35-40% of current plastic production and represent the most rapidly growing segment of plastic manufacture.Explosive recent growth in plastics production reflects a deliberate pivot by the integrated multinational fossil-carbon corporations that produce coal, oil and gas and that also manufacture plastics. These corporations are reducing their production of fossil fuels and increasing plastics manufacture. The two principal factors responsible for this pivot are decreasing global demand for carbon-based fuels due to increases in 'green' energy, and massive expansion of oil and gas production due to fracking.Plastic manufacture is energy-intensive and contributes significantly to climate change. At present, plastic production is responsible for an estimated 3.7% of global greenhouse gas emissions, more than the contribution of Brazil. This fraction is projected to increase to 4.5% by 2060 if current trends continue unchecked. Plastic Life Cycle: The plastic life cycle has three phases: production, use, and disposal. In production, carbon feedstocks-coal, gas, and oil-are transformed through energy-intensive, catalytic processes into a vast array of products. Plastic use occurs in every aspect of modern life and results in widespread human exposure to the chemicals contained in plastic. Single-use plastics constitute the largest portion of current use, followed by synthetic fibers and construction.Plastic disposal is highly inefficient, with recovery and recycling rates below 10% globally. The result is that an estimated 22 Mt of plastic waste enters the environment each year, much of it single-use plastic and are added to the more than 6 gigatons of plastic waste that have accumulated since 1950. Strategies for disposal of plastic waste include controlled and uncontrolled landfilling, open burning, thermal conversion, and export. Vast quantities of plastic waste are exported each year from high-income to low-income countries, where it accumulates in landfills, pollutes air and water, degrades vital ecosystems, befouls beaches and estuaries, and harms human health-environmental injustice on a global scale. Plastic-laden e-waste is particularly problematic. Environmental Findings: Plastics and plastic-associated chemicals are responsible for widespread pollution. They contaminate aquatic (marine and freshwater), terrestrial, and atmospheric environments globally. The ocean is the ultimate destination for much plastic, and plastics are found throughout the ocean, including coastal regions, the sea surface, the deep sea, and polar sea ice. Many plastics appear to resist breakdown in the ocean and could persist in the global environment for decades. Macro- and micro-plastic particles have been identified in hundreds of marine species in all major taxa, including species consumed by humans. Trophic transfer of microplastic particles and the chemicals within them has been demonstrated. Although microplastic particles themselves (>10 µm) appear not to undergo biomagnification, hydrophobic plastic-associated chemicals bioaccumulate in marine animals and biomagnify in marine food webs. The amounts and fates of smaller microplastic and nanoplastic particles (MNPs <10 µm) in aquatic environments are poorly understood, but the potential for harm is worrying given their mobility in biological systems. Adverse environmental impacts of plastic pollution occur at multiple levels from molecular and biochemical to population and ecosystem. MNP contamination of seafood results in direct, though not well quantified, human exposure to plastics and plastic-associated chemicals. Marine plastic pollution endangers the ocean ecosystems upon which all humanity depends for food, oxygen, livelihood, and well-being. Human Health Findings: Coal miners, oil workers and gas field workers who extract fossil carbon feedstocks for plastic production suffer increased mortality from traumatic injury, coal workers' pneumoconiosis, silicosis, cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer. Plastic production workers are at increased risk of leukemia, lymphoma, hepatic angiosarcoma, brain cancer, breast cancer, mesothelioma, neurotoxic injury, and decreased fertility. Workers producing plastic textiles die of bladder cancer, lung cancer, mesothelioma, and interstitial lung disease at increased rates. Plastic recycling workers have increased rates of cardiovascular disease, toxic metal poisoning, neuropathy, and lung cancer. Residents of "fenceline" communities adjacent to plastic production and waste disposal sites experience increased risks of premature birth, low birth weight, asthma, childhood leukemia, cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer.During use and also in disposal, plastics release toxic chemicals including additives and residual monomers into the environment and into people. National biomonitoring surveys in the USA document population-wide exposures to these chemicals. Plastic additives disrupt endocrine function and increase risk for premature births, neurodevelopmental disorders, male reproductive birth defects, infertility, obesity, cardiovascular disease, renal disease, and cancers. Chemical-laden MNPs formed through the environmental degradation of plastic waste can enter living organisms, including humans. Emerging, albeit still incomplete evidence indicates that MNPs may cause toxicity due to their physical and toxicological effects as well as by acting as vectors that transport toxic chemicals and bacterial pathogens into tissues and cells.Infants in the womb and young children are two populations at particularly high risk of plastic-related health effects. Because of the exquisite sensitivity of early development to hazardous chemicals and children's unique patterns of exposure, plastic-associated exposures are linked to increased risks of prematurity, stillbirth, low birth weight, birth defects of the reproductive organs, neurodevelopmental impairment, impaired lung growth, and childhood cancer. Early-life exposures to plastic-associated chemicals also increase the risk of multiple non-communicable diseases later in life. Economic Findings: Plastic's harms to human health result in significant economic costs. We estimate that in 2015 the health-related costs of plastic production exceeded $250 billion (2015 Int$) globally, and that in the USA alone the health costs of disease and disability caused by the plastic-associated chemicals PBDE, BPA and DEHP exceeded $920 billion (2015 Int$). Plastic production results in greenhouse gas (GHG) emissions equivalent to 1.96 gigatons of carbon dioxide (CO2e) annually. Using the US Environmental Protection Agency's (EPA) social cost of carbonmetric, we estimate the annual costs of these GHG emissions to be $341 billion (2015 Int$).These costs, large as they are, almost certainly underestimate the full economic losses resulting from plastics' negative impacts on human health and the global environment. All of plastics' economic costs-and also its social costs-are externalized by the petrochemical and plastic manufacturing industry and are borne by citizens, taxpayers, and governments in countries around the world without compensation. Social Justice Findings: The adverse effects of plastics and plastic pollution on human health, the economy and the environment are not evenly distributed. They disproportionately affect poor, disempowered, and marginalized populations such as workers, racial and ethnic minorities, "fenceline" communities, Indigenous groups, women, and children, all of whom had little to do with creating the current plastics crisis and lack the political influence or the resources to address it. Plastics' harmful impacts across its life cycle are most keenly felt in the Global South, in small island states, and in disenfranchised areas in the Global North. Social and environmental justice (SEJ) principles require reversal of these inequitable burdens to ensure that no group bears a disproportionate share of plastics' negative impacts and that those who benefit economically from plastic bear their fair share of its currently externalized costs. Conclusions: It is now clear that current patterns of plastic production, use, and disposal are not sustainable and are responsible for significant harms to human health, the environment, and the economy as well as for deep societal injustices.The main driver of these worsening harms is an almost exponential and still accelerating increase in global plastic production. Plastics' harms are further magnified by low rates of recovery and recycling and by the long persistence of plastic waste in the environment.The thousands of chemicals in plastics-monomers, additives, processing agents, and non-intentionally added substances-include amongst their number known human carcinogens, endocrine disruptors, neurotoxicants, and persistent organic pollutants. These chemicals are responsible for many of plastics' known harms to human and planetary health. The chemicals leach out of plastics, enter the environment, cause pollution, and result in human exposure and disease. All efforts to reduce plastics' hazards must address the hazards of plastic-associated chemicals. Recommendations: To protect human and planetary health, especially the health of vulnerable and at-risk populations, and put the world on track to end plastic pollution by 2040, this Commission supports urgent adoption by the world's nations of a strong and comprehensive Global Plastics Treaty in accord with the mandate set forth in the March 2022 resolution of the United Nations Environment Assembly (UNEA).International measures such as a Global Plastics Treaty are needed to curb plastic production and pollution, because the harms to human health and the environment caused by plastics, plastic-associated chemicals and plastic waste transcend national boundaries, are planetary in their scale, and have disproportionate impacts on the health and well-being of people in the world's poorest nations. Effective implementation of the Global Plastics Treaty will require that international action be coordinated and complemented by interventions at the national, regional, and local levels.This Commission urges that a cap on global plastic production with targets, timetables, and national contributions be a central provision of the Global Plastics Treaty. We recommend inclusion of the following additional provisions:The Treaty needs to extend beyond microplastics and marine litter to include all of the many thousands of chemicals incorporated into plastics.The Treaty needs to include a provision banning or severely restricting manufacture and use of unnecessary, avoidable, and problematic plastic items, especially single-use items such as manufactured plastic microbeads.The Treaty needs to include requirements on extended producer responsibility (EPR) that make fossil carbon producers, plastic producers, and the manufacturers of plastic products legally and financially responsible for the safety and end-of-life management of all the materials they produce and sell.The Treaty needs to mandate reductions in the chemical complexity of plastic products; health-protective standards for plastics and plastic additives; a requirement for use of sustainable non-toxic materials; full disclosure of all components; and traceability of components. International cooperation will be essential to implementing and enforcing these standards.The Treaty needs to include SEJ remedies at each stage of the plastic life cycle designed to fill gaps in community knowledge and advance both distributional and procedural equity.This Commission encourages inclusion in the Global Plastic Treaty of a provision calling for exploration of listing at least some plastic polymers as persistent organic pollutants (POPs) under the Stockholm Convention.This Commission encourages a strong interface between the Global Plastics Treaty and the Basel and London Conventions to enhance management of hazardous plastic waste and slow current massive exports of plastic waste into the world's least-developed countries.This Commission recommends the creation of a Permanent Science Policy Advisory Body to guide the Treaty's implementation. The main priorities of this Body would be to guide Member States and other stakeholders in evaluating which solutions are most effective in reducing plastic consumption, enhancing plastic waste recovery and recycling, and curbing the generation of plastic waste. This Body could also assess trade-offs among these solutions and evaluate safer alternatives to current plastics. It could monitor the transnational export of plastic waste. It could coordinate robust oceanic-, land-, and air-based MNP monitoring programs.This Commission recommends urgent investment by national governments in research into solutions to the global plastic crisis. This research will need to determine which solutions are most effective and cost-effective in the context of particular countries and assess the risks and benefits of proposed solutions. Oceanographic and environmental research is needed to better measure concentrations and impacts of plastics <10 µm and understand their distribution and fate in the global environment. Biomedical research is needed to elucidate the human health impacts of plastics, especially MNPs. Summary: This Commission finds that plastics are both a boon to humanity and a stealth threat to human and planetary health. Plastics convey enormous benefits, but current linear patterns of plastic production, use, and disposal that pay little attention to sustainable design or safe materials and a near absence of recovery, reuse, and recycling are responsible for grave harms to health, widespread environmental damage, great economic costs, and deep societal injustices. These harms are rapidly worsening.While there remain gaps in knowledge about plastics' harms and uncertainties about their full magnitude, the evidence available today demonstrates unequivocally that these impacts are great and that they will increase in severity in the absence of urgent and effective intervention at global scale. Manufacture and use of essential plastics may continue. However, reckless increases in plastic production, and especially increases in the manufacture of an ever-increasing array of unnecessary single-use plastic products, need to be curbed.Global intervention against the plastic crisis is needed now because the costs of failure to act will be immense.

Global assessment of nature's contributions to people.

Synergistically maintain or enhance the numerous beneficial contributions of nature to the quality of human life is an important but challenging question for achieving Sustainable Development Goals. However, the spatiotemporal distributions of global nature's contributions to people (NCPs) and their interactions remain unclear. We built a rapid assessment indicator framework and produced the first spatially explicit assessment of all 18 NCPs at a global scale. The 18 global NCPs in 1992 and 2018 were globally assessed in 15,204 subbasins based on two spatial indicator dimensions, including nature's potential contribution and the actual contribution to people. The results show that most of the high NCP values are highly localized. From 1992 to 2018, 6 regulating NCPs, 3 material NCPs, and 2 nonmaterial NCPs declined; 29 regulating-material NCP combinations (54 in total) dominated 76% of the terrestrial area, and the area with few NCPs accounted for 22%; and synergistic relationships were more common than tradeoff relationships, while the relationships among regulating and material NCPs generally traded-off with each other. Transitional climate areas contained few NCPs and have strong tradeoff relationships. However, the high synergistic relationship among NCPs in low latitudes could be threatened by future climate change. These findings provide a general spatiotemporal understanding of global NCP distributions and can be used to interpret the biogeographic information in a functional way to support regional coordination and achieve landscape multifunctionality for the enhancement of human well-being.

Optimal nitrogen rate strategy for sustainable rice production in China.

Avoiding excessive agricultural nitrogen (N) use without compromising yields has long been a priority for both research and government policy in China1,2. Although numerous rice-related strategies have been proposed3-5, few studies have assessed their impacts on national food self-sufficiency and environmental sustainability and fewer still have considered economic risks faced by millions of smallholders. Here we established an optimal N rate strategy based on maximizing either economic (ON) or ecological (EON) performance using new subregion-specific models. Using an extensive on-farm dataset, we then assessed the risk of yield losses among smallholder farmers and the challenges of implementing the optimal N rate strategy. We find that meeting national rice production targets in 2030 is possible while concurrently reducing nationwide N consumption by 10% (6-16%) and 27% (22-32%), mitigating reactive N (Nr) losses by 7% (3-13%) and 24% (19-28%) and increasing N-use efficiency by 30% (3-57%) and 36% (8-64%) for ON and EON, respectively. This study identifies and targets subregions with disproportionate environmental impacts and proposes N rate strategies to limit national Nr pollution below proposed environmental thresholds, without compromising soil N stocks or economic benefits for smallholders. Thereafter, the preferable N strategy is allocated to each region based on the trade-off between economic risk and environmental benefit. To facilitate the adoption of the annually revised subregional N rate strategy, several recommendations were provided, including a monitoring network, fertilization quotas and smallholder subsidies.

Goal-directed and habitual decision making under stress in gambling disorder: An fMRI study.

The development of addictive behaviors has been suggested to be related to a transition from goal-directed to habitual decision making. Stress is a factor known to prompt habitual behavior and to increase the risk for addiction and relapse. In the current study, we therefore used functional MRI to investigate the balance between goal-directed 'model-based' and habitual 'model-free' control systems and whether acute stress would differentially shift this balance in gambling disorder (GD) patients compared to healthy controls (HCs). Using a within-subject design, 22 patients with GD and 20 HCs underwent stress induction or a control condition before performing a multistep decision-making task during fMRI. Salivary cortisol levels showed that the stress induction was successful. Contrary to our hypothesis, GD patients did not show impaired goal-directed 'model-based' decision making, which remained similar to HCs after stress induction. Bayes factors provided three times more evidence against a difference between the groups or a group-by-stress interaction on the balance between model-based and model-free decision making. Similarly, no differences were found between groups and conditions on the neural estimates of model-based or model-free decision making. These results challenge the notion that GD is related to an increased reliance on habitual (or decreased goal-directed) control, even during stress.

Tracking progress towards universal health coverage for essential health services in China, 2008-2018.

INTRODUCTION: We comprehensively evaluate whether the Chinese Government's goal of ensuring Universal Health Coverage for essential health services has been achieved. METHODS: We used data from the 2008, 2013 and 2018 National Health Services Survey to report on the coverage of a range of Sustainable Development Goals (SDG) indicator 3.8.1. We created per capita household income deciles for urban and rural samples separately. We report time trends in coverage and the slope index (SII) and relative index (RII). RESULTS: Despite much lower levels of income and education, rural populations made as much progress as their urban counterparts for most interventions. Coverage of maternal and child health interventions increased substantially in urban and rural areas, with decreasing rich-poor inequalities except for antenatal care. In rural China, one-fifth women could not access 5 or more antenatal visits. Coverage of 8 or more visits were 34% and 68%, respectively in decile D1 (the poorest) and decile D10 (the richest) (SII 35% (95% CI 22% to 48%)). More than 90% households had access to clean water, but basic sanitation was poor for rural households and the urban poorest, presenting bottom inequality. Effective coverage for non-communicable diseases was low. Medication for hypertension and diabetes were relatively high (>70%). But adequate management, counting in preventive interventions, were much lower and decreased overtime, although inequalities were small in size. Screening of cervical and breast cancer was low in both urban and rural areas, seeing no progress overtime. Cervical cancer screening was only 29% (urban) and 24% (rural) in 2018, presenting persisted top inequalities (SII 25% urban, 14% rural). CONCLUSION: China has made commendable progress in protecting the poorest for basic care. However, the 'leaving no one behind' agenda needs a strategy targeting the entire population rather than only the poorest. Blunt investing in primary healthcare facilities seems neither effective nor efficient.

An authentic learner-centered planetary health assignment: A five-year evaluation of student choices to address Sustainable Development Goal 13 (Climate Action).

A Code Red has been declared for the planet and human health. Climate change (e.g., increasing temperatures, adverse weather events, rising sea levels) threatens the planet's already declining ecosystems. Without urgent action, all of Earth's inhabitants face an existential threat. Health professions education should therefore prepare learners to not only practice in a changing world, but authentic educational activities should also develop competencies for global and planetary citizenship. Planetary health has been integrated across the five-year Bond University (Australia) medical curriculum. It begins in the second week of Year 1 and ends with a session on Environmentally Sustainable Healthcare in the General Practice rotation in the final year. The purpose of this article is to describe the outcomes of the first 5 years (2018-2022) of a learner-centered planetary health assignment, underpinned by the 2030 United Nations (UN) Sustainable Development Goals (SDGs), in the second year of a five-year medical program. Using systems and/or design thinking with a focus on SDG13 (Climate Action) plus a second SDG of choice, self-selected teams of 4-6 students submit a protocol (with feedback) to develop a deliverable "product" for an intended audience. Data analysis of the first 5 years of implementation found that the most frequently selected SDGs in addition to SDG13 were: SDG12 Sustainable Production and Consumption (41% of teams), mostly relating to healthcare emissions and waste; SDG3 Health and Well-being (22%), generally involving the impact of air pollution; and SDG6 Clean Water and Sanitation (15%). A survey at the concluding conference garnered student feedback across various criteria. The planetary health assignment is authentic in that teams provide solutions to address climate change. Where appropriate, final "products" are sent to local or federal ministers for consideration (e.g., policy proposals) or integrated into the curriculum (e.g., learning modules). We believe that the competencies, attitudes, and values fostered through engagement with planetary health. Throughout the medical program, as evidenced by their evaluations, stands students in good stead to be change agents, not only in clinical practice but in society. An awareness has been created about the need for planetary citizenship in addition to global citizenship.

Review of the neglected tropical diseases programme implementation during 2012-2019 in the WHO-Eastern Mediterranean Region.

INTRODUCTION: The 2012-2020 WHO NTD roadmap set targets for control, elimination, and eradication of neglected tropical diseases (NTDs). It recommends 5 strategies, out of which preventive chemotherapy (PC) and intensified disease management were key to achieve targets. WHO estimated that globally, between 2012 and 2019, the number of persons affected by NTDs decreased from nearly 2.1 to 1.7 billion people. We analysed the situation of NTDs in the WHO Eastern Mediterranean Region (EMR) in 2020 to assess the progress with the 2012-2020 roadmap and to identify gaps. METHODS: We reviewed data repositories of national data sources for 2012 to 2019 including the Global Indicator Data Platform for Sustainable Development Goals, the Global Health Observatory data repository, the WHO PC databank, and the EMR data repository. We allocated countries a Red-Amber-Green (RAG) rating based on standardized criteria, on progress and current situation of each of 11 priority NTDs. RESULTS: All 22 countries in EMR were affected by 1 or more autochthonous or imported NTDs. In 2019, WHO estimated that in EMR, 78 million people required interventions for NTDs, a 38% decline compared with 2012. Twelve of 22 countries needed priority public health action (i.e., red) for 1 or more NTD. Of these, Sudan needed priority public health action for 6 NTDs and Yemen for 5. Eleven countries also needed priority public health action for cutaneous leishmaniasis, and 5 countries for rabies and trachoma. Visceral leishmaniasis is on the increase in Afghanistan, Libya, Syria, and Yemen. CONCLUSION: Since the first roadmap of NTDs in 2012, the EMR has made a substantial progress. Nevertheless, many challenges remain in the prevention and control of NTDs. EMR needs a regional approach to control NTDs in countries most affected and a coordinated strategy to stop the continuing increase of cutaneous leishmaniasis and a possible resurgence of visceral leishmaniasis.