Combination strategies to enhance treatment responses

Adaptive immunity is required for durable responses

RNAseq analysis of proliferation-associated tumor cell signatures

The unprecedented and multi-faceted challenges health and care workers faced during the COVID-19 pandemic inspired the world’s health ministers to call for a new Global Health and Care Worker Compact at the 74th World Health Assembly in 2021. The Care Compact identifies key areas where governments can use law and policy to prevent harm, provide support, ensure inclusivity, and safeguard rights of health and care workers toward improving population health. Using policy surveillance methods, we conducted an empirical analysis of the national law and policy environments on health and care workers’ protection and rights in 182 countries. Across 10 indicators, 1,262 laws and policies were identified and analyzed for their alignment with the international legal standards. Analysis shows significant gaps. 62% of all national laws are aligned. Nearly every country has multiple areas where national laws are not yet aligned with the Care Compact. Though alignment is feasible. In 5 of 6 regions at least one country has laws aligned on all indicators. Geographic region was not a significant predictor of alignment, while income level was only weakly associated. Comparing the key legal issues facing health and care workers, well over half of countries studied are fully aligned with the Care Compact on occupational health and safety, fair remuneration, enabling work environments, freedom of association, and collective bargaining. Approximately 50% of countries studied are fully aligned on protections against violence and harassment in the workplace and whistleblower protections. But less than 25% are fully aligned on access to health services in occupational settings and equal treatment and non-discrimination. Together this analysis highlights the need for, and opportunity of, law reform in countries throughout the world to elevate and protect the rights and well-being of health and care workers and, in doing so, improve health systems.

Background: The COVID-19 pandemic poses substantial health risks, especially for individuals with pre-existing physical illness. While its physical toll is well-documented, its impact on mental health remains less well understood. This study examines mental health changes during the pandemic in U.S. adults with and without pre-existing physical conditions. Methods: We analyzed data from the Medical Expenditure Panel Survey (MEPS), a nationally representative survey of the U.S. civilian population. Mental health outcomes, including psychological distress (Kessler-6 scale) and depressive symptoms (PHQ-2), were assessed pre-pandemic (typically between July and October 2019) and during the pandemic (between July and October 2020 in most cases). Linear regression models with individual fixed effects evaluated within-person changes in these outcomes. Results: Overall, depressive symptoms (PHQ-2) increased slightly during the pandemic (B = 0.064, p = .002), with similar effects in individuals with (B = 0.066) and without (B = 0.062) pre-existing conditions. Psychological distress (K6) remained stable overall, but trajectories varied across population subgroups defined by sociodemographic characteristics (e.g., age, education, living arrangements) primarily among individuals with pre-existing illness. Limitations: The magnitude of change in mental health may have been underestimated due to nonignorable sample attrition. Conclusions: While depressive symptoms increased modestly across the population, the impact on psychological distress was more nuanced, with certain sociodemographic factors moderating change in psychological distress among individuals with chronic conditions. Findings highlight the need for targeted mental health strategies that consider both medical and sociodemographic factors to better support at-risk populations in future public health emergencies.

The global health and care workforce (HCWF) is facing an evolving crisis, requiring urgent and sustained action. There is a critical need for enhanced workforce planning, management, and leadership, which are currently at risk of being overshadowed by political inertia, particularly in the post-COVID-19 context. A comprehensive approach tailored to the specific needs of different countries is outlined here, offering actionable insights for policymakers and stakeholders to address the HCWF crisis effectively. Key areas for critical analysis and improvement include identifying major challenges, developing policies that effectively address the HCWF crisis, and strengthening the implementation of evidence-based policies. These areas are detailed based on recent developments in the international debate, with the aim of providing comprehensive guidance for understanding the problems and identifying clear actions for improvement.

Background To investigate the impacts of the COVID-19 pandemic on the health workforce, we aimed to develop a framework that synergizes natural language processing (NLP) techniques and human-generated analysis to reduce, organize, classify, and analyze a vast volume of publicly available news articles to complement scientific literature and support strategic policy dialogue, advocacy, and decision-making. Objective This study aimed to explore the possibility of systematically scanning intelligence from media that are usually not captured or best gathered through structured academic channels and inform on the impacts of the COVID-19 pandemic on the health workforce, contributing factors to the pervasiveness of the impacts, and policy responses, as depicted in publicly available news articles. Our focus was to investigate the impacts of the COVID-19 pandemic and, concurrently, assess the feasibility of gathering health workforce insights from open sources rapidly. Methods We conducted an NLP-assisted media content analysis of open-source news coverage on the COVID-19 pandemic published between January 2020 and June 2022. A data set of 3,299,158 English news articles on the COVID-19 pandemic was extracted from the World Health Organization Epidemic Intelligence through Open Sources (EIOS) system. The data preparation phase included developing rules-based classification, fine-tuning an NLP summarization model, and further data processing. Following relevancy evaluation, a deductive-inductive approach was used for the analysis of the summarizations. This included data extraction, inductive coding, and theme grouping. Results After processing and classifying the initial data set comprising 3,299,158 news articles and reports, a data set of 5131 articles with 3,007,693 words was devised. The NLP summarization model allowed for a reduction in the length of each article resulting in 496,209 words that facilitated agile analysis performed by humans. Media content analysis yielded results in 3 sections: areas of COVID-19 impacts and their pervasiveness, contributing factors to COVID-19–related impacts, and responses to the impacts. The results suggest that insufficient remuneration and compensation packages have been key disruptors for the health workforce during the COVID-19 pandemic, leading to industrial actions and mental health burdens. Shortages of personal protective equipment and occupational risks have increased infection and death risks, particularly at the pandemic’s onset. Workload and staff shortages became a growing disruption as the pandemic progressed. Conclusions This study demonstrates the capacity of artificial intelligence–assisted media content analysis applied to open-source news articles and reports concerning the health workforce. Adequate remuneration packages and personal protective equipment supplies should be prioritized as preventive measures to reduce the initial impact of future pandemics on the health workforce. Interventions aimed at lessening the emotional toll and workload need to be formulated as a part of reactive measures, enhancing the efficiency and maintainability of health delivery during a pandemic.

PDF file, 51K, Human mAb1567 variants mediated ADCC activity against Cf2-CCR4 cells via human NK cells.

Development partners and global health initiatives are important actors in financing health systems in many countries. Despite the importance of the health workforce to the attainment of global health targets, the contribution of global health initiatives to health workforce strengthening is unclear. A 2020 milestone in the Global Strategy on Human Resources for Health is that "all bilateral and multilateral agencies have participated in efforts to strengthen health workforce assessments and information exchange in countries." This milestone exists to encourage strategic investments in the health workforce that are evidence-based and incorporate a health labour market approach as an indication of policy comprehensiveness. To assess progress against this milestone, we reviewed the activities of 23 organizations (11 multilaterals and 12 bilaterals) which provide financial and technical assistance to countries for human resources for health, by mapping grey and peer-reviewed literature published between 2016 and 2021. The Global Strategy states that health workforce assessment involves a "deliberate strategy and accountability mechanisms on how specific programming contributes to health workforce capacity-building efforts" and avoids health labour market distortions. Health workforce investments are widely recognized as essential for the achievement of global health goals, and some partners identify health workforce as a key strategic focus in their policy and strategy documents. However, most do not identify it as a key focus, and few have a published specific policy or strategy to guide health workforce investments. Several partners include optional health workforce indicators in their monitoring and evaluation processes and/or require an impact assessment for issues such as the environment and gender equality. Very few, however, have embedded efforts in their governance mechanisms to strengthen health workforce assessments. On the other hand, most have participated in health workforce information exchange activities, including strengthening information systems and health labour market analyses. Although there is evidence of participation in efforts to strengthen health workforce assessments and (especially) information exchange, the achievement of this milestone of the Global Strategy requires more structured policies for the monitoring and evaluation of health workforce investments to optimize the value of these investments and contribute towards global and national health goals.

Background: Ongoing tetanus cases and sporadic outbreaks of vaccine-preventable diseases associated with routine vaccination programmes remain problems in many low and middle-income countries, including Vietnam. With no human-to-human transmission or natural immunity, tetanus antibody levels indicate both individual risk of tetanus and gaps in vaccination programmes.Methods: To investigate gaps in immunity to tetanus in Vietnam, a country with a historically high level of tetanus vaccination coverage, tetanus antibodies were measure by ELISA from samples selected from a long-term serum bank, established for the purposes of general-population seroepidemiological investiga-tions in southern Vietnam. Samples were selected from 10 provinces, focussing on age-groups targeted by national vaccination programmes for infants and pregnant women (Expanded Programme on Immunization, EPI, and Maternal and Neonatal Tetanus, MNT).Results: Antibodies were measured from a total of 3864 samples. Highest tetanus antibody concentra-tions occurred in children under 4 years old, over 90 % of whom had protective levels. Approximately 70 % of children aged 7-12 years had protective antibody concentrations although there was variation among provinces. For infants and children, there were no significant differences in tetanus protection between males and females, but for adults aged 20-35 years, in five of the ten provinces surveyed, pro-tection against tetanus was higher in females (p < 0.05) who are eligible for booster doses under the MNT programme. In seven of ten provinces, antibody concentrations were inversely related to age (p < 0.01) and protection of older individuals was generally low.Conclusion: Widespread immunity to tetanus toxoid is seen in infants and young children consistent with the high coverage rates reported for diptheria tetanus toxoid and pertussis (DTP) in Vietnam. However, the lower antibody concentrations seen in older children and men suggest reduced immunity to tetanus in populations not targeted by EPI and MNT programmes.(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PDF file, 51K, Anti-CCR4 antibodies abrogate the suppressive function of Tregs on Teff proliferation.

PDF file, 209K, Epitope mapping of mAb1567.

PDF file, 456K, Affinity maturation of humanized anti-CCR4 mAb1567.

Advances in assistive exoskeleton technology, and a boom in related scientific literature, prompted a need to review the potential use of exoskeletons in defence and security. A systematic review examined the evidence for successful augmentation of human performance in activities deemed most relevant to military tasks. Categories of activities were determined a priori through literature scoping and Human Factors workshops with military stakeholders. Workshops identified promising opportunities and risks for integration of exoskeletons into military use cases. The review revealed promising evidence for exoskeletons’ capacity to assist with load carriage, manual lifting, and working with tools. However, the review also revealed significant gaps in exoskeleton capabilities and likely performance levels required in the use case scenarios. Consequently, it was recommended that a future roadmap for introducing exoskeletons to military environments requires development of performance criteria for exoskeletons that can be used to implement a human-centred approach to research and development. We assessed the state-of-the-art for the use of wearable assistive exoskeletons in UK defence and security use cases. A full systematic review of the literature was undertaken, informed by use cases developed in military stakeholder workshops. Clear gaps in exoskeleton capability and use case requirements were identified, leading to recommendations for future work.

PDF file, 51K, CDC activity of h1567, 1-44 and 2-3 variants against Mac-1 cells.

BackgroundDuring the COVID-19 pandemic, and recognising the sacrifice of health and care workers alongside discrimination, violence, poor working conditions and other violations of their rights, health and safety, in 2021 the World Health Assembly requested WHO to develop a global health and care worker compact, building on existing normative documentation, to provide guidance to 'protect health and care workers and safeguard their rights'. MethodsA review of existing international law and other normative documents was conducted. We manually searched five main sets of international instruments: (1) International Labour Organization conventions and recommendations; (2) WHO documents; (3) United Nations (UN) human rights treaties and related documents; (4) UN Security Council and General Assembly resolutions and (5) the Geneva Conventions and Additional Protocols. We included only legal or other normative documents with a global or regional focus directly addressing or relevant to health and care workers or workers overall. ResultsMore than 70 documents met our search criteria. Collectively, they fell into four domains, within which we identified 10 distinct areas: (1) preventing harm, encompassing (A) occupational hazards, (B) violence and harassment and (C) attacks in situations of fragility, conflict and violence; (2) inclusivity, encompassing (A) non-discrimination and equality; (3) providing support, encompassing (A) fair and equitable remuneration, (B) social protection and (C) enabling work environments and (4) safeguarding rights, encompassing (A) freedom of association and collective bargaining and (B) whistle-blower protections and freedom from retaliation. DiscussionA robust legal and policy framework exists for supporting health and care workers and safeguarding their rights. Specific human rights, the right to health overall, and other binding and non-binding legal documents provide firm grounding for the compact.However, these existing commitments are not being fully met. Implementing the compact will require more effective governance mechanisms and new policies, in partnership with health and care workers themselves.

Background Vietnam and Southeast Asia are hotspots for antimicrobial resistance; however, little is known on the prevalence of carriage of carbapenem resistance in non-hospitalized humans and in animals. Carbapenem-resistant Enterobacteriaceae (CRE), particularly Escherichia coli (CREC) and Klebsiella pneumoniae (CRKP) and also Acinetobacter baumannii (CRAB) are emerging threats worldwide. Methods We investigated healthy humans (n = 652), chickens (n = 237), ducks (n = 150) and pigs (n = 143) in 400 small-scale farms in the Mekong Delta of Vietnam. Samples (rectal swabs, faecal swabs) were investigated for carriage of CRE/CRAB and were further characterized phenotypically and genotypically. Results In the Mekong Delta of Vietnam, the prevalence of CRE isolates in human rectal swabs was 0.6%, including 4 CREC and 1 CRKP. One pig was infected with CREC (prevalence 0.7%). CRAB was isolated from chickens (n = 4) (prevalence 2.1%) and one duck (prevalence 0.7%). CRKP was isolated from a human who was also colonized with CREC. The CRKP strain (ST16), from an 80 year-old person with pneumonia under antimicrobial treatment, genetically clustered with clinical strains isolated in a hospital outbreak in southern Vietnam. The prevalence of CRE was higher among humans that had used antimicrobials within 90 days of the sampling date than those had not (4.2% versus 0.2%) (P = 0.005). All CRE/CRAB strains were MDR, although they were susceptible to colistin and neomycin. The carbapenemase genes identified in study strains were bla(NDM) and bla(OXA). Conclusions The finding of a CRKP strain clustering with previous hospital outbreak raises concerns about potential transmission of carbapenem-resistant organisms from hospital to community settings or vice-versa.

Background Diarrhoeagenic Escherichia coli (DEC) infections are common in children in low-middle income countries (LMICs). However, detecting the various DEC pathotypes is complex as they cannot be differentiated by classical microbiology. We developed four multiplex real-time PCR assays were to detect virulence markers of six DEC pathotypes; specificity was tested using DEC controls and other enteric pathogens. PCR amplicons from the six E. coli pathotypes were purified and amplified to be used to optimize PCR reactions and to calculate reproducibility. After validation, these assays were applied to clinical samples from healthy and diarrhoeal Vietnamese children and associated with clinical data. Results The multiplex real-time PCRs were found to be reproducible, and specific. At least one DEC variant was detected in 34.7% (978/2815) of the faecal samples from diarrhoeal children; EAEC, EIEC and atypical EPEC were most frequent Notably, 41.2% (205/498) of samples from non-diarrhoeal children was positive with a DEC pathotype. In this population, only EIEC, which was detected in 34.3% (99/289) of diarrhoeal samples vs. 0.8% (4/498) non-diarrhoeal samples ( p < 0.001), was significantly associated with diarrhoea. Multiplex real-time PCR when applied to clinical samples is an efficient and high-throughput approach to DEC pathotypes. Conclusions This approach revealed high carriage rates of DEC pathotypes among Vietnamese children. We describe a novel diagnostic approach for DEC, which provides baseline data for future surveillance studies assessing DEC burden in LMICs.