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Social media platforms are widely used to connect people across multiple settings, including country of origin, profession, race/ethnicity, sexual orientation, gender identity, seniority, and training. Groups that have been marginalized or historically excluded from decision-making encounters may lack formal mentors/sponsors because of a lack of representation of women and Black, Indigenous, People Of Color (BIPOC) in senior leadership positions. This can serve as a barrier to professional advancement at all stages of career development. Identifying and connecting with these potential mentors/sponsors outside of one’s institutional space can be challenging. For this reason, leveraging social media to develop these professional relationships through flattened hierarchies can allow for professional networking beyond traditional mechanisms. Here we aim to describe how individuals can connect through social media to advance their careers and scientific and clinical expertise, advocate for communities, and provide high-quality communication to the public.

Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.

Admissions to jails and prisons in the United States number 10 million yearly; persons entering locked correctional facilities have high prevalence of sexually transmitted infections (STIs). These individuals come disproportionately from communities of color, with lower access to care and prevention, compared with the United States as a whole. Following PRISMA guidelines, the authors present results of a systematic review of literature published since 2012 on STIs in US jails, prisons, Immigration and Customs Enforcement detention centers, and juvenile facilities. This updates an earlier review of STIs in short-term facilities. This current review contributed to new recommendations in the Centers for Disease Control and Prevention 2021 treatment guidelines for STIs, advising screening for Trichomonas in women entering correctional facilities. The current review also synthesizes recommendations on screening: in particular, opt-out testing is superior to opt-in protocols. Carceral interventions—managing diagnosed cases and preventing new infections from occurring (eg, by initiating human immunodeficiency virus preexposure prophylaxis before release)—can counteract structural racism in healthcare.

ObjectiveTo compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000–2020.DesignPopulation-based, multi-country study.SettingNational data systems in 15 middle- and high-income countries.MethodsWe used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], 90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types.Main outcome measuresMortality of six newborn types.ResultsOf 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6–73.9), PT + AGA (median 34.3, IQR 23.9–37.5) and PT + LGA (median 28.3, IQR 18.4–32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5–54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2–388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7–342.8) compared with those between 2500 g and 4000 g as a reference group.ConclusionPreterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

To prepare for the development of the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections treatment guidelines, the CDC convened a committee of expert consultants in June 2019 to discuss recent abstracts and published literature on the epidemiology, diagnosis, and management of sexually transmitted infections.This paper summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis (CT) infections in adolescents and adults that were reviewed and discussed for consideration in developing the guidelines. The evidence reviewed mostly focused on efficacy of doxycycline and azithromycin for urogenital, rectal, and oropharyngeal CT infection, CT risk factors in women, performance of CT nucleic acid amplification tests on self-collected meatal specimens in men, and performance of newer CT point-of-care tests.

The Minimally Invasive Tissue Sampling (MITS) Surveillance Alliance was created with funding from the Bill & Melinda Gates Foundation to expand pathology-based mortality surveillance and to support the generation of improved cause-of-death (CoD) data. MITS, also known as minimally invasive autopsy, has evolved to become an important tool to improve CoD ascertainment. Here, we describe the 18 articles included in this supplement that present advanced methods for improving MITS and related areas of research, summarize the expansion of the use of MITS, report on findings from a variety of research projects, and address the importance of postmortem approaches taken during the novel coronavirus disease 2019 pandemic. Support by the scientific and global health community for enhancements and innovation is needed for the broader adoption of MITS-informed CoD as a critical tool to better understand mortality in low- and middle-income countries and identify interventions for the prevention of premature death.

Background Minimally invasive tissue sampling (MITS) of organs has been used as an alternative to complete diagnostic autopsy in countries where refusal for autopsy in newborns is common for sociocultural reasons. There is a paucity of literature regarding the diagnostic utility of MITS of the brain after death in neonates with neurological insults, especially in India. Methods This was a prospective, preliminary single-center tertiary care hospital study in India, focused specifically on MITS of the brain after neonatal death as a diagnostic tool to identify the various neurological insults. All neonatal deaths with neurological symptoms occurring within the first 30 days of life were enrolled, irrespective of the suspected clinical diagnosis. Results Sixteen neonates were enrolled after death for MITS of the brain, performed for diagnostic purposes, during the study period from February 2020 to March 2021. Their gestational ages ranged from 26 to 38 weeks. All neonates had either a history of seizures and/or respiratory distress or clinical evidence of sepsis and were on ventilator support. Histopathology in all 16 neonates showed evidence of anoxia, with or without reactive astrogliosis or microgliosis. In 5 neonates with cranial ultrasound evidence of brain hemorrhage, MITS of the brain showed intraventricular hemorrhage, subdural hemorrhage, or intraparenchymal white matter microhemorrhages. Premortem blood culture–proven sepsis was seen in 9 neonates. In all cases (100%), MITS had a good diagnostic yield and was useful to establish the neurological insult in the brain. Conclusions MITS of the brain provides an accurate and adequate diagnosis and can be an alternative to complete diagnostic autopsy for establishing the cause of death due to neurological insults, especially in low-resource settings where obtaining consent for more invasive procedure is often challenging.

Background Review of data from multiple sources is often necessary to determine cause of death for stillbirths and neonatal deaths, especially in low- to middle-income countries (LMICs) where available data may vary. The minimally invasive tissue sampling (MITS) procedure provides granular histologic and microbiologic data that clinical reports and verbal autopsies cannot provide. Expert panel evaluation of data from individual deaths can be resource-intensive but remains essential to accurately infer causes of death. Methods The Project to Understand and Research Preterms and Stillbirths in South Asia (PURPOSe) study uses review panels to evaluate causes of death in 2 LMICs. To make the process manageable, a subset of the study variables was selected with professional input and organized into case reports. Case reports include clinical information, laboratory results, fetal or neonatal organ histology and polymerase chain reaction results from tissue obtained by MITS. Panelists evaluated the complete case report forms and then determined the cause of death based on available data. Results Computerized case reports averaged 2 to 3 pages. Approximately 6 to 8 cases were reviewed and discussed per 1-hour panel meeting. All panelists were provided the same information; missing data were noted. This limited bias between panelists and across meetings. Study teams notably took ownership of data quality. Conclusions Standardized case reports for cause-of-death determination panel evaluation improve the efficiency of the review process, clarify available information, and limit bias across panelists, time, and location.

Background Although much has been learned about the pathophysiology of coronavirus disease 2019 (COVID-19) infections, pathology data from patients who have died of COVID-19 in low- and middle-income country settings remain sparse. We integrated minimally invasive tissue sampling (MITS) into an ongoing postmortem surveillance study of COVID-19 in deceased individuals of all ages in Lusaka, Zambia. Methods We enrolled deceased subjects from the University Teaching Hospital Morgue in Lusaka, Zambia within 48 hours of death. We collected clinical and demographic information, a nasopharyngeal swab, and core tissue biopsies from the lung, liver, and kidneys for pathologic analysis. Individuals were considered eligible for MITS if they had a respiratory syndrome prior to death or a COVID-19+ polymerase chain reaction (PCR) nasopharyngeal swab specimen. Samples were retested using quantitative reverse transcriptase PCR. Results From June to September 2020 we performed MITS on 29 deceased individuals. PCR results were available for 28/29 (96.5%) cases. Three had a COVID-19+ diagnosis antemortem, and 5 more were identified postmortem using the recommended cycle threshold cut-point Conclusions Lung abnormalities typical of viral pneumonias were common among deceased COVID-19+ individuals, as were nonspecific findings in the liver and kidneys. Pulmonary vascular thrombi were rarely detected, which could be a limitation of the MITS technique. Nonetheless, MITS offers a valuable alternative to open autopsy for understanding pathological changes due to COVID-19.

Background Minimally invasive tissue sampling (MITS), an alternative to complete diagnostic autopsy, is a pathology-based postmortem examination that has been validated in low- and middle-income countries (LMICs) and can provide accurate cause of death information when used with other data. The MITS Surveillance Alliance was established in 2017 with the goal to expand MITS globally by increasing training capacity, accessibility, and availability in LMICs. Between January 2019 and May 2020, the MITS Surveillance Alliance convened a multidisciplinary team of technical advisors to attain this goal. Methods This article describes the process used to develop criteria and identify an optimal location for a MITS training hub, establish a cadre of LMIC-based trainers, refine standardized MITS sample collection protocols, develop a training program, and release a telepathology platform for quality assessment of MITS histological samples. Results Results include the creation of a training hub and curriculum, with a total of 9 pathologists and technicians trained as part of the training of the trainers. Those trainers trained 15 participants from seven MITS projects representing 6 LMICs trained in MITS sample collection. The 15 participants have gone on to train more than 50 project-level staff in MITS sample collection. Conclusions Lessons learned include an appreciation for using an iterative process for establishing standardized procedures, creating opportunities for all stakeholders to deliver critical feedback, and highlighting the importance of complementing in-person trainings with ongoing technical assistance.

Background Minimally invasive tissue sampling (MITS) is an alternative to complete autopsy for determining causes of death. Multiplex molecular testing performed on MITS specimens poses challenges of interpretation, due to high sensitivity and indiscriminate detection of pathogenic, commensal, or contaminating microorganisms. Methods MITS was performed on 20 deceased children with respiratory illness, at 10 timepoints up to 88 hours postmortem. Samples were evaluated by multiplex molecular testing on fresh tissues by TaqMan® Array Card (TAC) and by histopathology, special stains, immunohistochemistry (IHC), and molecular testing (PCR) on formalin-fixed, paraffin-embedded (FFPE) tissues. Results were correlated to determine overall pathologic and etiologic diagnoses and to guide interpretation of TAC results. Results MITS specimens collected up to 3 days postmortem were adequate for histopathologic evaluation and testing. Seven different etiologic agents were detected by TAC in 10 cases. Three cases had etiologic agents detected by FFPE or other methods and not TAC; 2 were agents not present on TAC, and 2 were streptococci that may have been species other than those present on TAC. Result agreement was 43% for TAC and IHC or PCR, and 69% for IHC and PCR. Extraneous TAC results were common, especially when aspiration was present. Conclusions TAC can be performed on MITS up to 3 days after death with refrigeration and provides a sensitive method for detection of pathogens but requires careful interpretation in the context of clinicoepidemiologic and histopathologic findings. Interpretation of all diagnostic tests in aggregate to establish overall case diagnoses maximizes the utility of TAC in MITS.

Metagenomic next-generation sequencing is a novel diagnostic test with the potential to revolutionize the diagnosis of pediatric meningitis and encephalitis through unbiased detection of bacteria, viruses, parasites, and fungi in cerebrospinal fluid. Current literature is mostly observational with variable indications, populations, and timing of testing with resulting variability in diagnostic yield and clinical impact. Diagnostic stewardship strategies are needed to direct testing toward high-impact pediatric populations, to optimize timing of testing, to ensure appropriate interpretation of results, and to guide prompt optimization of antimicrobials. This review highlights the high clinical potential of this test, though future studies are needed to gather clinical impact and cost-effectiveness data for specific indications in pediatric populations.

Summary Recently, there has been increasing interest in co-creation utilized for physical activity (PA) promotion and health promotion. Co-creation involves researchers and non-academic stakeholders conjointly developing and implementing interventions. In addition to the frequently reported benefits of co-creation, critical voices highlight the associated challenges (e.g. different interests that inhibit interaction). So far, research has not identified concrete solutions to these challenges and the limitations of co-creation. This article aims to introduce the Practice Dive Approach as a potential way to strengthen cooperation between researchers and non-academic stakeholders. We build on real-life experiences from a German research project, in which researchers moved into practice to familiarize themselves with the settings and end-users. After conducting a literature search on related concepts in PA/health promotion, we developed a comprehensive approach to fostering multi-sectoral cooperation. The introduced Practice Dive Approach assumes that a significant contribution to better cooperation among co-creators is the temporal immersion of researchers in their setting of interest, which has the potential to improve the success of co-creation in the PA/health promotion field. A four-level typology characterizes the intensity of researcher interactions with the setting and the non-academic stakeholders. Potential beneficial effects for both researchers and non-academic stakeholders can be hypothesized (e.g. familiarity with the setting structures and increased understanding of the end-users), while simultaneously, some challenges need to be considered. Future research should aim to validate the concept and its postulated effects., Lay Summary Collaboration among researchers and non-academic stakeholders is increasingly used to promote physical activity and health. For example, people involved in such collaborations jointly develop new interventions. Potential challenges include different interests or work routines that can complicate cooperation. This article aims to introduce the Practice Dive Approach as a potential way to improve cooperation between researchers and non-academic stakeholders. We developed the approach based on observations from a German research project and a literature search on related concepts. This approach assumes that the temporal involvement of researchers in their setting of interest can strengthen research-practice cooperation and improve its success. We describe different types of a Practice Dive and the requirements for conducting Practice Dive activities. Furthermore, we present the potential effects of a Practice Dive for the researchers and the non-academic stakeholders, such as increased familiarity between both groups. However, some challenges need to be considered when applying the Practice Dive Approach. Future research should test this approach and its potential effects.

BackgroundKlebsiella pneumoniae is a World Health Organization high-priority antibiotic-resistant pathogen. However, little is known about Klebsiella lineages circulating in Nigeria.MethodsWe performed whole-genome sequencing (WGS) of 141 Klebsiella isolated between 2016 and 2018 from clinical specimens at 3 antimicrobial-resistance (AMR) sentinel surveillance tertiary hospitals in southwestern Nigeria. We conducted in silico multilocus sequence typing; AMR gene, virulence gene, plasmid, and K and O loci profiling; as well as phylogenetic analyses, using publicly available tools and Nextflow pipelines.ResultsPhylogenetic analysis revealed that the majority of the 134 K. pneumoniae and 5 K. quasipneumoniae isolates from Nigeria characterized are closely related to globally disseminated multidrug-resistant clones. Of the 39 K. pneumoniae sequence types (STs) identified, the most common were ST307 (15%), ST5241 (12%), ST15 (~9%), and ST25 (~6%). ST5241, 1 of 10 novel STs detected, is a single locus variant of ST636 carrying dfrA14, tetD, qnrS, and oqxAB resistance genes. The extended-spectrum β-lactamase (ESBL) gene blaCTX_M-15 was seen in 72% of K. pneumoniae genomes, while 8% encoded a carbapenemase. No isolate carried a combination of carbapenemase-producing genes. Four likely outbreak clusters from 1 facility, within STs 17, 25, 307, and 5241, were ESBL but not carbapenemase-bearing clones.ConclusionsThis study uncovered known and novel K. pneumoniae lineages circulating in 3 hospitals in Southwest Nigeria that include multidrug-resistant ESBL producers. Carbapenemase-producing isolates remain uncommon. WGS retrospectively identified outbreak clusters, pointing to the value of genomic approaches in AMR surveillance for improving infection prevention and control in Nigerian hospitals.

Antibody-based assays have been a cornerstone of infectious disease diagnostics for over 100 years [1]. These assays rely on the exquisite sensitivity and specificity of humoral response to almost all infections. While next-generation sequencing (NGS) has tremendous potential to improve diagnostics and uncover host-microbial relationships by directly identifying nucleic acids from infectious microbes, challenges and opportunities for new approaches remain. Here, we review a group of cutting-edge techniques that couple antibody responses with flow cytometry of antibody tagged microbes and NGS. These studies are bringing into focus the dynamic relationship between our immune systems and endogenous microbial communities, which are an important source of pathogens. For simplicity, we use the umbrella term mFLOW-Seq (microbial flow cytometry coupled to NGS) to describe these approaches.

Summary To implement sustainable health-promoting structures in a setting, various agents must work together. In the Capital4Health research network, participatory stakeholder groups consisting of key persons, stakeholders, representatives of the target group, and facilitating experts are assembled in five settings (child care center, school, company, rural community, nursing home). In a Cooperative Planning process, the various groups meet regularly to plan and implement strategies to promote physical activity across different settings. This study evaluates whether participatory stakeholder groups have been established and also examines the capacity-building processes that took place in these stakeholder groups. For process evaluation, 78 group meetings were documented in 16 different stakeholder groups using a semi-structured protocol based on established capacity-building domains. For outcome evaluation, six semi-structured interviews (1–2 per setting) with facilitating experts were conducted. Data were analyzed by content analysis. Across all settings, capacity-building processes were successful to a certain degree (e.g. problem assessment, resource mobilization). However, in most groups it was difficult to broadly assess problems, to establish sustainable networks, or to find persons with leadership characteristics. Also, irregular participation, lack of motivation to take over responsibility, and minimal institutional readiness for structural and personal changes often hindered the progress of the projects. Stakeholder groups can actively involve setting members in the development of physical activity promotion programs. It seems challenging, however, to sustainably establish such groups that continue working independently without assistance from a facilitating expert., Lay Summary It is well known that public health programs are most effective when health experts, setting members and the target group work together in developing and implementing suitable interventions that fit the needs of the target group. Stakeholder groups are well suited to facilitate the regular exchange between the different agents and the health experts. Although stakeholders are experts in their various living environments, it is often necessary to expand various capacities in order to successfully plan, implement and maintain interventions in the long term. We are interested in what is required to successfully establish such stakeholder groups, and how the capacity-building processes will work in them, in order to understand which capacities are easiest to improve and in which domains it is more difficult. Therefore, we monitored 15 different stakeholder groups over a time span of 3 years; these were assembled in five settings (child care center, school, company, rural community, nursing home) and addressed interventions for encouraging a physically active lifestyle. In total, 78 group meetings were documented using a semi-structured protocol based on established capacity-building domains. Afterwards, we held interviews with the health experts involved to identify barriers and enablers of the group processes.

Physical education teacher educators’ health-related beliefs can impact public health. An interactive knowledge-to-action approach, such as Cooperative Planning, might challenge the health-related beliefs of physical education teacher educators, thus contributing to innovation in teacher education. We investigated what health-related beliefs physical education teacher educators had before a Cooperative Planning intervention, how these developed throughout the intervention and how teacher educators’ perceptions of Cooperative Planning can explain the identified changes and continuities. We established two Cooperative Planning groups that included physical education teacher educators (university lecturers and teacher trainers), researchers, study course coordinators and prospective teachers. The data of 13 teacher educators were collected before (t0) and after (t1) the Cooperative Planning using two methods: observations of teaching practice and interviews. The data analysis was based on the following categories: (i) epistemic beliefs about health (e.g. salutogenic understanding), (ii) beliefs about the health topic in physical education (e.g. health-related knowledge and understanding), (iii) beliefs about the health topic in physical education teacher education (e.g. health-related pedagogical content knowledge) and (iv) process-related beliefs about Cooperative Planning. The findings revealed that teacher educators’ health-related beliefs were rather stable but could be challenged through a Cooperative Planning intervention. Epistemic beliefs about health remained, whereas more practice-related beliefs about the health topic in physical education and physical education teacher education changed in individual ways. Here, a change in beliefs was more likely when the participants were open to change and when Cooperative Planning offered opportunities to engage in concrete lesson planning., Lay Summary The health-related beliefs of physical education teacher educators are assumed to play an important role in fostering and implementing the public health agenda. In this article, we report on a Cooperative Planning intervention in which physical education teacher educators (university lecturers and teacher trainers), physical education teacher students, study course coordinators and researchers worked together to develop health-related courses for physical education teacher education. Specifically, we investigated what health-related beliefs teacher educators had before a Cooperative Planning intervention, how these developed throughout the intervention and how teacher educators’ opinions of Cooperative Planning can explain how their beliefs changed. Based on interviews and observations, we analysed teacher educators’ epistemic beliefs about health, that is, their general understanding of health, their beliefs about the health topic in physical education and physical education teacher education and their process-related beliefs about Cooperative Planning. The findings showed that teacher educators’ health-related beliefs were rather stable but could be challenged through Cooperative Planning. Epistemic beliefs about health remained, whereas more practice-related beliefs about the health topic in physical education and physical education teacher education changed in individual ways. A change in beliefs was more likely when the Cooperative Planning participants were open to change and when the Cooperative Planning offered opportunities to engage in concrete lesson planning.

Summary A lack of communities’ readiness for change is reported as a major barrier toward an effective implementation of health promoting interventions in community settings. Adding an alternative readiness assessment approach to existing research practice, this study aimed to investigate how a selected community could be evaluated in-depth regarding its readiness for change based on multiple key informant perspectives, with the intention of using this knowledge for the preparation of improved local physical activity (PA) interventions for men above 50 years of age. We conducted semi-structured face-to-face key informant interviews with stakeholders and relevant persons from a local German community (N = 15). The interview guide was based on a comprehensive summary of community readiness dimensions. After verbatim transcription, we conducted thematic analysis to synthesize the complex results regarding community readiness related to PA. The data supported that the community disposed of a variety of resources regarding PA and showed signs of readiness for change. However, a certain degree of saturation regarding PA programs existed. The need for health enhancing PA interventions for men was only partly recognized. The local authority considered PA to be particularly important in the context of mobility and traffic safety. Including multiple stakeholders contributed to a balanced and in-depth assessment of community readiness and was helpful for determining starting points for tailored PA interventions due to the detection of complex relationships and structures. The study delivers preliminary evidence that a qualitative multi-perspective community readiness assessment adds value to quantified single-perspective readiness assessment research practice.

Background Low- and middle-income countries (LMICs) face disproportionately high mortality rates, yet the causes of death in LMICs are not robustly understood, limiting the effectiveness of interventions to reduce mortality. Minimally invasive tissue sampling (MITS) is a standardized postmortem examination method that holds promise for use in LMICs, where other approaches for determining cause of death are too costly or unacceptable. This study documents the costs associated with implementing the MITS procedure in LMICs from the healthcare provider perspective and aims to inform resource allocation decisions by public health decisionmakers. Methods We surveyed 4 sites in LMICs across Sub-Saharan Africa and South Asia with experience conducting MITS. Using a bottom-up costing approach, we collected direct costs of resources (labor and materials) to conduct MITS and the pre-implementation costs required to initiate MITS. Results Initial investments range widely yet represent a substantial cost to implement MITS and are determined by the existing infrastructure and needs of a site. The costs to conduct a single case range between $609 and $1028 per case and are driven by labor, sample testing, and MITS supplies costs. Conclusions Variation in each site’s use of staff roles and testing protocols suggests sites conducting MITS may adapt use of resources based on available expertise, equipment, and surveillance objectives. This study is a first step toward necessary examinations of cost-effectiveness, which may provide insight into cost optimization and economic justification for the expansion of MITS.

Summary The human and social implications of poor health literacy are substantial and wide-ranging. Health literacy represents the personal competencies and organizational structures, resources and commitment that enable people to access, understand, appraise and use information and services in ways that promote and maintain good health. A large-scale societal improvement of health literacy will require political buy-in and a systematic approach to the development of health literacy capacity at all levels. This article builds the case for enhancing health literacy system capacity and presents a framework with eight action areas to accommodate the structural transformation needed at micro, meso and macro levels, including a health literate workforce, health literate organization, health literacy data governance, people-centred services and environments based on user engagement, health literacy leadership, health literacy investments and financial resources, health literacy-informed technology and innovation, and partnerships and inter-sectoral collaboration. Investment in the health literacy system capacity ensures an imperative and systemic effort and transformation which can be multiplied and sustained over time and is resilient towards external trends and events, rather than relying on organizational and individual behavioural change alone. Nevertheless, challenges still remain, e.g. to specify the economic benefits more in detail, develop and integrate data governance systems and go beyond healthcare to engage in health literacy system capacity within a wider societal context., Lay Summary Health literacy represents the personal competencies and organizational structures and resources enabling people to access, understand, appraise and use information and services in ways that promote and maintain good health. To meet the needs related to impact of poor health literacy, this article introduces a framework for the development of health literacy system capacity with eight action areas including the development of a health literate workforce, health literate organization, health literacy data governance, people-centred services and environments based on user engagement, health literacy leadership, health literacy investments and financial resources, health literacy-informed technology and innovation, and partnerships and inter-sectoral collaboration. Investment in health literacy system capacity ensures a future-proof effort that can be multiplied and sustained over time, rather than relying on organizational or individual behavioural change alone.

Summary Interventions to promote physical activity (PA) in childcare centers have been shown to increase children’s PA levels; moreover, a growing number of evidence-based best practice guidelines exist for this setting. However, there is a lack of knowledge on the facilitators of and barriers to the successful implementation of PA guidelines and interventions. We used Cooperative Planning to improve capabilities for PA in childcare centers. This qualitative study aimed to explore childcare center directors’ views on the Cooperative Planning process and identify the facilitators of and barriers to its implementation. We conducted guided semi-structured interviews with the directors of nine childcare centers after completion of the 12-month Cooperative Planning process. The interviews were recorded, transcribed and analyzed using qualitative content analysis with inductive category development. Facilitators and barriers were systematized according to the Consolidated Framework for Implementation Research (CFIR). Cooperative Planning was regarded as being helpful for structuring the process and involving all team members. Several facilitators within the CFIR domains inner setting (structural characteristics, networks and communications, implementation climate), outer setting (support from parents and provider), characteristics of individuals (intrinsic motivation of the staff) and process (individual drivers) were identified. The reported barriers included structural characteristics (e.g. lack of time), networks and communications (e.g. team conflicts) and characteristics of individuals (e.g. lack of willingness to accept change). Several contextual and interpersonal factors seem to influence the extent to which a Cooperative Planning process can be implemented by a childcare center’s team. Future research is needed to evaluate the strategies needed to overcome the identified barriers.

For years Gross Domestic Product (GDP) has served as a key indicator of human progress and “successful” societies. Unfortunately, GDP has failed to robustly capture the human experience or predict resilience through crises; and obscures the presence of inequity -- a key determinant of suffering. It is clear the global community needs a new organizing principle: one that envisions and measures progress by focusing on the conditions that support health, resilience, and overall wellbeing. This paper examines key health promotion concepts and approaches, juxtaposed with philosophical underpinnings of the concept of wellbeing, alternative measurement strategies, and examples of wellbeing policy initiatives. In doing so, the paper highlights the relevance of wellbeing policy frameworks to health promotion, the utility of health promotion strategies for implementing wellbeing policy frameworks, and controversies and pitfalls that require consideration. The paper concludes by outlining how health promotion is uniquely poised to contribute to wellbeing policy frameworks that promote the sources of human and planetary thriving through sustainable development, and that promoting a wellbeing agenda can strengthen efforts to promote health by addressing social determinants and ensuring universal access to resources that support coping with emerging challenges and strengthen resilience.

The purpose of the Health.edu project was to develop, implement and evaluate effective and feasible measures addressing students' health-related knowledge and understanding (HKU) in physical education (PE) with a specific focus on a co-creation approach (Cooperative Planning). The general procedure was identical in the four intervention schools involved; however, effectiveness (i.e. an increase in HKU) differed. Therefore, the present study investigated how different contextual factors supported or hindered the Cooperative Planning approach (evaluation of program implementation). To consider different perspectives in the analysis, we used data triangulation. On the one hand, written protocols (N = 19) document relevant statements and decisions in each planning group meeting (scientific perspective). On the other hand, we captured the participating PE teachers’ (N = 8) individual attitudes after the Cooperative Planning process through semi-structured interviews (teachers’ perspective). Data were analysed via qualitative content analysis. We identified three relevant factors with influence on the Cooperative Planning approach. First, the Cooperative Planning intervention worked if teachers saw a benefit in providing evidence-based knowledge, reflected their teaching practices and made an effort to implement new teaching strategies. Second, it was beneficial to have students represented as partners in the decision-making process. Third, support from the principal appeared to be helpful but not mandatory for implementing progressive pedagogical concepts. Continuous monitoring and reflection on those factors by the leading project team might help facilitate subsequent interventions using Cooperative Planning.

Background Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. Methods From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Results The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. Conclusions MITS is useful for evaluating COVID-19–related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA.

Background Minimally invasive autopsies, also known as minimally invasive tissue sampling (MITS), have proven to be an alternative to complete diagnostic autopsies (CDAs) in places or situations where this procedure cannot be performed. During the coronavirus disease 2019 (COVID-19) pandemic, CDAs were suspended by March 2020 in Brazil to reduce biohazard. To contribute to the understanding of COVID-19 pathology, we have conducted ultrasound (US)–guided MITS as a strategy. Methods This case series study includes 80 autopsies performed in patients with COVID-19 confirmed by laboratorial tests. Different organs were sampled using a standardized MITS protocol. Tissues were submitted to histopathological analysis as well as immunohistochemical and molecular analysis and electron microscopy in selected cases. Results US-guided MITS proved to be a safe and highly accurate procedure; none of the personnel were infected, and accuracy ranged from 69.1% for kidney, up to 90.1% for lungs, and reaching 98.7% and 97.5% for liver and heart, respectively. US-guided MITS provided a systemic view of the disease, describing the most common pathological findings and identifying viral and other infectious agents using ancillary techniques, and also allowed COVID-19 diagnosis confirmation in 5% of the cases that were negative in premortem and postmortem nasopharyngeal/oropharyngeal swab real-time reverse-transcription polymerase chain reaction. Conclusions Our data showed that US-guided MITS has the capacity similar to CDA not only to identify but also to characterize emergent diseases.

Summary The World Health Organization defines health promotion as process of enabling people to increase control over their health and its determinants, and thereby improve their health. As the world transitions into the information age, incorporating digital technologies into health promotion is becoming commonplace. This article discusses current applications of digital health promotion (DHP) and addresses its potential benefits, challenges, as well as how differences in cultures, governance models and digital readiness across the globe will shape the implementation of DHP differently in each society. The benefits include expanding access to health information and health promoting services, lowering scaling up costs, personalizing health advice and real-time ‘nudging’ toward healthier options. Key challenges would involve privacy control, appropriate use of data including secondary usage beyond the original intention, defining the limits of ‘nudging’ and the right of free choice, and ensuring widespread accessibility and affordability to minimize the exacerbation of social inequities. Finally, we discuss the enabling factors for successful DHP implementation, suggesting measures that should be taken at both individual and system levels. At the individual level, we explore the factors necessary to access and benefit from DHP meaningfully; at the system level, we examine the infrastructure required to provide wide access, establish trust among users and enable sustainability of behavioral changes.

Health promotion has paid a lot of attention to the social determinants of health and to health equity but much less attention to the ecological determinants. Yet the most fundamental determinants of health are the natural systems that make the Earth liveable and are the source of our air, water, food, fuels and materials. Yet they are threatened by the very economic and social development that we have created to meet the social determinants of health. Moreover, the benefits and burdens of that development are inequitably distributed, resulting in both ecological and social injustice. In the past few years the new field of planetary health—‘the health of human civilization and the state of the natural systems on which it depends’—has emerged, while WHO has confirmed that ‘the source of human health [is] nature’. So arguably the most important task facing health promotion in the 21st century is to turn its attention to planetary health: health promotion workers must become planetary health promoters. Local health promotion in the 21st century needs to incorporate the concept of planetary health promotion and its application in the creation of healthy ‘One Planet’ communities and must become part of the emerging network of community organizations and individuals working to create sustainable, just and healthy communities.

Summary Governance is an important factor in urban health, and law is an important element of healthy governance. Law can be an intervention local government wields to influence behavior and shape environments. Law can also be an important target of health promotion efforts: Law and the enforcement and implementation behaviors it fosters can promote unhealthy behaviors and environmental conditions, and can act as a barrier to healthy interventions or practices. Finally, law is a design and construction tool for the organization of governance. Law is the means through which cities are formally established. Their powers and duties, organizational structure, boundaries and decision-making procedures are all set by law. Regardless of the form of government, cities have legal levers they can manipulate for health promotion. Cities can use tax authority to influence the price of unhealthy products, or to encourage consumption of healthy foods. Cities can use their legal powers to address incidental legal effects of policies that they themselves cannot control. Cities may also have the authority to use law to address deeper determinants of health. The overall level of income or wealth inequality in a country reflects factors well-beyond a local government’s control, but city government nonetheless has levers to directly and indirectly reduce economic and social inequality and their effects. A renewed focus on law and urban governance is the key to assuring health and well-being and closing the health equity gap.

Health promotion increasingly employs participatory approaches, but the question arises whether the likely higher costs of participation also translate into greater benefits. This article takes a first step toward a full health economic evaluation by comprehensively reporting the costs of a specific participatory approach, Cooperative Planning, in a German research consortium to promote physical activity. We conducted a costing analysis of Cooperative Planning at 22 sites across six settings. Project teams used a custom template to record resource use. We calculated average costs per meeting, site and setting using the opportunity costs approach, and obtained feedback from participating researchers. A total of 144 planning meetings with an average of nine participants were conducted. Costs per meeting varied significantly across settings. Differences were mostly attributable to varying meeting duration, preparation time and numbers of participants. Across settings, human resources accounted for roughly 95% of the costs. Implementing researchers reported challenges regarding the logic and methods of the health economic analysis. A participatory approach to physical activity promotion may cause substantially varying costs in different settings despite similar cost structures. However, their value for money could turn out comparably favorable if (and only if) the expected benefits is indeed forthcoming. Despite some challenges implementing the costing exercise into the logistics of ongoing participatory projects, this analysis may pave the way toward a full health economic evaluation, and the template may be useful to future participatory health promotion projects.

Hospital outbreak investigations are high-stakes epidemiology. Contacts between staff and patients are numerous; environmental and community exposures are plentiful; and patients are highly vulnerable. Having the best data is paramount to understanding an outbreak in order to stop ongoing transmission and prevent future outbreaks. In the past 5 years, the high-resolution view of transmission offered by analyzing pathogen whole-genome sequencing (WGS) is increasingly part of hospital outbreak investigations. Concerns over speed and actionability, assay validation, liability, cost, and payment models lead to further opportunities for work in this area. Now accelerated by funding for COVID-19, the use of genomics in hospital outbreak investigations has firmly moved from the academic literature to more quotidian operations, with associated concerns involving regulatory affairs, data integration, and clinical interpretation. This review details past uses of WGS data in hospital-acquired infection outbreaks as well as future opportunities to increase its utility and growth in hospital infection prevention., The use of genomics in infectious disease outbreaks and hospital epidemiology has undergone a significant growth spurt over the past several years. This review details past experiences and future opportunities for WGS in hospital outbreak investigations.

Background Bacterial diseases are the leading cause of mortality globally, and due to haphazard use of antibiotics, antimicrobial resistance has become an emerging threat. Methods This cross-sectional observational study utilized a minimally invasive tissue sampling procedure to determine the cause of death among an adult population. Bacterial cultures (blood, cerebrospinal fluid, lung tissue) and antibiotic susceptibility were evaluated, and the results were compared between community and hospital deaths. Results Of 100 deceased persons studied, 76 (76%) deaths occurred in the community and 24 (24%) in the hospital. At least 1 bacterial agent was cultured from 86 (86%) cases; of these, 74 (86%) had a bacterial disease attributed as the primary cause of death, with pneumonia (35, 47.3%), sepsis (33, 44.6%), and meningitis (3, 4.1%) most common. Of 154 bacterial isolates (76.6% from the community and 23.4% from the hospital) detected from 86 culture-positive cases, 26 (16.8%) were multidrug-resistant (MDR). Klebsiella species were the most common (13 of 26) MDR organisms. The odds of getting an MDR Klebsiella infection was 6-fold higher among hospital deaths compared with community deaths (95% confidence interval [CI], 1.37–26.40; P = .017) and almost 23-fold higher (CI, 2.45–213.54; P = .006) among cases with prior antibiotic use compared to those without. Conclusions High incidence of serious bacterial infections causing death of adults in the community, with most MDR organisms isolated from hospitalized cases, calls for robust surveillance mechanisms and infection prevention activities at the community level and evidence-driven antibiotic stewardship in healthcare settings.

Burn injuries are a severe form of skin damage with a significant risk of scarring and systemic sequelae. Approximately 11 million individuals worldwide suffer burn injuries annually, with 180,000 people dying due to their injuries. Wound healing is considered the main determinant for the survival of severe burns and remains a challenge. The surgical treatment of burn wounds entails debridement of necrotic tissue, and the wound is covered with autologous skin substitutes taken from healthy donor areas. Autologous skin transplantation is still considered to be the gold standard for wound repair. However, autologous skin grafts are not always possible, especially in cases with extensive burns and limited donor sites. Allografts from human cadaver skin and xenografts from pig skin may be used in these situations to cover the wounds temporarily. Alternatively, dermal analogs are used until permanent coverage with autologous skin grafts or artificial skins can be achieved, requiring staged procedures to prolong the healing times with the associated risks of local and systemic infection. Over the last few decades, the wound healing process through tissue-engineered skin substitutes has significantly enhanced as the advances in intensive care ensuring early survival have led to the need to repair large skin defects. The focus has shifted from survival to the quality of survival, necessitating accelerated wound repair. This special volume of JBCR is dedicated to the discoveries, developments, and applications leading the reader into the past, present, and future perspectives of skin tissue engineering in burn injuries.

Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging public health problem. This study explores the specifics of CRKP epidemiology in Colombia based on whole genome sequencing (WGS) of the National Reference Laboratory at Instituto Nacional de Salud (INS)’s 2013–2017 sample collection. Methods A total of 425 CRKP isolates from 21 departments were analyzed by HiSeq-X10®Illumina high-throughput sequencing. Bioinformatic analysis was performed, primarily using the pipelines developed collaboratively by the National Institute for Health Research Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance (AMR), and AGROSAVIA. Results Of the 425 CRKP isolates, 91.5% were carbapenemase-producing strains. The data support a recent expansion and the endemicity of CRKP in Colombia with the circulation of 7 high-risk clones, the most frequent being CG258 (48.39% of isolates). We identified genes encoding carbapenemases blaKPC-3, blaKPC-2, blaNDM-1, blaNDM-9, blaVIM-2, blaVIM-4, and blaVIM-24, and various mobile genetic elements (MGE). The virulence of CRKP isolates was low, but colibactin (clb3) was present in 25.2% of isolates, and a hypervirulent CRKP clone (CG380) was reported for the first time in Colombia. ST258, ST512, and ST4851 were characterized by low levels of diversity in the core genome (ANI > 99.9%). Conclusions The study outlines complex CRKP epidemiology in Colombia. CG258 expanded clonally and carries specific carbapenemases in specific MGEs, while the other high-risk clones (CG147, CG307, and CG152) present a more diverse complement of carbapenemases. The specifics of the Colombian situation stress the importance of WGS-based surveillance to monitor evolutionary trends of sequence types (STs), MGE, and resistance and virulence genes.

BackgroundKlebsiella pneumoniae is a critically important pathogen in the Philippines. Isolates are commonly resistant to at least two classes of antibiotics, yet mechanisms and spread of its resistance are not well studied.MethodsA retrospective sequencing survey was performed on carbapenem-, extended spectrum beta-lactam- and cephalosporin-resistant Klebsiella pneumoniae isolated at 20 antimicrobial resistance (AMR) surveillance sentinel sites from 2015-2017. We characterized 259 isolates using biochemical methods, antimicrobial susceptibility testing, and whole genome sequencing (WGS). Known AMR mechanisms were identified. Potential outbreaks were investigated by detecting clusters from epidemiologic, phenotypic and genome-derived data.ResultsPrevalent AMR mechanisms detected include blaCTX-M-15 (76.8%) and blaNDM-1 (37.5%). An epidemic IncFII(Yp) plasmid carrying blaNDM-1 was also detected in 46 isolates from 6 sentinel sites and 14 different sequence types (ST). This plasmid was also identified as the main vehicle of carbapenem resistance in 2 previously unrecognized local outbreaks of ST348 and ST283 at 2 different sentinel sites. A third local outbreak of ST397 was also identified but without the IncFII(Yp) plasmid. Isolates in each outbreak site showed identical STs, K- and O-loci, and similar resistance profiles and AMR genes. All outbreak isolates were collected from blood of children aged ConclusionWGS provided an in-depth understanding of the epidemiology of AMR in the Philippines, which was not possible with only phenotypic and epidemiologic data. The identification of three previously unrecognized Klebsiella outbreaks highlights the utility of WGS in outbreak detection, as well as its importance in public health and in implementing infection control programs.summaryWhole genome sequencing identified three distinct previously unrecognized local outbreaks in a retrospective study in the Philippines, along with an epidemic plasmid carrying antimicrobial resistance genes, highlighting its importance in antimicrobial resistance surveillance, outbreak detection and infection control.

Performing whole genome sequencing (WGS) for the surveillance of antimicrobial resistance offers the ability to determine not only the antimicrobials to which rates of resistance are increasing, but also the evolutionary mechanisms and transmission routes responsible for the increase at local, national, and global scales. To derive WGS-based outputs, a series of processes are required, beginning with sample and metadata collection, followed by nucleic acid extraction, library preparation, sequencing, and analysis. Throughout this pathway there are many data-related operations required (informatics) combined with more biologically focused procedures (bioinformatics). For a laboratory aiming to implement pathogen genomics, the informatics and bioinformatics activities can be a barrier to starting on the journey; for a laboratory that has already started, these activities may become overwhelming. Here we describe these data bottlenecks and how they have been addressed in laboratories in India, Colombia, Nigeria, and the Philippines, as part of the National Institute for Health Research Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance. The approaches taken include the use of reproducible data parsing pipelines and genome sequence analysis workflows, using technologies such as Data-flo, the Nextflow workflow manager, and containerization of software dependencies. By overcoming barriers to WGS implementation in countries where genome sampling for some species may be underrepresented, a body of evidence can be built to determine the concordance of antimicrobial sensitivity testing and genome-derived resistance, and novel high-risk clones and unknown mechanisms of resistance can be discovered.

Despite recent developments in therapy for inflammatory bowel diseases (IBDs), there have been limited advances in diagnostic tools available to aid in disease management. A growing body of evidence suggests that there are important host-microbe interactions at the mucosal interface that modulate the inflammatory response in patients with IBD. Additionally, the importance of mucosal integrity and its disruption appears to be important in the pathophysiology and perpetuation of the disease. The ability to characterize this interface may provide valuable information for both disease monitoring and identification of new treatment targets. Endoscopy remains the primary tool for disease monitoring, and mucosal healing is the primary therapeutic target in IBD treatment. However, establishing mucosal healing requires repetitive endoscopic procedures, and endoscopy is limited by factors such as invasiveness, cost, and risk of adverse events. Moreover, the use of a bowel preparation for colonoscopies alters the mucus layer and thus perturbs evaluation of the host-microbe interaction. Stool sampling may also be inaccurate because it reflects the end state of metabolites and proteins, failing to take into account the degradation or alteration of substrates of interest by bacterial proteases and other enzymes during passage through the colon. A novel sampling capsule, called the Recoverable Sampling System (RSS), is being developed as a complementary tool to colonoscopy. The RSS is intended to be a platform for noninvasive autonomous sampling, preservation, handling, and storage of analytes of interest found in the gastrointestinal fluids. A proprietary preservative contained within the chambers of the capsule has been developed to stabilize DNA and proteins for ex vivo microbiome and metabolomics analyses. Surrogate markers such as SPP24 and GUCA2a have been identified to correlate with gut health, intestinal permeability, and inflammation and could be locally sampled by the RSS. The potential clinical utility of an RSS device is broad and would likely be able to guide therapy by allowing for more frequent disease monitoring, aiding in disease characterization, and facilitating in the identification of novel therapeutic targets.A new technology is being developed, Recoverable Sampling System (RSS), that may allow sampling without a colonoscopy. This may lead to new biomarkers and even drug targets which may ultimately improve the care of these patients.

There has been a dramatic rise in mental health difficulties during the coronavirus disease 2019 (COVID-19) pandemic. While young adults have the lowest risk of hospitalization and mortality due to COVID-19, they have been identified as being at highest risk of detrimental mental health outcomes during the pandemic, along with women, those with lower socioeconomic status and those with pre-existing mental health conditions. Somewhat of a crisis in mental health has emerged across the general population through the evolution of the pandemic. A national Canadian survey identified a quadrupling of those experiencing pervasive elevated anxiety symptoms early in the pandemic compared to pre-pandemic levels, and a doubling of those with pervasive elevated depressive symptoms. Independent of the pandemic, persons with inflammatory bowel disease (IBD) can face multiple challenges related to their disease, which can result in a significant psychosocial burden and psychologic distress. Anxiety and depression have been found to be more prevalent in persons with IBD. Many potential factors contribute to the increased psychologic distress and negative impacts on mental health of the COVID-19 pandemic on persons with IBD. These include the fears of contracting COVID-19 or infecting other people. Many believe that IBD or its treatments predispose them to an increased risk of COVID-19 or a worse outcome if acquired. Concerns about access to health care add to mental distress. People with IBD generally report lower quality of life (QOL) compared to community controls. Psychologic interventions, in addition to adequate disease control, have been shown to improve health-related QOL. Uncertainty is another factor associated with reduced health-related QOL. Most studies suggest that persons with IBD have suffered QOL impairment during the pandemic in comparison to the pre-pandemic period. Uncertainties brought on by the pandemic are important contributors for some of the reduction in QOL.

The risk of hospitalization and death from Coronavirus disease-19 (COVID-19) increases with age. The extreme elderly have been particularly vulnerable, with those above the age of 80 having a case-fatality rate as high as 15%. Aging of the immune system can lead to impaired inflammatory responses where eradication of an organism such as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) is inadequate but is exaggerated in such a way as to enhance pneumonia and acute respiratory distress syndrome. Frailty and comorbidity are both more common in the elderly, and these can enhance the morbidity and mortality from COVID-19. Studies from Northern California and Italy suggest that elderly persons with inflammatory bowel disease (IBD) were more likely to acquire SARS-CoV-2 infection than youths with IBD. While the specific impact of age-related comorbidity is less well established among people with IBD who acquire COVID-19, data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) database reported that having two or more chronic illnesses was independently associated with developing severe COVID-19 among people with IBD. Despite having exaggerated auto-inflammatory responses, people with IBD do not appear to have an overall increased risk of developing severe COVID-19 than the general population. However, whether seniors with IBD do worse once they acquire COVID-19 compared with seniors without IBD is not known. The advent of telehealth care has posed an information technology challenge for many seniors with and without IBD. Most persons with IBD have expressed satisfaction with virtual IBD health care (phone or video-based visits). While the elderly may have less robust immune responses to vaccinations, learning from experiences with other vaccination programs, especially influenza, have shown that vaccinating seniors decreases both morbidity and mortality and, in turn, healthcare resources.

The prevalence of inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, in Canada, is over 0.75% in 2021. Many individuals with IBD are immunocompromised. Consequently, the World Health Organization’s declaration of a global pandemic uniquely impacted those with IBD. Crohn’s and Colitis Canada (CCC) formed the COVID-19 and IBD Taskforce to provide evidence-based guidance during the pandemic to individuals with IBD and their families. The Taskforce met regularly through the course of the pandemic, synthesizing available information on the impact of COVID-19 on IBD. At first, the information was extrapolated from expert consensus guidelines, but eventually, recommendations were adapted for an international registry of worldwide cases of COVID-19 in people with IBD. The task force launched a knowledge translation initiative consisting of a webinar series and online resources to communicate information directly to the IBD community. Taskforce recommendations were posted to CCC’s website and included guidance such as risk stratification, management of immunosuppressant medications, physical distancing, and mental health. A weekly webinar series communicated critical information directly to the IBD community. During the pandemic, traffic to CCC’s website increased with 484,755 unique views of the COVID-19 webpages and 126,187 views of the 23 webinars, including their video clips. CCC’s COVID-19 and IBD Taskforce provided critical guidance to the IBD community as the pandemic emerged, the nation underwent a lockdown, the economy reopened, and the second wave ensued. By integrating public health guidance through the unique prism of a vulnerable population, CCC’s knowledge translation platform informed and protected the IBD community.

Inflammatory bowel disease (IBD) is a disease that results from dysregulation of the immune system and frequently requires medications that can affect the immune response to infections; therefore, it was imperative to quickly understand the risk of coronavirus disease 2019 (COVID-19) infection on persons living with IBD and how that risk may be increased by commonly used IBD medications. The IBD research community in Canada and beyond quickly established collaborative efforts to better understand the specific risk posed by COVID-19 on persons with IBD. We learned that IBD itself was not a risk factor for death or serious complications of COVID-19, and that most commonly used drug classes (with the notable exception of corticosteroids) do not increase the risk of COVID-19-related adverse outcomes. The risk factors for serious complications and death from COVID-19 appear to be similar to those identified in the wider population; those being advanced age, having pre-existing heart or lung disease, and smoking. We recommend that persons with IBD do not alter their course of therapy to avoid complications of COVID-19, though the indiscriminate use of corticosteroids should be avoided. Persons with IBD should follow the same public health recommendations as the general population to reduce their personal risk of acquiring COVID-19.

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there were many unknowns: transmission vectors of the virus, appropriate intervention strategies and if being immunocompromised due to inflammatory bowel disease (IBD), for example, or medications put a person at increased risk for severe COVID-19. Imposing and relaxing of public health restrictions at different times and in different regions in Canada led to different epidemiologies of the virus in different provinces and territories. In order to understand the waxing and waning of waves of the COVID-19 pandemic, it is necessary to understand the effective reproductive number (Rt) and the countervailing forces that exert upward or downward pressure on the spread of the virus at a given point in time. As many regions in Canada deal with a third wave, the primary forces affecting the Rt of severe acute respiratory syndrome coronavirus 2 are variants of concern and the increasing vaccinations of Canadians leading to increased population-level immunity. Fortunately, for the IBD population, current research suggests that those with IBD are not at increased risk of contracting COVID-19, nor of having a more severe disease course when compared to the general population.

Background To inform the World Health Organization’s full value of vaccine assessment for group B Streptococcus (GBS) vaccines, a rapid literature appraisal was conducted to inform the operationalization of maternal GBS vaccination. We found limited published information on stakeholder perceptions of the public health importance of GBS disease and vaccination, and we therefore undertook a multicountry survey. Methods An online survey was conducted in late 2019 to collect information on stakeholders’ awareness of GBS disease and the priority accorded to vaccination. The survey was distributed by email to 395 representatives of national pediatric, gynecology, and obstetrics associations, national immunization technical advisory groups (NITAGs), national regulatory agencies, academia, and United Nations organizations. Results Among 101 survey respondents from 66 countries, 36% were pediatricians, 25% obstetricians/gynecologists, 21% immunization specialists, and 18% other public health specialists. More than half (58%) of respondents reported being familiar with GBS disease as a public health problem; familiarity decreased by country income level. Knowledge of GBS disease was greatest in the Americas (68%) and Europe (66%) and lowest in Asia (13%–38%). Perception of GBS disease as a public health problem was highest among pediatricians (71%) and lowest among public health policy makers and NITAG members (30%) across country groupings. Approximately half of respondents (49%) considered the introduction of a GBS vaccine as a priority. Conclusions The information obtained will inform the appropriate packaging and presentation of information to address stakeholder perceptions and promote evidence-based decision making on GBS vaccination.

BACKGROUND Despite Group B streptococcus being a leading cause of maternal and infant morbidity and mortality, no vaccine is currently available to prevent this disease. To inform vaccine developers, countries, and funders, we analyse in this paper the key factors likely to influence the demand for a GBS vaccine and the long-term financial sustainability for a commercial entity considering the development of such a vaccine. METHODS By using population-based forecasting, we estimated the demand for a GBS vaccine based on the burden of disease, the strength of the maternal immunisation systems, the fiscal space, and the track record in introducing new vaccines. Furthermore, we estimated the financial viability for a vaccine developer by estimating the Net Present Value of the vaccine development project using a Discounted Cash Flow model. RESULTS Demand for this vaccine can be significant if policy recommendations for use are adopted by countries, in particular the largest ones, most of which have a burden that justifies the use of the vaccine and if financing for the vaccine will be made available either by countries themselves or by funding mechanisms such as Gavi, the Vaccine Alliance. Different administration schedules may result in even larger demand. With a widespread policy recommendation, the commercial viability of this vaccine can be achieved. The cost of clinical development - particularly the type of pivotal trial required - and the number of competitors are the factors that can strongly influence the long-term financial sustainability and hence the interest of vaccine developers. CONCLUSIONS This analysis suggests the potential for full financial and commercial viability for a manufacturer pursuing the development and commercialization of a GBS vaccine. Risks exists in relation to the clinical trial design and costs, the level of competition, countries' ability to pay, the administration schedule and the availability of policies that encourage use of the vaccine. To reduce those risks and ensure equitable access to a GBS vaccine, the role of donors or financers can prove very important; as can a coordinated operational research agenda that aims at clarifying those areas of uncertainty.

Background Survivors of invasive group B Streptococcus (iGBS) disease, notably meningitis, are at increased risk of neurodevelopmental impairment. However, the limited studies to date have a median follow-up to 18 months and have mainly focused on moderate or severe neurodevelopmental impairment, with no previous studies on emotional-behavioral problems among iGBS survivors. Methods In this multicountry, matched cohort study, we included children aged 18 months to 17 years with infant iGBS sepsis and meningitis from health demographic surveillance systems, or hospital records in Argentina, India, Kenya, Mozambique, and South Africa. Children without an iGBS history were matched to iGBS survivors for sex and age. Our primary outcomes were emotional-behavioral problems and psychopathological conditions as measured with the Child Behavior Checklist (CBCL). The CBCL was completed by the child’s primary caregiver. Results Between October 2019 and April 2021, 573 children (mean age, 7.18 years) were assessed, including 156 iGBS survivors and 417 non-iGBS comparison children. On average, we observed more total problems and more anxiety, attention, and conduct problems for school-aged iGBS survivors compared with the non-iGBS group. No differences were found in the proportion of clinically significant psychopathological conditions defined by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Conclusions Our findings suggested that school-aged iGBS survivors experienced increased mild emotional behavioral problems that may affect children and families. At-risk neonates including iGBS survivors need long-term follow-up with integrated emotional-behavioral assessments and appropriate care. Scale-up will require simplified assessments that are free and culturally adapted.

Background Invasive group B Streptococcus disease (iGBS) in infancy, including meningitis or sepsis, carries a high risk of mortality and neurodevelopmental impairment (NDI). We present data on iGBS from 2 decades of surveillance in Manhiça, Mozambique, with a focus on NDI. Methods Morbidity surveillance databases in a rural Mozambican district hospital were screened for iGBS cases. From February 2020 to March 2021, surviving iGBS patients (n = 39) plus age- and sex-matched children without iGBS (n = 119) were assessed for neurocognitive development, vision, and hearing. The role of GBS in stillbirths and infant deaths was investigated using minimally invasive tissue sampling (MITS). Results Ninety iGBS cases were included, with most children being Conclusions In absence of preventive strategies, such as intrapartum antibiotics, iGBS remains a significant cause of perinatal and infant disease and death. GBS also causes major longer-term neurodevelopmental sequelae, altogether justifying the need for maternal GBS vaccination strategies to increase perinatal and infant survival.

The global burden of Group B Streptococcus (GBS) was estimated for 2015 prompting inclusion of GBS as a priority in the Global Meningitis Roadmap. New estimates for the year 2020 and a WHO report analysing the full value of GBS maternal vaccines has been launched to advance evidence based decision making for multiple stakeholders. In this first of a 10-article supplement, we discuss the following (1) gaps in evidence and action, (2) new evidence in this supplement, and (3) what actions can be taken now and key research gaps ahead. We call for investment in the research pipeline, notably description, development, and delivery, in order to accelerate progress and address the large burden of GBS for every family in every country.

Brain metastases from solid tumors are increasing in incidence, especially as outcomes of systemic therapies continue to extend patients’ overall survival. The long-held notion that the brain is an immune sanctuary has now been largely refuted with increasing evidence that immunotherapy can induce durable responses in brain metastases. Single agent immune checkpoint inhibition with anti-CTLA4 and anti-PD1 antibodies induces durable responses in 15%–20% in melanoma brain metastases as long as patients are asymptomatic and do not require corticosteroids. The combination of anti-CTLA4 with anti-PD-1 antibodies induces an intracranial response in over 50% of asymptomatic melanoma patients, and much lower rate of otherwise durable responses (20%) in symptomatic patients or those on steroids. Data in other cancers, such as renal cell carcinoma, are accumulating indicating a role for immunotherapy. Emerging immunotherapy approaches will have to focus on increasing response rates, decreasing toxicity, and decreasing steroid dependency. The path to those advances will have to include a better understanding of the mechanisms of response and resistance to immunotherapy in brain metastases, the use of novel agents such as anti-LAG3 checkpoint inhibitors, targeted therapy (oncogene directed or TKIs), and possibly surgery and SRS to improve the outcomes of patients with brain metastases.

Coronavirus disease 2019 (COVID-19) in children with inflammatory bowel disease (IBD) typically results in a mild infection, similar to those without IBD. Children and adolescents have less severe manifestations of COVID-19 compared to older people, whether or not they have IBD. However, some IBD medications (in particular, corticosteroids) are associated with more severe COVID-19. During the first year of the global pandemic, more IBD care was provided with online technology, necessitated by efforts to reduce hospital and clinic visits. Additionally, non-endoscopic monitoring of inflammation has been required due to the cancellation of non-urgent procedures, resulting in longer endoscopy wait-times. In contrast, pregnant people (with and without IBD) who contract COVID-19 are at increased risk of severe manifestations, death and preterm delivery, making them a priority for severe acute respiratory syndrome coronavirus 2 protective measures and vaccination. Few studies have examined effect of COVID-19 on IBD-related disease activity in pregnant people with IBD. The pandemic has significantly affected the mental health and sense of well-being of children and their families, as well as pregnant people with IBD. These groups were much more likely to experience anxiety and depression compared with prior to the pandemic, even while concern has mostly abated regarding the effect of IBD medications and COVID-19 severity. Unfortunately, the availability of mental health care providers who specialize in people with IBD has not kept pace with the increasing demand.

Melanoma is the most aggressive of the common forms of skin cancer. Metastasis to the central nervous system is one of the most common and deadly complications of this disease. Historically, melanoma patients with brain metastases had a median survival of less than 6 months. However, outcomes of melanoma patients have markedly improved over the last decade due to new therapeutic approaches, including immune and targeted therapies. Targeted therapies leverage the high rate of driver mutations in this disease, which result in the activation of multiple key signaling pathways. The RAS-RAF-MEK-ERK pathway is activated in the majority of cutaneous melanomas, most commonly by point mutations in the Braf serine-threonine kinase. While most early targeted therapy studies excluded melanoma patients with brain metastases, subsequent studies have shown that BRAF inhibitors, now generally given concurrently with MEK inhibitors, achieve high rates of tumor response and disease control in Braf-mutant melanoma brain metastases (MBMs). Unfortunately, the duration of these responses is generally relatively short- and shorter than is observed in extracranial metastases. This review will summarize current data regarding the safety and efficacy of targeted therapies for MBMs and discuss rational combinatorial strategies that may improve outcomes further.

Brain metastases (BM) present a common cause of mortality and morbidity in several metastatic cancer entities. New therapeutic developments during the last decades, including targeted and immune-related therapies, have shown considerable extra- and intracranial response rates in specific subgroups of BM patients. However, differences in the molecular alteration in the BM tumor tissue compared to extracranial tumors leads to heterogeneous therapeutic responses. Therefore, an accurate molecular analyzation of BM tissue, if possible, has become an essential part in therapeutic decision making in BM patients. The concordance of predictive molecular biomarkers between multiple sites including extracranial and intracranial tumor tissue have been analyzed for some but not all biomarkers routinely applied in modern precision medicine approaches. In the present review, we summarize the current evidence of predictive biomarkers for personalized therapy approaches in the treatment of parenchymal BM.