The prognostic effect of tumor-associated macrophages in stage I-III colorectal cancer depends on T cell infiltration.

BACKGROUND: Tumor-associated macrophages (TAMs) are associated with unfavorable patient prognosis in many cancer types. However, TAMs are a heterogeneous cell population and subsets have been shown to activate tumor-infiltrating T cells and confer a good patient prognosis. Data on the prognostic value of TAMs in colorectal cancer are conflicting. We investigated the prognostic effect of TAMs in relation to tumor-infiltrating T cells in colorectal cancers. METHODS: The TAM markers CD68 and CD163 were analyzed by multiplex fluorescence immunohistochemistry and digital image analysis on tissue microarrays of 1720 primary colorectal cancers. TAM density in the tumor stroma was scored in relation to T cell density (stromal CD3+ and epithelial CD8+ cells) and analyzed in Cox proportional hazards models of 5-year relapse-free survival. Multivariable survival models included clinicopathological factors, MSI status and BRAFV600E mutation status. RESULTS: High TAM density was associated with a favorable 5-year relapse-free survival in a multivariable model of patients with stage I-III tumors (p = 0.004, hazard ratio 0.94, 95% confidence interval 0.90-0.98). However, the prognostic effect was dependent on tumoral T-cell density. High TAM density was associated with a good prognosis in patients who also had high T-cell levels in their tumors, while high TAM density was associated with poorer prognosis in patients with low T-cell levels (pinteraction = 0.0006). This prognostic heterogeneity was found for microsatellite stable tumors separately. CONCLUSIONS: This study supported a phenotypic heterogeneity of TAMs in colorectal cancer, and showed that combined tumor immunophenotyping of multiple immune cell types improved the prediction of patient prognosis.

Understanding the connection between hospital goals and patient and family engagement: A scoping review.

The person-centered care movement has influenced hospitals to make patient and family engagement (PE) an explicit commitment in their strategic plans. This is often reflected in mission, vision, and value (MVV) statements, which are organizational artifacts intended to influence the attitudes, beliefs, and actions of hospital teams and employees because of their saliency in organizational documents and communications. Previous research has found that organizational goals for PE, like those articulated in MVV statements, can lead to effective and meaningful PE. However, a deeper understanding of how and under which circumstances MVV statements encourage and promote PE practices is needed. A scoping review was conducted to understand the connection between hospital PE goals (such as MVV statements) and PE processes and practices. The research question was: what is known about how hospital MVV statements relate to PE processes and activities? Following Arksey and O'Malley's scoping review approach, 27 articles were identified as relevant to the research question. These articles revealed five strategies that help realize hospital PE goals: communicating organizational goals; aligning documents that convey organizational goals; aligning organizational processes to support PE; providing employees with resources and support; and motivating and empowering employees to integrate PE into their work. We discuss the implications of misalignment between hospital goals and practices, which reduce team and individual motivation toward hospital PE goals.

Mental health outcomes in health care providers during the COVID-19 pandemic: an umbrella review.

As we head into the third year of the COVID-19 pandemic, there is an increasing need to consider the long-term mental health outcomes of health care workers (HCWs) who have experienced overwhelming work pressure, economic and social deprivation, burnout, and post-traumatic stress disorder (PTSD). This scoping umbrella review summarizes the mental health outcomes of published evidence syntheses on HCWs worldwide. We analyzed 39 evidence syntheses representing the findings from 1297 primary studies. We found several persistent fears and concerns (job-related fears, fear of stigmatization, worries about the pandemic, and infection-related fears) that shaped HCW experiences in delivering health care. We also describe several risk factors (job-related, social factors, poor physical and mental health, and inadequate coping strategies) and protective factors (individual and external factors). This is the first scoping umbrella review comprehensively documenting the various risk and protective factors that HCWs have faced during the COVID-19 pandemic. HCWs continue to fear the risk that they may infect their family and friends since they regularly interact with COVID-19 patients. This places HCWs in a precarious situation requiring them to balance risk to their family and friends and potential social deprivation from isolation.

This review summarizes the mental health outcomes of health care workers (HCWs) during the COVID-19 pandemic, including their worries and concerns. The fear of infecting loved ones was one of the essential fears faced by HCWs. Job-related fears included job instability, career uncertainty, the fear of losing control in the workplace, and increased workload. Furthermore, HCWs expressed concerns about stigmatization and uncertainty associated with the pandemic's magnitude, duration, and effects. Several risk factors and protective factors for the mental health of HCWs were identified in this review. Risk factors included the lack of personal protective equipment (PPE), the increased workload, the lack of timely information regarding the pandemic, involuntary conscription, social restrictions, pre-existing physical and mental illnesses, and improper coping strategies. In contrast, protective factors included personal characteristics such as altruism and humor, perceived control and self-efficacy, adequate training and education regarding the pandemic, adequate supply of PPE, and favorable work environments. These findings can serve as a basis for the formulation of interventions by governing bodies that promote the mental health of HCWs.

A systematic review of fear, stigma, and mental health outcomes of pandemics.

BACKGROUND: The COVID-19 pandemic has negatively affected the mental health of people globally. Despite substantial research on the short-term psychological impact of COVID-19, its long-term consequences on mental health remain relatively unexplored. AIMS: We aimed to examine mental health literature on prior outbreaks to provide recommendations for developing effective strategies to mitigate the short- and long-term psychological impact of the current pandemic. METHODS: We conducted a narrative review of 41 studies to analyze the adverse impact of the following epidemics and pandemics on the mental health of individuals, groups, and communities: Middle East Respiratory Syndrome, Severe Acute Respiratory Syndrome, Influenza A/H1N1, and Ebola Virus Disease. RESULTS: We noted that these past epidemics and pandemics escalated stress, distress, anxiety, fear, and stigma that persisted in countries and communities. We also identified the role of misinformation in propagating discrimination and prejudice towards certain groups. CONCLUSIONS: We discuss how the mental health outcomes of previous pandemics differed from the COVID-19 outbreak. We believe that strategies that reduce misinformation, educational initiatives, and mental health programs when introduced at the individual and community level have the potential to effectively diminish the negative psychological impact of COVID-19. PRISMA: This study followed the PRISMA guidance and was not registered in PROSPERO. This is a narrative review that used qualitative thematic analysis. Publishing a protocol on a protocol repository for such reviews is not the standard of practice.

Bridging the Macro-micro Divide: A Qualitative Meta-synthesis on the Perspectives and Experiences of Health Care Providers on the Extramedical Use and Diversion of Buprenorphine.

OBJECTIVES: Opioid agonist therapy using buprenorphine is one of the most effective treatments for opioid use disorder. However, concerns regarding its extramedical use and diversion, such as adverse patient outcomes and damage to the legitimacy of addictions practice, are persistent. The aim of this review is to synthesize the perspectives and experiences of health care providers around the extramedical use of buprenorphine. METHODS: A qualitative meta-synthesis was conducted based on a systematic search of 8 databases. All primary qualitative and mixed-methods studies relating to the views of health care providers on the extramedical use of buprenorphine were included. A qualitative analysis informed by the constant comparative method was conducted, using NVivo for data management. RESULTS: Sixteen studies were included in this review. Findings were organizedunder 2 key themes: (1) Harm-producing versus harm-reducing effects of extramedical buprenorphine use and (2) driving forces of and responses to extramedical buprenorphine use. CONCLUSIONS: The studies included in our review identified a disconnect-health care providers noted that macro, health care system-level challenges drove extramedical use whereas the recommended solutions for prevention and management were primarily aimed at the micro, individual level. This study emphasizes the critical role that health care providers can play, in partnership with patients, in informing appropriate policies and health care system design to optimize the care for people with opioid use disorder.

COVID-19 vaccine hesitancy and acceptance: a comprehensive scoping review of global literature.

As countries continue the third year of the pandemic, we believe that there has been unfair attention to COVID-19 vaccine efficacy and safety, while tacitly ignoring serious challenges with vaccine uptake, without which vaccination may not be effective against the spread of COVID-19. While several studies have been published on COVID-19 vaccine hesitancy, there remains a need to conduct a comprehensive global analysis of vaccine hesitancy. We conducted a scoping review of 60 studies published globally on vaccine hesitancy and acceptance. We conducted a qualitative analysis to identify motivators and barriers to vaccination across several cultural and demographic contexts. We found the following factors to be relevant in any discussion about addressing or minimizing vaccine hesitancy: risk perceptions, trust in health care systems, solidarity, previous experiences with vaccines, misinformation, concerns about vaccine side effects and political ideology. We combine our insights from this comprehensive review of global literature to offer an important and practical discussion about two strategies that have been used to improve vaccine uptake: (i) communication and education and (ii) vaccine rollout and logistics.

Single-cell transcriptomic analysis of human colonic macrophages reveals niche-specific subsets.

Macrophages are a heterogeneous population of cells involved in tissue homeostasis, inflammation, and cancer. Although macrophages are densely distributed throughout the human intestine, our understanding of how gut macrophages maintain tissue homeostasis is limited. Here we show that colonic lamina propria macrophages (LpMs) and muscularis macrophages (MMs) consist of monocyte-like cells that differentiate into multiple transcriptionally distinct subsets. LpMs comprise subsets with proinflammatory properties and subsets with high antigen-presenting and phagocytic capacity. The latter are strategically positioned close to the surface epithelium. Most MMs differentiate along two trajectories: one that upregulates genes associated with immune activation and angiogenesis, and one that upregulates genes associated with neuronal homeostasis. Importantly, MMs are located adjacent to neurons and vessels. Cell-cell interaction and gene network analysis indicated that survival, migration, transcriptional reprogramming, and niche-specific localization of LpMs and MMs are controlled by an extensive interaction with tissue-resident cells and a few key transcription factors.

Health care provider trust in vaccination: a systematic review and qualitative meta-synthesis.

BACKGROUND: Vaccine hesitancy is a growing issue globally amongst various populations, including health care providers. This study explores the factors that influence vaccine hesitancy amongst nurses and physicians. METHODS: We performed a qualitative meta-synthesis of 22 qualitative and mixed-method studies exploring the factors that may contribute to vaccine hesitancy amongst nurses and physicians. We included all articles that mentioned any aspect of trust concerning vaccination, including how trust may influence or contribute to vaccine hesitancy in nurses and physicians. RESULTS: Our findings revealed that vaccine hesitancy amongst nurses stemmed predominantly from two factors: distrust in health authorities and their employers, and distrust in vaccine efficacy and safety. Both nurses and physicians had a precarious relationship with health authorities. Nurses felt that their employers and health authorities did not prioritize their health over patients' health, provided inaccurate and inconsistent vaccine information, and were mistrustful of pharmaceutical company motives. Like nurses, physicians were also skeptical of pharmaceutical company motives when it came to vaccination. Additionally, physicians also held doubts regarding vaccine efficacy and safety. CONCLUSIONS: The relationship health care providers or their patients have with health authorities and other providers regarding vaccination serves as unsystematic clinical experiences that may bolster vaccine hesitancy. Providing accurate and tangible information to emphasize the safety and efficacy of vaccines to health care providers may help address their specific concerns that may ultimately increase vaccine uptake.

A qualitative meta-synthesis on how autonomy promotes vaccine rejection or delay among health care providers.

In spite of the overwhelming evidence that highlights the effectiveness of routine vaccination, an increasing number of people are refusing to follow recommended vaccination schedules. While the majority of research in this area has focussed on vaccine hesitancy in parents, there is little research on the factors that promote vaccine hesitancy in health care providers (HCPs). Identifying factors that promote vaccine hesitancy in HCPs is essential because it may help broaden our understanding of vaccine hesitancy in patients. Therefore, the goal of this investigation was to review 21 studies and examine how professional autonomy and risk perception may promote vaccine acceptance, rejection and delay in physicians and nurses. We found that vaccine hesitant nurses and physicians shared similar views towards vaccines; both groups believed that their decision to vaccinate was separate from their role as an HCP. This belief comprised of three themes: decisional autonomy, personal risk perception and alternatives to vaccination. Both groups believed that mandatory vaccine policies reduced their ability to decide whether vaccination was in their best interests. We argue that decisional autonomy may weaken risk perception of disease, which in turn may encourage beliefs and behaviours that reinforce a 'hero persona' that reduces appropriate preventive and hygiene measures. We employ the Health Belief Model to discuss the crucial role that risk perceptions may play in reinforcing autonomy in vaccine hesitant physician and nurses. We conclude this paper by providing a set of recommendations that aim to improve the decision-making process surrounding mandatory vaccinations for HCPs.

What factors promote vaccine hesitancy or acceptance during pandemics? A systematic review and thematic analysis.

Examine the factors that promote vaccine hesitancy or acceptance during pandemics, major epidemics and global outbreaks. A systematic review and thematic analysis of 28 studies on the Influenza A/H1N1 pandemic and the global spread of Ebola Virus Disease. We found seven major factors that promote vaccine hesitancy or acceptance: demographic factors influencing vaccination (ethnicity, age, sex, pregnancy, education, and employment), accessibility and cost, personal responsibility and risk perceptions, precautionary measures taken based on the decision to vaccinate, trust in health authorities and vaccines, the safety and efficacy of a new vaccine, and lack of information or vaccine misinformation. An understanding of participant experiences and perspectives toward vaccines from previous pandemics will greatly inform the development of strategies to address the present situation with the COVID-19 pandemic. We discuss the impact vaccine hesitancy might have for the introduction and effectiveness of a potential COVID-19 vaccine. In particular, we believe that skepticism toward vaccines can still exist when there are no vaccines available, which is contrary to contemporary conceptualizations of vaccine hesitancy. We recommend conducting further research assessing the relationship between the accessibility and cost of vaccines, and vaccine hesitancy.

Beyond harm-producing versus harm-reducing: A qualitative meta-synthesis of people who use drugs' perspectives of and experiences with the extramedical use and diversion of buprenorphine.

INTRODUCTION: This review synthesizes the literature on the perspectives and experiences of people who use drugs to better understand motivations and behaviors related to the extramedical use and diversion of buprenorphine. Given the particular social construction of buprenorphine against methadone, and the centrality of concerns around extramedical use in delivering opioid agonist therapies, a focus on extramedical buprenorphine use can provide an important lens through which to analyze treatment for opioid use disorder. This review is framed within persistent tensions between potential harm-producing versus harm-reducing effects of extramedical use that have long been described for opioid agonist therapies. METHODS: The research team conducted a qualitative meta-synthesis based on a systematic search of eight databases as well as hand searching. The review includes all primary qualitative and mixed-methods studies related to the perspectives and experiences of people who use drugs on extramedical buprenorphine use. The study team carried out three rounds of qualitative coding using NVivo 12, and constructivist grounded theory and the constant comparative method informed the synthesis. RESULTS: The review includes twenty-one studies. Findings are organized into the following three themes: 1) the experiences of people who use drugs (PWUD) with extramedical use of buprenorphine and their motivations to engage in it (including the desire to self-medicate and achieve "stability", to manage ongoing use of other opioids, and to "get high"); 2) the relationship between extramedical use and formal medical opioid agonist therapy programs; and 3) the established drug economy of extramedical buprenorphine. CONCLUSIONS: The review identified varied and often divergent perspectives and experiences with extramedical buprenorphine use. An examination of the reported "normalizing" effects of extramedical buprenorphine suggests this practice as extending medicalized discipline beyond the clinical environment. Taken together, these findings identify a need to move beyond the tension of harm-reducing versus harm-producing effects toward forms of health care and promotion that focus on the needs, perspectives, and priorities of people who use drugs.

Mal/adaptations: A qualitative evidence synthesis of opioid agonist therapy during major disruptions.

BACKGROUND: Opioid agonist therapy (OAT) has been severely disrupted by the COVID-19 pandemic. The risks of opioid withdrawal, overdose, and diversion have increased, so there is an urgent need to adapt OAT to best support people who use drugs (PWUD). This review examines the views and experiences of PWUD, health care providers, and health system administrators on OAT during major disruptions to medical care to inform appropriate health system responses during the current pandemic and beyond. METHODS: We conducted a systematic review and qualitative evidence synthesis. We searched three comprehensive datasets for qualitative and mixed-methods studies that examined OAT in the context of major disruptions such as natural disasters, and analyzed included studies using thematic analysis and the constant comparative method. We used conceptual frameworks of health systems resilience and adaptive systems to interpret our findings. RESULTS: We included 10 studies published between 2002 and 2020 that examined OAT in the context of hurricanes, earthquakes, and terrorist attacks. We organized our results into three themes: uncertainty, inconsistency, and vulnerability; regulatory inflexibility; and lack of coordination. The highly regulated but poorly coordinated systems of OAT provision lacked flexibility to adapt to major disruptions, thereby manufacturing vulnerability for both PWUD and health workers. CONCLUSIONS: OAT programs must be resilient and adaptable to face major disruptions while maintaining quality care. Our findings provide guidance to develop and implement innovative strategies that increase the adaptive potential of OAT programs while focusing on the needs of PWUD.

Indigenous women's experiences of cervical cancer screening: Incorporating Indigenous ways of knowing into a systematic review and meta-synthesis of qualitative research.

Due to historical and contextual factors, cervical cancer is typically detected at a later stage in Indigenous women, and so has higher morbidity and mortality. Increasing participation in cervical cancer screening (CCS) could ameliorate this health inequity by detecting cancer when it is more easily treatable. To understand the perspectives, preferences, and experiences of Indigenous women related to participation in CCS, we conducted a systematic review and meta-synthesis of nine qualitative research studies. To advance decolonised qualitative evidence synthesis approaches, we use a modified version of the Two Row Wampum-Covenant Chain Tradition, a Haudenosaunee two-eyed seeing analytic approach that integrates Western approaches with Indigenous worldviews. Using the metaphor of a network of forest plants, we illustrate the systemic and topical barriers and facilitators to CCS, as reported by Indigenous women. We use this metaphor to reiterate the importance of all levels of change to improve CCS experiences for Indigenous women.

Understanding Black Women's Perspectives and Experiences of Cervical Cancer Screening: A Systematic Review and Qualitative Meta-synthesis.

Cervical cancer is the third most common gynecological cancer. Effective population-based cervical cancer screening programs exist, but improvements in morbidity and mortality continue to demonstrate racial disparities. For example, Black women are 41% more likely to develop cervical cancer than White women and are 75% more likely to die from it. It is therefore important to understand whether these inequities in cervical cancer outcomes are related to differential access and uptake of screening programs. In this systematic review and qualitative meta-synthesis, we used an intersectional lens to understand Black women's experiences and perspectives of cervical cancer screening (CCS). We identified 12 factors related to the perspectives and experiences of Black women participating in CCS. Understanding Black women's experiences and perspectives of CCS can help individual clinicians and policymakers implement CCS in a way that is culturally appropriate and cognizant of structural oppression.

Challenges in the sociocultural milieu of South Asia: a systematic review of community health workers.

INTRODUCTION: Community health workers (CHWs) connect patients in rural and remote communities to health service organizations. This diverse group of healthcare workers has helped improve healthcare access and outcomes and enhance the quality of life for people in hard-to-reach communities. However, CHWs face numerous challenges rooted in the sociocultural milieu of the region and country in which they reside. METHODS: This systematic review and qualitative meta-synthesis of 38 studies examines the sociocultural challenges that CHWs experience; it focuses on the unique history, geography, and sociocultural milieu of South Asia. RESULTS: This study found the following challenges that CHWs regularly face when working in communities: religious and cultural norms and practices, gender and biological sex, caste, and generation. All challenges in some way relate to one another and stem from the unique sociocultural milieu of South Asia, and the various subcultures that exist in this diverse region. CONCLUSION: This article presents important guidance for program planning and CHW deployment that reflects the sociocultural realities of practice. The findings of this investigation may serve as an essential resource for program planners and decision-makers in improving the effectiveness and reach of CHW programs.

A Systematic Map of Non-Clinical Evidence Syntheses Published Globally on COVID-19.

STUDY OBJECTIVE: Evidence syntheses perform rigorous investigations of the primary literature and they have played a vital role in generating evidence-based recommendations for governments worldwide during the Covid-19 pandemic. However, there has not yet been an attempt to organize them by topic and other characteristics. This study performed a systematic mapping exercise of non-clinical evidence syntheses pertaining to Covid-19. METHODS: This study conducted a systematic search on December 5, 2020 across 10 databases and servers: CINAHL (EBSCO Information Services, Ipswich, Massachusetts, United States), Embase (Elsevier, Aalborg, Denmark), Global Health (EBSCO Information Services, Ipswich, Massachusetts, United States), Healthstar (NICHSR and AHA, Bethesda, United States), MEDLINE (NLM, Bethesda, United States), PsychINFO (APA, Washington, DC, United States), Web of Science (Clarivate Analytics, London, UK), Research Square (Research Square, Durham, North Carolina), MEDRxiv (Cold Spring Harbor Laboratory, New York, United States), and PROSPERO (NIHR, York, United Kingdom). Only full evidence syntheses published in a peer-reviewed journal or preprint server were included. RESULTS: This study classified all evidence syntheses in the following topics: health service delivery (n = 280), prevention and behavior (n = 201), mental health (n = 140), social epidemiology (n = 31), economy (n = 22), and environment (n = 19). This study provides a comprehensive resource of all evidence syntheses categorized according to topic. CONCLUSIONS: This study proposes the following research priorities: governance, the impact of Covid-19 on different populations, the effectiveness of prevention and control methods across contexts, mental health, and vaccine hesitancy.

The design and delivery of maternal health interventions in Pakistan: a scoping review.

Hundreds of women die daily due to preventable causes related to pregnancy and childbirth. Multiple programs have been developed to support efforts to reduce maternal mortality. However, no synthesis has been conducted to date that reviews the design, delivery, and impact of these initiatives in Pakistan. After conducting a systematic literature search, we found 23 articles describing interventions. We analyzed these articles for intervention characteristics. In this scoping review the authors identify the characteristics of interventions to improve maternal health services in Pakistan and priorities for future programs and research. Recommendations include multi-level interventions, stakeholder engagement, and rigorous evaluations of existing interventions.

"Death from a broken heart": A systematic review of the relationship between spousal bereavement and physical and physiological health outcomes.

The loss of a loved one is often associated with "death from a broken heart" for the survivor, and there is evidence that shows that widowers and widows are at risk for higher morbidity and mortality than the general population. This systematic review will summarize the physical and physiological health outcomes of spousal bereavement. A systematic database search was conducted, and 38 studies were analyzed. The majority of studies found a statistically significant and positive association between spousal bereavement and adverse physical and physiological health outcomes such as inflammation, cardiovascular risk, chronic pain, and mortality.

The rationales for and challenges with employing arts-based health services research (ABHSR): a qualitative systematic review of primary studies.

Health services research (HSR) is an interdisciplinary field that investigates and improves the design and delivery of health services from individual, group, organisational and system perspectives. HSR examines complex problems within health systems. Qualitative research plays an important role in aiding us to develop a nuanced understanding of patients, family, healthcare providers, teams and systems. However, the overwhelming majority of HSR publications using qualitative research use traditional methods such as focus groups and interviews. Arts-based research-artistic and creative forms of data collection such as dance, drama and photovoice-have had limited uptake in HSR due to the lack of clarity in the methods, their rationales and potential impacts. To address this uncertainty, we conducted a qualitative systematic review of studies that have employed arts-based research in HSR topics. We searched four databases for peer-reviewed, primary HSR studies. Using conventional content analysis, we analysed the rationales for using arts-based approaches in 42 primary qualitative studies. We found four rationales for using arts-based approaches for HSR: (1) Capture aspects of a topic that may be overlooked, ignored or not conceptualised by other methods (ie, quantitative and interview-based qualitative methods). (2) Allow participants to reflect on their own experiences. (3) Generate valuable community knowledge to inform intervention design and delivery. (4) Formulate research projects that are more participatory in nature. This review provides health services researchers with the tools, reasons, rationales and justifications for using arts-based methods. We conclude this review by discussing the practicalities of making arts-based approaches commensurable to HSR.