Interhospital Transfer of Patients With Acute Respiratory Failure in the United States: A Scoping Review.

OBJECTIVES: Interhospital transfer of patients with acute respiratory failure (ARF) is relevant in the current landscape of critical care delivery. However, current transfer practices for patients with ARF are highly variable, poorly formalized, and lack evidence. We aim to synthesize the existing evidence, identify knowledge gaps, and highlight persisting questions related to interhospital transfer of patients with ARF. DATA SOURCES: Ovid Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, CINAHL Plus, and American Psychological Association. STUDY SELECTION: We included studies that evaluated or described hospital transfers of adult (age > 18) patients with ARF between January 2020 and 2024 conducted in the United States. Using predetermined search terms and strategies, a total of 3369 articles were found across all databases. After deduplication, 1748 abstracts were screened by authors with 45 articles that advanced to full-text review. This yielded 16 studies that fit our inclusion criteria. DATA EXTRACTION: The studies were reviewed in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews by three authors. DATA SYNTHESIS: Included studies were mostly retrospective analyses of heterogeneous patients with various etiologies and severity of ARF. Overall, transferred patients were younger, had high severity of illness, and were more likely to have commercial insurance compared with nontransferred cohorts. There is a paucity of data examining why patients get transferred. Studies that retrospectively evaluated outcomes between transferred and nontransferred cohorts found no differences in mortality, although transferred patients have a longer length of stay. There is limited evidence to suggest that patients transferred early in their course have improved outcomes. CONCLUSIONS: Our scoping review highlights the sparse evidence and the urgent need for further research into understanding the complexity behind ARF transfers. Future studies should focus on defining best practices to inform clinical decision-making and improve downstream outcomes.

"I Don't Believe in Age; I Believe in Staying Enthusiastic": An Exploratory Qualitative Study into Recruitment Strategies Stimulating Middle-Aged and Older Adults to Join Physical Activity Interventions.

Many middle-aged and older adults (MAOAs) do not engage in sufficient physical activity (PA), despite its well-documented benefits for healthy aging. Existing PA interventions often fail to reach or engage the target population effectively. This study investigates MAOAs' preferences for recruitment strategies to optimize the reach and uptake of PA interventions, thereby enhancing their impact on healthy aging and public health. Qualitative interviews were conducted with 39 MAOA participants (69% female, mean age = 69.46, SD = 7.07), guided by McGuire's Theory on Persuasive Communication. Factors related to the source, message content, channel, receiver characteristics and target behavior of recruitment strategies were analyzed. Our findings suggest a preference for trustworthy sources (e.g., healthcare professionals over commercial entities) and positive, non-ageist messaging. MAOAs vary in their channel preferences but emphasize the importance of personalization. Despite heterogeneity, MAOAs commonly perceive themselves as sufficiently active, indicating a need for improved knowledge on what constitutes sufficient PA, as well as easy enrollment or trying out interventions. Tailoring recruitment strategies to diverse MAOA segments based on age seems crucial for effective engagement. Future research could explore quantitative research into how communication factors relate to various target population characteristics.

State of the Science: Treatment of comorbid posttraumatic stress disorder and substance use disorders.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) co-occur at high rates, with research showing that up to nearly 60% of individuals with PTSD also suffer from an alcohol and/or drug use disorder. PTSD/SUD is complex; associated with adverse health, social, and economic outcomes; and can be challenging to treat. Over the past decade, the landscape of treatment research addressing PTSD/SUD has significantly expanded. Ongoing efforts aimed at developing and evaluating novel treatments for PTSD/SUD, encompassing both psychotherapy and pharmacotherapy approaches, are steadily advancing. As such, this State of the Science paper reviews the literature on the latest scientific advances in treating PTSD/SUD. Clinical practice guidelines for the treatment of PTSD/SUD are discussed, along with evidence-based psychotherapies and emerging interventions. Rigorously conducted clinical trials demonstrate that individual, manualized, trauma-focused treatments are the most efficacious psychotherapies to use among individuals with PTSD/SUD. Moreover, patients do not need to be abstinent to initiate or benefit from evidence-based PTSD treatment. To date, no medications have been established for this comorbidity. We highlight ongoing research on novel treatments for PTSD/SUD, such as new forms of integrated trauma-focused psychotherapies, pharmacological augmentation strategies, and technology-based enhancements. Finally, promising future directions for the field are discussed.

Functional Domains of Substance Use and their Implications to Trauma: A Systematic Review of Neuroimaging Studies.

Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma-reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.

Polyomavirus ALTOs, but not MTs, downregulate viral early gene expression by activating the NF-κB pathway.

Polyomaviruses are small, circular dsDNA viruses that can cause cancer. Alternative splicing of polyomavirus early transcripts generates large and small tumor antigens (LT, ST) that play essential roles in viral replication and tumorigenesis. Some polyomaviruses also express middle tumor antigens (MTs) or Alternate LT ORFs (ALTOs), which are evolutionarily related but have distinct gene structures. MTs are a splice variant of the early transcript whereas ALTOs are overprinted on the second exon of the LT transcript in an alternate reading frame and are translated via an alternative start codon. Merkel cell polyomavirus (MCPyV), the only human polyomavirus that causes cancer, encodes an ALTO but its role in the viral lifecycle and tumorigenesis has remained elusive. Here, we show MCPyV ALTO acts as a tumor suppressor and is silenced in Merkel cell carcinoma (MCC). Rescuing ALTO in MCC cells induces growth arrest and activates NF-κB signaling. ALTO activates NF-κB by binding SQSTM1 and TRAF2&3 via two N-Terminal Activating Regions (NTAR1+2), resembling Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1).. Following activation, NF-κB dimers bind the MCPyV non-coding control region (NCCR) and downregulate early transcription. Beyond MCPyV, NTAR motifs are conserved in other polyomavirus ALTOs, which activate NF-κB signaling, but are lacking in MTs that do not. Furthermore, polyomavirus ALTOs downregulate their respective viral early transcription in an NF-κB and NTAR dependent manner. Our findings suggest that ALTOs evolved to suppress viral replication and promote viral latency and that MCPyV ALTO must be silenced for MCC to develop.

The efficacy of online physical activity interventions with added mobile elements within adults aged 50 years and over: Randomized controlled trial.

Electronic health (eHealth) and mobile health (mHealth) could stimulate physical activity (PA) in a time-efficient and cost-effective way. This randomized controlled trial aims to investigate effects on moderate-to-vigorous PA (MVPA) of different combined computer- and mobile-based PA interventions targeted at adults aged 50 years and over. Participants (N = 954) were randomly allocated to a basic existing computer-based intervention (Active Plus [AP] or I Move [IM]) supplemented with one of three mobile elements being (1) activity tracker (AT), (2) ecological momentary intervention (EMI), or (3) chatbot (CB) or a control group (CG). MVPA was assessed via the SQUASH at baseline (T0), 3 months (T1), and 6 months (T2) and via accelerometers at T0 and T2. No intervention effects were found on objective (p = .502) and subjective (p = .368) MVPA for main research groups (AP/IM + AT, AP/IM + EMI, AP/IM + CB). Preliminary MVPA findings for subgroups (AP + AT, AP + EMI, AP + CB, IM + AT, IM + EMI, IM + CB) combined with drop-out data showed potential for the computer-based intervention AP with an integrated AT. Based on these preliminary findings, eHealth developers can be recommended to integrate ATs with existing computer-based PA interventions. However, further research is recommended to confirm the findings as a result of the exploratory nature of the subgroup analyses.

Clinical Implementation of DIGEST as an Evidence-Based Practice Tool for Videofluoroscopy in Oncology: A Six-Year Single Institution Implementation Evaluation.

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT.

PURPOSE: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need. METHODS: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. RESULTS: After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). At 5 years, the recurrence-free interval (RFI) was 98.3% (95% CI, 97.0 to 99.7), the overall survival was 97.8% (95% CI, 96.3 to 99.3), and the breast cancer-specific survival was 99.4% (95% CI, 98.6 to 100). Comparable iDFS was observed with T-DM1 irrespective of tumor size, hormone receptor status, centrally determined HER2 immunohistochemical score, and receipt of T-DM1 for more or less than 6 months. Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%. Among patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes significantly differed according to HER2DX risk score, with better RFI (98.1% v 81.8%, hazard ratio [HR], 0.10, P = .01) and iDFS (96.3% v 81.8%, HR, 0.20, P = .047) among patients with HER2DX low-risk versus high-risk tumors, respectively. CONCLUSION: Adjuvant T-DM1 for 1 year leads to outstanding long-term outcomes for patients with stage I HER2-positive breast cancer. A high HER2DX risk score predicted a higher risk of recurrence in ATEMPT.

COVID-19 Vaccine Motivation and Hesitancy among a Sample of African American, Afro-Caribbean, and African Respondents in the United States.

Understanding the motivations and decisions behind COVID-19 vaccine acceptance is crucial for designing targeted public health interventions to address vaccine hesitancy. We conducted a qualitative analysis to explore COVID-19 vaccine acceptance among diverse ethnic subgroups of Black Americans in the United States. This study investigates the 2021-2022 responses of 79 African American, Afro-Caribbean, and African respondents over the age of 18 in Washington State and Texas. Respondents were asked "Do you plan to get the COVID-19 vaccination?" Qualitative responses were analyzed by content category and ethnic subgroup. Of the 79 responses, 60 expressed favorable perceptions, 16 expressed unfavorable perceptions, and 3 expressed neutral perceptions. Dominant categories among participants in favor of the vaccine included personal health (26), concern for health of family/or community members (13), and desire to protect others (11). Among the 42 vaccinated African American respondents, the primary motivation was personal health (20). The 12 unvaccinated African American respondents cited fear of side effects as their dominate motivation. Caribbean respondents cited family or elders as motivation for their decision. African respondents were nearly unanimous in taking the vaccine (13/16), citing trust in health care, protecting friends and family, and personal health as reasons. Community and personal relationships were critical decision-making factors in accepting the COVID-19 vaccine, with African Americans having the strongest hesitancy.

Clinician and health service interventions to reduce the greenhouse gas emissions generated by healthcare: a systematic review.

OBJECTIVE: To synthesise the available evidence on the effects of interventions designed to improve the delivery of healthcare that reduces the greenhouse gas (GHG) emissions of healthcare. DESIGN: Systematic review and structured synthesis. SEARCH SOURCES: Cochrane Central Register of Controlled Trials, PubMed, Web of Science and Embase from inception to 3 May 2023. SELECTION CRITERIA: Randomised, quasi-randomised and non-randomised controlled trials, interrupted time series and controlled or uncontrolled before-after studies that assessed interventions primarily designed to improve the delivery of healthcare that reduces the GHG emissions of healthcare initiated by clinicians or healthcare services within any setting. MAIN OUTCOME MEASURES: Primary outcome was GHG emissions. Secondary outcomes were financial costs, effectiveness, harms, patient-relevant outcomes, engagement and acceptability. DATA COLLECTION AND ANALYSIS: Paired authors independently selected studies for inclusion, extracted data, and assessed risk of bias using a modified checklist for observational studies and the certainty of the evidence using Grades of Recommendation, Assessment, Development and Evaluation. Data could not be pooled because of clinical and methodological heterogeneity, so we synthesised results in a structured summary of intervention effects with vote counting based on direction of effect. RESULTS: 21 observational studies were included. Interventions targeted delivery of anaesthesia (12 of 21), waste/recycling (5 of 21), unnecessary test requests (3 of 21) and energy (1 of 21). The primary intervention type was clinician education. Most (20 of 21) studies were judged at unclear or high risk of bias for at least one criterion. Most studies reported effect estimates favouring the intervention (GHG emissions 17 of 18, costs 13 of 15, effectiveness 18 of 20, harms 1 of 1 and staff acceptability 1 of 1 studies), but the evidence is very uncertain for all outcomes (downgraded predominantly for observational study design and risk of bias). No studies reported patient-relevant outcomes other than death or engagement with the intervention. CONCLUSIONS: Interventions designed to improve the delivery of healthcare that reduces GHG emissions may reduce GHG emissions and costs, reduce anaesthesia use, waste and unnecessary testing, be acceptable to staff and have little to no effect on energy use or unintended harms, but the evidence is very uncertain. Rigorous studies that measure GHG emissions using gold-standard life cycle assessment are needed as well as studies in more diverse areas of healthcare. It is also important that future interventions to reduce GHG emissions evaluate the effect on beneficial and harmful patient outcomes. PROSPERO REGISTRATION NUMBER: CRD42022309428.

Fusion Harboring Mast Cells Can Explain Molecular Positivity in Flow Cytometric MRD Negative Core Binding Factor AML.

Molecular measurable residual disease (MRD) can persist in core binding factor acute myeloid leukemia (AML) in otherwise disease-free patients. Utilizing cell sorting followed by fluorescent in situ hybridization, we show that detection is due to mast cells.

Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. AREAS OF UNCERTAINTY: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. DATA SOURCES: We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. THERAPEUTIC ADVANCES: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. CONCLUSION: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Recruitment strategies for reaching adults aged 50 years and older with low socioeconomic status for participation in online physical activity interventions.

Background: Generally, the health condition of those with higher socioeconomic status (SES) is better compared to those with lower SES. The application of appropriate strategies to reach low SES populations with electronic health (eHealth) interventions is thus of major importance to reduce health inequalities. eHealth-studies providing detailed information on recruitment strategies are scarce, despite the fact that this information is crucial for comparable research and implementation. Objective: To provide insight into the reach, sample characteristics and costs of three pre-planned strategies for recruiting adults aged 50 years and older with low SES for participation in an online physical activity intervention, as part of a field study. Methods: Recruitment took place via (1) invitation letters via a municipality, (2) gyms and (3) social media advertisements, aiming to include 400 participants. Additional procedures were followed to reach specifically the low SES group. Response rates, sociodemographic characteristics and costs per strategy were assessed. Results: The highest response was shown for the municipality approach (N = 281), followed by social media (N = 71) and gyms (N = 45). Ten participants were recruited via family/friends. The most low-educated participants were reached via the municipality (N = 128) followed by social media (N = 9), gyms (N = 8) and family/friends (N = 5). Recruitment costs were with €2,142.37 the highest for the municipality compared to €96.81 for social media and no costs for gyms. Conclusions: Recruitment via invitation letters through a municipality has the highest potential for reaching low SES participants of the three applied strategies, although the higher recruitment costs need to be taken into account.

Advancing genomics to improve health equity.

Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in genomics and health equity research to make recommendations and performed a review of current literature to identify the landscape of gaps and opportunities at the interface between human genomics and health equity research. This Perspective describes these findings and examines health equity within the context of human genomics and genomic medicine.

Oral leiomyomatous hamartoma: presentation of 3 cases and review of the literature.

Oral leiomyomatous hamartoma (OLH) is a rare lesion, with only 40 cases reported in the literature. It typically presents early in life as a nodule on the anterior maxillary alveolar tissues or the tongue. Its growth potential is limited, with few cases reaching dimensions >2.0 cm, and its microscopic composition includes an intact surface mucosa with an underlying fibrovascular stroma possessing an unencapsulated proliferation of smooth muscle fascicles. Excision is considered the definitive treatment. Here we describe the clinical, microscopic, histochemical, and immunohistochemical features and management of 3 cases of OLH and review the literature. The findings we present here can assist in performing differential diagnosis, particularly in discriminating between OLH and similar yet non-hamartomatous processes and in selecting appropriate management.

Food insecurity in urban American Indian and Alaska Native populations during the COVID-19 pandemic.

BACKGROUND: Food insecurity is an important social determinant of health that was exacerbated by the COVID-19 pandemic. Both food insecurity and COVID-19 infection disproportionately affect racial and ethnic minority groups, particularly American Indian and Alaska Native communities; however, there is little evidence as to whether food insecurity is associated with COVID-19 infection or COVID-19 preventive behaviors such as vaccination uptake. The purpose of this study was to evaluate associations between food insecurity, COVID-19 infection, and vaccination status among urban American Indian and Alaska Native adults seen at 5 clinics serving urban Native people. METHODS: In partnership with health organizations in Alaska, Colorado, Kansas, Minnesota, and New Mexico, the study team conducted a cross-sectional survey in 2021 to assess food security status and attitudes, barriers, and facilitators for COVID-19 testing and vaccination. Logistic regression was used to examine the association of food security status with sociodemographic factors and COVID-19 infection and vaccination status. Marginal standardization was applied to present results as prevalence differences. RESULTS: Among 730 American Indian and Alaska Native adults, the prevalence of food insecurity measured during the pandemic was 38%. For participants who reported persistent food security status before and during the pandemic (n = 588), the prevalence of food insecurity was 25%. Prevalence of COVID-19 infection and vaccination did not vary by food security status after adjustment for confounders. CONCLUSIONS: High rates of food insecurity among American Indian and Alaska Native communities likely increased during the COVID-19 pandemic. However, despite the high prevalence of food insecurity, community-led efforts to reduce COVID-19 infection and increase vaccination uptake across Indian Health Service and Tribal healthcare facilities may have mitigated the negative impacts of the pandemic for families experiencing food insecurity. These successful approaches serve as an important reference for future public health efforts that require innovative strategies to improve overall health in American Indian and Alaska Native communities.