The OCT: implementation and protocol. Factors in developing the oxytocin challenge test as a standard hospital procedure.
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Female↗
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Results for “Implementation challenges”
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A Multitrait Locus Regulates Sarbecovirus Pathogenesis.
Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.
Animals↗
Implementing HIV protection regulations is nursing's next challenge.
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HIV Infections↗
Implementing practice guidelines through a utilization management strategy: the potential and the challenges.
Although there is currently much enthusiasm for practice guidelines, far more energy and resources have been expended on their development than on their implementation. A prospective interventional trial was performed using a previously validated explicit practice guideline (decision aid) to decrease the hospital length of stay for selected "low-risk" patients with chest pain. Utilization management (UM) coordinators (RNs) and physicians were chosen to implement the guideline since these resource people are available in most hospitals, allowing for generalization of the experience. With explicit review criteria used for 624 patients, it was found that when the guideline was applied by UM coordinators, it had a sensitivity of 0.85, a specificity of 0.90, a positive predictive value of 0.76, and a negative predictive value of 0.94. The attending physicians failed to override falsely classified low-risk patient recommendations 51% of the time. Implicit review judged that outcome might have theoretically been worsened in two of these patients. Follow-up at 30 days after admission, however, revealed no untoward sequelae in falsely categorized patients discharged according to the guideline. Utilization management appears to be a promising mechanism for guideline implementation that is available in most institutions. However, the accuracy with which UM coordinators implement guidelines should be assessed rigorously. Guidelines should be implemented in an environment of checks and balances in which physicians have the ultimate responsibility for their patients' care.
Adult↗
Artificial Intelligence for Colorectal Surgeons-Part II: Research Applications, Challenges in Adoption, and Practical Resources.
BACKGROUND: This is part II of a 2-part series examining artificial intelligence in colorectal surgery. Part I established foundational concepts and clinical applications. Implementation, however, requires understanding research methodologies, available resources, and the specific challenges currently limiting widespread adoption. These topics are the focus of part II. OBJECTIVE: To examine artificial intelligence's transformation of surgical research, provide practical implementation resources, address adoption challenges, and explore future directions in colorectal surgery. METHODS: Comprehensive literature review focusing on artificial intelligence research methodology, implementation barriers, educational resources, and emerging technologies relevant to colorectal surgeons. RESULTS: Artificial intelligence streamlines clinical trial design through predictive modeling and natural language processing, reducing enrollment challenges that contribute to failed or inadequate trial accrual. Machine learning enables heterogeneity analysis within clinical trials, identifying treatment-responsive subgroups. Foundation models unlock analysis of unstructured electronic health record data at scale. Professional societies and universities offer specialized artificial intelligence education programs, with open-access data sets facilitating research participation. However, implementation faces multifaceted challenges: technical infrastructure demands, with real-time processing requiring dedicated graphics processing unit clusters; regulatory frameworks struggling with continuously evolving algorithms; undefined liability distribution for artificial intelligence-assisted decisions; algorithmic bias risking health care disparities; and the "black box" problem limiting clinical trust. Economic barriers include substantial initial costs without clear reimbursement pathways. Future directions include multimodal artificial intelligence integrating imaging, genomics, and histopathology; cognitive robotic systems with real-time decision support; digital twin technology for patient-specific surgical simulation; and global surgical artificial intelligence networks enabling distributed learning across institutions. CONCLUSIONS: Although artificial intelligence offers transformative potential for colorectal surgery research and practice, successful implementation requires addressing technical, regulatory, ethical, and economic challenges. The surgeon's evolving role demands both traditional expertise and computational fluency. Future advances in multimodal integration, autonomous systems, and global collaboration will fundamentally reshape surgical practice but will require thoughtful implementation prioritizing patient benefit and clinical value.
Humans↗
Validation of an integrated metagenomic pipeline combining optimized wet-lab processing and tiered reporting for CSF pathogen detection.
UNLABELLED: Metagenomic next-generation sequencing (mNGS) in the infectious disease diagnostic space has been gaining traction and is popular for aiding in the diagnosis of central nervous system infections. However, many challenges and obstacles remain in making this technology a gold standard for infectious disease diagnostic testing. One major challenge is being able to distinguish between the clinically relevant organisms from background contamination. We performed a validation study for mNGS on cerebrospinal fluid (CSF) that utilized positive clinical samples and contrived samples that incorporated a bioinformatics pipeline that can better distinguish between background contamination and clinically relevant organisms and used a three-tiered reporting algorithm meant to decrease the inherent subjectivity that comes with interpreting and reporting data from clinical metagenomic sequencing. The validation of this assay and category-based reporting pipeline revealed an overall concordance of 91.8%, with a sensitivity of 100% and a specificity of 72.4%. In addition, we improved the detection of clinically relevant RNA viruses to almost 100% in the CSF by modifying the wet lab processing of the sample. This bioinformatics pipeline with a category-based reporting algorithm will provide more confidence in reporting microorganisms detected with this technology, mNGS, and improving patient care. IMPORTANCE: Metagenomic next-generation sequencing (mNGS) can offer a broad, unbiased approach for the detection of infectious pathogens and has shown promise in diagnosing central nervous system infections. Despite its potential, clinical implementation remains limited by challenges in distinguishing clinically relevant organisms from background contamination. This study validated an mNGS assay for cerebrospinal fluid that incorporates an optimized bioinformatics pipeline with a three-tiered reporting algorithm designed to reduce subjectivity and enhance diagnostic confidence. The assay also has improved detection of clinically relevant RNA viruses through modified wet-lab processing. These findings support the clinical utility of a structured, category-based reporting approach for mNGS, advancing its reliability as a diagnostic tool in infectious disease testing.
Metagenomics↗
The elderly population. Opportunities for cancer prevention and detection.
Interest in the elderly population, persons 65 years of age or older, as a target group for cancer control has not been great. Age recommendations rarely are made for prevention and early detection of cancer for elderly persons. However, cancer incidence and mortality rates are known to rise rapidly with increasing age. This paper takes a long-term public-health perspective to look toward the year 2030 to discuss the challenges of organizing and implementing prevention and early detection incentives for our nation's current and future elderly population. Cancer prevalence estimates in the context of the geriatric imperative of the 21st century are provided for three cancers--breast, prostate, and lung and bronchus. The sheer magnitude of numbers created by the aged population expansion can greatly increase the number of cancer survivors and newly diagnosed cases. Current efforts in cancer prevention and early detection should anticipate the health-care demands of the elderly in the first three decades of the next century.
Adult↗
Attitudes toward presymptomatic testing in Huntington disease.
One hundred thirty-one individuals at 50% risk of inheriting Huntington disease (HD) responded to a survey to study their attitudes toward taking a genetic test based on the identification of a genetically linked DNA polymorphism. Ninety-six percent of the respondents believe that presymptomatic testing should be available, and 66% say they will use it themselves. Fewer married individuals, in comparison to those single, separated, and divorced, intend to take the test. Many respondents (40%) said their primary reason for wanting to be tested is to end the uncertainty in their lives. Results suggest that there will be self-selection in test use, with many individuals who believe they will be depressed or possibly suicidal with a positive test result deciding not to be tested or unsure about testing. However, 15% of those who want to be tested acknowledge that they may be at risk for suicide if they are probable gene carriers. Only 12% of all respondents say they will be likely to use prenatal testing, suggesting that initial demand may be low in New England. Implementation of presymptomatic testing challenges health care providers to develop strategies to care for otherwise healthy persons who will be given a diagnosis years before the onset of illness.
Adult↗
Clinical economics education in the International Clinical Epidemiology Network. INCLEN Economics Faculty.
The application of rigorous epidemiologic methods to clinical questions has broadened the scope of research in epidemiology and enhanced the quality of clinical research. The International Clinical Epidemiology Network (INCLEN) has enabled physicians from developing countries to obtain training in epidemiologic methods and to provide leadership in clinical epidemiology in their home schools of medicine. The INCLEN program has recently incorporated another major theme of research training, clinical economics, which introduces research related to the effective use of limited resources. This article describes the rationale for the development of the INCLEN Clinical Economics program, outlines its organization and curriculum, and explores the challenges to its successful implementation.
Cost-Benefit Analysis↗
Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.
Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of hematological malignancies, yet its broader application to solid tumors, chronic viral infections, and autoimmune diseases remains constrained by antigen heterogeneity, immunosuppressive tissue microenvironments, T-cell exhaustion, limited persistence, and treatment-associated toxicities. These challenges have shifted the field from optimizing individual receptor constructs toward engineering CAR-T cells as programmable immune systems capable of adapting to diverse disease contexts. This review synthesizes recent advances in molecular engineering strategies that enhance CAR-T cell function beyond conventional receptor design. We discuss how receptor engineering, genome editing, transcriptional and epigenetic regulation, metabolic reprogramming, synthetic gene circuits, and safety-control platforms collectively reshape CAR-T cell fate, persistence, and therapeutic efficacy. Rather than functioning independently, these engineering strategies are increasingly integrated to generate context-specific cellular therapies capable of adapting to diverse disease environments, including cancer, autoimmune diseases, and chronic viral infections. We also highlight the potential for translation into clinical practice or clinical translation and discuss the major challenges associated with clinical implementation. Next-generation CAR-T therapies will increasingly integrate molecular engineering strategies or will rely on molecular engineering strategies to integrate antigen recognition, cellular fitness, immune regulation, and longevity rather than simply maximizing cytotoxic activity. Recent advances in programmable cellular engineering coupled with rigorous clinical evaluation as well as scalable manufacturing technologies or scalable manufacturing platforms in the treatment of other diseases beyond oncology will facilitate the development of safer, more durable, and broadly applicable cellular therapies.
Humans↗
The urgency of substance abuse education in schools of nursing.
The abuse of alcohol and drugs has become a major health and social problem in the United States. Nurses comprise the largest segment of health-care professionals, yet report their educational experiences offer little to prepare them to develop substance abuse prevention and intervention programs. This article identifies factors that contribute to this educational gap, discusses challenges in planning and implementing substance abuse curricula, and offers specific guidelines for improving educational experiences.
Curriculum↗
The older adult. A comparative assessment.
Thorough assessment of older men and women is a complex but vital part of their health care. The ability to differentiate the changes owing to normal aging from those resulting from pathologic processes is necessary if their lives are to be as productive and enjoyable as they are prolonged. Each body system and function must be examined or tested with this difference in mind. Because aging occurs in different individuals at differing rates, a variety of functions may all be considered healthy or normal. Assessment findings must be viewed through the focus of the individual person as well as that of the population. The nurse will find opportunities to use assessment skills for older adults in many settings, ranging from independent living arrangements to institutional residential areas. In the community, social meeting places, day-care facilities, meal sites, and shopping areas are but a few of the places where older adults may be found, alone or in groups. Assessment opportunities can be identified or structured in any milieu. The setting itself, as well as the needs of the older adult(s), will help to determine the complexity of the assessment activities. The benefit to nursing of increased and expanded ability to assess the older adult is considerable. The organized concern of science and health care with aging is a relatively recent phenomenon. The older adults of today are unique--there are more of them than ever before, and they are living longer. Although their lives are not without health complications, they are, in a sense, role models for the rest of us: pathfinders in aging who can, if we observe them carefully, give us insight and direction for our own healthy aging processes and those of generations to come. Nursing is uniquely poised to use our caring methodology with the older adult. The elderly are interested in their health and willingly cooperate with those whose assessments are knowledgeable and realistic. Nursing is challenged to develop and implement advanced and specialized ways to identify and meet their needs.
Aged↗
New fee schedule tests staff skills. The Health Care Group.
The Medicare Fee Schedule (MFS) picture is quite incomplete, with myriad details unsettled. But one thing is clear: the shift to a new reimbursement system is loaded with significant practice management implications and challenges. Now, before the MFS is implemented, physicians should evaluate their management operations and business systems, to meet the challenges ahead. Most physicians understand that practice viability will depend on increasing their patient base and the scope of services delivered to non-Medicare patients. Yet many do not understand the marketing and management challenges implied in such growth. The issues are these: how can a practice attract more non-Medicare patients? And how can such growth be accommodated without disproportionately increasing costs or inconveniencing patients and staff?
Fees, Medical↗
Cultural diversity: a resource in planning and implementing nursing care.
America's cultural diversity challenges the ability of nurses to respond with sensitivity to client needs. Enhancement of the client's health practices is contingent on the nurse's ability to use the individual's culturally based beliefs and values as an integral component in the design of nursing interventions. Nurse and client engage in a truly collaborative planning and implementation of care only after there is mutual understanding of the special meaning of beliefs and values from which health behaviors are derived. Educational preparation with experience in applying cultural knowledge is essential to the development of sensitive nursing practice. Integrating such information and experiences into baccalaureate nursing curricula through a sociocultural project will enhance student awareness of client values and beliefs and their potential nursing implications. Strategies exist for helping students recognize, accept, and use these features in planning and implementing nursing care.
Community Health Nursing↗
Implementation of nursing diagnoses through integration with quality assurance.
Implementation of nursing diagnosis is both a challenging and frustrating procedure. Guidelines and published experiences are limited. Efforts of one hospital to implement nursing diagnosis demonstrated the value of using quality assurance techniques to monitor the effectiveness of the implementation. Implementation of nursing diagnosis without consideration of intervention and outcome criteria results in trial and error practice. Monitoring the quality and appropriateness of care using standards and criteria for nursing diagnosis leads to new knowledge and insights. The nursing profession now faces the test of managing and disseminating the information that comes from the implementation of nursing diagnosis.
Accidental Falls↗
Program evaluation within a health promotion framework.
Program evaluation can assist in assessing the conceptualization, design, implementation and utility of health promotion action. Evaluation of health promotion, with multiple strategies combining individual, social and policy action, lends itself to an evaluation-as-politics paradigm. Consideration of the interests of all major stakeholders, use of a series of related studies, and a commitment to multiple methods and multiple perspectives characterize this paradigm. Simple, practical research that is adequate for answering relevant questions is required. The program evaluator is not a neutral, scientific observer--he/she is a participant in the political arena along with other stakeholder groups. A model of the areas of interest in evaluation of health promotion, some potential evaluation questions, and a health promotion impact evaluation model are presented to emphasize unique aspects involved in evaluation of health promotion action. The evaluator can take a proactive role and challenge problems in conception and implementation of health promotion action. He/she can advocate for health promotion.
Health Policy↗
Targeted Next-Generation Sequencing for Improved Clinical Outcomes in People Living With Rare Diseases in Global South: Protocol for a Systematic Review and Meta-Synthesis.
BACKGROUND: Rare diseases affect many individuals and pose major challenges in diagnosis and treatment, especially in Global South countries where health care resources are limited. Targeted next-generation sequencing (NGS) has significantly advanced diagnostic accuracy and clinical care for rare diseases globally; however, its implementation and impact within the Global South context remain insufficiently studied. OBJECTIVE: This study aims to evaluate the use, clinical benefits, challenges, and implementation outcomes of targeted NGS for diagnosing and managing rare diseases in Global South populations. Specifically, it seeks to quantify the diagnostic yield of NGS, examine its influence on subsequent clinical decision-making, and identify principal barriers to, and facilitators of, the implementation of targeted NGS approaches in these contexts. METHODS: This protocol follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We will systematically search PubMed, Scopus, and Web of Science for studies published between 2005 and 2025 that report on the use of targeted NGS in Global South population with rare diseases. Two reviewers will independently perform study selection, data extraction, quality assessment, and evaluation of risk of bias by using QUADAS-2 for diagnostic accuracy studies and the risk of bias assessment tool for nonrandomized studies. Meta-analyses will be conducted to estimate pooled outcomes for diagnostic yield, with heterogeneity assessed using random effects models. Heterogeneity will be further examined through visual inspection of forest plots and by evaluating the chi-square test and I² statistic. RESULTS: The protocol has been registered with PROSPERO (CRD420251078455). Database search or screening, data extraction, and data synthesis are planned to commence in June 2026 and conclude by September 2026. Study findings will synthesize the diagnostic yield, clinical impact, and contextual determinants influencing the implementation of targeted NGS in Global South health care settings. CONCLUSIONS: This review will provide evidence on the application, advantages, limitations, and clinical outcomes of targeted NGS for individuals affected by rare diseases in countries of the Global South. The finding will identify priorities for capacity strengthening, policy development, and future genomic research. TRIAL REGISTRATION: PROSPERO CRD420251078455; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251078455. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/85150.
Rare Diseases↗
Physiologic consequences of local heart irradiation in rats.
Noninvasive methods have been used to study the long-term cardiovascular and pulmonary functional changes at rest and after exercise in adult rats following local heart irradiation with single x-ray doses of 15, 17.5 or 20 Gy, and in non-irradiated control animals. Rats that had undergone a chronic exercise program were compared with untrained cohorts. The earliest dysfunction detected was an increased respiratory rate (f) at 10 weeks after irradiation in the highest dose group. In contrast, both telemetric heart-rate (HR) and rhythm and indirect systolic blood pressure measurements performed at rest only revealed changes starting at 43 weeks after irradiation with 20 Gy, up to which point the rats showed no clinical signs of heart failure. However, the number of minutes required for the recovery of the HR to pre-exercise levels following the implementation of a standardized exercise challenge was elevated in untrained rats compared with their trained cohorts at 18 weeks after irradiation with 20 Gy. Increases in recovery times were required in the two lowest dose groups, starting at 26 weeks after irradiation. It was concluded that the reserve capacity of the cardiopulmonary system masks functional decrements at rest for many months following local heart irradiation, necessitating the use of techniques which reveal reductions in reserve capacities. Further, the influence of local irradiation to the heart and lungs deserves closer scrutiny due to mutual interactions.
Animals↗