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PubMed2026

ARHGAP22 as a Potential Prognostic Biomarker in Clear Cell Renal Cell Carcinoma: Insights into Tumor Immunity and Co-Expression Networks.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is characterized by substantial clinical heterogeneity, highlighting the need for reliable prognostic biomarkers. This study evaluated the expression pattern, prognostic relevance, and immune-related associations of ARHGAP22 in ccRCC using transcriptomic and clinical data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) cohort, together with external validation data and protein-expression information from the Human Protein Atlas (HPA). ARHGAP22 expression was compared between tumor and adjacent normal tissues, and its associations with overall survival, clinicopathological characteristics, tumor microenvironment scores, and estimated immune-cell fractions were assessed. Co-expression and functional-enrichment analyses were also performed to characterize potential biological associations. ARHGAP22 was significantly upregulated in ccRCC tissues at the transcriptomic level, with corresponding differences observed in immunohistochemical images. High ARHGAP22 expression was associated with shorter overall survival, advanced clinicopathological features, and higher ImmuneScore, StromalScore, and ESTIMATEScore values. CIBERSORT-based analysis showed that the high-expression group had higher estimated fractions of M2 macrophages and regulatory T cells and lower estimated fractions of naïve B cells, resting mast cells, and activated dendritic cells after false discovery rate correction. Functional-enrichment analyses linked ARHGAP22-associated genes to immune-related processes, cell migration, and chemokine- and cytokine-mediated signaling pathways. These findings suggest that ARHGAP22 may represent a potential prognostic and immune-related biomarker in ccRCC, although further independent clinical and experimental validation is required.

Humans↗
PubMed2006

A physicians' agenda for partnering with employers and insurers: fresh ideas.

We report the results of the second phase of a multiphase qualitative investigation of the ways physicians, employers, and insurers can work together more effectively to provide better ambulatory care to employees and their dependents. This article focuses on ways physicians can develop more useful relationships among these groups. We used a grounded theory approach to conduct 71 interviews from August 12, 2004, to December 27, 2005, with 25 practicing physicians in large and small groups, urban and rural areas, private and academic settings, and primary care and specialty practices; 33 hospital administrators, medical association executives, health insurance medical officers, and health policy analysts; and 13 senior executives of large and small companies. The study identifies 2 approaches to the structuring of ambulatory care that can lead to improved health care outcomes and value. In the first approach, direct contracting between physicians and employers transfers tasks previously performed by insurers to employers or other intermediaries who may be able to provide better service or lower cost. In the second approach, insurer-mediated relationships between physicians and employers are restructured, particularly in ways that improve information flow. Such relationships may strengthen physicians' ability to provide quality services while enabling patients to make more informed decisions about physician selection, treatments, and spending. We believe that broader use of these approaches may improve the quality and efficiency of ambulatory care for the large proportion of the population that has work-related health insurance. Although the findings are promising, our intent is not to claim broad external validity but rather to encourage greater experience with these approaches and more formal studies of their effectiveness.

Attitude of Health Personnel↗
PubMed2001

Strike action by nurses in South Africa: a value clarification.

The Labour Relations Act (South Africa, 1991) made provision for protected strike action by employees, subject to certain conditions, procedures and negotiated agreements. This led to the removal of the strike clause in the Nursing Act (South Africa, 1992). The labour rights of all citizens are entrenched in the Constitution of the country (South Africa, 1996). Participation in strike action by the nurse/midwife, regardless of the legal requirements and specifications, does, however, pose an ethical question. It is therefore necessary to conduct a value clarification on strike action by nurses in South Africa. The purpose of this research is to explore and describe the perceived values of participants from an accessible population on this phenomenon. A qualitative, exploratory and descriptive research design was deployed. The perceived values of nurses on strike action were collected by means of an open-ended questionnaire/sketch. Over a period of three years a purposive and convenient sampling method was used, involving all the enrolled post basic nursing/midwifery students/learners at a particular Nursing Education Institution. The justification of the sample was further enhanced by also collecting data on the participants' age and provincial distribution location. Although a 63% sample realisation (of the accessible population) was achieved, this represents only 1.5% of the registered nursing/midwifery population in the country. A descriptive analysis of the participants' age and provincial distribution was undertaken, as well as a content analysis of their perceived values on strike action. The mean age of the participants was 48 years, which could be attributed to the fact that most of them were enrolled for a post-basic Diploma in Community Nursing Science. Most of the responses (52.7%) were against strike action and 32.5% supported strike action by nurses as a constitutional and legal right. A fairly substantial number of participants (14.8%) expressed mixed views as to whether strike action by nurses is right or wrong. Some respondents (15.7%) also reflected confusion regarding the enactment of strike action and the removal of the strike clause from the nursing legislation. Although this study does not claim external validity due to inappropriate representation of the nursing profession, the nurse of today opposes strike action. It is recommended that the study be replicated at national level and that the values be entrenched and published in position papers of and by the regulatory and organised nursing profession.

Adult↗
PubMed2026

Polygenic risk score and its role in cancer susceptibility.

BACKGROUND: Polygenic risk score (PRS) has the ability to stratify inherited susceptibility to cancer and, as a complement to monogenic testing, can identify individuals at increased genetic risk even when no pathogenic variant is detected in high- or moderate-penetrance genes. It reflects the combined additive effects of a large number of low-penetrance variants across the genome, and represents a continuum of genetic susceptibility with an approximately normal distribution. Clinically relevant differences are typically observed in individuals in the highest and lowest percentiles of the PRS distribution, while relative risk gradients depend on the cancer type, the specific PRS model, and the reference population used. PRS is not a single test but rather a family of statistical models that differ in their design, predictive performance, and transferability across populations, underscoring the need for external validation and population-specific calibration of absolute risk. Broader implementation is thus still held back by differences between individual PRS models, limited transferability, and the lack of harmonized guidance on indication, reporting, and clinical decision-making. Consequently, clinical use in the European Union remains largely confined to pilot studies and local projects. Within these initiatives, PRS is most commonly applied in two main ways - either as a triage tool for intensified diagnostics or screening in higher-risk groups, or as a component of multifactorial absolute-risk models (e. g. BOADICEA/CanRisk) that integrate PRS with other risk factors such as pathogenic variants in moderate-penetrance genes (e. g. ATM or CHEK2), family history, or lifestyle factors. By refining absolute-risk estimates, PRS may shift individuals across clinical decision thresholds for more intensive surveillance and preventive strategies. AIM: This review summarizes the principles of PRS, the main sources of variability between models, and its potential applications in risk stratification and personalized cancer screening. It also addresses limitations in transferability, the need for calibration, and the currently limited evidence for improvements in hard clinical outcomes.

Humans↗
PubMed2004

A framework for evaluating safety-net and other community-level factors on access for low-income populations.

The framework presented in this article extends the Andersen behavioral model of health services utilization research to examine the effects of contextual determinants of access. A conceptual framework is suggested for selecting and constructing contextual (or community-level) variables representing the social, economic, structural, and public policy environment that influence low-income people's use of medical care. Contextual variables capture the characteristics of the population that disproportionately relies on the health care safety net, the public policy support for low-income and safety-net populations, and the structure of the health care market and safety-net services within that market. Until recently, the literature in this area has been largely qualitative and descriptive and few multivariate studies comprehensively investigated the contextual determinants of access. The comprehensive and systematic approach suggested by the framework will enable researchers to strengthen the external validity of results by accounting for the influence of a consistent set of contextual factors across locations and populations. A subsequent article in this issue of Inquiry applies the framework to examine access to ambulatory care for low-income adults, both insured and uninsured.

Ambulatory Care↗
PubMed2026

A comprehensive review of AI innovations for tackling antimicrobial resistance.

Antimicrobial resistance (AMR) represents a major global public health concern, rendering available antimicrobials ineffective and leading to infections that are difficult to treat. Artificial intelligence (AI) has been increasingly applied across the AMR continuum, including resistance prediction, rapid diagnostics, new antimicrobial discovery, drug repurposing, antimicrobial surveillance, and clinical decision support. In this review, we aim to highlight recent developments in the use of artificial intelligence (AI) to address antimicrobial resistance (AMR). In addition, we review computational methods that help interpret genomic, phenomic, clinical, and epidemiological data to support the development of treatment strategies and novel antimicrobial agents. The key issues addressed include data quality, model interpretability, external validation, regulatory requirements, privacy, and fairness. While AI is not a complete solution to AMR, it can certainly strengthen the global AMR response by complementing key areas of AMR such as antimicrobial stewardship, infection prevention, laboratory diagnostics, and global surveillance.

Antimicrobial resistance (AMR)↗
PubMed2026

Host Genetic Regulation of NLRP3 Inflammasome Cytokines Reveals Immune and Vascular Pathways in HIV.

People with HIV exhibit elevated inflammation and cardiovascular risk despite antiretroviral therapy. To define the genetic architecture of inflammasome-associated inflammation, we performed whole-genome sequencing and quantified plasma IL-6, IL-1β, and IL-18 in 1,000 ART-suppressed PWH from the U.S. Military HIV Natural History Study. Genome-wide analyses identified 14 loci implicating antiviral defense (DDX17, DDX41, EEA1, BCL11A), lipid metabolism (ABCA1, ABCA12, ABCC1, AGMO), and vascular remodeling (KLHL29, RNF213, ETV1). Transcriptome-wide analyses across cardiovascular and immune tissues identified regulatory programs linking interferon signaling, immune activation, and vascular biology to circulating cytokine levels. Mendelian randomization analyses supported causal relationships between inflammasome-associated cytokines and vascular events. Functional integration with genome-wide CRISPR perturbation datasets in primary CD4+ T cells linked cytokine-associated loci to HIV antiviral pathways and cytokine regulatory networks. External validation in cohorts without HIV demonstrated pathway-level convergence despite limited variant-level overlap. These findings define genetic mechanisms linking inflammasome signaling, antiviral defense, and cardiovascular risk.

HIV↗
PubMed1976

Health care from a behavioral-ecological viewpoint.

While the intended thrust of this paper has been to elicidate the tremendous potential of the behavioral-ecological perspective for health care research and application, the intent has not been to underplay the important role of the biological sciences in the same venture. However, it is my contention that a behavioral-ecological approach to the study of health care has been widely neglected in health care functions and research. In terms of conventional research designs and terminology, the behavioral-ecological research implications can be summarized as follows: a behavioral-ecological perspective of health care research suggests research that is experimental rather than correlational-descriptive; that focuses, because of its naturalistic thrust, on external validity more than internal validity; that incorporates as independent design variables the environmental context in which health behaviors occur; and that allows single-subject as well as multiple-group designs as research strategy. Finally, in terms of dependent variables, the research design requires a clear identification of the observable characteristics of the target health behaviors under consideration. In summary, health research geared toward professional goals appears to profit significantly from an ecological-behavioral approach which provides a model of high explication, specificity, and objectivity for knowledge generation and immediate application.

Behavior Therapy↗
PubMedDate not supplied

Developing an outcomes report card for hospitals: a case study and implementation guidelines.

Except for a few state mandates and dominant business coalitions in selected markets, the provider report card initiative is a voluntary response to a perceived public desire for performance data on healthcare providers. This study uses a detailed investigation of a single "typical" case to collect information about one hospital's decision processes and the operational activities required to develop a report card for communicating clinical outcomes and financial indicators to its external stakeholders. Three research questions are addressed: How did the organization identify who its key stakeholders for outcomes information were? How were the stakeholders' outcomes information needs determined? What were the stakeholders' information needs and preferred reporting formats? The research findings are reported as a case study. A general model for developing and implementing a report card for public dissemination is proposed. Crucial steps include: Hospital leaders should define the intent of the report card and identify key performance domains. Stakeholders' needs, desires, and intended use of the information should be explored when determining the format of the report card. External validation of the information presented should be obtained. The report should be made available through several mediums including direct mailing, print media, and the Internet. Usefulness of the information included in the report card should be continually evaluated. The outcomes report card can be useful to organizations and their stakeholders in many ways. They provide information about clinical outcomes, cost-effectiveness, and organizational performance in an era when healthcare organizations are competing for marketshare and consumers are demanding to be informed about their healthcare providers.

Alabama↗
PubMed1999

Hepatitis B vaccine and liver problems in U.S. children less than 6 years old, 1993 and 1994.

Data to assess the benefits and risks of hepatitis B vaccine for the general population of U.S. children are sparse. This study addressed the problem of external validity found in previous studies of high risk populations by evaluating the benefit of hepatitis B vaccination for the general population of American children. We calculated the risk of liver problems among hepatitis B vaccinated and non-hepatitis B vaccinated children using logistic regression. Hepatitis B vaccinated children had an unadjusted odds ratio of 2.94 and age-adjusted odds ratio of 2.35 for liver problems compared with non-hepatitis B vaccinated children in the 1993 National Health Interview Survey. Hepatitis B vaccinated children had an unadjusted odds ratio of 2.57 and age-adjusted odds ratio of 1.53 for liver problems compared with non-hepatitis B vaccinated children in the 1994 National Health Interview Survey dataset.

Age Distribution↗
PubMed1985

Strategic marketing applications of conjoint analysis: an HMO perspective.

The purpose of this article is to demonstrate how data from a conjoint analysis study can be used to help determine the most appropriate marketing mix for an operational HMO which is entering a new market--the geriatric population. Included are two features which are absent in previous articles on health care applications of conjoint analysis: external validation of results, and a demonstration of how conjoint analysis can be used to simulate market responses to changes in the provider's marketing mix.

Analysis of Variance↗
PubMedDate not supplied

[1-Year follow-up of inpatient treatment in a psychosomatic rehabilitation clinic with either a psychoanalytic or behavior therapy oriented treatment].

In a naturalistic setting, we studied the long-term effects of an inpatient treatment program at a psychosomatic rehabilitation clinic, where patients were assigned to a department with either a psychoanalytic or behavior therapeutic orientated treatment after one week of comprehensive diagnosis. The study is based on a self-developed questionnaire which gathers retrospective information in a broad spectrum of problem areas at the point of admittance and release (t0 and t1) as well as current assessments one year following treatment (t2). Additionally, a symptom checklist (Giessener Beschwerdebogen) and a questionnaire assessing depression (Allgemeine Depressionsskala) were prospectively employed at t0 and t2. We asked a consecutive sample of 376 patients to participate, of which 56% answered at t2. Despite limitations of the internal and external validity of the study, we were able to show that substantial improvements are maintained following treatment for both therapies at one-year follow-up, whereas only small difference are found between the outcomes of the two different schools implemented in the clinic.

Adult↗
PubMed1999

[Evidence-based medicine: context and relevance].

Currently, evidence-based medicine is subject of a controversial discussion. This review is focused on the different types of evidence in clinical medicine and elaborates the history and context of evidence-based medicine. Evidence-based medicine insists that the theoretical plausibility of a therapeutical concept alone does not substitute for the empirical proof of its efficacy. Evidence-based medicine emphasizes the necessity to complement the individual physician's clinical experience with valid external evidence. This evidence has to be obtained by laborious systematic reviews rather than the traditional fragmentary study of the literature. The Cochrane Collaboration stands for this concept. The application of evidence-based medicine links the individual patient's problems with external evidence by asking defined answerable questions and supplies criteria for the critical evaluation of the evidence found. Evidence-based medicine, however, is not devoid of problems and contradictions. Above all, it has to be subjected to its own criteria and has to prove its efficacy.

Evaluation Studies as Topic↗
PubMed1999

Lessons from the Oslo Study Diet and Anti-smoking Trial: a qualitative study of long-term behaviour change.

The aim of this study was to identify factors associated with sustainable behaviour change among persons at increased risk for future cardiovascular disease. A qualitative approach based on focus group interviews was used. Twenty-five men aged 62-71 years who participated in the Oslo Study Diet and Anti-smoking Trial were interviewed in four focus groups. The study identified five categories of factors linked to the process of lifestyle changes: the doctor-patient relationship, significant others, motivators, barriers, and empowerment. A strong personal attachment to the principal investigator of the Oslo Study was revealed. The relationship was described as friendly and supportive. The family based approach and the impact of spouses, in particular, was emphasized by the participants. Somatic symptoms and fear often acted as motivators to behavioural change. Individual feedback was also identified as an important motivator. Psychological resistance to external pressure, concerns regarding behaviour change, and benefits from current (unhealthy) behaviour were identified as barriers. Participants reported a process of empowerment and personal control as an important element of sustainable change. The importance of the unique relationship with a certain provider has implications for future healthcare planning. This factor may also limit the external validity of studies of human behaviour.

Aged↗
PubMed1999

Deriving treatment recommendations from evidence within randomized trials. The role and limitation of meta-analysis.

Meta-analysis is commonly used in reviews of the effectiveness of medical technologies, but this approach has not been used in direct support of guidelines development groups. This paper describes the approach of the North of England Guidelines Development Project in describing the evidence using meta-analyses that were conducted explicitly to address questions on the choice of therapy raised by the guidelines development groups. Particular emphasis is placed on the context within which the contributing trials were conducted and the extent to which systematic differences between trials (heterogeneity) was observed, described, and explained. There is a trade-off between internal and external validity for different metrics when presenting the results of trials. More interpretable metrics, such as risk differences or weighted mean differences, are confounded by study design issues and strong assumptions. More robust measures such as odds ratios or standardized weighted mean differences are difficult to interpret physically. Individual patient data may prove particularly helpful in addressing pivotal questions on the magnitude of effects of interventions, though accessing and reanalyzing these data requires a substantial investment in time and other resources.

Bias↗
PubMed1999

A disease severity scale for systemic sclerosis: development and testing.

OBJECTIVE: To develop and test a severity scale for individual organ involvements in systemic sclerosis (SSc, scleroderma). METHODS: An international study group completed the following tasks: (1) developed a glossary of terms including all pertinent variables for 9 potentially affected organ systems; (2) collected prospective data to determine the feasibility and practicality of each proposed variable; (3) revised the initial list of variables; (4) determined the association of each variable with mortality (a proxy for morbidity) using 579 patients in an existing comprehensive longitudinal scleroderma databank; (5) developed a severity grading scale for each organ system by discussion and consensus; and (6) externally validated the scale using an independent group of 680 patients from the same databank. RESULTS: Nine organ-specific severity scales were developed from 0 (no documented involvement) to 4 (endstage disease). The data required for scale completion are relatively easy and practical for all physicians to obtain. CONCLUSION: This preliminary severity scale will be useful for assessing disease severity status in individual patients both at one point in time and longitudinally. The severity scale will assist in the design and conduct of clinical trials and the comparison of study populations with one another. The scale will serve as a framework for developing a scleroderma disease activity index.

Humans↗
PubMed1999

A genetic algorithm to select variables in logistic regression: example in the domain of myocardial infarction.

Actual use of regression models in clinical practice depends on model simplicity. Reducing the number of variables in a model contributes to this goal. The quality of a particular selection of variables for a logistic regression model can be defined in terms of the number of variables selected and the model's discriminatory performance, as measured by the area under the ROC curve. A genetic algorithm was applied to search for the best variable combinations for modeling presence of myocardial infarction in a data set of patients with chest pain. Using an external validation set, the resulting model was compared with models constructed with standard backward, forward and stepwise methods of variable selection. The improvement in discriminatory ability yielded by the genetic algorithm variable selection method was statistically significant (p < 0.02).

Algorithms↗
PubMed1999

[Levels of evidence in the prevention and control of nosocomial infection].

BACKGROUND: Sanitary, economic and social importance of nosocomial infections justifies the introduction and development of control and surveillance systems in hospitals. The practice of a rational medicine needs the scientific evidence evaluation of the control measures employed, in terms of efficacy, efficiency and effectivity. METHODS: Critical appraisal of medical literature with special emphasis in recommendations provided by Centers for Disease Control and Prevention (CDC). RESULTS: A minimum proportion of prevention and control recommendations provided by Centers for Disease Control and Prevention (CDC) are included in the Category IA (demonstrated evidence in well-designed epidemiological or experimental studies), while sanitary impact (reduction of the nosocomial infection incidence or prevalence) or economic impact (the benefit derived of this nosocomial infection frequency reduction) of numerous interventions keeps being a motive for study and discussion because its evidence level is not demonstrated due to internal or external validity problems. CONCLUSIONS: An appropriate strategy to be adopted by sanitary professionals in charge of nosocomial infection control is the application of the evidence-based medicine methodology and principles.

Bacterial Infections↗