Pharmaceutical Interventions for Inpatients with Liver Cirrhosis and Liver Transplantation: A Systematic Review of Experimental Studies.

Liver cirrhosis, which is considered one of the leading causes of death in the world, can lead to severe complications, and is often followed by a liver transplantation. These patients take an average of nine medications daily. If not managed adequately, it can be accompanied by serious drug-related problems. To reduce this risk, a clinical pharmacist may be included as part of the healthcare team to optimize medication therapy in this population. This study aimed to systematically identify the pharmaceutical interventions which reduced drug-related problems and improved medication therapy for adult hospitalized liver cirrhotic and liver transplant patients when compared to standard care. Three databases (PubMed, Embase, and CENTRAL) were systematically searched from the inception of each database to 25 October 2023, and interventional studies in the English language were included. The risk of bias was assessed according to RoB-I for the UBA study and RoB2 for the identified RCT. The detected interventions to reduce drug-related problems in liver cirrhotic and liver transplant patients were extracted and classified according to a "Hierarchy of Controls" model. Two studies from Germany and the USA met our inclusion criteria, respectively. In these studies, we identified two interventions that included education, expert consultation, and the monitoring of the immunosuppressive medications serum level. The main objective of the two included studies was improving patients' compliance through adherence. These pharmaceutical interventions identified were classified as administrative controls, which is one of the lowest levels in the "Hierarchy of Controls" with which to address a potential risk. Pharmaceutical interventions to optimize medication therapy were found to be rare in the examined population, and were limited to "administrative controls". These interventions were limited to transplant patients' education and the monitoring of the immunosuppressive medication serum levels. No interventional studies were found to have investigated pharmaceutical interventions in patients with liver cirrhosis. Especially regarding this patient group, future studies to reduce DRPs using pharmaceutical interventions are needed. This study received no external funding and its PROSPERO registration number is CRD42022309122.

How to report incidental findings from population whole-body MRI: view of participants of the German National Cohort.

OBJECTIVES: In the German National Cohort (GNC), 30,000 individuals are examined with whole-body MRI (wbMRI), of which about 3000 participants are expected to receive an incidental finding (IF) disclosure. In order to get feedback from participants and to evaluate the IF-management procedure of the wbMRI substudy, a follow-up questionnaire was developed. This single-center pilot trial was aimed to get a first impression on feasibility reproducibility and validity of such a survey in order to take necessary adjustments before initiating the survey among several thousand participants. METHODS: The questionnaires were sent out in test-retest manner to 86 participants who received a wbMRI examination in January-February 2016 at the imaging center in Neubrandenburg. The ratio of participants with and without IF notification was 1:1. Descriptive statistics was performed. RESULTS: A first response of 94% and completion proportion of 99% were achieved. Participants were satisfied with the examination procedure. Ninety-five percent of participants considered it very important to receive notification of IFs. Participants reported minimal stress levels while waiting for a possible IF notification letter, but high stress levels when an IF letter was received. Phrasing of the IF reports was rated in 97% as well understandable and in 55% as beneficial to health status. CONCLUSIONS: This questionnaire will serve researchers within the GNC as a fundamental instrument not only for quality management analyses but also for the investigation of still unacknowledged scientific and ethical questions contributing to evidence-based guidelines concerning the complex approach to IFs in future population-based imaging. KEY POINTS: • Evidence-based guidelines for reporting incidental findings in population whole-body MRI are lacking. • Pilot-testing of a questionnaire for the evaluation of practical and ethical aspects of the procedure to report incidental findings in the German National Cohort shows a high level of acceptance and high return rate by participants. • Participants reported minimal stress levels while waiting for a possible incidental finding notification letter, which increased significantly, when such a letter was received.

The Ambivalence of Early Diagnosis - Returning Results in Current Alzheimer Research.

OBJECTIVES: Based on an analysis of the potential consequences of disclosing AD suspicions from respective research and using the research ethical principle of non-maleficence, the authors of this paper argue for the thesis that the benefits of early AD detection in research outweigh the risk of potential adverse effects only in cases where studies are conducted with symptomatic people actively seeking for support, e.g. as they utilize the services of memory clinics. CONCLUSION: In the case of non-symptomatic volunteers, the result of the risk-benefit-assessment seems to be less distinctive. Given that disclosing results can, at least initially, cause severe distress and harm and taking into account that research examinations have a significantly increased risk of producing false-positive findings, we suggest to make use of a research-ethical "princple of caution" that supports a restrictive disclosure policy for the second group of potential study participants. This differentiated view on the benefits of disclosed findings in AD research is reflected in recommendations for the set-up of return of result processes.

How do people with dementia utilise primary care physicians and specialists within dementia networks? Results of the Dementia Networks in Germany (DemNet-D) study.

Outpatient dementia healthcare is predominantly fragmented, and dementia networks (DNs) represent an integrated care concept to overcome this problem. Little is known about the patients of these networks with regard to utilisation of physicians and associated factors. We interviewed 560 caregivers of people with dementia in 13 different DNs in Germany in 2013 and assessed socio-demographics, clinical data and physician utilisation. Networks were categorised in predominantly medical DNs and community-oriented DNs. Descriptive and multivariate statistical models were used to identify associated factors between DNs and users' data. Overall, the users of networks received high rates of physician care; 93% of the sample stated at least one contact with a primary care physician within the last 6 months, and 74% had been treated by a specialist (neurology/psychiatry physician). Only 5% of the sample had no contact with a physician in the 6 months preceding the interview. Females showed a lower odds for physician specialist consultations (OR = 0.641). Users of medical DNs receive greater specialist consultations overall (OR = 8.370). Compared to the German general population and people with dementia in other settings, users of DNs receive physician care more regularly, especially with regard to the consultations of neurologist/psychiatrists. Therefore, DNs seem to perform a supportive role within the integration of physician healthcare. More research is needed on the appropriate relationship between the needs of the people with dementia and utilisation behaviour.

Systems Medicine: hype or revolution?

Research and innovation in healthcare can change existing practices aiming at constant improvement of diagnosis, treatment and prevention. As a new holistic approach Systems Medicine (SM) may revolutionize the healthcare system. This paper analyzes ethical and economic obstacles of SMs development from a niche innovation to a standard solution. We adapt a model of innovation theory to structure the barriers of adopting SM to become standard in the medical system. SM has the potential to change the medical system if barriers to this innovation can be overcome. The article discusses the potential of SM in becoming the future health paradigm considering these barriers and provides an overview of the current situation.

Cohort profile: Greifswald approach to individualized medicine (GANI_MED).

BACKGROUND: Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the "Greifswald Approach to Individualized Medicine" (GANI_MED) project to address major challenges of Individualized Medicine. Herein, we describe the implementation of the scientific and clinical infrastructure that allows future translation of findings relevant to Individualized Medicine into clinical practice. METHODS/DESIGN: Clinical patient cohorts (N > 5,000) with an emphasis on metabolic and cardiovascular diseases are being established following a standardized protocol for the assessment of medical history, laboratory biomarkers, and the collection of various biosamples for bio-banking purposes. A multi-omics based biomarker assessment including genome-wide genotyping, transcriptome, metabolome, and proteome analyses complements the multi-level approach of GANI_MED. Comparisons with the general background population as characterized by our Study of Health in Pomerania (SHIP) are performed. A central data management structure has been implemented to capture and integrate all relevant clinical data for research purposes. Ethical research projects on informed consent procedures, reporting of incidental findings, and economic evaluations were launched in parallel.

Implications of the incidentalome for clinical pharmacogenomics.

Incidental findings have long posed challenges for healthcare providers, but the scope and scale of these challenges have increased with the introduction of new technologies. This article assesses the impact of incidental findings on the introduction of prospective pharmacogenomic testing into clinical use. Focusing on the challenges of the incidentalome, the large set of incidental findings potentially generated through genotyping, the paper argues that provisional approaches to managing incidental findings may be implemented if necessary to allow benefits of pharmacogenomic testing to be realized in the clinical setting. In the longer term, approaches to returning incidental findings may need to focus on limiting the number of incidental findings to a number that can be addressed by patients and providers.

Psychosocial consequences and severity of disclosed incidental findings from whole-body MRI in a general population study.

OBJECTIVES: Little is known about the psychosocial impact and subjective interpretation of communicated incide ntal findings from whole-body magnetic resonance imaging (wb-MRI). This was addressed with this general population study. METHODS: Data was based on the Study of Health in Pomerania (SHIP), Germany. SHIP comprised a 1.5-T wb-MRI examination. A postal survey was conducted among the first 471 participants, aged 23-84 years, who received a notification about incidental findings (response 86.0 %, n = 405). The severity of incidental findings was assessed from the participants' and radiologists' perspective. RESULTS: In total, 394 participants (97.3 %) wanted to learn about their health by undergoing wb-MRI. Strong distress while waiting for a potential notification of an incidental finding was reported by 40 participants (9.9 %), whereas 116 (28.6 %) reported moderate to severe psychological distress thereafter. Strong disagreement was noted between the subjective and radiological evaluation of the findings' severity (kappa = 0.02). Almost all participants (n = 389, 96.0 %) were very satisfied with their examination. CONCLUSIONS: Despite the high satisfaction of most participants, there were numerous adverse consequences concerning the communication of incidental findings and false expectations about the likely potential benefits of whole-body-MRI. KEY POINTS: • Disclosed incidental findings from MRI may lead to substantial psychosocial distress. • Subjective and radiological evaluations of incidental findings' severity differ strongly. • Disclosing incidental findings is strongly endorsed by study volunteers. • Study volunteers tend to have false expectations about potential benefits from MRI. • Minimizing stress in study volunteers should be a key aim in MRI research.

Comparing different scientific approaches to personalized medicine: research ethics and privacy protection.

In this article, two different scientific approaches to personalized medicine are compared. Biorepository at Vanderbilt University (BioVU) is a genomic biorepository at Vanderbilt University Medical Center in Nashville, TN, USA. Genetic biosamples are collected from leftover clinical blood samples; medical information is derived from an electronic medical records. Greifswald Approach to Individualized Medicine is a research resource at the University of Greifswald, Germany, comprised of clinical records combined with biosamples collected for research. We demonstrate that although both approaches are based on the collection of clinical data and biosamples, different legal milieus present in the USA and Germany as well as slight differences in scientific goals have led to different 'ethical designs'. While BioVU can successfully operate with an 'opt-out' mechanism, an informed consent-based 'opt-in' model is indispensable to allow GANI_MED to reach its scientific goals.