Exploring long-term cancer survivors' care experiences and unmet needs: protocol for a qualitative study.

BACKGROUND: The number of cancer survivors has increased in recent decades, and the majority of them suffer from sequelae of their disease and treatment. This study, which is part of the larger research project OPTILATER, aims to explore different aspects of care services for long-term survivors (≥ 5 years after initial cancer diagnosis) in Germany. The study places an emphasis on the situation of people from different age groups, with different socio-demographic and cultural backgrounds, and sexually and gender diverse individuals. METHODS: To investigate experiences related to follow-up care, focus groups (n = 2) will be conducted with members of patient advisory councils and advocacy groups, representatives of communities, healthcare workers and networks, as well as members of Associations of Statutory Health Insurance Physicians. Guided interviews will be carried out with patients and relatives (n = 40) to investigate needs, barriers and obstacles in terms of follow-up care. On this basis, additional focus groups (n = 2) will be carried out to derive possible scenarios for improving the consideration of needs. Focus groups and interviews will follow a semi-structured format and will be analysed content-analytically. Focus groups and interviews will be conducted online, recorded, transcribed, and analysed independently by two persons. DISCUSSION: The qualitative approach is considered suitable because of the exploratory research aims. The identification of experiences and barriers can reveal disparities and optimization potential in the care of long-term cancer survivors.

Corrigendum: Integration of digital health applications into the German healthcare system: development of "The DiGA-Care Path".

[This corrects the article DOI: 10.3389/frhs.2024.1372522.].

[Health economic evaluation of rehabilitative short-term care : Analysis of the costs of geriatric patients with and without rehabilitative short-term care after inpatient hospital stay]. / Gesundheitsökonomische Evaluation einer rehabilitativen Kurzzeitpflege : Ermittlung der Kosten von geriatrischen Patienten mit und ohne rehabilitative Kurzzeitpflege nach stationärem Krankenhausaufenthalt.

BACKGROUND: Geriatric patients requiring rehabilitation and admitted to short-term care after an acute inpatient hospital stay seldom receive rehabilitative services later. Rehabilitative short-term care (REKUP) supplements short-term care with rehabilitative measures, aiming to prevent functional restrictions and long-term care. STUDY OBJECTIVE: To conduct a cost and cost-effectiveness analyses of REKUP and provide data for a nationwide rollout. MATERIAL AND METHODS: A non-randomized controlled prospective study was carried out. The intervention group (IG) was paired 1:2 with a control group (KG), resulting in the formation of three collectives with follow-up periods of either 30, 90 or 180 days (each with IG and KG). Using administrative claims data from the AOK Baden-Württemberg, the mean total costs from the perspective of the health insurance were calculated. A potential impact of the intervention on costs was analyzed using the difference in differences approach. RESULTS: The analysis comprised 129 patients (IG 43; KG 86). During the follow-up periods, the IG presented higher rates of rehabilitation and lower rates of long-term care and mortality. Regarding costs, no statistically significant differences were found between the IG and KG in any of the three collectives. For nursing care and medication costs, costs were significantly higher in the follow-up period for the KG, whereas costs for rehabilitation were significantly higher for the IG (p < 0.001). DISCUSSION: Patients receiving REKUP utilize rehabilitation services more often and have a lower likelihood of requiring nursing care or dying with no statistically significant differences in costs. There are potential advantages of REKUP in the target population, which warrant further investigation due to methodological limitations.

Integration of digital health applications into the German healthcare system: development of "The DiGA-Care Path".

Introduction: Since 2019 people who have insured in the German statutory health insurance are entitled to use certified apps called the Digitale Gesundheitsanwendungen [Digital Health Applications (DiGAs)]. The prerequisite for this is that an app certified as DiGA and suitable for their diagnosis exists. The DiGA can then either be prescribed by a physician or psychotherapist or requested by the patient from the statutory health insurance fund. Given the novelty of this type of healthcare, the implementation of a DiGA should be closely monitored to identify potential weaknesses and achieve quality improvements. To enable an analysis of the supply of DiGAs step-by-step, we aimed to create the DiGA-Care Path. Methods: We conducted three steps to create the DiGA-Care Path. First, a knowledge base was created based on a structured literature research matched with knowledge gathered from the superordinate research project "QuaSiApps" funded by the German Federal Joint Committee. Second, we aimed to create an "ideal-typical" DiGA-Care Path using a flowchart. Third, based on the first path, a final path was developed using the graphical modeling language "Event-Driven Process Chain." Results: The DiGA-Care Path was developed to depict the supply of DiGAs in Germany. The final path is constituted by a "main path" as well as a corresponding "sub-path". While the "main path" focuses more on the supply environment in which a DiGA is used, the "sub-path" depicts the supply delivered by the DiGA itself. Besides the process itself, the paths include relevant actors to indicate responsibilities for individual process steps. Discussion: The DiGA-Care Path helps to analyze the current supply of DiGAs step-by-step. Thereby, each step can be investigated in detail to identify problems and to detect further steps where quality improvements can be enabled. Depending on the perspective, focused either on the supply environment, or the supply delivered by the DiGA itself, the "main path" or the "sub-path" can be used, respectively. Besides the potential of the DiGA-Care Path to improve the current supply of DiGAs, it can help as an orientation for international policymakers or further stakeholders either to develop their own integration of apps into healthcare systems or for international manufacturers to consider entering the German market.

Assessment of innovative living and care arrangements for persons with dementia: a systematic review.

BACKGROUND: Alternative forms of housing for persons with dementia have been developed in recent decades. These concepts offer small groups of residents familiar settings combined with efforts to provide normal daily life. The aim of this systematic review is to collate and analyze these more innovative forms of housing regarding residents' quality of life, behavioral aspects, as well as functional, cognitive and emotional aspects. METHODS: Searches were conducted in PubMed, EMBASE and PsycInfo in November 2020. Studies comparing traditional and more innovative living environments for persons with dementia were eligible. Concepts are described based on the results of additional searches. Risk of bias of included studies was assessed using checklists from the Joanna Briggs Institute. RESULTS: A total of 21 studies corresponding to 11 different concepts were included, namely Green Houses (USA), Group Living (Sweden), Cantou (France), Group Homes (Japan), Small-scale Group Living (Austria), Special Care Facilities (Canada), Shared-housing Arrangements (Germany), Residential Groups (Germany), Residential Care Centers / Woodside Places (USA/Canada), Small-scale Living (Netherlands/ Belgium), and Green Care Farms (Netherlands). The concepts are broadly similar in terms of care concepts, but partly differ in group sizes, staff qualifications and responsibilities. Several studies indicate that innovative forms of housing may encourage social behavior, preserve activity performance and/or positively influence emotional status compared to more traditional settings, while other studies fail to demonstrate these effects. Some studies also show increased behavioral and psychological symptoms of dementia (BPSD) in residents who live in more innovative housing concepts. The effect on cognition remains indistinct. DISCUSSION: The positive effects may be attributable to the inherent characteristics, including small group sizes, a stimulating design, and altered staff roles and responsibilities. Arguably, some of these characteristics might also be the reason for increased BPSD. Studies had variable methodological quality and results have to be considered with caution. Future research should examine these effects more closely and should investigate populations' preferences with regards to housing in the event of dementia.

Time spent on self-management by people with diabetes: results from the population-based KORA survey in Germany.

AIMS: Time needed for health-related activities in people with diabetes is assumed to be substantial, yet available data are limited. Time spent on self-management and associated factors was analysed using cross-sectional data from people with diagnosed diabetes enrolled in a population-based study. METHODS: Mean total time spent on self-management activities was estimated using a questionnaire for all participants with diagnosed diabetes in the KORA FF4 study (n = 227, 57% men, mean age 69.7, sd 9.9 years). Multiple two-part regression models were fitted to evaluate associated factors. Multiple imputation was performed to adjust for bias due to missing values. RESULTS: Some 86% of participants reported spending time on self-management activities during the past week. Over the entire sample, a mean of 149 (sd 241) min/week were spent on self-management-activities. People with insulin or oral anti-hyperglycaemic drug treatment, better diabetes education, HbA1c 48 to < 58 mmol/mol (6.5% to < 7.5%) or lower quality of life, spent more time on self-management activities. For example, people without anti-hyperglycaemic medication invested 66 min/week in self-management, whereas those taking insulin and oral anti-hyperglycaemic drugs invested 269 min/week (adjusted ratio 4.34, 95% confidence interval 1.85-10.18). CONCLUSIONS: Time spent on self-management activities by people with diabetes was substantial and varied with an individual's characteristics. Because of the small sample size and missing values, the results should be interpreted in an explorative manner. Nevertheless, time needed for self-management activities should be routinely considered because it may affect diabetes self-care and quality of life.

Critical appraisal of RCTs by 3rd year undergraduates after short courses in EBM compared to expert appraisal.

Introduction: An essential aim of courses in evidence-based medicine (EBM) is to improve the skills for reading and interpreting medical literature adequately. Regarding the conceptual framework, it is important to consider different educational levels. Aim: Our primary aim was to investigate the applicability of different instruments for the assessment of methodological study quality by 3rd grade students after short courses in EBM. Our secondary outcomes were agreement with expert assessments and student's knowledge and competences. Methods: We conducted four short courses in EBM of 90 minutes each for health care management and medical students focused on critical appraisal of the literature. At the end, the students assessed five publications about randomized controlled trials (RCTs) using five different instruments; the results were compared to expert assessments. Results: In total, 167 students participated in our EBM courses. Students' assessments showed a non-systematic over- and underestimation of risk of bias compared to expert assessments with no clear direction. Agreement with expert assessments ranged between 66% to over 80%. Across RCTs, evidence was found that the choice of instrument had an impact on agreement rates between expert and student assessments (p=0.0158). Three RCTs showed an influence of the instrument on the agreement rate (p<0.05 each). Discussion: Our results contrast sharply with those of many other comparable evaluations. Reasons may be a lack of students' motivation due to the compulsory courses, and the comparison to a reference standard in addition to self-ratings causing objectivity. Conclusion: Undergraduates should become familiar with the principles of EBM, including research methods, and the reading of scientific papers as soon as possible. For a deeper understanding, clinical experience seems to be an indispensable precondition. Based on our results, we would recommend an integration of lectures about EBM and critical appraisal at least twice during studies and with greater intensity shortly before graduation.

[Delineating Concept for Defining the Country Practitioner - - An Objective Approach for Implementation in the Field of Health Services Research]. / Abgrenzungskonzeption zur Definition Landarzt.

In the context of the scientific discussions on health care research, a concrete and uniform definition of a country practitioner is still lacking. This would be essential, however, for the future design of the medical care structure in Germany. In particular, the ongoing discussions on the predicted shortage of physicians in rural and mostly economically undeveloped regions - a shortage that is already affecting parts of Germany - suggest the need for clarification of the concept of a country practitioner. Only on the basis of a uniform definition does it seem possible to develop and discuss effective solutions across regions and to be able to use them in a targeted manner. The multitude of existing approaches to solutions, which include, among others, telemedicine, health centres, community nurses, outpatient care services being undertaken by hospitals, and youth development, must be evaluated and adapted to actual needs. The article presents a newly developed multi-stage plan for the differentiation between rural and urban doctors, which enables the definition of "country practitioner" to be adapted according to the region. With the aid of the definition, a review and further development of the aforementioned approaches to solutions can take place. Moreover, by applying the concept of delineation, there is an opportunity to create completely new ideas and solutions in the context of health services research. The basis of the new approach to rural and urban medical delineation essentially consists of the following delineation steps: basic centre (Step I), rural settlement (Step II) and central geographic location (Step III). In the following, these 3 successive delineation steps are first separately and theoretically derived. Thereafter, the presented concept is applied to the region of Westphalia-Lippe. The developed model collectively offers a standardized approach that is feasible from a temporal and financial perspective. The primary aim of this paper is to contribute to the ongoing discussion on outpatient care research and, in particular, to the definition of the country practitioner. Using the model approach presented here, this definition also enables comparisons to be made between different regions of Germany.

[Medical care of patients with spasticity following stroke : Evaluation of the treatment situation in Germany with focus on the use of botulinum toxin]. / Versorgung von Patienten mit Spastik nach Schlaganfall : Evaluation der Versorgungssituation in Deutschland mit dem Fokus auf den Einsatz von Botulinumtoxin.

BACKGROUND: Upper limb spasticity is a common complication following stroke. Cohort studies found 19% of post-stroke patients had upper limb spasticity at 3 months and 38% of patients at 12 months. For focal spasticity, intramuscular injections of botulinum toxin are indicated. In Germany, it is assumed that patients with the described indication are undersupplied with botulinum toxin. OBJECTIVE: The aim of the present study is to evaluate the medical care of patients with upper limb spasticity post-stroke with the focus on the use of botulinum toxin as one treatment option. METHODS: A standardized questionnaire was developed and a postal survey of a representative national random sample of 800 neurologists to capture the actual medical care situation. RESULTS: The response rate amounted to 37% (n = 292). 59% of the neurologists surveyed had never used botulinum toxin. In total, 87% of neurologists noticed barriers regarding the use of botulinum toxin, where the amount of the doctor's remuneration in 40% and the lack of reimbursement of costs in off-label use in 60% were the most commonly used answers. The achievement of an advanced training in using botulinum toxin was also stated as a general obstacle for resident neurologists. DISCUSSION: Due to a response rate of 37% for the postal survey a selection bias cannot be excluded. Although botulinum toxin is recommended in the national treatment guidelines, many neurologists do not use botulinum toxin. The reasons can be seen from the barriers described.

[Exposure to limited resources in the gastroenterology - results of a survey of hospital physicians]. / Umgang mit Mittelknappheit in der Gastroenterologie ­ Ergebnisse einer Befragung von Krankenhausärzten.

Background and research question: The hospital sector is currently characterized by a high economic pressure. As well the DRG system as the investment financing by the federal states imply financial limitations. Hospitals react to this situation by trying to reduce costs and to increase case volume. It is questionable whether and to what extent patient care and the working conditions of the physicians are affected by these circumstances. Especially, gastroenterological patients were considered to be insufficiently covered by the DRG system in the past. Therefore, this study focuses on the gastroenterology. Method: Based on prior studies and several semi-structured interviews with gastroenterologists working in hospitals a discipline-specific questionnaire was developed. Three versions of the questionnaire were differentiated to correspond to the respective experiences of the target population (chief physician, senior physician, assistant physician). All in all, 1751 members of the "Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten" (DGVS) were addressed. The questionnaire was answered by 642 participants resulting in a response rate of 36.7 %. The answers were interpreted by using descriptive and multivariate analyses. Results: A significant economic pressure is perceived by the participating gastroenterologists. This pressure manifests itself primary in perceived deficits in nursing care and human attention towards the patients. Moreover, the work satisfaction is negatively affected. Identified difficulties in the personnel recruitment can only be partially attributed to economic reasons. However, rationing of services is relatively seldom. Also, a financially-oriented overprovision is not perceived as a primary concern. In general, assistant physicians were a bit more skeptical about the situation in the gastroenterology, e. g. patient care, than the chief physicians. Conclusions: In total, the situation in the gastroenterology is similar to other stationary disciplines. However, in certain questions (e. g. increased surgery) differences are observed. Concerning perceived insufficient coverage of gastroenterologic services in the DRG system further projects should be initiated to improve coverage of these services.

Nursing Care Deficits in German Hospitals - Results of a Nationwide Survey of Supervisory Staff in Hospital.

Introduction: Currently, almost every second hospital is in financial deficit. Because of financial restrictions in the nursing profession, the staff has not been adequately adjusted to the increasing case volume. Current studies emphasize the rising workload of nursing staff and the resulting deficits in patient care. The aim of this study was to research whether the supervisory staff (nursing directors, chief physicians and hospital managers) also perceives these problems. Method: First, semi-structured interviews with chief physicians, nursing directors, hospital managers and hospital owners were conducted. Based on these qualitative insights, occupational group-specific questionnaires were developed. In spring 2014, these were sent to almost 5 000 supervisors. Results: There was a response rate of 43%. All respondents confirmed considerable economic restrictions related to the patient care - the greatest deficits were perceived concerning nursing care and personal attention given to patients. Moreover, the nursing directors were of the opinion that the nursing staff did not have enough time to perform all the necessary services. In particular, inadequate staffing was seen to be the cause of the rationing of nursing services. However, not only financial constraints but also a shortage of skilled staff increased the likelihood of withholding nursing services. Conclusion: In sum, all supervisory groups perceived large deficits in nursing care. With the current staff levels, nursing directors can hardly ensure provision of all necessary nursing services. The nurse support program will improve this situation slightly. In the medium term, the implementation of other instruments is necessary.

[Service productivity in hospital nursing--conceptual framework of a productivity analysis]. / Dienstleistungsproduktivität in der Krankenhauspflege--Konzeptionelle Grundlagen einer Produktivitätsanalyse.

BACKGROUND AND OBJECTIVES: Decreasing staff numbers compounded by an increasing number of cases is regarded as main challenge in German hospital nursing. These input reductions accompanied by output extensions imply that hospital nursing services have had to achieve a continuous productivity growth in the recent years. Appropriately targeted productivity enhancements require approved and effective methods for productivity acquisition and measurement. However, there is a lack of suitable productivity measurement instruments for hospital nursing services. This deficit is addressed in the present study by the development of an integrated productivity model for hospital nursing services. Conceptually, qualitative as well as quantitative aspects of nursing services productivity are equally taken into consideration. METHODS: Based on systematic literature reviews different conceptual frameworks of service productivity and the current state of research in hospital nursing services productivity were analysed. On this basis nursing sensitive inputs, processes and outputs were identified and integrated into a productivity model. RESULTS: As an adequate framework for a hospital nursing services productivity model the conceptual approach by Grönroos/Ojasalo was identified. The basic structure of this model was adapted stepwise to our study purpose by integrating theoretical and empirical findings from the research fields of service productivity, nursing productivity as well as national and international nursing research. Special challenges existed concerning the identification of relevant influencing factors as well as the representation of nursing sensitive outputs. The final result is an integrated productivity model, which can be used as an adequate framework for further research in hospital nursing productivity. CONCLUSIONS: Research on hospital nursing services productivity is rare, especially in Germany. The conceptual framework developed in this study builds on established knowledge in service productivity research. The theoretical findings have been advanced and adapted to the context of German hospital nursing services. The presented productivity model represents a unique combination of services and nursing services research, which did not exist so far. By operationalisation of the model's components it can be used as the basis for further empirical -research.

Prevalence and treatment costs of type 2 diabetes in Germany and the effects of social and demographical differences.

Treatment costs for type 2 diabetes account for a substantial amount of the expenses for statutory health care funds. Within a study sample of the year 2005, 6.8% of the insured were being treated for type 2 diabetes mellitus. Compared to the non-diabetic insured in the sample, patients included more males and older persons. Employed diabetics also showed lower mean gross salary when compared to the non-diabetic employed of the sample. In 2007, their mean costs for in- and outpatient care and drug prescriptions amounted to 2,622 Euros per patient. The impacts of social and demographical patient characteristics on total treatment costs were measured with a multiple linear regression model, controlling for the hypoglycemic therapy of the patient. Here, the impact of age, gender and intensive insulin therapy became evident. A higher annual salary had a negative, yet non-significant, effect.

Evaluation of an integrated care program for schizophrenia: concept and study design.

Concept and design of an independent scientific evaluation of different pathways of care for schizophrenia patients in Germany with respect to effectiveness and efficiency are presented. In this prospective, observational study, schizophrenia patients receiving an integrated care treatment, the intervention group (IG), are compared with patients under routine care conditions treated by the same physician (first control group, CG 1). A second control group (CG 2) of patients treated by office-based psychiatrists not participating in the integrated care program will be recruited and their data compared with the two other groups. The total amount of psychiatric hospital days after 12 months is defined as primary outcome parameter. Secondary outcome parameters comprise the frequency of psychiatric inpatient readmissions, severity of schizophrenia symptoms, remission rates and quality of life. Patients undergo assessments at baseline, month 6 and 12 using standardized and experimental questionnaires. Routine data of a regional German social health insurance fund complement information on included patients. Additionally, a cost-effectiveness and cost-utility analysis will be performed. Until now, 137 psychiatrists included 980 patients in the integrated care project in Lower Saxony, Germany, and 47 psychiatrists (IG and both CGs) are willing to participate in the independent evaluation. For the first time, a prospective observational controlled evaluation study of a countrywide integrated care project planning to recruit 500 schizophrenia patients has started using comprehensive assessments as well as routine data of a social health insurance fund.

[Assessment of risk of bias in controlled studies]. / Bewertung des Risikos für Bias in kontrollierten Studien.

BACKGROUND: Practicing physicians are faced with many medical decisions daily. These are mainly influenced by personal experience but should also consider patient preferences and the scientific evidence reflected by a constantly increasing number of medical publications and guidelines. With the objective of optimal medical treatment, the concept of evidence-based medicine is founded on these three aspects. It should be considered that there is a high risk of misinterpreting evidence, leading to medical errors and adverse effects without knowledge of the methodological background. OBJECTIVES: This article explains the concept of systematic error (bias) and its importance. Causes and effects as well as methods to minimize bias are discussed. This information should impart a deeper understanding, leading to a better assessment of studies and implementation of its recommendations in daily medical practice. CONCLUSION: Developed by the Cochrane Collaboration, the risk of bias (RoB) tool is an assessment instrument for the potential of bias in controlled trials. Good handling, short processing time, high transparency of judgements and a graphical presentation of findings that is easily comprehensible are among its strengths. Attached to this article the German translation of the RoB tool is published. This should facilitate the applicability for non-experts and moreover, support evidence-based medical decision-making.

[Secondary data analysis of the prevalence of alcohol dependence (F10.2) in Germany]. / Sekundärdatenanalyse der Prävalenz der Alkoholabhängigkeit (F10.2) in Deutschland.

BACKGROUND AND AIM: Compared to other European countries, alcohol consumption and abuse in Germany is on a high level. Even in smaller quantities, frequent alcohol consumption can generate organic damages and thus lead to secondary diseases that have a significant societal relevance regarding direct and indirect costs for the healthcare system. After several publications have already addressed the prevalence of acute alcohol intoxication and alcohol abuse in adolescents, the question arises how the prevalence of alcohol abuse develops on the basis of the accounting data of outpatient and inpatient care providers in the population of adults aged 18 and over and what tendency can be observed within a multi-year period. Within this study, the coding of alcohol abuse (F10.2 diagnosis) was analyzed separately for outpatient and inpatient sector in the insured population ≥ 18 years and presented over time. PATIENTS AND METHODS: The development of the prevalence of alcohol abuse was analyzed on the basis of secondary random sample data from one nation-wide working statutory health insurance with a total population of more than 3 million insurants in the 5-year period from 2006 to 2010. For the presentation of the prevalences, insurant numbers were used. For the identification of the relevant insurants, only confirmed outpatient F10.2 diagnoses or inpatient F10.2 diagnoses were used. The age and sex distributions of the dataset were adjusted to the distribution in the statutory health insurance to ensure representativeness. The analyses of each single year only allude to insured persons aged ≥ 18 years. With the help of the statistics of the insured of statutory health insurance, for each calendar year, projections of the detected prevalence rates were determined to estimate the number of cases on the statutory health insurance level and their development over time. RESULTS: The results show a tendency of slightly increasing prevalence of alcohol dependence from 2006 to 2010. For insured persons with at least one inpatient or outpatient F10.2 diagnosis, the prevalence continuously rises from 1,04% in 2006 to 1.14% in 2010; the prevalence of insured persons who received an alcohol dependence diagnosis only in the outpatient sector, increased from 0,67% to 0,79% in that time scale. In all analyzes, there was a ratio of 30% affected women to 70% affected men. From 2006 to 2010, the proportion of insured persons with hospitalization caused by alcohol dependence decreased steadily from 14,51% to 12,24%. CONCLUSION: For the analyzed group of persons aged ≥ 18 years, the present analysis results show a tendency of slightly increasing prevalences of alcohol abuse, however at the same time combined with a decreasing proportion of hospitalized patients. Similar nationwide studies from 2010 on the basis of secondary data of a health insurance company and inclusion of outpatient and inpatient diagnoses also indicate prevalences of alcohol dependence of about 1.18%, but they base on the age range of 15- to 64-year-old insurants.

[The Onco-hematology clinical research unit at the Geneva University Hospital: example of a fruitful public-private partners]. / L'Unité de recherche clinique en onco-hématologie aux HUG: un exemple réussi de partenariat public-privé.

A better understanding of the molecular deregulation leading to carcinogenesis allows the development of numerous novel targeted therapeutic candidates. Clinical research in oncology is a critical step to evaluate in a thorough manner the safety and efficacy of these innovative compounds. During the last four years the fruitful partnership between the Geneva University Hospitals and the Dr. Henri Dubois-Ferriere Dinu Lipatti Foundation lead to a dedicated clinical research unit for cancer patients with a staff of ten people. Since 2010, more than 300 patients were enrolled in more than 70 distinct clinical trials evaluating novel therapies for both solid tumors and hematologic malignancies. Interestingly, classical cytostatic drugs now represent only a small fraction of the new anti-cancer therapies in the pipeline.

Prognostic significance of FLT3 internal tandem duplication, nucleophosmin 1, and CEBPA gene mutations for acute myeloid leukemia patients with normal karyotype and younger than 60 years: a systematic review and meta-analysis.

Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. An increasing number of gene mutations have been found, and some are used for risk classification in AML patients with normal karyotype (cytogenetically normal (CN)-AML). In this systematic review and meta-analysis, we examined three frequent mutations in CN-AML: mutations of fms-related tyrosine kinase 3 (FLT3-ITD), mutated nucleophosmin (NPM1), and mutations of the CCAAT enhancer-binding protein alpha (CEBPA) gene. A systematic literature search of publications listed in the electronic databases (Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge and Cochrane) from 2000 up to March 2012 was performed (Fig. 1). Nineteen studies were included and qualitatively analyzed. Two to four studies entered the quantitative meta-analysis incorporating 1,378 to 1,942 patients with CN-AML. Meta-analysis for overall survival (OS) and relapse-free survival (RFS) showed FLT3-ITD to predict an unfavorable prognosis, with hazard ratios (HR) of 1.86 and 1.75, respectively. In contrast, meta-analysis of the impact of NPM1 and CEBPA mutations on OS yielded an HR of 0.56 for each mutation, while analysis of impact on RFS produced HRs of 0.37 and 0.42, respectively. This systematic review and meta-analysis aimed to evaluate the prognostic value of mutations in the NPM1, CEBPA, and FLT3 genes. FLT3-ITD was associated with worse prognosis, whereas mutations in NPM1 and CEBPA genes were associated with a favorable prognosis.