[Evaluation of the fluid balance in geriatric patients-What contribution can abdominal ultrasound make?] / Evaluation des Flüssigkeitshaushalts bei geriatrischen Patienten ­ Was kann die Abdomensonographie beitragen?

The assessment of the fluid balance as well as the identification of hyperhydration and dehydration often represent a diagnostic challenge, especially in older patients. In principle, various diagnostic procedures and approaches are suitable for assessment of the various facets, by which such a disorder can be recognized. The contribution of abdominal ultrasound is described and evaluated in the context of the different diagnostic procedures. An overview of the current situation with respect to assessment of the vena cava is provided. In many respects there is no strict consensus concerning the thresholds of the individual measurements and the value of the different measurements. Currently, an orthograde diameter of the inferior vena cava > 2 cm is accepted as being a good indicator for hyperhydration. Less certain are analogously derived thresholds as indicators for dehydration.

Diagnostic efficacy of bedside ultrasound to detect dehydration in older patients attending an emergency care unit.

BACKGROUND: The diagnosis of dehydration in older patients remains a challenge because clinical and laboratory signs are unspecific. The use of B­Mode ultrasound of the inferior vena cava is proposed to aid in the diagnosis but data concerning diagnostic efficacy of bedside ultrasound are lacking. METHODS: In this study 78 patients ≥65 years old referred to the emergency unit of a university hospital and identified as being dehydrated by applying clinical signs were compared with a reference of 121 patients. The diameter of the inferior vena cava (IVC) was assessed by ultrasound while compressing the IVC during an inspiratory maneuver and the minimum and maximum diameter in M­Mode. RESULTS: Significant differences were found concerning compressibility, variability of the diameter assessed by M­Mode and the diameter during an inspiratory maneuver of the IVC (<0.001); however, a receiver operator characteristics (ROC) showed only moderate values for diagnostic efficacy for all these parameters where the best result was found for the inspiratory maneuver (Area under the curve [AUC] = 0.73). To reach a specificity of 0.8 to diagnose dehydration, a cut-off value of ≤0.4 cm for IVC diameter was suitable. CONCLUSION: Ultrasound of the IVC can easily be applied in a bedside setting and may be helpful in identifying dehydration in older patients; however, this remains challenging and a synopsis covering clinical and technical data is indispensable.

Immunogenicity assay development and validation for biological therapy as exemplified by ustekinumab.

Introduction of biotherapeutics has been a major milestone in the treatment of different chronic diseases. Nevertheless, the immune system can recognize the administered biological as non-self and respond with generation of anti-drug antibodies (ADA), including neutralizing ADA (nADA). Immunogenic responses may result in altered drug dynamics and kinetics leading to changes in safety and efficacy. However, there are several challenges with standard techniques for immunogenicity testing. Ustekinumab (UST), used in different inflammatory diseases, is a therapeutic antibody directed against the shared p40 subunit of interleukin (IL)-12 and IL-23, interfering in the pathogenically crucial T helper type 1 (Th1)/Th17 pathway. We established and validated different approaches for detection and quantitation of UST, UST-specific ADA and nADA. Addressing the obstacle of complex formation of UST with nADA, we developed an acidification assay to approach the total amount of nADA. Validated methods were based on surface plasmon resonance spectroscopy (SPR), enzyme-linked immunosorbent assay (ELISA) and a cell-based approach to characterize neutralizing capacity of nADA. Parameters assessed were determination and quantitation limits, linearity, range, precision, accuracy and selectivity. Quantitation of ADA and UST was feasible at lower concentrations using ELISA, whereas SPR showed a wider linear range for determination of ADA and UST. Accuracy, precision and linearity for quantitation were comparable using ELISA, SPR and the cell-based approach. All validated parameters fulfill the requirements of regulatory agencies. A combination of the testing approaches could address the increasing demand of precision medicine as it can be suitable for capturing the whole spectrum of immunogenicity and is transferable to other biologicals.

Addition or removal of concomitant methotrexate alters adalimumab effectiveness in rheumatoid arthritis but not psoriatic arthritis.

Objective: Randomized trials have shown that concomitant methotrexate (MTX) augments the effectiveness of tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA), but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The goal of this study was to examine whether the impact of concomitant MTX on therapeutic outcomes in patients with PsA was similar to its effects in RA. Methods: We used data from highly comparable and concurrent observational studies of patients with PsA (N = 1424) or RA (N = 3148) who initiated adalimumab therapy during routine clinical care. The 28-joint Disease Activity Score (DAS28) and patient-reported pain scores were evaluated in patients who received 24 months of continuous treatment with adalimumab monotherapy or adalimumab + MTX and in patients who initiated or stopped concomitant MTX during ongoing adalimumab therapy. Results: Twenty-four months of continuous treatment with adalimumab + MTX was superior to adalimumab monotherapy in RA patients, while no significant difference was observed in patients with PsA. RA patients who added MTX during the study showed significant individual improvements in DAS28 and pain scores at 6 months after the change in therapy, while those who removed MTX had slight increases in disease activity. In contrast, in patients with PsA, neither initiation nor removal of MTX during continuous adalimumab therapy had a significant effect on therapeutic outcomes. Conclusion: Addition of MTX to adalimumab confers further therapeutic benefit in patients with RA, but not in those with PsA, suggesting differences in MTX effects in these two patient populations. Clinicaltrials.gov NCT01078090, NCT01077258, NCT01111240.

[Value of combining biologics with methotrexate for treatment of psoriatic arthritis-questions remain]. / Stellenwert der Kombination von Biologika mit Methotrexat in der Behandlung der Psoriasisarthritis ­ Fragen bleiben offen.

BACKGROUND: Concomitant methotrexate (MTX) improves the therapeutic effect of biologic therapies in rheumatoid arthritis treatment. However, the influence of MTX on biologic therapy in psoriasis arthritis (PsA) has not yet been fully clarified, as data from randomized clinical studies are lacking. So far, it is only known, that PsA patients with inadequate response to MTX or non-steroidal anti-inflammatory drugs alone respond equally well to a subsequent biologic therapy. OBJECTIVES: The aim of this study is to investigate whether MTX-naive patients achieve greater disease improvement with the combination of MTX and a biologic than with biologic monotherapy alone, and whether patients on MTX in whom a biologic therapy is additionally started would worsen if MTX is discontinued. METHODS: The current data situation and its limitations are presented. Furthermore, an investigator-initiated multicenter randomized clinical study in patients with active PsA is introduced (MUST study), which investigates the influence of placebo-controlled MTX combination therapy with the interleukin 12/23 inhibitor ustekinumab (UST) in order to close the existing evidence gap. RESULTS: The primary objective of the study is to demonstrate the non-inferiority of UST monotherapy compared to MTX/UST combination therapy as measured by mean DAS28 values at week 24. Of 196 planned patients, 77 have been included so far. Recruitment is still open. CONCLUSION: The MUST study offers the ideal opportunity to investigate the influence of concomitant MTX in a controlled study design and to assess whether the addition of MTX to UST therapy or its continuation is beneficial for PsA patients.

[Biomarkers and imaging for diagnosis and stratification of rheumatoid arthritis and spondylarthritis in the BMBF consortium ArthroMark]. / Biomarker und Bildgebung zur Diagnose und Stratifizierung der rheumatoiden Arthritis und Spondylarthritis im BMBF-Verbund ArthroMark.

Rheumatic diseases are among the most common chronic inflammatory disorders. Besides severe pain and progressive destruction of the joints, rheumatoid arthritis (RA), spondyloarthritides (SpA) and psoriatic arthritis (PsA) impair working ability, reduce quality of life and if treated insufficiently may enhance mortality. With the introduction of biologics to treat these diseases, the demand for biomarkers of early diagnosis and therapeutic stratification has been growing continuously. The main goal of the consortium ArthroMark is to identify new biomarkers and to apply modern imaging technologies for diagnosis, follow-up assessment and stratification of patients with RA, SpA and PsA. With the development of new biomarkers for these diseases, the ArthroMark project contributes to research in chronic diseases of the musculoskeletal system. The cooperation between different national centers will utilize site-specific resources, such as biobanks and clinical studies for sharing and gainful networking of individual core areas in biomarker analysis. Joint data management and harmonization of data assessment as well as best practice characterization of patients with new imaging technologies will optimize quality of marker validation.

[S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. / S2e-Leitlinie: Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten.

BACKGROUND: Medication-based strategies to treat rheumatoid arthritis are crucial in terms of outcome. They aim at preventing joint destruction, loss of function and disability by early and consistent inhibition of inflammatory processes. OBJECTIVE: Achieving consensus about evidence-based recommendations for the treatment of rheumatoid arthritis with disease-modifying anti-rheumatic drugs in Germany. METHODS: Following a systematic literature research, a structured process among expert rheumatologists was used to reach consensus. RESULTS: The results of the consensus process can be summed up in 6 overarching principles and 10 recommendations. There are several new issues compared to the version of 2012, such as differentiated adjustments to the therapeutic regime according to time point and extent of treatment response, the therapeutic goal of achieving remission as assessed by means of the simplified disease activity index (SDAI) as well as the potential use of targeted synthetic DMARDs (JAK inhibitors) and suggestions for a deescalating in case of achieving a sustained remission. Methotrexate still plays the central role at the beginning of the treatment and as a combination partner in the further treatment course. When treatment response to methotrexate is inadequate, either switching to or combining with another conventional synthetic DMARD is an option in the absence of unfavourable prognostic factors. Otherwise biologic or targeted synthetic DMARDs are recommended according to the algorithm. Rules for deescalating treatment with glucocorticoids and-where applicable-DMARDs give support for the management of patients who have reached a sustained remission. DISCUSSION: The new guidelines set up recommendations for RA treatment in accordance with the treat-to-target principle. Modern disease-modifying drugs, now including also JAK inhibitors, are available in an algorithm.

[Expectations and attitudes concerning geriatric counseling : Results of a survey among general practitioners and hospital-based providers in two German states]. / Erwartungen und Einstellungen zum geriatrischen Konsil : Ergebnisse einer Befragung in ambulanten und stationären Versorgungsstrukturen zweier Bundesländer.

BACKGROUND: Expertise in geriatrics in the field of ambulatory and hospital-based treatment does not have access to comparable medical specialist structures, such as those in internal medicine and neurology; therefore, it is recommended that geriatric diagnostics by general practitioners can be supported by networking with hospital-based geriatric centers for geriatric counseling. The attitudes and experiences of both faculties in Germany are, however, not well known. METHODS: Representative samples of general practitioners and hospital-based faculty departments for internal medicine in two regions of Germany (Baden-Württemberg and Hessen) were identified using a systematic selection method. All departments of geriatrics in these regions were also contacted. Participants were asked to give their attitudes and experiences regarding geriatric counseling using a questionnaire. RESULTS: Responses to the questionnaire were received from 48 general practices (14.9%), 42 internal medicine departments (38.5%) and 25 hospital-based geriatric centers (34.7%). Of the general practices 79.2% reported performing geriatric assessments but only 31.3% had access to geriatric counseling. Of the faculties of internal medicine 71.4% reported providing geriatric counseling of which 16.7% also provided counseling on an outpatient basis. With respect to the spectrum of actual reasons for geriatric counseling, initiation of rehabilitative measures was the main reason in both geriatric and internal medicine departments. There were differences in the estimation of suitable rating topics for geriatric counseling. Geriatric departments more frequently indicated preventive aspects compared to general internal medicine (80% vs 47.6%) and general practices (56.3%). With respect to the domain level, general practitioners rated these in the order of cognition (72.9%), social situation (70.8%), emotion (50%), locomotion (50%) and incontinence (27.1%). Noteworthy was that they also rated much lower compared to hospital-based providers particularly with respect to locomotion and incontinence problems. CONCLUSION: Geriatric assessment is widely used by general practitioners and there is generally a positive attitude to geriatric counseling and networking with hospital-based geriatric centers. At present, only a minority of general practitioners find local providers of geriatric counseling. Preventive aspects do not reach the same significance as rehabilitation topics and this discloses some potential for improvement. Differences in rating usefulness between the two groups may be explained by competing providers, e. g. specialists in these fields.

Zytopenien : Anämie, Leukopenie und Thrombopenie.

Hematological alterations can often be observed during rheumatic diseases. The effects can be clinically severe, ranging from anemia of different grades of severity, through increased risk of hemorrhage due to thrombocytopenia up to severe infections as a result of high-grade leukocytopenia. The clinical sequelae for patients are predominantly determined by the extent of cytopenia. The underlying disease itself can initially be considered as the cause. Examples are anemia as a result of chronic inflammation, antibody-mediated thrombocytopenia as in systemic lupus erythematosus (SLE) or granulocytopenia within the framework of Felty's syndrome. Immunosuppressive treatment also often leads to alterations in the blood constituents. Although some substances, such as cyclophosphamide can suppress all three cell types, there are also selective effects, such as isolated thrombocytopenia under treatment with tocilizumab and JAK inhibitors. The differential diagnostic clarification of cytopenia can be difficult and necessitates a systematic work-up of the course of the disease and the subsequent treatment. The reviews of anemia, leukocytopenia and thrombocytopenia presented here summarize the most important components of the differentiation of hematological alterations in patients with rheumatic diseases.

[Malignancies of the skin and immunomodulatory antirheumatic therapy]. / Hautmalignome und immunmodulierende Antirheumatikatherapie.

For the clinical practice there is uncertainty as to what degree the therapeutic immunomodulation of rheumatoid arthritis (RA) is associated with a weakening of protective tumor immunity. Neoplasms of the skin in particular are known to exhibit increased incidence rates in association with therapeutic immunosuppression in transplantation medicine; however, the immunosuppression required for the prevention of allogenic graft rejection is much more intensive and thus not directly transferable to the potential risks for an onset or relapse of melanoma or non-melanoma skin cancers (NMSC), e. g. spinocellular and basal cell carcinomas in association with the antirheumatic treatment of RA. This review covers the association of RA and its pharmacotherapy with conventional synthetic (cs) and biologic disease-modifying antirheumatic drugs (DMARD) on the basis of a systematic literature search. The incidence rates of NMSC are twice as high in biologic-naive RA patients compared to the general population, whereas the respective incidence rates for melanoma do not differ. A biologic treatment with tumor necrosis factor (TNF) blockers compared with administration of csDMARD only has a minor, if any effect on the increase of NMSC risk but is associated with a trend towards an elevated incidence rate of new onset melanoma although significance level was not reached in all of the reviewed studies. The data on non-TNF blocking biologics is sparse. Accordingly, it is inappropriate to draw any strong conclusions on potentially associated skin cancer risks from the present lack of safety signals. The consideration of individual risk factors, recommendations on sufficient UV protection and regular skin monitoring may serve to improve the safety of DMARD therapy in RA.

[Do we still need clinical studies in rheumatology?]. / Brauchen wir noch klinische Studien in der Rheumatologie?

Despite a large number of approved therapies demonstrating efficacy in the treatment of rheumatic diseases, only 60-85 % of patients with the indications for rheumatoid arthritis are adequately treated in Germany. Additionally, approved therapies for other immune-mediated diseases are often entirely lacking, indicating the great medical need for the development of new innovative therapies in this specialized field. The development of new drugs is expensive due to the high costs of conducting clinical trials in all phases of development up to obtaining approval; therefore, pharmaceutical companies are looking for ways to save costs in the particular developmental stages. Although the classical regions for drug development (i.e. western Europe, the USA and Japan) offer both a high level of data quality and a good infrastructure to conduct clinical trials due to high standards of education and quality, clinical trials are expensive in these regions. Beside high costs, the comparatively low recruitment rates in these regions are one of the main reasons for the shifting of drug developmental stages from classical regions to eastern European, Latin American and Asian countries, which provide services for drug development and high recruitment rates for comparatively less money. However, there are many strong arguments for the participation of regions in western Europe, especially German sites in clinical trials. In this article these arguments are discussed and possible solutions and strategies for conducting and compensation of study centers in Germany for clinical trials in the field of rheumatology are provided.

Certolizumab pegol in rheumatoid arthritis patients with low to moderate activity: the CERTAIN double-blind, randomised, placebo-controlled trial.

OBJECTIVES: This 52-week, randomised, double-blind phase IIIb study assessed efficacy and safety of certolizumab pegol (CZP) as add-on therapy to non-biologic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with low to moderate disease activity, and stopping therapy in patients in sustained remission. METHODS: Patients were randomised 1:1 to CZP (400 mg at weeks 0, 2 and 4, then 200 mg every 2 weeks) or placebo (every 2 weeks) plus current non-biologic DMARDs. At week 24, patients who achieved the primary endpoint of Clinical Disease Activity Index (CDAI) remission at both weeks 20 and 24 stopped study treatment and continued in the study until week 52. RESULTS: Of 194 patients (CZP=96; placebo=98), >90% had moderate disease activity at baseline. Significantly more CZP patients met the primary endpoint than placebo patients (week 20 and 24 CDAI remission rates: 18.8% vs 6.1%; p≤0.05). At week 24, 63.0% vs 29.7% of CZP versus placebo patients (p<0.001) achieved LDA. Disease activity score (ESR) based on 28-joint count and Simplified Disease Activity Index remission rates were also significantly higher with CZP versus placebo (19.8% vs 3.1%; p≤0.01 and 14.6% vs 4.1%; p≤0.05). CZP patients reported improvements in physical function versus placebo (mean Health Assessment Questionnaire-Disability-Index change from baseline: CZP, -0.25 vs placebo, -0.03; p≤0.01). During the period following withdrawal of CZP or placebo, only 3/17 prior CZP patients and 2/6 prior placebo patients maintained CDAI remission until week 52, but CZP reinstitution allowed renewed improvement. Adverse and serious adverse event rates were comparable between CZP and placebo groups. CONCLUSIONS: Addition of CZP to non-biologic DMARDs is an effective treatment in RA patients with predominantly moderate disease activity, allowing low-disease activity or remission to be reached in a majority of the patients. However, the data suggest that CZP cannot be withdrawn in patients achieving remission. TRIAL REGISTRATION NUMBER: NCT00674362.

[Non-opioid pain medication in the elderly]. / Pharmakotherapie des Schmerzes bei älteren Patienten mit Nichtopioiden.

Non-opioid analgesics are frequently used to control chronic pain in elderly patients; however some of these drugs show high rates of adverse drug reactions. Among these are significant clinical problems which impede an effective and safe pain control. This review provides recent data concerning non-steroidal anti-inflammatory drugs (NSAID), acetaminophen, metamizol and flupirtin. Due to their risk profile NSAIDs are less appropriate due to high incidence rates and drug-related risk patterns. Acetaminophen, metamizol and flupirtin may be recommended instead; however a shortcoming of acetaminophen in comparison to NSAIDs is its weaker action to control pain. Metamizol is still banned in some countries due to rare but potentially severe hematological side effects and flupirtin frequently causes unfavorable sedation.

[Common German language nomenclature for systemic sclerosis]. / Gemeinsame deutschsprachige Nomenklatur für die systemische Sklerose.

Large data bases and the projects arising from them have led to a much improved understanding of systemic sclerosis over the last decade. Serology has developed further so that more autoantibodies are available for routine testing. Capillary microscopy has become standard and relevant progress has also been made in therapy. Many diagnostic terms found in medical documentation do not adequately reflect this progress. The nomenclature is inconsistent and, therefore, confusing. The international classification of diseases (ICD) nomenclature is, from our point of view, also in need of improvement. This article aims to reestablish a common German language standard for systemic sclerosis, which reflects current knowledge and is suitable for implementation in the clinical routine.

Current state of evidence on 'off-label' therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland--a consensus report.

Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.

[Biomarkers in rheumatology. Biomarkers and imaging for the diagnosis and stratification of rheumatoid arthritis and spondylarthritis in the ArthroMark network funded by the Federal Ministry of Education and Research]. / Biomarker in der Rheumatologie. Biomarker und Bildgebung zur Diagnose und Stratifizierung der rheumatoiden Arthritis und Spondylarthritis im BMBF-Verbund ArthroMark.

The introduction of biologics has continuously increased the demand for biomarkers for early diagnosis and therapeutic stratification. ArthroMark, a research network funded by the Federal Ministry of Education and Research, aims to establish such biomarkers for rheumatoid arthritis and spondyloarthritides. Biobanks and previous work on genotyping, gene expression and autoreactivity profiling build the basis. Bioinformatic networks will help to harmonize the investigations and a clinical study with modern imaging techniques to characterize the functional relevance of the new biomarkers as effectively as possible. To validate the markers for diagnostic application the network aims to expand gradually.

[German 2012 guidelines for the sequential medical treatment of rheumatoid arthritis. Adapted EULAR recommendations and updated treatment algorithm]. / S1-Leitlinie der DGRh zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis 2012. Adaptierte EULAR-Empfehlungen und aktualisierter Therapiealgorithmus.

Following the EULAR recommendations published in 2010 German guidelines for the medical treatment of rheumatoid arthritis were developed based on an update of the systematic literature search and expert consensus. Methotrexate is the standard treatment option at the time of diagnosis, preferably in combination with low dose glucocorticoids. Combined disease-modifying antirheumatic drugs (DMARD) therapy should be considered in patients not responding within 12 weeks. Treatment with biologicals should be initiated in patients with persistent high activity no later than 6 months after conventional treatment and in exceptional situations (e.g. early destruction or unfavorable prognosis) even earlier. If treatment with biologicals remains ineffective, changing to another biological is recommended after 3-6 months. In cases of long-standing remission a controlled reduction of medical treatment can be considered.

[Outcome and predictors of early geriatric rehabilitation in an acute care setting]. / Ergebnisse und Prädiktoren der geriatrischen Frührehabilitation im Akutkrankenhaus.

BACKGROUND: Geriatric assessment and treatment including an interdisciplinary team is a well accepted method to improve functionality and mortality in the elderly. Nevertheless, only little evidence and limited data are available concerning the outcome of this approach in an acute care setting and early rehabilitation. PATIENTS AND METHODS: All patients included in a comprehensive geriatric program within 1 year were eligible for inclusion in a retrospective chart analysis. Admission to the program was allowed after counseling by an experienced geriatrician applying pre-defined criteria including significant deconditioning, preserved rehabilitation prognosis and/or ongoing instable medical condition requiring an acute care setting. Patients who refused therapy or died within the first week of treatment were excluded. A telephone interview was performed 6 months after patient discharge and data concerning mortality, functional course and quality of life (activities of daily life ADL) were retrieved. All patients were treated in an acute care setting in two geriatric and general internal medicine wards. RESULTS: A total of 138 patients were included in the program. In 128 cases data concerning the 6 month mortality could be retrieved and 92 patients agreed to participate in a complete telephone interview. Mortality within the early rehabilitation course was 4%, the 6 month mortality however was 28%. Functionality improved during early rehabilitation and a median increment of 10 points in the Barthel index was found (range 0-100). Analysis of individual increments showed high interindividual variability throughout the whole range of the ADL score at the beginning of the treatment. Concerning the 6 month course after hospital discharge functionality remained at a steady median value but showed a large range of both increasing and decreasing ADL values. Analysis of predictors by logistic regression revealed the ADL score on admission to the early rehabilitation program as the predominant predictor overriding other factors such as depression or cognitive impairment. An ADL value ≤15 on admission was a strong predictor for an unfavorable outcome in early rehabilitation defined as death or an ADL increment ≤10. An ADL value ≤15 on admission was also a strong predictor for overall mortality within 6 months. On the other hand an ADL value ≤15 on admission was a strong predictor for a steady or increasing functionality among the survivors of the 6 month postdischarge interval. CONCLUSIONS: The mortality rate in the early rehabilitation course in this preliminary and observational study was relatively low and may be explained by both the exclusion of patients not surviving the first week of treatment and an effective inclusion algorithm. The high overall 6 month mortality rate may also be explained by the selection of patients focusing on those severely functionally impaired. This subpopulation of elderly inpatients in acute care units reveals a high vulnerability to critical incidents. Besides scale effects there is also a remarkable variability in the 6 month postdischarge course pointing to heterogeneity and different patterns concerning the time course of functionality.