[Characteristics of pharmacotherapy in older patients with rheumatism]. / Besonderheiten der Pharmakotherapie des älteren Rheumapatienten.

Due to medical advances and the availability of efficient immunosuppressive therapies, the life-expectancy of people suffering from inflammatory rheumatic diseases is continuously increasing. In Germany, geriatric patients (definition: age older than 70 years combined with geriatric multimorbidity) affected, e. g. by rheumatoid arthritis (RA) frequently receive corticosteroids and less often biologic disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs), which is justified by additionally existing comorbidities and polypharmacy. Using geriatric typical assessments as well as detailed medication regimens the treatment risk of bDMARD and cDMARD administration can be properly evaluated. Current data on biological therapy in older patients with rheumatism support this recommendation. Following the "choosing wisely" initiative of the German Association of Internal Medicine the authors listed 5 positive and 5 negative recommendations concerning the pharmacotherapy of older patients suffering from rheumatism (e. g. RA) as practical guidance towards safer bDMARD and cDMARD treatment for geriatric RA patients.

[Hospital financing in 2012 - Relevant changes for rheumatology]. / Krankenhausfinanzierung 2012 - Relevantes für die Internistische Rheumatologie.

The following article presents the major general and specific changes for the financing of rheumatology in Germany for 2012. Besides relevant changes in the German diagnosis-related groups (G-DRG) classification system and for the coding, the new legislation and the resulting incentives are covered. The consequences for hospitals specialized in rheumatology are discussed.

[Treat-to-target (T2T) from the perspective of inpatient rheumatology]. / "Treat-to-Target" (T2T) aus der Sicht der stationären Rheumatologie.

Publication of the treat-to-target (T2T) concept at the end of the Bone and Joint Decade almost coincided with the 15 treatment recommendations of the EULAR as well as with the new classification and revised remission criteria for rheumatoid arthritis (RA).The treat-to-target initiative is solely focused on the description of benchmarks for an effective treatment management of RA to reach its priority target of remission.From the perspective of inpatient rheumatology parallels are shown to the quality projects of the Association of Rheumatology Clinics (VRA), which were initiated in 2001 for the first time.The quality management started up by the VRA not only benefited from the development of the German diagnosis-related groups (G-DRG) system which was also supported by the VRA and the German Society of Rheumatology (DGRh) but also from projects realized to improve the structural and operational quality in inpatient rheumatology units.By launching its own outcome benchmarking project (OBRA) in 2003, which was financially supported by the German Ministry of Health and its continuation with Kobra-1 and future Kobra-2, the VRA already successfully incorporated all benchmarks of management guidelines outlined in the T2T initiative.By steadily improving the outcome, even of RA patients, inpatient rheumatology offers a special quality project for participating clinics who are otherwise competitors, not only to learn from each other but to support each other to find the best way (T2T) to reach a remission and a good quality of life for RA patients and patients with other systemic rheumatic diseases.

[Amendment of the structural quality for inpatient rheumatology. A forward-looking concept]. / Neufassung der Strukturqualität der akut-stationären Rheumatologie. Ein zukunftsweisendes Projekt.

In 2010 a total of 9 guidelines on structural quality were endorsed by the Association of Rheumatology Clinics in Germany (VRA). These 9 structural criteria replace the regulations published in 2002 and were elaborated with the support of the German Rheumatology League. With guideline number 9 even the structural requirements for university hospitals are defined for the first time.Along with taking part in the quality project "Kobra" (continuous outcome benchmarking in rheumatology inpatient treatment) compliance with the new structural criteria constitutes a prerequisite for acquiring a quality certificate, which is awarded by an external institution.By this means the VRA sets the stage for its members to be prepared for future challenges and quality competition among hospitals. Furthermore, the provision of a high quality treatment for chronically diseased patients in rheumatology clinics will be effectively supported.

Ultrasound-assisted microsurgery for Cushing's disease.

OBJECTIVE: Localization of microadenomas in Cushing's disease may be difficult as in up to 45% of patients sellar MRI fails to detect a pituitary tumor. Intraoperative transsphenoidal ultrasound may identify microadenomas as hyperechoic structures. We report on the first 18 consecutive cases with intraoperative use of a new device for direct contact high-frequency-ultrasound in patients with Cushing's disease. PATIENTS AND TECHNIQUE: 18 patients (14 female, 4 male, age 24-71 years) with typical endocrinological findings for Cushing's disease were included in the study. One macroadenoma and 13 microadenomas were suspected or identified preoperatively by MRI. In 4 cases, two of them with recurrent disease, sellar MRIs were negative. During transsphenoidal microsurgery an end fire ultrasound-probe (B-mode frequency range 7.5-13 Mhz, field of view 5 mm, penetration 20 mm) was introduced after opening of sellar floor. The pituitary gland was scanned in direct contact to the capsule. RESULTS: In 13 out of 17 cases (77%) with later on proven microadenomas high-frequency-ultrasound identified the tumors as hyperechoic masses, including 3 of the 4 cases with negative preoperative MRI. In 2 cases ultrasound correctly localized the tumor at a site different from MRI finding (MRI false positive). In the macroadenoma, identification of the border between tumor and anterior pituitary gland was not possible. In all 18 patients postoperative early decline of serum cortisol to subnormal levels confirmed remission of hypercortisolism (100%). Other pituitary functions were unaltered in 17 cases (94%). CONCLUSIONS: Intraoperative scanning of the pituitary gland with high-frequency-ultrasound probes may identify intrapituitary anatomy and pathologies even in MRI-negative cases. This may prevent extensive exploration of the gland with the risk of subsequent hypopituitarism.

[The G-DRG System 2009--relevant changes for rheumatology]. / Das G-DRG-System 2010--Relevantes für die Rheumatologie.

The following article presents the major general and specific changes in the G-DRG system, in the classification systems for diagnoses and procedures as well as for the billing process for 2010. Since the G-DRG system is primarily a tool for the redistribution of resources, every hospital needs to analyze the economic effects of the changes by applying the G-DRG transition-grouper to its own cases. Depending on their clinical focus, rheumatological departments may experience positive or negative consequences from the adjustments. In addition, relevant current case law is considered.

[The G-DRG system 2008. Relevant changes for rheumatology]. / Das G-DRG-System 2008. Relevante Neuerungen für die Rheumatologie.

The G-DRG system 2008 once again brings many changes to rheumatological departments in Germany. The following article presents the main general and specific changes in the G-DRG system, as well as in the classification systems for diagnoses and procedures and in invoicing for 2008. Since the G-DRG system is only a tool for the redistribution of resources, every hospital needs to analyze the economic effects of the system by applying the G-DRG transition grouper to its own cases. Depending on their clinical focus, rheumatological departments may experience positive or negative effects from the system's application. The strain placed on hospitals by the inadequate funding of increased costs needs to be assessed separately from the effects of redistribution by the G-DRG system.

[What changes for rheumatologists in the G-DRG system 2006?]. / Was ändert sich für die Rheumatologie im G-DRG-System 2006?

Once more, the revision of the German DRG catalogue 2006 provides for more accurate reimbursement, particularly for specialised medical services. The newly established DRG I97Z (Rheumatologische Komplexbehandlung bei Krankheiten und Störungen an Muskel-Skelett-System und Bindegewebe) for the complex and multimodal treatment of rheumatic diseases allows an accurate picture of clinical practice in specialized rheumatologic departments and hospitals. Using this specific DRG-description, it will be possible to reduce the financial pressure which results from the redistribution of budgets in the second year of the period of convergence. A precondition for the affected hospitals is to deal with budget planning and calculation of G-DRGs without calculated cost weights for 2006. In addition, this article discusses the relevance of other modifications to the G-DRG system, additional payments, the conditions for payment, the coding standards, and the classification systems for diagnosis and procedures.

[Rheumatologic treatment in the G-DRG system]. / Rheumatologie im G-DRG-Fallpauschalensystem.

On June 27 2000, the German Self-Administration and lately the German Ministry of Health set the general conditions for a new reimbursement system for the inpatient hospital sector which is based nearly exclusively on lump-sum payments. The Association of Acute Rheumatology Hospitals (VRA) and the DRG-Research-Group, Münster University Hospital, conducted a multi-center trial which included 7266 cases from 22 different hospitals. The data were used to analyze how well the not yet German healthcare adjusted G-DRG system (version 1.0) accounts for rheumatologic diagnostics and treatment as well as problems of specialized hospitals. 7 Adjacent-DRGs covered 91% of all cases, 68% of all cases were grouped into only two different Adjacent-DRGs (169 Bone Diseases and Specific Arthropathies and 166 Other Connective Tissue Disorders). Groups with different complexity which are not appropriately covered by the existing G-DRG system could be identified. The data further revealed a systematically longer length of stay in rheumatology clinics opposed to the average length of stay in the data used for calculating the G-DRGs, due to different structures and procedures of the complex rheumatologic treatment. The results strongly supported the assumption that an accurate reimbursement of rheumatologic cases in the current G-DRG system 1.0 would not have been possible. Adaptations made in the new G-DRG Version 2004 can only partly solve these problems, despite an improved construction of the DRGs. In order to guarantee an appropriate reimbursement of rheumatology clinics from 2005 on, the G-DRG system must be adapted to specific rheumatological pathways and/or alternative or additional reimbursement systems have to be found.

[Structural quality of acute internal medicine rheumatology clinics--Project Group of the Association of Rheumatologic Acute Clinics]. / Strukturqualität akut-internistischer rheumatologischer Kliniken--Projektgruppenarbeit des VRA.

A study group representing the VRA (Association of Rheumatology Clinics in Germany) has worked out the structural quality paper presented here. Five guidelines for structural quality have been established by the VRA and are laid out in this paper. Required space and personnel for implementing these guidelines are considered. A highly competent, multi-disciplinary team must be available to ensure the long-term quality of in-patient treatment of rheumatic patients, the majority of whom are chronically ill and are suffering from chronic pain of varying intensity which restricts their daily activities. The necessity for such in-patient treatment is reflected in a 6-point-questionnaire (draft) adapted to the Appropriateness Evaluation Protocol. Considering the introduction of a flat-rate fee system (DRG-system) the structural quality paper describes the implementation of a specified electronic data processing documentation which is linked to a central hospital information system. According to the concept of benchmarking, the paper takes into account future developments of the German health system. It will be adjusted continuously to changing political guidelines for health services.

[Enzyme immunoassay for the detection of autoantibodies to nRNP and Sm: a rapid and sensitive alternative to current procedures]. / Enzymimmunoassays zum Nachweis von Autoantikörpern gegen nRNP und Sm: eine schnelle und sensitive Alternative zu den bisherigen Nachweisverfahren.

Antinuclear antibodies are of major importance in the diagnosis of inflammatory rheumatic diseases. Sm and nRNP antibodies can be found in sera from patients with systemic lupus erythematosus and mixed connective tissue disease. Usually, these antibodies have been detected with one of the following methods: Ouchterlony immunodiffusion, passive hemagglutination or counterimmunoelectrophoresis (CIE). In this work results obtained by Ouchterlony and CIE techniques were compared with those obtained by ELISA. Purified proteins from cellular extracts (HeLa) were used as antigens for Sm- and nRNP-ELISA: D polypeptide for Sm-ELISA and the 68 kD, A, C, B,B' and D polypeptides for nRNP-ELISA. Compared with the other two techniques, ELISA was less time consuming and showed greater sensitivity. Quantitative titration proved to be of advantage in monitoring the course of the diseases mentioned above.

[Nuclear antibodies as serologic markers in progressive systemic scleroderma]. / Kernantikörper als serologische Marker der progressiv systemischen Sklerodermie (PSS).

In all, 36 patients with progressive systemic sclerosis (29 women, 7 men) were studied clinically and immunologically; 15 patients had acrosclerosis (type I) and 21, sclerosis extending beyond the wrist (type II). The sera of all patients were evaluated for ANA (HEp-2-cells), Scl-70, centromere and other ENA antibodies. The centromere antigen was characterized by immunoblotting. All patients had high-titer ANA antibodies (100%); 36% of patients had the Scl-70 antibody (a marker antibody for PSS); and in 22% of our patients a centromere antibody was detected. In all cases the anti-centromere sera reacted with a 19.5-kd polypeptide and in 2 cases they reacted with 23- and 25.5-kd proteins in addition. In patients with centromere antibodies there was increased organ involvement (heart, lung, kidney) compared with patients who had anti-Scl-70 or other nuclear antibodies.

Anti-(U1)RNP and anti-Sm autoantibody profiles in patients with systemic rheumatic diseases: differential detection of immunoglobulin G and M by immunoblotting.

Autoimmune sera from patients with systemic lupus erythematosus, scleroderma, or both disorders reactive with the (U1)RNP and Sm antigens were analyzed according to their IgG- and IgM-autoantibody profiles by immunoblotting with HeLa nuclear extracts. Anti-(U1)RNP-specific autoantibodies directed against the 68-kDa polypeptide were found to be predominantly of the IgG type, whereas for the other (U1)RNP-specific protein, 33 kDa, a concomitant occurrence of IgG and IgM class autoantibodies was observed for most patients. In contrast, Sm-specific anti-29/28-kDa autoantibodies were found to be more frequently of the IgM than of the IgG type, while Sm-specific anti-16-kDa antibodies of both classes were present simultaneously in most sera. Of the serum collection reported here only one (U1)RNP-specific serum has been found which lacks anti-Sm antibodies of either class. In general, preclassification of sera by immunodiffusion and counterimmunoelectrophoresis corresponds to the IgG but not to the IgM profile as determined by immunoblotting.

Scl 70 autoantibodies from scleroderma patients recognize a 95 kDa protein identified as DNA topoisomerase I.

Sera of patients suffering from the autoimmune disease progressive systemic sclerosis (PSS) are known to contain autoantibodies which have been reported to recognize a 70 kDa antigenic protein, designated the Scl 70 antigen. By immunoblotting of nuclear extracts from HeLa cells with sera from scleroderma patients we observed that the size of the antigen present in such cells depends on the conditions of antigen isolation. When protease inhibitors were included in the extraction buffer, a 95 kDa protein was identified instead of a 70 kDa protein. When protease inhibitors were omitted, a number of polypeptides in the size range 66 to 95 kDa was found. Furthermore, antibodies which had been affinity purified on the 95 kDa antigen, crossreacted with the 66 to 95 kDa polypeptides. These results suggest that the smaller proteins were degradation products of the 95 kDa antigen. Immunofluorescence studies on PtK-2 cells with the antibody specific for the 95 kDa protein gave staining of nuclei, nucleoli and of chromosomes and the nucleolar organizer region in mitotic cells. Since this distribution of antigens within the nucleus was reminiscent of the intranuclear distribution of DNA topoisomerase I found by others we probed purified DNA topoisomerase I from calf thymus directly with the autoantibodies from PSS patients, and also the 95 kDa antigens of HeLa cell nuclei with antibodies raised against the bovine DNA topoisomerase I. From the crossreaction pattern observed with the different antigens and antibodies we conclude that DNA topoisomerase I is one of the antigenic components against which autoantibodies are formed in scleroderma patients.

Human anti-centromere sera recognise a 19.5 kD non-histone chromosomal protein from HeLa cells.

Autoimmune sera from 18 scleroderma patients were found to give a centromere positive immunofluorescence response on formaldehyde fixed HeLa cells and on chromosome spreads. Immunoblotting experiments with a protein fraction enriched in HeLa chromosomal proteins revealed that the antigenic target common to all 18 sera is a polypeptide of 19.5 kD. This polypeptide, which is not one of the core histones, is not soluble under conditions which favour the release of nuclear ribonucleoprotein particles. Antigen specific purification of autoantibodies with subsequent immunofluorescence studies confirmed that the 19.5 kD antigen is restricted to cell cycle-dependent single or double spheres at the centromere of HeLa chromosomes. Two additional polypeptides of 23 kD and 25.5 kD immunoreactive with five of the 18 centromere positive sera are not located at the centromere region, suggesting that other autoantibody systems are present in these sera.

Identification of human Sm and (U1) RNP antigens by immunoblotting.

When HeLa nuclear extracts or ribonucleoproteins (RNPs) from rat liver nuclei were used as antigens, a monospecific anti-(U1)RNP serum recognized in each preparation only 1 polypeptide of 68 or 70 kilodalton (kd) respectively. With a serum of combined anti-Sm/(U1)RNP specificity, HeLa nuclear extracts showed 3 additional antigenic polypeptides of 29, 28, and 16 kd, whereas only 2 additional polypeptides of 27 and 16 kd were observed in rat liver RNPs. However, no antigenic reaction at 68/70 kd was detected with a monospecific anti-Sm serum, indicating that the 68/70 kd antigen is specific for anti-(U1)RNP antibodies. When commercially available ENA extract was used as antigen source only weak immunostaining in the range 70-40 kd and at 16 kd was seen. Elution experiments with anti-Sm antibodies bound to their specific polypeptides demonstrated that neither protein degradation nor cross-reaction was responsible for recognition of the 29/28 and 16 kd antigens by this serum, and that in fact 2 different autoantibody systems are involved.