[High burden of disease in patients with ANCA-associated vasculitis : A claims data study in Germany]. / Hohe Krankheitslast bei Patienten mit ANCA-assoziierter Vaskulitis : Versorgungsdatenstudie in Deutschland.

BACKGROUND & OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of rare chronic autoimmune diseases characterized by recurrent systemic inflammation provoking multiple morbidities. AAV patients suffer from various organ manifestations and treatment-related severe adverse effects. This retrospective study investigated the concrete burden of AAV disease on patients in Germany. METHODS: Based on anonymized longitudinal German statutory health insurance (SHI) claims data from the years 2011-2016, a representative cohort of approximately 3 million insured persons was used to identify patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and selected clinical aspects were systematically assessed. RESULTS: The most frequent concomitant morbidities of GPA and MPA were renal and respiratory disorders. Severe renal involvement occurred in 11.6% of GPA and 24.3% of MPA patients within 15 quarters of diagnosis. Severe infections developed in one third of AAV patients within the first three quarters post-diagnosis. The annual rate of major relapses was 5-8%. AAV patients with renal impairment or infections showed increased annual mortality rates of 14.4 and 5.6%, respectively. CONCLUSION: Based on this analysis of German health care data, disease-specific assumptions regarding the burden on AAV patients were confirmed and concretized for the German context. AAV patients suffer from a high burden of morbidity, including multiple disease manifestations, relapses, and severe complications due to AAV treatment.

[Challenge prevention. From curative to preventive medicine-strategic and operational challenges]. / Herausforderung Prävention. Von der kurativen zur präventiven Medizin - strategische und operative Herausforderungen.

The potentials of preventive medicine to reduce the costs of illness have been inadequately exploited to date. Even if there is still massive dissent regarding the legal setup of a prevention law, prevention should play a significantly higher role in practice. Clinicians and practitioners could use preventive medicine as another differentiating factor in the increasingly competitive healthcare field. Prevention as a new strategic business segment allows a directed reaction to the demands of the payment system and opens up enormous value-added potential at the same time. Those who seize the chance to integrate prevention into their medical services portfolio and into the structure and processes of their respective hospitals will develop an important competitive advantage for the future.

[Cost-effectiveness evaluation of predictive molecular diagnostics using the example of hereditary non-polyposis colorectal cancer (HNPCC)]. / Kosteneffektivitätsbewertung Prädiktiver Molekulardiagnostik am Beispiel des Hereditären Nichtpolypösen Kolorektalkarzinoms (HNPCC).

STUDY OBJECTIVE: Four different diagnostic strategies, with and without various molecular diagnostic tests, are compared and contrasted not only by years gained and the cost of therapy and diagnosis, but also by the cost-effectiveness of the diagnostic strategies. METHODOLOGY: A fictitious cohort of 100,000 people, whose genetic pre-disposition leading to the development of colorectal cancer corresponds to a representative average amongst the current population, will be studied from their 1st to their 85th year. This data will be then put through Markov models specifically developed for the study. At the end of the Markov process, it will then be possible to compile a cost-effectiveness report in regard to the various diagnostic and treatment strategies. RESULTS: A tiered diagnosis (with family case history, micro-satellite instability, molecular diagnostic diagnosis of an index person and subsequent genetic analysis of all people at risk) represents the most cost-effective method at a rate of euro 3,867 per year gained. The cost-effectiveness of a purely clinical diagnosis has a rate of euro 4,397 per year gained and is followed by the cost of direct gene testing of people at risk from families at risk at a rate of euro 6,208. The worst level of cost-effectiveness, with a rate of euro 15,705, was shown by nationwide gene screening. The incremental cost-effectiveness of Strategy IV and Strategy II is euro 124,168 per gained year. CONCLUSIONS: With the scenarios put forward we can show that a 65% reduction in gene test costs is necessary in order for a cost-effective nationwide gene screening for HNPCC to take place. The break-even level, however, depends only on a few cost-effectiveness drivers such as screening and therapy costs, proportion of HNPCC of all colorectal cancer and discounting rate. Should these changes (e.g., through a restructured medical environment), then we would see such a change in the break-even cost of a gene test and that a cost-effective nationwide gene screening could be made plausible. In a final evaluation of the use of predictive molecular diagnostics, other dimensions (such as possible psychological problems and discriminatory risks) apart from cost-effectiveness should also be included.

Expression pattern of the plasminogen activator-plasmin system in human cholesteatoma.

The plasminogen activator-plasmin system plays a pivotal role in the delicately regulated process of extracellular matrix remodeling. Recent studies have shown that an imbalance of proteolytic enzymes over specific inhibitors in this system may lead to an aggressive, expanding, and infiltrating cellular phenotype. As cholesteatoma resembles a tumor in many ways, we investigated the pattern of expression for members of the plasminogen activator-plasmin system in 12 human cholesteatomas, using immunohistochemistry. As controls, 3 tympanic membranes and 4 ear canal skin specimens were used. In contrast to the tympanic membranes, all cholesteatoma specimens showed a strong expression of plasminogen at the basal epithelial cell layers. In ear canal skin, only the basal surface of the most basal epithelia stained discretely positive. The urokinase-type plasminogen activator (uPA) could be detected in the basal stratum of the cholesteatoma matrix and in the surrounding granulation tissue, while tissue-type plasminogen activator (tPA) was not detectable at all. Plasminogen activator inhibitor-1 (PAI-1) was expressed in both the granulation tissue and the granular cell layer of the matrix, but not in the basal epithelial cells; PAI-2 showed a pericellular expression pattern in the subbasal and granular cell layers. Neither uPA, tPA, nor the PAIs could be detected in tympanic membrane controls; ear canal skin showed the same staining pattern as cholesteatoma only for PAI-2. Our data demonstrate that there is a clear imbalance in favor of proteolytic activity in the basal epithelial layers of the cholesteatoma matrix, which might at least partly account for the aggressive behavior of this tumorlike lesion. Further, the pattern of expression resembles the pattern described for several epithelial malignancies.

Q-switched ruby laser treatment of tattoos and benign pigmented skin lesions: a critical review.

The Q-switched ruby laser (694 nm, 25-40 nsec) is an effective and safe therapeutic device for the treatment of tattoos and well-defined, benign, pigmented epidermal and dermal lesions. Because of its selective mode of action, dermal pigments of natural and artificial origin are destroyed photothermically and removed without scar. This method is exceptionally suited for the elimination of lay and professional tattoos, traumatic tattoos, and permanent makeup. Other frequent indications include benign pigmented lesions such as lentigines, freckles, café-au-lait spots, seborrheic keratosis, and Becker nevi. As a dermal pigmented lesion, the nevus of Ota is perfectly treatable. However, chloasma can no longer be considered an indication for ruby laser treatment due to unsatisfactory results. Melanocytic nevi and congenital nevi should be treated only in clinical studies. The effectiveness of the long-term epilation of dark hair with this laser device has to be verified in future investigations. Particularly attractive is the nonproblematic and straightforward removal of pigmented lesions in precarious anatomic regions like the lips, eyelids, and genitals (e.g., benign melanosis of the lips or of the penis, seborrheic keratosis of the lid angle).

Minocycline-induced hyperpigmentation: treatment with the Q-switched Nd:YAG laser.

BACKGROUND AND OBJECTIVE: Cutaneous hyperpigmentations are well-documented, but nevertheless rare side-effects of high-dose or long-term minocycline therapy. The pigmental changes, may last for years, even though therapy has been abrogated. To date, no safe and effective therapy has been described to target this cosmetically disturbing sequela. STUDY DESIGN/MATERIALS AND METHODS: A 57-year-old female patient with extensive pigmental changes of the face due to long-term minocycline therapy was treated in eight consecutive sessions with the Q-switched Nd:YAG-laser (1,064-nm wavelength, 5- to 7-nsec impulse length). RESULTS: A 90% resolution of the pigmentation could be achieved after five treatments. After the last session the lesions were completely gone; no hypopigmentation scars, or other side-effects were observed. CONCLUSION: Treatment with the Q-switched Nd:YAG laser seems to be an effective, safe, and easily applicable strategy for the therapy of minocycline-induced hyperpigmentations.

Fibroinflammatory pseudotumor of the temporal bone.

Chronic inflammatory tumor-like lesions of the temporal bone represent a difficult clinical task for the skull base surgeon. Their osteolytic aggressiveness endangers vital structures and may not be controlled by surgery alone. We present the course of four cases of fibroinflammatory pseudotumor of the temporal bone which were treated by a combined approach of skull base surgery and chemotherapy. Three patients were deafened by the disease and underwent several operafive measures. One patient was lost, most likely due to an arrosive bleeding of the internal carotid artery. The chronic and recurrent process could only be stopped by petrosectomy, followed by antiproliferative chemotherapy. Two patients were subsequently provided with a cochlear implant. The differential diagnosis, diagnostic, and operative options of this rare but severe disease are discussed.

Cochlear implantation in patients with chronic otitis: indications for subtotal petrosectomy and obliteration of the middle ear.

Normally, active chronic suppurative otitis media is regarded as a contraindication for cochlear implantation. In case of a radical cavity after surgical treatment for cholesteatoma, the electrode covered by the epithelial lining of the mastoid will likely become exposed or extruded. Under these circumstances we suggest the subtotal petrosectomy, obliteration of the middle ear cleft with abdominal fat, and the blindsac closure of the external ear canal before cochlear implantation.Fourteen patients with chronic otitis media were successfully implanted with an intracochlear multichannel cochlear implant. After an average follow-up of 28 months a temporary facial palsy in one patient and an insufficient closure of a retroauricular fistula over the mastoid cavity in two cases were observed as postoperative complications. One patient with a tumefactive inflammatory pseudotumor developed a massive inflammation in the implanted ear 2 months after surgery which could not be controlled by conservative treatment. The implant had to be removed and after administration of cyclophosphamide she could be successfully reimplanted 7 months later.Implantation of a foreign body in a potentially infected space which communicates with the endocranium means a surgical challenge which can be managed by obliteration of the middle ear. In case of massive inflammation we prefer a two-stage procedure.