[Comorbidity in medical guidelines: comparison of the current state, epidemiologic models and expert opinion]. / Komorbidität in Leitlinien: Ist-Zustand, epidemiologische Modelle und Expertenmeinung im Vergleich.

INTRODUCTION: Medical guidelines focusing on monomorbidities can be associated with adverse events in multimorbid patients. This study investigates how comorbidities are actually particularised in a set of German guidelines. In addition, it evaluates whether two epidemiologic approaches (disease combinations or clusters of comorbidities) can be used to systematically integrate multimorbidity in guideline development. METHODS: Based on a matrix of 30 comorbidities, mentioning of comorbidities in 8 current German guidelines (diabetes mellitus, hypertension, heart failure, coronary heart disease, chronic obstructive lung disease/asthma, coxarthrosis, low back pain, osteoporosis) was investigated. These so called index diseases were selected on the basis of the hypothetical case of a multimorbid patient published by Cynthia Boyd and colleagues in 2005. Mentioning of comorbidities in the guidelines was compared to the epidemiologic approaches of disease combinations and clusters of comorbidities. In addition, using the comorbidity matrix, 36 physicians involved in everyday care of multimorbid patients assessed whether an explicit recommendation for the listed comorbidities would be helpful. RESULTS: Mentioning of comorbidities was very heterogeneous across the guidelines investigated, ranging from 0 to more than 10. The proportion of the comorbidities that were considered relevant by the survey participants ranged from 0 % to 62 % with a focus on cardiovascular and metabolic diseases. When using disease combinations, only 0 to 3 of the "relevant" comorbidities were identified. Using the cluster model may be helpful in identifying whether a particular comorbidity is thematically close to the index disease or whether it is associated with an interacting thematic area. CONCLUSIONS: Methodological support is needed for addressing comorbidities in guidelines in a more consistent way. The currently existing epidemiologic approaches should not be used in their current form without being further developed and re-evaluated. Expert opinion of physicians involved in the care of multimorbid patients should be systematically included in methodological refinement studies.

Trials of prostate-cancer screening are not worthwhile.

About 3% of men in developed countries die from prostate cancer. No conclusive evidence, however, either supports or refutes the benefit of prostate-cancer screening. More than 200 000 participants are needed for a screening study with prostate-cancer-specific death as the endpoint. A relative reduction in prostate-cancer mortality of 25% leads to a decrease in absolute risk of less than 1%-a difference of 75 individuals between the control and screening group. Participant non-compliance and small inaccuracies in attributing cause of death need to be compensated for in study size, requiring several million participants. Screening trials with insufficient sample sizes might show a lowering of cancer-specific mortality but not detect increases in all-cause mortality related to screening. Studies of a manageable size have too little discriminatory power and last a long time. Furthermore, results become available decades after trial initiation, by which time they are probably antiquated. Whether screening for prostate cancer is beneficial cannot be assessed in trials, a statement that might also be true for other diseases with low specific mortality.

No effect of the hemoglobin solution HBOC-201 on the response of the rat R1H tumor to fractionated irradiation.

BACKGROUND AND PURPOSE: Tumor hypoxia is regarded as one important underlying feature of radioresistance. The authors report on an experimental approach to improve tumor response to radiation by combining fractionated irradiation with HBOC-201, an ultrapurified polymerized hemoglobin solution, which is currently used in clinical phase II/III trials as alternative oxygen carrier and proved to be highly effective in tissue oxygenation (tpO(2)). MATERIAL AND METHODS: Subcutaneously growing rhabdomyosarcoma R1H tumors of the rat were treated with either 40 Gy (2 Gy/fraction, 20 fractions in 2 weeks, ambient) followed by graded top-up doses (clamped) alone, or in combination with HBOC-201, or with HBOC-201 plus carbogen (95% O(2) + 5% CO(2)). Local tumor control (TCD50%) and growth delay were used as endpoints. In addition, the effect of HBOC-201 alone or in combination with carbogen on the tpO(2) of tumor and muscle was determined using a flexible stationary probe (Licox, GMS). RESULTS: TCD50% values of 119 Gy (95% confidence interval 103;135), 111 Gy (84;138), and 102 Gy (83;120) were determined for tumors irradiated alone, in combination with HBOC-201, and with HBOC-201 plus carbogen, respectively. Although the dose-response curves showed a slight shift to lower doses when HBOC-201 or HBOC-201 plus carbogen was added, the differences in TCD50% were not statistically significant. No effect was seen on the growth delay of recurrent tumors. HBOC-201 alone did not effect tumor or muscle tpO(2). In combination with carbogen the mean tpO(2) of muscle raised from 23.9 mmHg to 59.3 mmHg (p < 0.05), but this effect was less pronounced than the increase in tpO(2) by carbogen alone. CONCLUSION: Low-dose application of HBOC-201 does not improve the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation.

[The value of radiotherapy in treatment of meningeal melanocytoma]. / Stellenwert der Strahlentherapie bei der Behandlung des meningealen Melanozytoms.

BACKGROUND: Meningeal melanocytoma is described as rare benign lesion with a high risk of recurrence. There are no well-substantiated treatment recommendations in the literature. Only case reports have been published by now. PATIENTS AND METHODS: In 1997 a patient was irradiated for a recurrent spinal meningeal melanocytoma and 2 years later for brain metastases indicating malignant transformation. This case gave rise to a literature review for therapeutic options. All sufficiently documented cases published since 1972, when the term meningeal melanocytoma was established, were evaluated. Based on published and on original data recurrence and overall survival rates up to 5 years were calculated for three different therapeutic approaches, namely complete tumor resection, incomplete resection with subsequent radiotherapy, and incomplete resection alone. Statistical evaluation was performed using the chi 2 test and Kaplan-Meier-analysis. RESULTS: 53 patients (including our patient) met selection criteria. Complete tumor resection was superior to incomplete resection alone with lower recurrence (4-38% versus 50-92%) and better overall survival rates (86-95% versus 30-58%). After incomplete resection radiotherapy seemed to improve prognosis (recurrence 15-45%; overall survival 91-92%). Between complete resection and incomplete resection plus radiotherapy no significant differences were observed. CONCLUSIONS: For meningeal melanocytoma complete resection must be regarded as the best of the modalities compared. After incomplete resection radiotherapy should be considered, although a specific radiotherapeutic regimen cannot be recommended at present. However, for multiple cranial or spinal lesions total cranial irradiation or craniospinal irradiation is indicated.