Combining cross-sectional data on prevalence with risk estimates from a prediction model. A novel method for estimating the attributable risk.

OBJECTIVES: Estimation of the attributable risk for fatal diseases by combining two different data sources. METHODS: We derive a method to estimate the attributable risks of different risk factors by combining general mortality risks with up-to-date prevalences of the risk factors using estimates from a risk prediction model and cross-sectional data of a cohort study. Partial attributable risks have been used to illustrate the proportions of the different risk factors for the attributable risk. In addition we derive standard errors for the attributable risk based on the Taylor series expansion. Since the data of our cohort study was sampled with the same size in each 10 years age stratum which does not reflect the age-structure of the general population, the attributable risk and its standard errors are calculated using an approach that allows the weighting of the data according to population proportions of age. The formula for the standard errors has been evaluated using bootstrap-techniques. RESULTS: We successfully implemented the method for the estimation of the attributable risk and its standard errors by integrating risk information using data of the HeartScore Germany and cross-sectional data emerging from the Gutenberg Health Study. The attributable risk can now be calculated without using the information of the overall disease rate. The bootstrap method shows, that the formula for the standard errors is useful. CONCLUSION: Our method allows for the combination of different data sources in order to estimate attributable risks and our formula for the standard errors seems to yield a good approximation. But the validity of our method highly depends on the validity of the underlying data sources.

Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity.

Common autoimmune disorders tend to co-exist in the same subjects and cluster in families. The objective of this study was to determine the prevalence of autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with and without thyroid-associated orbitopathy (TAO). This was a cross-sectional study conducted at an academic tertiary referral centre. Of 1310 patients with AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's thyroiditis (HT)] followed at a specialized joint thyroid-eye out-patient clinic, 176 (13·4%) had an adult type of the autoimmune polyglandular syndrome, 129 (9·8%) type 1 diabetes, 111 (8·5%) coeliac disease, 60 (4·6%) type A autoimmune gastritis, 57 (4·4%) vitiligo and 25 (1·9%) Addison's disease. Coeliac disease and autoimmune gastritis were associated positively with GD [odds ratio (OR) = 2·18; P = 0·002 and OR = 6·52; P < 0·001], whereas type 1 diabetes, Addison's disease, autoimmune primary hypogonadism, alopecia areata, rheumatoid arthritis and Sjögren's syndrome were 'protective' for GD and thus linked to HT, OR = 0·49 (P < 0·001), 0·06 (P < 0·001), 0·25 (P < 0·001), 0·50 (P = 0·090) and 0·32 (P = 0·003), respectively. Of 610 (46·6%) AITD patients with TAO, 584 (95·7%) and 26 (4·3%) had GD and HT, respectively (P < 0·001). TAO was most prevalent in GD patients with coeliac disease (94%, OR = 1·87, P < 0·001). Multivariate analysis showed high OR for coeliac disease and autoimmune gastritis (3·4 and 4·03, both P < 0·001) pertaining to the association with TAO while type 1 diabetes, Addison's disease and alopecia areata were protective for TAO. In patients with TAO, coeliac disease is the most prevalent co-morbid autoimmune condition and rates are increased compared to GD patients without TAO.

History of depression but not current depression is associated with signs of atherosclerosis: data from the Gutenberg Health Study.

OBJECTIVES: To test the vascular depression hypothesis in the general population, we analyzed the association between current depression, medical history of depression, cognitive and somatic depressive symptom dimensions and measures of atherosclerosis [intima-media thickness (IMT) and carotid plaques]. METHOD: We included a representative sample of 5000 participants from the Gutenberg Health Study (GHS). Depression was assessed by the nine-item Patient Health Questionnaire (PHQ-9), and IMT and carotid plaques were measured at both common carotid arteries using an edge detection system. Regression analyses were performed separately for participants with and without cardiovascular disease, adjusting for medical history, cardiovascular risk factors and psychotropic medication. RESULTS: Contrary to hypotheses, we found no increased IMT for somatic symptoms of depression; the same was true for depression and cognitive symptoms in the fully adjusted model. Only a moderate relationship between medical history of depression and the presence of atherosclerotic plaques was maintained after correction. CONCLUSIONS: The relationship between depression and atherosclerosis may be more complex than previously assumed. Although the vascular depression hypothesis was not supported, our results support the hypothesis that lasting depression leads to arteriosclerosis.

Evaluation of cannabinoid type 1 receptor expression in the rat brain using [¹8F]MK-9470 microPET.

PURPOSE: The ligand [(18)F]MK-9470 is an inverse agonist binding with high affinity and specificity to the cannabinoid type 1 (CB1) receptor. In this study, a semiquantitative acquisition and analysis protocol for investigation of the CB1 receptor distribution in the rat brain was established. METHODS: Two C57BL/6N mice (one CB1 (-/-) and one wild-type) and 19 Sprague Dawley rats were investigated using a Focus 120 microPET scanner. Seven rats were scanned twice for test-retest evaluation, six rats were scanned for blocking experiments using the inverse CB1 receptor agonist rimonabant, and 19 rats were scanned for baseline studies. Percentage injected dose per millilitre (%ID/ml) or uptake ratios (VOItarget/VOIwhole brain) were calculated. A Bland-Altman-plot was computed and mean values were compared using a two-sided paired t test. RESULTS: Comparing the data from the CB1 (-/-) mouse and the wild-type mouse, [(18)F]MK-9470 showed good specificity. Regarding the rat data, there was no relationship between the difference between the test and retest measurements or their mean value. The test and retest data showed a strong correlation (ρ c = 0.846, p ≤ 0.01; r Pearson = 0.857). Equivalence was not found for all regions and not even in the pons at baseline or under blocking condition. Only the baseline studies showed the highest levels of uptake in the caudate-putamen and thalamus, whereas moderate uptake was found in the hippocampus, hypothalamus and cerebellum, and the lowest uptake was observed in the cortex, amygdala and pons. CONCLUSION: A reference region is not available; however, the proposed analysis method using the parameter uptake ratio is simple and delivers stable results allowing the discrimination of distinct brain regions.

Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH).

PURPOSE: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. PATIENTS AND METHODS: Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. RESULTS: During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 ± 5 % after EFRT and 65 ± 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. CONCLUSION: EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative.

[Is there a connection between intraocular pressure and blood pressure? Results of the Gutenberg Health Study and review of the current study situation]. / Hängt der Intraokulardruck mit dem Blutdruck zusammen? Ergebnisse der Gutenberg Gesundheitsstudie und Übersicht über die aktuelle Studienlage.

Intraocular pressure (IOD) is the most important risk factor for the occurrence and progression of glaucoma because it is the only measurable risk factor. There is a positive connection between IOD and both systolic and diastolic blood pressure. The clinical relevance is, however, limited because the moderate alterations in IOD are less than the known measurement error and daily physiological oscillation.

What's in a name? Intracranial peripheral primitive neuroectodermal tumors and CNS primitive neuroectodermal tumors are not the same.

BACKGROUND: Intracranial peripheral primitive neuroectodermal tumors (P-PNET) are extremely rare. They can be easily misdiagnosed as central nervous system primitive neuroectodermal tumors (CNS-PNET) or meningiomas. Little is known about the optimal treatment and prognosis of these tumors. PATIENTS AND METHODS: We evaluated the treatment and outcome of 17 patients with intracranial, nonmetastatic, genetically confirmed P-PNET. Three patients were treated at our institutions. Thirteen other cases providing sufficient treatment and follow-up information were extracted from the literature. RESULTS: The median age at diagnosis was 17 years. All patients underwent initial surgery. Complete resection was achieved in 9 of the 17 cases (53 %). Combined adjuvant treatment consisting of radiotherapy (focal, n = 10; craniospinal, n = 1) and chemotherapy was administered to 11 of the 17 patients (59 %). The median follow-up time was 1.4 years. In 8 of the 17 patients (47 %), the disease progressed; 4 of the 17 patients (24 %) died. The 2-year progression-free and overall survival rates were 64 % and 76 %, respectively. CONCLUSION: The differential diagnosis for intracranial, meningeal-based, small, round-cell tumors should include P-PNET. It is highly probable that complete resection has a positive impact on survival--as previously reported for extracranial P-PNET--but this cannot be shown by our data. Intensive adjuvant treatment consisting of radiotherapy and chemotherapy seems to be essential. A statistically grounded recommendation for the appropriate target volume and radiation dose is not yet possible. However, in most case reports of primary intracranial P-PNET published to date, patients were treated with focal irradiation. The optimal chemotherapy regimen has yet to be established, with both the Ewing tumor and CNS-PNET protocols being promising candidates for effective treatment.

Type D personality as a cardiovascular risk marker in the general population: results from the Gutenberg health study.

BACKGROUND: Type D personality is considered as an independent risk factor for morbidity and mortality in cardiovascular patients and a vulnerability factor for distress in the general population. Because representative community studies are rare, we sought to determine the prevalence of type D personality and its relationship with demographic characteristics, different features of mental disorders, cardiovascular risk factors, health behavior, endothelial function and cardiovascular biomarkers in the general population. METHODS: The prevalence of type D personality and its correlates were analyzed cross-sectionally in a population-based sample of 5,000 Mid-Europeans aged 35-74 years from the Gutenberg Health Study. RESULTS: The prevalence of type D personality was 22.2% without remarkable differences in sex distribution. Type D subjects were characterized by lower socioeconomic status, lack of a partnership, increased depression, anxiety, depersonalization and health care utilization. Despite its strong association with mental disorders, type D personality emerged as psychometrically distinct. Although type D personality was independently associated with coronary heart disease (OR = 1.54, p = 0.044), no associations with traditional cardiovascular risk factors were found independently from depression or anxiety. CONCLUSIONS: Although type D personality is strongly associated with depression, anxiety, impaired mental and somatic health status, and increased health care utilization, the type D construct seems to comprise dysfunctional personality patterns not covered by depression and anxiety scales. Beyond these associations, the pathways of the cardiotoxic impact of type D personality remain to be elucidated. There is a need for prospective population studies on potential links between type D personality and cardiac disease.