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Objective: Active and passive opening of the Eustachian tube (ET) enables direct aeration of the middle ear and a pressure balance between middle ear and the ambient pressure. The aim of this study was to characterize standard values for the opening pressure (ETOP), the opening frequency (ETOF), and the opening duration (ETOD) for active tubal openings (Valsalva maneuver, swallowing) in healthy participants. Design/Participants: In a hypobaric/hyperbaric pressure chamber, 30 healthy participants (19 women, 11 men; mean age, 25.57 +/- 3.33 years) were exposed to a standardized profile of compression and decompression. The pressure values were recorded via continuous impedance measurement during the Valsalva maneuver and swallowing. Based on the data, standard curves were identified and the ETOP, ETOD, and ETOF were determined. Results: Recurring patterns of the pressure curve during active tube opening for the Valsalva maneuver and for active swallowing were characterized. The mean value for the Valsalva maneuver for ETOP was 41.21 +/- 17.38 mbar; for the ETOD, it was 2.65 +/- 1.87 seconds. In the active pressure compensation by swallowing, the mean value for the ETOP was 29.91 +/- 13.07 mbar; and for the ETOD, it was 0.82 +/- 0.53 seconds. Conclusion: Standard values for the opening pressure of the tube and the tube opening duration for active tubal openings (Valsalva maneuver, swallowing) were described, and typical curve gradients for healthy subjects could be shown. This is another step toward analyzing the function of the tube in compression and decompression.

To assess the effects of chemoimmunotherapy on post-chemotherapy cognitive impairments (PCCI) in patients with B-cell non-Hodgkin lymphoma (NHL), we used objective and subjective measures of cognitive functions in combination with serum parameters and neuroelectric recordings. Self-perceived status of cognition, fatigue and emotional functioning were reduced in patients (n = 30) compared to healthy controls (n = 10). Cognitive performance was impaired in patients with NHL compared to controls and a norm sample (n = 1179). PCCI was more severe in patients treated with rituximab and bendamustine (BR) than in patients who received R in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) polychemotherapy (R-CHOP). Individual alpha peak frequency and serum brain-derived neurotrophic factor (BDNF) levels in patients with NHL correlated with accuracy in the objective cognition test. Higher serum interleukin-6 (IL-6) concentrations were associated with higher fatigue levels. Patients with NHL and especially those who were treated with BR were affected by PCCI. BDNF and IL-6 might be involved in the pathogenesis of PCCI and fatigue.

Objective: People feeling severely affected by multiple sclerosis (MS) comprise a heterogeneous group, and this heterogeneity leads to very distinct needs and makes planning for needs difficult. To provide optimal care, it is important to identify specific needs in specific subgroups. Our objective was to identify the specific palliative care (PC) needs of patients who felt severely affected by the disease by analyzing their feeling (1) more or (2) less severely affected and their possible differences in expressed care needs. Method: A self-report questionnaire with 25 needs categories including 7 categories pertaining to carewas applied to patients who felt severely affected by MS. An additional single question identified patients feeling more (>= 7, median-split) and less (<7) severely affected. Differences were analyzed by chi-squared and Mann-Whitney U tests. The sample (N = 573) was composed of respondents who replied to an invitation by the German Multiple Sclerosis Society to participate in a survey on unmet needs of severely affected patients. Results: Of 573 patients (median age 51), 358 (62.48%) felt more severely affected. Compared to patients feeling less severely affected, they found the stress on their next of kin to be higher (p < 0.001), were in greater need of home visitation (p < 0.001), did not have permanent neurologists (p = 0.016), and felt that they visited them too rarely (p < 0.0001). They also needed more emotional support from their nursing care service (p = 0.006). Significance of results: A self-rating scale can identify two groups of patients with different care needs. These data may help shaping patient-centered support structures. Palliative care, with its multidisciplinary approach, might be one further option to meet the specific needs of patients and their relatives.

Objective: Reliable and validated instruments are needed in order to study the desire for hastened death (DHD). As there isno instrument in the German language to measure DHD, our aim was to validate a German version of the Schedule of Attitudes Toward Hastened Death (SAHD-D). Method: The SAHD was translated following guidelines promulgated by the European Organization for Research and Treatment of Cancer (EORTC). In eligible patients (clinical situation adequate, MMSE >= 21), the following instruments were employed: a symptom checklist (HOPE), the HADS-D (Hospital Anxiety and Depression Scale), the EORTC-QLQ-PAL15, and the SAHD-D, as well as an external estimation of DHD provided by the attending physician. A high level of DHD was defined as the mean plus one standard deviation (SD). Results: Of the 869 patients assessed, 92 were eligible for inclusion (66% females, mean age of 64.5 years). The SAHD-D total score ranged from 0 to 18, with a mean of 5 and a standard deviation (SD) of 3.7. A high level of DHD was found in 20% (n = 19). For discriminant validity, significant correlations were found between the SAHD-D and depression (r(rho) = 0.472), anxiety (r(rho) = 0.224), and clinical state (r(rho) = 0.178). For criterion validity, the external estimate of DHD showed a low significant correlation with patient score (r(rho) = 0.290). Factor analysis of the SAHD-D identified two factors. Significance of results: Validation of the SAHD-D illustrated good discriminant validity, confirming that a desire to hasten death is a construct separate from depression, anxiety, or physical state. The unidimensionality of the SAHD could not be reproduced. Our findings support the multifactorial interdependencies on DHD and suggest that the SAHD-D should be refined by considering actual wishes, general attitudes, and options of patients.

Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). Results. In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 x 10(-6); 2-6x/week: OR: 1.67, P = 7.98 x 10(-5)) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2-6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. Conclusion. Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD.

PURPOSE. To investigate the role of allergy on AMD. METHODS. Age-related macular degeneration staging was performed for 3585 individuals (1878 from Cologne, Germany, and 1707 from Nijmegen, The Netherlands). Interviewer-assisted questionnaires were evaluated for the factors smoking, use of corticosteroids, and history of allergy, including causative allergens. Serum complement component C3d and C3 levels were measured and the C3d:C3 ratio was calculated. Associations of allergy with AMD/late AMD were assessed by logistic regression analysis; C3d:C3 ratio was compared between groups. RESULTS. The discovery cohort from Cologne included 864 AMD patients and 1014 controls; 495 patients had late AMD. Positive history of allergy showed strong protective effects on the phenotype AMD (OR 0.52; P = 3.42 x 10(-9)) and late AMD (OR 0.32; P x 2.57 X 10(-13)). Subclassification in allergy-provoking agents showed significant protective effects in all groups. After adjustment for age, sex, smoking, and corticosteroid use, protective effects for AMD (OR 0.75; P = 0.018) and late AMD (OR 0.49; P = 2.87 x 10(-5)) were confirmed. Although the C3d: C3 ratio was higher in AMD/late AMD patients (both P < 0.001), there was no association with allergy in AMD (P = 0.22). The protective effect of allergy on AMD was confirmed in the replication cohort from Nijmegen (P = 0.002 for AMD; P = 0.0001 for late AMD). CONCLUSIONS. Allergy has a protective effect on the development of AMD independent of the provoking allergen, which cannot be explained by complement activation. Further investigations are necessary to elucidate the molecular mechanisms underlying the protective effect of allergy on AMD.

Age-related macular degeneration (AMD) is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs) in or near 23 AMD associated risk genes. Component 3 (C3) and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH) genes and complement factor B (CFB) genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002), higher age (p = 1.56x10(-7)), AMD phenotype (p = 1.15x10(-11)) and the two SNPs in the C3 gene rs6795735 (p = 0.04) and rs2230199 (p = 0.04). Lower C3d/C3 ratios were found for diabetes (p = 2.87x10(-6)), higher body mass index (p = 1.00x10(-13)), the SNPs rs1410996 (p = 0.0001), rs800292 (p = 0.003), rs12144939 (p = 4.60x10(-6)) in CFH, rs4151667 (p = 1.01x10(-5)) in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation.

Objectives: To assess the influence of an infusion of clonidine 1 mu g/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants. Design: Prospective, double-blind, randomized controlled multicenter trial. Controlled trials. com/ISRCTN77772144. Setting: Twenty-eight level 3 German PICUs/neonatal ICUs. Patients: Ventilated newborns and infants: stratum I (1-28 d), stratum II, (29-120 d), and stratum III (121 d to 2 yr). Interventions: Patients received clonidine 1 mu g/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score. Measurements and Main Results: Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 +/- 1.8 mu g/kg/hr, placebo: 3.2 +/- 3.1 mu g/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 +/- 100.1 mu g/kg/hr, placebo: 180.2 +/- 204.0 mu g/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups. Conclusions: Clonidine 1 mu g/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

PURPOSE. We studied associations of genetic polymorphisms in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) in nonagenarians with age-related macular degeneration (AMD). METHODS. This case-control study comprised 2737 persons (1204 controls, 1433 AMD cases), including 166 nonagenarians (52 controls, 114 AMD cases). Single nucleotide polymorphisms (SNPs) in the genes ARMS2 and CFH were determined. Risk scores were computed by multiple logistic regression analysis, including genetic and environmental risk factors (smoking, hypertension, body mass index, diabetes) for different age groups (<70, 70-79, 80-89, >= 90 years [nonagenarians]). RESULTS. In nonagenarians, ARMS2 showed the weakest associations with AMD (odds ratio [OR] = 1.52, P = 0.127) compared to the other groups (OR, 70 years = 2.23, P = 1.03 x 10(-13); OR, 70-79 years = 2.70, P = 1.00 x 10(-13); OR, 80-89 years = 3.11, P = 6.56 x 10(-8)). For CFH, ORs for AMD increased with age (<70 years OR = 1.96, P = 1.80 x 10(-11); 70-79 years OR = 1.89, P = 4.48 x 10(-13); 80-89 years OR = 2.71, P = 1.28 x 10(-7)), but decreased again in the nonagenarians (OR = 2.21, P = 0.005). Compared to the group <70 years, reduced minor allele frequencies (MAFs) for AMD patients were observed in the nonagenarians (CFH 0.54 vs. 0.43, P = 0.009; ARMS2 0.44 vs. 0.29, P = 2.97 x 10(-5)), while the MAFs in controls were not significantly different. The genetic risk score revealed the lowest discriminative power in the nonagenarians with an area-under-curve (AUC) of 0.658 for receiver-operating characteristics (AUC 80-89 years = 0.768, 70-79 years = 0.704, <70 years = 0.682), while no significant difference was seen for the environmental risk score (AUC <70 years = 0.579, 70-79 years = 0.567, 80-89 years = 0.600, >90 years = 0.608). CONCLUSIONS. Risk alleles in CFH and ARMS2 have a significantly smaller effect on AMD development in nonagenarians, while environmental factors retain a similar effect.

PURPOSE. To create a risk model for neovascular age-related macular degeneration (nAMD) based on nongenetic factors. METHODS. In this case-control study, 1459 individuals were included, 445 patients showed nAMD and 1014 were healthy controls. Participants were randomly assigned into a training set (containing two-thirds of individuals) and a validation set. Stepwise logistic regression analysis was performed for 25 environmental risk factors in the training set. The risk model with the remaining factors was then validated in the validation set using receiver operating characteristics (ROC) curve and Hosmer-Lemeshow-Test. Additionally, a genetic risk model including variants in the complement factor H gene (CFH, rs1061170) and the age-related maculopathy susceptibility 2 gene (ARMS2, rs10490924) was generated. RESULTS. The environmental risk model with the factors age, alcohol use, allergy, education, sunlight exposure, fish consumption, and physical exercise showed an AUC of 0.80 (95% confidence interval [CI] 0.76-0.84) in the training set. Validation of the model showed adequate calibration (Hosmer-Lemeshow P = 0.81). The AUC for the genetic model was 0.77 (95% CI 0.730-0.808), for the combined environmental and genetic model 0.92 (95% CI 0.887-0.947). CONCLUSIONS. Seven nongenetic factors are able to provide equivalent discrimination between nAMD patients and controls to genetic risk models. Most of them are modifiable and give the opportunity for counseling patients.

Background: Moderately and late preterrn infants represent a considerable and increasing proportion of infants cared for in neonatal departments worldwide. Parents of preterm infants are at risk of postpartal depression (PPD) and posttraumatic stress disorder (PTSD), and preterm infants are at risk of developmental impairment. Aim: This study aimed to assess (1) the incidence of parental PPD and PTSD in moderate to late preterm infants in comparison to full-term infants and (2) the influence of infants' motor repertoire assessed by Prechtl's general movements and illness severity on parental PPD and PTSD. Subjects: We studied 60 mothers and 56 fathers of 69 preterm infants (born at 32 to 37 weeks of gestation) and 32 mothers and 29 fathers of 34 full-term infants. Outcome measures: We assessed the incidence of parental PPD, PTSD and perceived social support as well as infants' illness severity and motor repertoire at birth, term and 3 months corrected age. Results: Preterm mothers and fathers had significant higher depression scores after birth compared to full-term parents (p = 0.033 and 0.021). Preterm fathers also had higher traumatization scores compared to full-term fathers (p = 0.007). Probable or possible PPD/PTSD was not associated with infant's illness severity or quality of motor repertoire. No differences in motor development were found between preterm and full-term infants. Conclusion: Moderate to late preterm infants' parents are at increased risk for PPD irrespective of infants' motor repertoire or illness severity. (C) 2014 Elsevier Ireland Ltd. All rights reserved.