Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies.

Objective: To identify imaging subtypes of the cortico-basal syndrome (CBS) based solely on a data-driven assessment of MRI atrophy patterns, and investigate whether these subtypes provide information on the underlying pathology. Methods: We applied Subtype and Stage Inference (SuStaIn), a machine learning algorithm that identifies groups of individuals with distinct biomarker progression patterns, to a large cohort of 135 CBS cases (52 had a pathological or biomarker defined diagnosis) and 252 controls. The model was fit using volumetric features extracted from baseline T1-weighted MRI scans and validated using follow-up MRI. We compared the clinical phenotypes of each subtype and investigated whether there were differences in associated pathology between the subtypes. Results: SuStaIn identified two subtypes with distinct sequences of atrophy progression; four-repeat-tauopathy confirmed cases were most commonly assigned to the Subcortical subtype (83% of CBS-PSP and 75% of CBS-CBD), while CBS-AD was most commonly assigned to the Fronto-parieto-occipital subtype (81% of CBS-AD). Subtype assignment was stable at follow-up (98% of cases), and individuals consistently progressed to higher stages (100% stayed at the same stage or progressed), supporting the model's ability to stage progression. Interpretation: By jointly modelling disease stage and subtype, we provide data-driven evidence for at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy in CBS that are associated with different underlying pathologies. In the absence of sensitive and specific biomarkers, accurately subtyping and staging individuals with CBS at baseline has important implications for screening on entry into clinical trials, as well as for tracking disease progression.

A data-driven model of brain volume changes in progressive supranuclear palsy.

The most common clinical phenotype of progressive supranuclear palsy is Richardson syndrome, characterized by levodopa unresponsive symmetric parkinsonism, with a vertical supranuclear gaze palsy, early falls and cognitive impairment. There is currently no detailed understanding of the full sequence of disease pathophysiology in progressive supranuclear palsy. Determining the sequence of brain atrophy in progressive supranuclear palsy could provide important insights into the mechanisms of disease progression, as well as guide patient stratification and monitoring for clinical trials. We used a probabilistic event-based model applied to cross-sectional structural MRI scans in a large international cohort, to determine the sequence of brain atrophy in clinically diagnosed progressive supranuclear palsy Richardson syndrome. A total of 341 people with Richardson syndrome (of whom 255 had 12-month follow-up imaging) and 260 controls were included in the study. We used a combination of 12-month follow-up MRI scans, and a validated clinical rating score (progressive supranuclear palsy rating scale) to demonstrate the longitudinal consistency and utility of the event-based model's staging system. The event-based model estimated that the earliest atrophy occurs in the brainstem and subcortical regions followed by progression caudally into the superior cerebellar peduncle and deep cerebellar nuclei, and rostrally to the cortex. The sequence of cortical atrophy progresses in an anterior to posterior direction, beginning in the insula and then the frontal lobe before spreading to the temporal, parietal and finally the occipital lobe. This in vivo ordering accords with the post-mortem neuropathological staging of progressive supranuclear palsy and was robust under cross-validation. Using longitudinal information from 12-month follow-up scans, we demonstrate that subjects consistently move to later stages over this time interval, supporting the validity of the model. In addition, both clinical severity (progressive supranuclear palsy rating scale) and disease duration were significantly correlated with the predicted subject event-based model stage (P < 0.01). Our results provide new insights into the sequence of atrophy progression in progressive supranuclear palsy and offer potential utility to stratify people with this disease on entry into clinical trials based on disease stage, as well as track disease progression.

Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration.

INTRODUCTION: Leisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD). METHODS: A total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans. RESULTS: Greater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates. DISCUSSION: Active lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Maternal thyroid hormone is required for parvalbumin neurone development in the anterior hypothalamic area.

Thyroid hormone (TH) is crucial for brain development and function. This becomes most evident in untreated congenital hypothyroidism, leading to irreversible mental retardation. Likewise, maternal hypothyroxinaemia, a lack of TH during pregnancy, is associated with neurological dysfunction in the offspring, such as autism and reduced intellectual capacity. In the brain, TH acts mainly through TH receptor α1 (TRα1). Consequently, mice heterozygous for a dominant-negative mutation in TRα1 display profound neuroanatomical abnormalities including deranged development of parvalbumin neurones. However, the exact timing and orchestration of TH signalling during parvalbumin neurone development remains elusive. In the present study, we dissect the development of parvalbumin neurones in the anterior hypothalamic area (AHA) in male mice using different mouse models with impaired pre- and postnatal TH signalling in combination with bromodeoxyuridine birth dating and immunohistochemistry. Our data reveal that hypothalamic parvalbumin neurones are born at embryonic day 12 and are first detected in the AHA at postnatal day 8, reaching their full population number at P13. Interestingly, they do not require TH postnatally because their development is not impaired in mice with impaired TH signalling after birth. By contrast, however, these neurones crucially depend on TH through TRα1 signalling in the second half of pregnancy, when the hormone is almost exclusively provided by the mother. For the first time, our findings directly link a maternal hormone to a neuroanatomical substrate in the foetal brain, and underline the importance of proper TH signalling during pregnancy for offspring mental health. Given the role of hypothalamic parvalbumin neurones in the central control of blood pressure, the present study advocates the inclusion of cardiovascular parameters in the current discussion on possible TH substitution in maternal hypothyroxinaemia.

Laparoscopic-assisted vaginal hysterectomy versus vaginal hysterectomy for benign uterine diseases: a prospective, randomized, multicenter, double-blind trial (LAVA).

OBJECTIVE: To compare the impact of peritoneal closure on postoperative pain after vaginal (VH) and laparoscopic-assisted vaginal hysterectomy (LAVH). STUDY DESIGN: A prospective, randomized, double-blind study was designed to investigate as primary outcome the postoperative pain after VH and LAVH with and without peritoneal closure. The postoperative pain was measured using visual analogue scale (VAS). RESULTS: The patients were recruited between August, 2007 and July, 2014. A total of 192 patients with benign uterine diseases were eligible for analysis and were divided in four groups: LAVH and VH with and without peritoneal closure (PC), respectively. The patients' characteristics including parity, BMI, previous abdominal operations, and uterus weight were well balanced between the groups. The patients who received LAVH were significantly younger (p = 0.0443). LAVH was associated with increased postoperative pain and reduced patients' mobility in the first 72 and 24 h, respectively, after surgery. The use of analgesics remained similar in all four groups. The operating time was significantly shorter after VH (VH + PC 59 ± 17; VH - PC 56 ± 19) than after LAVH (LAVH + PC 106 ± 29 min; LAVH - PC 99 ± 30) (p < 0.0001). The PC did not affect the patients' outcome. The blood loss, the hemoglobin drop, the hospital stay, and the rate of intra- and postoperative complications rate were similar in all four groups. No conversation to laparotomy occurred in whole study population. CONCLUSION: VH is associated with shorter operating time and reduced postoperative pain compared to LAVH.

The Role of Hypothalamic NF-κB Signaling in the Response of the HPT-Axis to Acute Inflammation in Female Mice.

A large proportion of critically ill patients have alterations in the hypothalamus-pituitary-thyroid (HPT) axis, collectively known as the nonthyroidal illness syndrome. Nonthyroidal illness syndrome is characterized by low serum thyroid hormone (TH) concentrations accompanied by a suppressed central component of the HPT axis and persistent low serum TSH. In hypothalamic tanycytes, the expression of type 2 deiodinase (D2) is increased in several animal models of inflammation. Because D2 is a major source of T3 in the brain, this response is thought to suppress TRH expression in the paraventricular nucleus via increased local bioavailability of T3. The inflammatory pathway component RelA (the p65 subunit of nuclear factor-κB) can bind the Dio2 promoter and increases D2 expression after lipopolysaccharide (LPS) stimulation in vitro. We aimed to determine whether RelA signaling in tanycytes is essential for the LPS-induced D2 increase in vivo by conditional elimination of RelA in tanycytes of mice (RelA(ASTKO)). Dio2 and Trh mRNA expression were assessed by quantitative in situ hybridization 8 or 24 hours after saline or LPS injection. At the same time points, we measured pituitary Tshß mRNA expression and serum T3 and T4 concentrations. In RelA(ASTKO) mice the LPS-induced increase in Dio2 and decrease in Trh mRNA levels in the hypothalamus were reduced compared with the wild-type littermates, whereas the drop in pituitary Tshß expression and in serum TH concentrations persisted. In conclusion, RelA is essential for the LPS-induced hypothalamic D2 increase and TRH decrease. The central changes in the HPT axis are, however, not required for the down-regulation of Tshß expression and serum TH concentrations.

Pharmacokinetics and safety of an 8 week continuous treatment with once-daily versus twice-daily inhalation of tobramycin in cystic fibrosis patients.

OBJECTIVES: We evaluated the pharmacokinetics, safety and tolerability of two different continuous treatment regimens of tobramycin inhalation solution (TIS) in 29 cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. PATIENTS AND METHODS: In this randomized, multicentre, open-label, two-period crossover study, TIS (300 mg/5 mL) was administered via PARI eFlow(®) rapid once daily and twice daily each for 8 weeks. Serum pharmacokinetics of these two regimens was analysed. Tobramycin levels were determined before the morning dose and at 30, 60 and 90 min after the end of nebulization in the middle and at the end of each 8 week cycle. At these timepoints, trough and peak serum tobramycin concentrations (Cmax, mg/L) as well as the area under the curve for 0-90 min of tobramycin (AUC0-90min) were assessed in order to evaluate the risk of systemic toxicity. Safety parameters and forced expiratory volume in 1 s (FEV1) were assessed. RESULTS: For once-daily treatment, tobramycin levels were 10% higher after 8 weeks compared with 4 weeks (AUC0-90min ratio = 1.096, 90% CI = 0.860-1.396, P = 0.5237). For twice-daily treatment, tobramycin levels after 8 weeks showed a 40% decrease compared with 4 weeks (AUC0-90min ratio = 0.608, 90% CI = 0.461-0.802, P = 0.0055). The AUC0-90min ratio at 8 weeks (once daily versus twice daily) did not differ significantly (AUC0-90min ratio = 0.749, 90% CI = 0.514-1.092, P = 0.2009). The mean FEV1 did not differ markedly compared between treatment periods or with baseline. No audiological or nephrotoxic side effects were noted. CONCLUSIONS: Continuous treatment with TIS (once daily or twice daily) over 8 weeks appears to be safe and tolerable.

Guideline-adherent therapy in patients with acute coronary syndromes. The EPICOR registry in Germany.

BACKGROUND: Representative data on the current management of patients with acute coronary syndromes (ACS) are of high interest. The EPICOR registry aimed to prospectively collect such real-life data with particular focus on antithrombotic drug utilization and outcomes. METHODS: As part of the international prospective EPICOR registry, 29 hospitals in Germany documented 296 patients with ST-elevation myocardial infarction (STEMI)-ACS and 333 with unstable angina or non-STEMI (NSTEMI)-ACS surviving the hospital phase. The statistical analysis was performed in a descriptive manner. The ClinicalTrials.gov identifier is NCT01171404. RESULTS: The mean age of patients was 62 ± 13 years, and 77.4 % were men. Treatment with antithrombotic agents was initiated in the prehospital phase in 50.7 % of STEMI and 33.3 % of NSTEMI patients. During the hospital stay (median 7.0 days), cardiac catheterization was performed in 97.6 %, percutaneous coronary intervention in 85.6 %, thrombolysis in 4.6 %, and coronary bypass surgery in 2.7 % patients. The use of acetylic salicylic acid (ASA) was reported in 95.6 % vs. 96.1 %, clopidogrel in 60.8 % vs. 73.0 %, prasugrel in 45.6 % vs. 22.5 %, any GP IIb/IIIa inhibitor in 52.4 % vs. 18.9 % [any dual combination of ASA+(clopidogrel/prasugrel)in 94.0 vs. 91.0 %], statins in 94.6 % vs. 92.2 %, beta blockers in 96.3 % vs. 94.6 %, and ACE-I/ARB in 91.6 % vs. 87.7 % of STEMI vs. NSTEMI patients, respectively. Combined use of the five drug classes recommended in the guidelines-ASA, P2Y12 antagonists, statin, beta blocker, and ACE-I/ARB-was reported in 81.1 % vs. 69.4 % of STEMI vs. NSTEMI patients, respectively. CONCLUSION: In Germany a high proportion of patients with ACS are treated according to current guidelines, receiving primary revascularization as well as antithrombotic drugs and other agents for prevention of secondary events; associated bleeding complications were less frequent as compared with published registries.

First Report of the Root-Knot Nematode Meloidogyne hapla Parasitizing Roses in Ethiopia.

Meloidogyne hapla is one of the most damaging plant-parasitic nematodes in temperate regions. This nematode has a wide host range with more than 500 plant taxa including roses. In Ethiopia, rose production has developed over the past 10 years to the second most important export market after coffee. Considering the high damage potential of M. hapla, infestation of roses in Ethiopia with this nematode could result in major economic losses. Therefore, awareness of this nematode species is extremely important. During two surveys conducted in August 2011 and April 2012, M. hapla was detected in soil samples from six out of nine rose producing farms located in the districts of Ziway, Holleta, Sebeta, and Menagesha. At infested farms, rose plants appeared stunted and less productive and often showed symptoms of chlorosis and wilting. Identification was based on morphological and morphometrical characters of females, males, and second-stage juveniles, which were all within the range of variability known for this species (4). Shape of juvenile stylet knobs, shape of male head, and perennial pattern of the females with characteristic punctuations between the anus and tail terminus were also typical for M. hapla. The morphological identification was confirmed by sequence analysis of the D2-D3 expansion segment of the 28S rDNA gene following amplification with the primers D2A (5'-ACAAGTACCGTGAGGGAAAGTT-3') and D3B (5'-TCGGAAGGAACCAGCTACTA-3') (1). PCR products were purified and sequenced at the Macrogene sequencing facility service (Amsterdam, The Netherlands). Sequences were deposited in GenBank (KJ645427 to 33). The sequences were compared with previously published sequences in NCBI database and showed 96 to 100% sequence similarity with M. hapla accession nos. GQ130139, DQ328685, KF430798, and DQ145641. Unfortunately, comparison of sequences did not provide further information about the origin of this Ethiopian population, if it is native to Ethiopia or was imported with infected plant material. To the best of our knowledge, this is the first record of M. hapla occurring in Ethiopia. M. hapla is known as a serious pest of roses in colder climate regions. In Africa, it was previously reported from Tanzania (3) and South Africa (2). Thus, it appears that this species has now become also established in Ethiopia at higher altitudes (1,400 to 2,100 m above sea level) within the urban hinterland of Addis Ababa. References: (1) Baldwin et al. Mol. Phy. Evol. 8:248, 1887. (2) J. H. O'Bannon. Institute Agri. Res. 29, 1975. (3) E. Onkendi and L. N. Moleleki. Eur. J. Pl. Pathol. 136:1, 2013. (4) A. G. Whitehead. Trans. Zool. Soc. Lon.31:263, 1968.

Can axillary reverse mapping avoid lymphedema in node positive breast cancer patients?

BACKGROUND: Tracing lymphatic drainage of the ipsilateral arm of node positive breast cancer patients, termed "axillary reverse mapping" (ARM), has recently been described in several reports. We analyzed our experience with this new technique in patients scheduled for axillary lymph node dissection (ALND) and evaluated its usefulness for reducing the incidence of lymphedema. METHODS: Blue dye was injected subcutaneously along the intermuscular groove of the upper inner arm; radioisotope was injected subcutaneously in the interdigital webspace of the hand. All blue and radioactive lymph vessels and lymph nodes were recorded. Only unsuspicious "ARM lymph nodes" located in the lateral part of the axillary basin were preserved. All other level I and II axillary lymph nodes were removed. Resected ARM nodes were immediately separated from all other lymph nodes. RESULTS: ARM was performed in 143 patients subsequently undergoing ALND. ARM lymph nodes were successfully identified in 112 cases (78%). In 55 patients at least one ARM lymph node had to be removed. In 14 of these, tumor involvement was confirmed. In 71 patients one or more ARM nodes were preserved. During a median follow-up time of 19 months no axillary recurrence was noted. 35 of 114 evaluated patients developed lymphedema. Preservation of ARM lymph nodes did not significantly decrease the incidence of lymphedema. CONCLUSION: ARM is feasible for patients with node positive breast cancer. However, we found no evidence that it reduces the incidence of lymphedema.

Unintended hand movements after abrupt cessation of variable and constant opposing forces.

Humans are highly efficient in moving in a world of variable resistive forces which result, e.g., from different masses of objects or different directions of movements relative to gravity. However, the underlying mechanisms are challenged when an opposing force is suddenly removed. The resulting involuntary movements are known as accident risks in everyday life. We studied their characteristics upon abrupt cessations of opposing forces of 1, 2, and 4N which were presented in a series of variable or constant forces. The characteristics of the involuntary hand movements are largely determined by the mechanical impedance of the limb. The involuntary movements are oscillatory in nature, and their amplitude increases with stronger opposing force. Limb impedance is modulated both in a reactive and in an anticipatory manner. The reactive modulation occurs during each involuntary movement as a consequence of the neural responses elicited by the rapid limb acceleration consequent upon the cessation of the opposing force. Anticipatory modulation of limb impedance may serve to produce similar involuntary movements in spite of different opposing forces. The modulation is thus stronger with variable forces, where differences between resulting involuntary movements can be experienced more easily, than with constant forces.

Multicenter validation of a bedside antisaccade task as a measure of executive function.

OBJECTIVE: To create and validate a simple, standardized version of the antisaccade (AS) task that requires no specialized equipment for use as a measure of executive function in multicenter clinical studies. METHODS: The bedside AS (BAS) task consisted of 40 pseudorandomized AS trials presented on a laptop computer. BAS performance was compared with AS performance measured using an infrared eye tracker in normal elders (NE) and individuals with mild cognitive impairment (MCI) or dementia (n = 33). The neuropsychological domain specificity of the BAS was then determined in a cohort of NE, MCI, and dementia (n = 103) at UCSF, and the BAS was validated as a measure of executive function in a 6-center cohort (n = 397) of normal adults and patients with a variety of brain diseases. RESULTS: Performance on the BAS and laboratory AS task was strongly correlated and BAS performance was most strongly associated with neuropsychological measures of executive function. Even after controlling for disease severity and processing speed, BAS performance was associated with multiple assessments of executive function, most strongly the informant-based Frontal Systems Behavior Scale. CONCLUSIONS: The BAS is a simple, valid measure of executive function in aging and neurologic disease.

The influence of the dynamic transformation of a sliding lever on aiming errors.

Human movements are quickly adjusted to variations of inertial load. However, this adjustment does not always imply a full compensation, so that kinematic movement characteristics vary. The present experiment served to explore the consequences of a complex dynamic transformation, implemented by a sliding first-order lever, on the endpoint distributions of goal-directed movements. Whereas the endpoint distributions were clearly affected by the inertial anisotropy of the arm, there was no effect of the dynamic transformation of the lever, neither on the parameters of endpoint distributions nor on the covariations of endpoints of successive movements (error propagation). However, when the lever was used, the effect of the inertial anisotropy of the arm on movement amplitudes was reduced, accompanied by a longer movement time overall, in particular for movements with higher inertial load of the arm. These observations suggest an interaction of the use of internal models and impedance control in the presence of variable inertial loads. Most likely the influence of the dynamic transformation of the sliding lever is absorbed by increased joint impedance, which also reduces the influence of the inertial anisotropy of the arm which otherwise is (incompletely) compensated based on an internal model of the dynamic transformation of the arm.

Dementia among older in-hospital patients with obstructive airway disease: frequency and consequences.

BACKGROUND: Dementia may influence as a co-morbid condition the management of chronic obstructive airway disease. However, the frequency and the consequences of dementia in older people with chronic obstructive airway disease are largely unknown. PATIENTS AND METHODS: The frequency and the severity of dementia in geriatric in-hospital patients and its impact on feasibility of lung function testing and drug treatment provided were determined. RESULTS: Out of a total of 1,424 patients with obstructive airway disease, 433 (30%) suffered from mild and 307 (22%) suffered from moderate to severe dementia. The frequency of any treatment for obstructive airway disease on admission decreased from 58% in subjects without dementia to 51% of those with mild and to 36% of those with moderate to severe dementia (p<0.01). The feasibility of performing lung function testing also decreased with increasing prevalence of dementia from 86% to 66% and 43%, respectively (p<0.001). CONCLUSION: Dementia is a frequent finding in older in-hospital patients with obstructive airway disease. The majority of subjects with dementia were not able to perform lung function testing. Furthermore, the risk of undertreatment for chronic obstructive airway disease increased. Future guidelines for management of obstructive airway disease must also take into account the special needs and skills of older subjects with dementia.

The terminal phase of life as a team-based clinical global judgment: prevalence and associations in an acute geriatric unit.

BACKGROUND: In most elderly people, the final-terminal-phase of life is characterized by permanent dependency and a complete inability to perform activities of daily living. Treatment targets usually switch from rehabilitation to palliation. However, the prevalence of the clinical judgment "last phase of life" and its association with in-hospital death is unknown in geriatric patients. PATIENTS AND METHODS: We retrospectively analyzed GEMIDAS data from two geriatric units. Patients without cancer and an in-hospital stay of at least 1 week were included in our study. Prevalence of the terminal phase of life was clinically assessed according to the proposals made by M. Gillick. This clinical judgment was pronounced by the geriatric team after a stay in the hospital of at least 1 week. The clinical judgment took into account all available assessment parameters, as well as the impact of a geriatric treatment trial. In addition, the association between the clinical judgment and the risk of in-hospital mortality was analyzed. RESULTS: Records from 2,433 (56%) patients in hospital A and from 1,912 (44%) patients in hospital B were analyzed. The frequency of a terminal phase of life was 30% and 9% (p<0.01), respectively. The frequency depended on the manner of admission to the hospital. In both hospitals, mortality was significantly higher in terminal patients (27% and 37%) than in other patients (0-8% and 0-6%). In both hospitals, the risk of in-hospital mortality was significantly associated with the clinical judgment (OR 3.1 and 2.7), heart failure (OR 2.2 and 2.1), and dementia (OR 2.0 and 1.8). Age, residency in a nursing home, and the Barthel Index on admission were all without relevant impact. CONCLUSION: The frequency of the clinical construct "terminal phase of life" varies in geriatric units between 9% and 30%. This clinical construct is significantly associated with increased in-hospital mortality. Therefore, this construct possesses external validity. Further studies are needed in order to assess the significance of such a clinical judgment, the associations with clinical burdens of symptoms, and the supply structure required to cover the needs of patients and their families.

Feasibility of the Epworth Sleepiness Scale in a sample of geriatric in-hospital patients.

Excessive daytime sleepiness (EDS) is a major health concern in geriatric patients. EDS affects quality of life, daytime function, and mortality. The Epworth Sleepiness Scale (ESS) is a standard tool for the assessment daytime sleepiness, but the feasibility of the ESS has never been investigated in elderly subjects. We applied the ESS to a random sample of geriatric in-hospital patients. The aim of the study was to reveal the frequency and the risk factors for processing failure of the ESS in geriatric patients. 458 patients with a mean age of 82+/-8 years were included. One hundred sixty six (36%) completed the ESS, 118 (28%) patients had omissions of items, and 174 (38%) patients were unable to respond to any item. Completion of the ESS correlated significantly with age, disability, dementia, impairment of vision, and hearing. Omitted items were related to mobility and activities outside the house. Logistic regression analysis with completed ESS as a dependent variable revealed that dementia, disability, heart failure, and COPD were independent and significant risk factors for processing failure. The majority of patients of a geriatric unit are unable to complete the ESS. Since EDS is a frequent finding with a negative impact on health, the development of a reliable and valid tool for the assessment of EDS in elderly subjects is needed.

Influence of type of treatment for sleep apnea on activities of daily living in a sample of elderly patients with severe sleep apnea.

Sleep disordered breathing (SDB) is a frequent finding in the elderly. SDB is related to morbidity, mortality, quality of life, disability, and cognitive impairment. Treatment of choice for SDB is nasal positive airway pressure breathing (nCPAP). The impact of treatment for SDB on activities of daily living (ADLs) is unclear. We therefore investigated the relationship between SDB and ADLs in a sample of elderly in-hospital patients with severe SDB defined as a oxygen desaturation index of 30 events per hour. All patients eligible were assigned to nCPAP therapy. Patients with refusal of nCPAP were offered nocturnal oxygen supply via nasal prongs. The Barthel-index (BI) at admission and discharge was used to measure ADLs. Two hundred patients with a mean age of 81+/-7 years were included. 22 (11%) patients accepted nCPAP therapy, 42 (21%) patients accepted oxygen therapy and 136 (68%) patients refused both treatment options. The subgroups did not differ significantly in BI at admission and length of stay in hospital. BI increased from 42+/-28 to 49+/-30 in patients with refusal of any treatment, from 39+/-23 to 61+/-20 in patients with oxygen therapy and from 48+/-35 to 72+/-28 in patients with nCPAP therapy. The BI at discharge differed significantly between all three patients groups (p< 0.03). Logistic regression analysis revealed that Barthel Index at admission and treatment with nCPAP or treatment with oxygen were independently associated with a gain in BI of at least 30 points. Age, dementia or length of in-hospital stay showed no association with gain in BI. This is the first study that shows an impact of treatment for severe SDB on ADLs in elderly patients. Furthermore, treatment with nCPAP and oxygen supply nearly had the same impact on ADLs. Since the higher rate of acceptance of oxygen therapy and the important impact of oxygen supply on BI, administration of oxygen seems to be a rational alternative in elderly subjects with severe sleep apnea and refusal of nCPAP.

Distal embolic protection during percutaneous intervention of aorto-coronary venous bypass grafts: the FIRST Trial.

OBJECTIVE: Interventions in aorto-coronary venous bypass grafts (CABG) can cause acute procedural complications due to distal embolization of debris. In the FIRST (First European Investigation Regarding the Systematic use of the TriActiv device) multicenter trial the distal endovascular protection system TriActiv (Kensey Nash) was evaluated during intervention of CABG. METHODS: 195 patients in 17 centers in Germany with significant disease of a vein graft were enrolled. Inclusion and exclusion criteria were comparable to the SAFER trial. RESULTS: Acute procedural success was achieved in 98% of cases. Aspirated debris was found in 96.5% of patients. Primary endpoints (MACE at 30 days) occurred in 8.7% of all pts. (ITT). No patient died and 7.2% of patients suffered from MI. The rate of early revascularization was 1.5%. Secondary endpoints (MACCE at 30 days) were found in 9.2% and at hospital discharge in 8.7% of patients. CONCLUSIONS: The TriActiv system is safe and effective. Normal post procedural flow can be preserved and the MACE rate is with 8.7% considerably low. The FIRST trial supports the growing belief that PCI of CABG should be performed with protection systems.