Purpose: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and is associated with a growing and substantial socioeconomic burden. Long-term oxygen therapy (LTOT), recommended by current treatment guidelines for COPD patients with severe chronic hypoxemia, has shown to reduce mortality in this population. The aim of our study was to assess the standardized mortality ratios of incident and prevalent LTOT users and to identify predictors of mortality. Patients and methods: We conducted a 2-year follow-up population-based cohort study comprising all COPD patients receiving LTOT in the canton of Bern, Switzerland. Comparing age-and sex-adjusted standardized mortality ratios, we examined associations between all-cause mortality and patient characteristics at baseline. To avoid immortal time bias, data for incident (receiving LTOT,6 months) and prevalent users were analyzed separately. Results: At baseline, 475 patients (20% incident users, n=93) were receiving LTOT because of COPD (48/100,000 inhabitants). Mortality of incident and prevalent LTOT users was 41% versus 27%, respectively, p<0.007, and standardized mortality ratios were 8.02 (95% CI: 5.64-11.41) versus 5.90 (95% CI: 4.79-7.25), respectively. Type 2 respiratory failure was associated with higher standardized mortality ratios among incident LTOT users (60.57, 95% CI: 11.82-310.45, p=0.038). Conclusion: Two-year mortality rate of COPD patients on incident LTOT was somewhat lower in our study than in older cohorts but remained high compared to the general population, especially in younger patients receiving LTOT <6 months. Type 2 respiratory failure was associated with mortality.

Nasal high-flow oxygen therapy (HFOT) is a novel treatment option for patients suffering from acute or chronic respiratory failure. Aim of our study was to compare safety and efficacy of HFOT with those of conventional oxygen treatment (COT) in normo- and hypercapnic COPD patients.

ABSTRACT In this study, the efficacy of ceftaroline fosamil was compared with that of cefepime in an experimental rabbit meningitis model against two Gram-negative strains (Escherichia coli QK-9 and Klebsiella pneumoniae 1173687). The penetration of ceftaroline into inflamed and uninflamed meninges was also investigated. Both regimens were bactericidal, but ceftaroline fosamil was significantly superior to cefepime against K. pneumoniae and E. coli in this experimental rabbit meningitis model (P < 0.0007 against K. pneumoniae and P < 0.0016 against E. coli). The penetration of ceftaroline was approximately 15% into inflamed meninges and approximately 3% into uninflamed meninges.

INTRODUCTION:The "Comprehensive ICF Core Set for Chronic Obstructive Pulmonary Diseases (COPD)" is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of patients with COPD. The objective of this study was to validate this ICF Core Set from the perspective of physicians.MATERIALS AND METHODOLOGY:Physicians experienced in COPD treatment were asked about the patients' problems treated by physicians in patients with COPD in a three-round electronic mail survey using the Delphi technique. Responses were linked to the ICF.RESULTS:Seventy-six physicians in 44 countries gave a total of 1330 responses that were linked to 148 different ICF categories. Nine ICF categories were not represented in the Comprehensive ICF Core Set for COPD although at least 75% of the participants have rated them as important. Nineteen concepts were linked to the not yet developed ICF component personal factors and seventeen concepts were not covered by the ICF.CONCLUSION:The high percentage of ICF categories represented in the ICF Core Set for COPD indicates satisfactory content validity from the perspective of the physicians. However, some issues were raised that were not covered and need to be investigated further.

ABSTRACT Ceftobiprole medocaril, a new cephalosporin, is highly active against a broad spectrum of Gram-positive and Gram-negative clinical pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant pneumococci. In this study, we tested ceftobiprole against various Gram-negative pathogens in a rabbit meningitis model and determined its penetration into the cerebrospinal fluid (CSF). In this animal model, ceftobiprole produced an antibacterial activity similar to that of cefepime against an Escherichia coli strain, a Klebsiella pneumoniae strain, and a β-lactamase-negative Haemophilus influenzae strain. Against a β-lactamase-positive H. influenzae strain, ceftobiprole was significantly superior. The penetration of ceftobiprole through inflamed meninges reached about 16% of serum levels compared to about 2% of serum levels through uninflamed meninges.

OBJECTIVESIn this study the efficacy of doripenem, a new broad-spectrum carbapenem, was tested against an Escherichia coli strain and a Klebsiella pneumoniae strain in an experimental animal model. The comparator was cefepime monotherapy.METHODSThe rabbit meningitis model was used in this study and the penetration of doripenem through uninflamed and inflamed meninges was determined.RESULTSDoripenem, injected three times (75 mg/kg), led to serum peak levels around 100 mg/L and trough levels around 5 mg/L, resulting in a penetration rate of 14% through inflamed meninges and 7% through uninflamed meninges. Against K. pneumoniae, doripenem was slightly but not significantly more efficacious than cefepime over 8 h (5.40 ± 1.37 log(10) cfu/mL versus 3.59 ± 0.89 log(10) cfu/mL for cefepime). Also against the E. coli strain doripenem was slightly superior to the comparator (5.55 ± 0.87 log(10) cfu/mL versus 3.80 ± 1.10 log(10) cfu/mL for cefepime), although the difference was not significant.CONCLUSIONSDoripenem is a potential monotherapy for the treatment of meningitis due to Gram-negative microorganisms.

The objective of this systematic review and content analysis was to identify and quantify the concepts contained in patient-administered health status measures in sleep medicine practice and research using the International Classification of Functioning, Disability and Health (ICF) as a reference. Both generic and condition-specific patient-administered measures/questionnaires used in sleep medicine practice and research were identified and selected. A comprehensive search strategy for reviews, National/International Guidelines and Standard References to ensure that all areas of functioning, disability and health were captured was used. The contents of the selected measures were examined and linked to the ICF using established linking rules. The frequencies of ICF categories covering the concepts contained in the 115 patient-administered measures were used for the descriptive analysis and content comparison. Of these, 35 were of a generic nature, 17 were symptom-related, and 63 condition-specific. The concepts identified in the questionnaires' items were predominantly linked to categories of the ICF component related to body functions (61.4%), followed by activities and participation (15.3%), and then environmental factors (9.8%). The measures vary greatly with regard to the number and specificity of the ICF categories covered, as indicated by the proportional indices of content density and content diversity. The ICF provides a useful reference to identify, quantify and compare the concepts contained in health status measures used in sleep medicine practice and research.

Background/objectives: The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive and universally accepted framework to classify changes in functioning related to health conditions. Comprehensive and Brief Core Sets have been defined for various disorders but not for sleep disorders. Such a Core Set would greatly enhance the techniques available to describe the impact of sleep disorders on patients. The overarching purpose of this paper is to report on phase 1 of the international and World Health Organization (WHO) endorsed consensus process in identifying ICF Core Sets for sleep disorders.Methods: A formal decision-making and consensus process which integrated evidence gathered from preparatory studies was carried out. Relevant ICF categories were selected by a sample of international experts from different backgrounds using the nominal group technique.Results: Twenty-six experts from 22 countries and different professional backgrounds attended the consensus conference. Altogether 120 second- or third-level ICF categories were included in the Comprehensive ICF Core Set with the following ICF component split: 49 categories from body functions, 8 from body structures, 31 from activities and participation and 32 from environmental factors. The Brief ICF Core Set included a total of 15 second-level categories: 5 body functions (sleep, energy and drive, attention, consciousness, respiration functions); 3 body structures (brain, respiratory system, pharynx); 4 activities and participation (focusing attention, driving, handling stress and other psychological demands, carrying out daily routine); and 3 environmental factors (immediate family; health services, systems, and policies; and health professionals).Conclusion: A formal consensus process integrating evidence and expert opinion led to the first version of the ICF Core Sets for persons with sleep disorders. Further validation of the Core Set is needed. (C) 2010 Elsevier B.V. All rights reserved.

We examined the cerebrospinal fluid penetration of daptomycin after the addition of dexamethasone and its bactericidal efficacy with and without ceftriaxone in an experimental rabbit model of pneumococcal meningitis. The combination of daptomycin with ceftriaxone was the most efficacious regimen for pneumococcal meningitis. The previous addition of dexamethasone affected the antibacterial activity of daptomycin only marginally, either as monotherapy or combined with ceftriaxone, although the penetration of daptomycin into inflamed meninges was significantly reduced from 6 to 2%. Daptomycin with ceftriaxone might be a potential candidate for the empirical therapy of bacterial meningitis, although the activity of this regimen against Listeria monocytogenes remains to be demonstrated.

BackgroundDue to the increasing importance of quality of life assessments in chronic obstructive pulmonary disease (COPD) patients, and the increased use of the International Classification of Functioning, Disability and Health (ICF) for comparative purposes it is essential to understand the relationship between health-related quality of life (HRQL) instruments and the ICF.ObjectiveThe objective of this study was to compare the content of recommended COPD-specific HRQL instruments using the ICF as reference. COPD-specific instruments mentioned in widely accepted guidelines were linked to the ICF using standardized linking rules. The degree of agreement between various health professionals was assessed by calculating the kappa statistic.ResultsEleven instruments were included. They varied strongly in the number of concepts contained and the number of ICF categories used to map these concepts. A total of 548 concepts were identified and linked to 60 different ICF categories. Only the single category ‘dyspnea’ was covered by all instruments, whilst 21 categories were unique to specific instruments. The relationships of the measures with the ICF were identified.ConclusionsThis study may aid researchers and clinicians to choose the most appropriate instrument for a specific purpose as well as help compare studies that have used different instruments for HRQL assessment.

OBJECTIVES:To test the efficacy of EDP-420, a new ketolide, in experimental pneumococcal meningitis and to determine its penetration into the CSF.METHODS:The experimental rabbit model was used in this study and EDP-420 was tested against a penicillin-resistant and a penicillin- and quinolone-resistant mutant. EDP-420 was also tested against both strains in time-killing assays over 8 h in vitro.RESULTS:In experimental meningitis, EDP-420 produced a bactericidal activity comparable to the standard regimen based on a combination of vancomycin with ceftriaxone against a penicillin-resistant Streptococcus pneumoniae and a penicillin- and quinolone-resistant S. pneumoniae isolate. The penetration of EDP-420 into inflamed meninges was 38% after an i.v. injection of 10 mg/kg. The bactericidal activity of EDP-420 was also confirmed in in vitro time-killing assays.CONCLUSIONS:EDP-420 is an efficacious alternative treatment in pneumococcal meningitis, especially when resistant strains are suspected.

ABSTRACT Daptomycin monotherapy was superior to ceftriaxone monotherapy and was highly efficacious in experimental pneumococcal meningitis, sterilizing the cerebrospinal fluid (CSF) of three of three rabbits after 4 to 6 h. With daptomycin therapy only a negligible release of [ 3 H]choline as marker of cell wall lysis was detectable in the CSF, peaking around 250 cpm/min after 4 h, compared to a peak of around 2,400 cpm/min after 4 to 6 h for the ceftriaxone-treated rabbits.

Background Et Aims: Starvation and weight toss are common accompaniments of severe illness. The functional consequences of such malnutrition include not only physical changes but also psychological changes such as depression, anxiety, irritability, apathy, poor steep pattern and loss of concentration. We carried out a pilot observational. study in 22 undernourished patients at the time of referral to the nutritional team and after 8 days of nutritional support, using the Profile of Mood States Score (POMS) questionnaire to determine whether measurable and clinically significant changes in mood occurred with treatment.Methods: Twenty-two undernourished patients with gastrointestinal disease were studied during the first week of treatment by the nutrition team. Psychological assessment was performed using a structured and standardised questionnaire assessing mood states (tension, depression, anger, vigour, fatigue, confusion). The questionnaire was administered to the patients by the same interviewer on days 1 (start of treatment by the nutrition team) and 8.Results: Median (IQR) scores for tension, depression, anger, vigour, fatigue and confusion were 21.5 (11.5), 29.0 (15.8), 15.0 (11.8), 6.0 (7.5), 20.0 (8.5) and 12.0 (7.0) respectively on day 1. Corresponding scores on day 8 were 4.0 (8.8), 3.5 (6.0), 1.0 (1.8), 20.0 (7.5), 10.0 (8.8) and 2.5 (6.8). The improvement in scores seen on day 8 was statistically significant (P<0.01).Conclusion: Nutritional status and treatment have important effects on the psychology of patients and formal measurements of psychological function will form an important part of nutritional assessment and monitoring in the future. (c) 2007 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

ABSTRACT The penetration of telavancin was 2% into inflamed meninges and ca. 1‰ into noninflamed meninges after two intravenous injections (30 mg/kg of body weight). In experimental meningitis, telavancin was significantly superior to vancomycin combined with ceftriaxone against a penicillin-resistant pneumococcal strain. Against a methicillin-sensitive staphylococcal strain, telavancin was slightly but not significantly superior to vancomycin.

OBJECTIVES To test the efficacy of daptomycin, a cyclic lipopeptide antibiotic, against a methicillin-susceptible Staphylococcus aureus strain in experimental rabbit meningitis and to determine its penetration into non-inflamed and inflamed meninges RESULTS Over a treatment period of 8 h, daptomycin (15 mg/kg) was significantly superior to the comparator regimen vancomycin (-4.54 +/- 1.12 log(10)/mL for daptomycin versus -3.43 +/- 1.17 log(10)/mL for vancomycin). Daptomycin managed to sterilize 6 out of 10 CSFs compared with 4 out of 10 for vancomycin. The penetration of daptomycin into inflamed meninges was approximately 5% and approximately 2% into non-inflamed meninges. CONCLUSIONS The superior bactericidal activity of daptomycin was confirmed in vivo and in time-killing assays in vitro.

PRINCIPLESCoeliac disease (gluten sensitive enteropathy) is a genetically determined disorder with an incidence in the general population that is comparable to type 2 diabetes mellitus. Awareness of this fact and of the often atypical and oligosymptomatic manifestations is only now gaining ground in the medical profession. A high index of suspicion is important in order to minimise diagnostic and therapeutic delay.METHODSTesting patterns and follow-up for coeliac disease in our institution have been analysed retrospectively for the past five years. The current literature was reviewed with respect to recommendations for clinical practice.RESULTSA total of 271 patients were tested for coeliac disease over a period of five years. Only in 24 patients were positive results found; after further work-up, the final number of cases with certain or presumed coeliac disease was four. Followup was often difficult, many patients being lost after a single visit.CONCLUSIONSThis study showed that the number of tests ordered in our institution, more often for abdominal than atypical symptoms, has started to increase in the past two years. It also showed that screening tests have found their place in general clinical practice, while the final choice of tests needs to be determined in accordance with available guidelines and local resources. Upper endoscopy with small bowel biopsy remains the gold standard for diagnosis, but its place in follow-up is less certain. Coeliac disease is a disorder for which there is a definite treatment (gluten free diet); if it is left untreated diminished quality of life and potentially serious complications may ensue. Further education of the medical profession regarding coeliac disease, its incidence, presentation and treatment, is clearly indicated..

Microscopic pulmonary tumor embolism (MPTE) is an uncommon cause of dyspnea in patients with cancer and one of the most difficult to diagnose. MPTE is a syndrome that is pathologically characterized by the occlusion of small pulmonary arteries and arterioles by aggregates of tumor cells. Because the clinical picture resembles that of thromboembolic disease, it is rarely recognized before death. The most common clinical symptom is subacute progressive dyspnea over weeks to months. We recently observed a case of MPTE of exceptional interest as the patient was under aggressive anticoagulant treatment and developed fulminant pulmonary hypertension with fatal right heart failure.

The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%). Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of -1.20 +/- 0.32 Deltalog(10) CFU/ml (.) h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of -0.97 +/- 0.32 Deltalog(10) CFU/ml (.) h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF). For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h. In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC.

Armin Stucki, Thomas Stoll, Alarcos Cieza, Martin Weigl, Anna Giardini, Daniel Wever, Nenad Kostanjsek and Gerold Stucki From the Department of Internal Medicine, University Hospital Bern, Switzerland, AarReha Schinznach, Schinznach-Bad, Switzerland, ICF Research Branch, WHO FIC Collaborating Center (DIMDI), IMBK, Ludwig-Maximilians-University, Munich, Germany, Psychology Unit, Fondazione S. Maugeri, Clinica del Lavoro e della Riabilitazione, IRCCS, Istituto Scientifico di Montescano (PV), Italy, Rehab Center Rössingh Enschede, Enschede, The Netherlands, Classification, Assessment, Surveys and Terminology Team, World Health Organization, Geneva, Switzerland and Department of Physical Medicine and Rehabilitation, Ludwig-Maximilians-University, Munich, Germany