Efficacy and safety of nasal high-flow oxygen in COPD patients.

BACKGROUND: 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. METHODS: A single cohort of 77 clinically stable hypoxemic patients with an indication for long-term oxygen treatment (LTOT) with or without hypercapnia successively received COT and HFOT for 60 min each, including oxygen adaption and separated by a 30 min washout phase. RESULTS: HFOT was well-tolerated in all patients. A significant decrease in PaCO2 was observed during oxygen adaption of HFOT, and increased PaO2 coincided with significantly increased SpO2 and decreased AaDO2 during both treatment phases. Even at a flow rate of 15 L/min, oxygen requirement delivered as air mixture by HFOT tended to be lower than that of COT (2.2 L/min). Not only was no increase in static or dynamic lung volumes observed during HFOT, but even was a significant reduction of residual lung volume measured in 36 patients (28%). CONCLUSIONS: Thus, short-term use of HFOT is safe in both normocapnic and hypercapnic COPD patients. Lower oxygen levels were effective in correcting hypoxemic respiratory failure and reducing hypercapnia, leading to a reduced amount of oxygen consumption. Long-term studies are needed to assess safety, tolerability, and clinical efficacy of HFOT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01686893 13.09.2012 retrospectively registered (STIT-1) and NCT01693146 14.09.2012 retrospectively registered (STIT-2). Studies were approved by the local ethics committee (Ethikkommission der Medizinischen Universität Innsbruck, Studienkennzahl UN3547, Sitzungsnummer 274/4.19).

Efficacy of doripenem against Escherichia coli and Klebsiella pneumoniae in experimental meningitis.

OBJECTIVES: In 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. METHODS: The rabbit meningitis model was used in this study and the penetration of doripenem through uninflamed and inflamed meninges was determined. RESULTS: Doripenem, 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. CONCLUSIONS: Doripenem is a potential monotherapy for the treatment of meningitis due to Gram-negative microorganisms.

[An Unusual Hemisphere Syndrome]. / Ein nicht alltägliches Hemisyndrom.

An Unusual Hemisphere Syndrome Abstract. A patient with known hereditary hemorrhagic telangiectasia presents with transient right arm weakness and dizziness. A transient ischemic attack is diagnosed on clinical and risk factors. In the course of the disease, the patient suffers a convulsive event and fever occurs twice without a clear focus on the infection. The initial skull MRI shows a centroparietal lesion on the left with signs of accompanying edema. Due to this unusual concomitant edema, a neoplastic event must also be considered for differential diagnosis. However, the further examinations show no evidence of neoplasia, but the course MRI of the skull shows the image of septic embolisms with a brain abscess. After neurosurgical remediation and appropriate antibiotic treatment, the clinical course is pleasing. The cause of the septic embolisms was a pulmonary arteriovenous malformation due to hereditary hemorrhagic telangiectasia, which could be coiled without complications.

Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model.

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.

Content comparison of health-related quality of life instruments for obstructive sleep apnea.

BACKGROUND AND PURPOSE: Due to the increasing importance of quality of life assessments in obstructive sleep apnea (OSA) patients and due to an 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 (HRQOL) instruments and the ICF. The purpose of this study was to compare the content covered by OSA-specific instruments using the ICF. PATIENTS AND METHODS: OSA-specific instruments were identified, including the Calgary Sleep Apnea Quality of Life Index, the Functional Outcomes of Sleep Questionnaire, the Obstructive Sleep Apnea Patient-Oriented Severity Index, and the Quebec Sleep Questionnaire, and linked to the ICF by six health professionals according to standardized guidelines. The degree of agreement between health professionals was calculated by means of the kappa statistic. RESULTS: A total of 308 concepts were identified and linked to 78 different ICF categories; 35 categories of the component body function, one category of the component body structure, 38 categories of the component activities and participation, and four categories of the component environmental factors. Only contents within the chapters mental functions, mobility and social life were addressed by all instruments. Forty-seven categories were covered by only one instrument. CONCLUSION: The ICF proved highly useful for the comparison of HRQOL instruments. This analysis may help researchers and clinicians to choose the most appropriate HRQOL instrument for a specific purpose as well as help to compare study outcomes of studies using different instruments for HRQOL assessment.

Long-term oxygen therapy in COPD patients: population-based cohort study on mortality.

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.

The effect of nutritional management on the mood of malnourished patients.

BACKGROUND & AIMS: Starvation and weight loss 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 sleep 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.

Content comparison of health-related quality of life instruments for COPD.

BACKGROUND: Due 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. OBJECTIVE: The 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. RESULTS: Eleven 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. CONCLUSIONS: This 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.

Testing strategies and follow-up for coeliac disease in a general internal medicine outpatient department from 2000 to 2005.

PRINCIPLES: Coeliac 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. METHODS: Testing 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. RESULTS: A 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. CONCLUSIONS: This 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..

A rare cause of fatal right heart failure.

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.

Identifying the concepts contained in outcome measures of clinical trials on four internal disorders using the International Classification of Functioning, Disability and Health as a reference.

OBJECTIVES: To systematically identify and compare the concepts contained in outcome measures of clinical trials on chronic ischaemic heart disease, diabetes mellitus, obesity, and obstructive pulmonary disease, including asthma using the International Classification of Functioning, Disability and Health (ICF) as a reference. METHODS: Randomized controlled trials between 1993 and 2003 were located in MEDLINE and selected according predefined criteria. The outcome measures were extracted and the concepts contained in the outcome measures were linked to the ICF. RESULTS: 166 trials on chronic ischaemic heart disease, 227 trials on diabetes mellitus, 428 trials on obesity, and 253 trials on obstructive pulmonary disease were included. Ten different health status questionnaires (fulfilling the inclusion criteria) were extracted in chronic ischaemic heart disease, 19 in diabetes mellitus, 47 in obesity, and 39 in obstructive pulmonary disease. Across conditions at least 75% (range 75-92%) of the extracted concepts could be linked to the ICF. In diabetes mellitus and obesity the most used ICF categories were general metabolic functions (b540), in obstructive pulmonary disease respiration functions (b440) and in chronic ischaemic heart disease heart functions (b410). CONCLUSION: In all 4 health conditions the majority of studies were drug trials focusing on clinically relevant parameters and not on functioning. The ICF provides a useful reference to identify and quantify the concepts contained in outcome assessment used in clinical trials.

ICF Core Sets for obstructive pulmonary diseases.

OBJECTIVE: To report on the results of the consensus process integrating evidence from preliminary studies to develop the first version of the Comprehensive ICF Core Set and a Brief ICF Core Set for obstructive pulmonary diseases. METHODS: A formal decision-making and consensus process integrating evidence gathered from preliminary studies was followed. Preliminary studies included a Delphi exercise, a systematic review and an empirical data collection. After training in the ICF and based on these preliminary studies relevant ICF categories were identified in a formal consensus process by international experts from different backgrounds. RESULTS: The preliminary studies identified a set of 287 ICF categories at the second, third and fourth ICF levels with 97 categories on body functions, 33 on body structures, 104 on activities and participation, and 53 on environmental factors. Seventeen experts from 8 different countries attended the consensus conference on obstructive pulmonary diseases. Altogether 67 second-level and 4 third-level categories were included in the Comprehensive ICF Core Set with 19 categories from the component "body functions", 5 from "body structures", 24 from "activities and participation" and 23 from "environmental factors". The Brief ICF Core Set included a total of 17 second-level categories with 5 on "body functions", 3 on "body structures", 5 on "activities and participation" and 4 on "environmental factors". CONCLUSION: A formal consensus process integrating evidence and expert opinion based on the ICF framework and classification led to the definition of ICF Core Sets for obstructive pulmonary diseases. Both the Comprehensive ICF Core Set and the Brief ICF Core Set were defined.

ICF Core Sets for chronic ischaemic heart disease.

OBJECTIVE: To report on the results of the consensus process integrating evidence from preliminary studies to develop the first version of a Comprehensive ICF Core Set, and a Brief ICF Core Set for chronic ischaemic heart disease. METHODS: A formal decision-making and consensus process integrating evidence gathered from preliminary studies was followed. Preliminary studies included a Delphi exercise, a systematic review and an empirical data collection. After training in the ICF and based on these preliminary studies relevant ICF categories were identified in a formal consensus process by international experts from different backgrounds. RESULTS: The preliminary studies identified a set of 253 ICF categories at the second, third and fourth ICF levels with 89 categories on body functions, 25 on body structures, 82 on activities and participation and 57 on environmental factors. Sixteen experts attended the consensus conference on CIHD (11 physicians with various sub-specializations and 3 physical therapists). Altogether 61 second-level categories were included in the Comprehensive ICF Core Set with 14 categories from the component body functions, one from body structures, 17 from activities and participation and 29 from environmental factors. The Brief ICF Core Set included a total of 36 second-level categories with 10 on body functions, one on body structures, 13 on activities and participation and 12 on environmental factors. CONCLUSION: A formal consensus process integrating evidence and expert opinion based on the ICF framework and classification led to the definition of ICF Core Sets for CIHD. Both the Comprehensive ICF Core Set and the Brief ICF Core Set were defined.

ICF Core Sets for obesity.

OBJECTIVE: To report on the results of the consensus process integrating evidence from preliminary studies to develop the first version of the Comprehensive ICF Core Set and the Brief ICF Core Set for obesity. METHODS: A formal decision-making and consensus process integrating evidence gathered from preliminary studies was followed. Preliminary studies included a Delphi exercise, a systematic review and an empirical data collection. After training in the ICF and based on these preliminary studies relevant ICF categories were identified in a formal consensus process by international experts from different backgrounds. RESULTS: The preliminary studies identified a set of 219 ICF categories at the second, third and fourth ICF levels with 87 categories on body functions, 34 on body structures, 53 on activities and participation and 45 on environmental factors. Twenty-one experts attended the consensus conference on obesity (18 physicians with various sub-specializations and 3 physical therapists). Altogether 109 categories (108 second-level and one third-level categories) were included in the Comprehensive ICF Core Set with 30 categories from the component body functions, 18 from body structures, 28 from activities and participation and 33 from environmental factors. The Brief ICF Core Set included a total of 9 second-level categories with 3 on body functions, 4 on activities and participation and 2 on environmental factors. No body-structures categories were included in the Brief ICF Core Set. CONCLUSION: A formal consensus process integrating evidence and expert opinion based on the ICF framework and classification led to the definition of ICF Core Sets for obesity. Both the Comprehensive ICF Core Set and the Brief ICF Core Set were defined.

[Pulmonary rehabilitation - a modern and patient-centred treatment approach in COPD]. / Pulmonale Rehabilitation - Ein moderner und patientenorientierter Therapieansatz in der COPD.

Physical exercise is highly effective to improve exercise capacity and quality of life of patients with COPD and to reduce the risk for hospital admissions in patients with exacerbations.The combination of physical exercise,patient education and pharmacotherapy,as typically performed during pulmonary rehabilitation, has become the modern disease management for COPD patients. Unfortunately, there is still a lack of evidence on effective treatments to increase levels of physical activity. But there are currently major research efforts to evaluate drug and non-drug treatments for increasing levels of physical activity. This raises hopes that effective treatments could,through an increase in physical activity,reduce the risk for hospital admissions and early death in COPD patients.

Content Validity of the Comprehensive ICF Core Set for Chronic Obstructive Pulmonary Diseases: An International Delphi Survey.

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.

Content comparison of 115 health status measures in sleep medicine using the International Classification of Functioning, Disability and Health (ICF) as a reference.

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.

Part 1. International Classification of Functioning, Disability and Health (ICF) Core Sets for persons with sleep disorders: results of the consensus process integrating evidence from preparatory studies.

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.

Unexpected metastatic pheochromocytoma - an unusual presentation.

The classic triad of pheochromocytoma consists of episodic headache, sweating, and tachycardia. General clinicians should be aware, however, that this rare entity might present with a wide spectrum of clinical symptoms. We recently observed a noteworthy case of malignant pheochromocytoma where there was a lack of specific symptoms despite an advanced tumor stage. Malignancy is an important cause of mortality. Reliable diagnosis of malignancy depends upon evidence of local invasion, distant metastases, or recurrence. As in our case, new scintigraphic methods, such as 111-In-pentetreotide scintigraphy (Octreoscan), may occasionally reveal 123-I-metaiodobenzylguanidine-negative distant metastases and help to establish an early diagnosis of malignancy. Tumor size, and perhaps even biochemical profile, may be factors increasing the likelihood of a malignant process and may contribute to early identification of patients at risk.