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Access to large, annotated samples represents a considerable challenge for training accurate deep-learning models in medical imaging. Although at present transfer learning from pre-trained models can help with cases lacking data, this limits design choices and generally results in the use of unnecessarily large models. Here we propose a self-supervised training scheme for obtaining high-quality, pre-trained networks from unlabelled, cross-modal medical imaging data, which will allow the creation of accurate and efficient models. We demonstrate the utility of the scheme by accurately predicting retinal thickness measurements based on optical coherence tomography from simple infrared fundus images. Subsequently, learned representations outperformed advanced classifiers on a separate diabetic retinopathy classification task in a scenario of scarce training data. Our cross-modal, three-stage scheme effectively replaced 26,343 diabetic retinopathy annotations with 1,009 semantic segmentations on optical coherence tomography and reached the same classification accuracy using only 25% of fundus images, without any drawbacks, since optical coherence tomography is not required for predictions. We expect this concept to apply to other multimodal clinical imaging, health records and genomics data, and to corresponding sample-starved learning problems. The thickness of the retina is an important medical indicator for diabetic retinopathy. Holmberg and colleagues present a self-supervised deep-learning method that uses cross-modal data to predict retinal thickness maps from easily obtainable fundus images.

In Deutschland sind die Kosten im Gesundheitswesen gedeckelt, d. h. Mehrausgaben in einem Bereich fuhren zu Defiziten in anderen Bereichen. Deswegen ist es sinnvoll, in der arztlichen Arbeit kluge Entscheidungen zu treffen. Dazu gehoren auch wirtschaftliche Uberlegungen. Diese verbessern nicht nur die Gesundheitsversorgung als Ganzes, sondern fuhren auch dazu, dass eigene Ressourcen fur andere Tatigkeiten frei werden. In der Medizin allgemein sowie in der Pneumologie gibt es viele Bereiche, in denen eine Uber- und Fehlversorgung vorliegen. Eine Reduktion unnotiger Diagnostik und Therapie hilft auch dem Patienten, da sich Komplikationen durch ggf. riskante Folgeuntersuchungen und Nebenwirkungen vermeiden lassen.Die Uberversorgung wird begunstigt durch die oft unzulassige Verallgemeinerung (Induktion) von randomisierten kontrollierten Studien (RCT) in Leitlinien, deren Resultate an sich nur fur den eingeschlossenen Patientenkreis gelten. Dieser unterscheidet sich haufig von der klinischen Realitat. Viel zu selten werden Auslassversuche bei Medikamenten durchgefuhrt („n-of-1 trial“). In dem Artikel werden Beispiele fur die Therapieoptimierung des Asthma bronchiale, der COPD, der Intensivmedizin und des Lungenkarzinoms genannt.

Die nicht-invasive Beatmung (NIV) ist in der klinischen Medizin weit verbreitet und hat mittlerweile einen hohen Stellenwert im klinischen Alltag erlangt. Der Einsatz der NIV reduziert die Intensiv- und Krankenhausaufenthaltsdauer sowie die Mortalitat von Patienten mit akutem hyperkapnischen Atemversagen. Patienten mit akuter respiratorischer Insuffizienz im Rahmen eines Lungenodems sollten neben den notwendigen kardiologischen Interventionen mit CPAP oder NIV behandelt werden. Bei anderen Formen des akuten hypoxamischen Atemversagens wird empfohlen, den Einsatz der NIV auf lediglich mildes ARDS zu begrenzen, da eine NIV bei schweren Formen mit hoheren Raten von Therapieversagen und Mortalitat assoziiert ist. Im Weaning von invasiver Beatmung reduziert die NIV die Reintubationsraten im Wesentlichen bei hyperkapnischen Patienten. Eine verzogerte Intubation bei Auftreten eines NIV-Versagens fuhrt zu einem Anstieg der Mortalitat und sollte deshalb vermieden werden. Bei entsprechendem Monitoring auf der Intensivstation kann die NIV auch bei padiatrischen Patienten mit akuter respiratorischer Insuffizienz erfolgreich eingesetzt werden. Weiterhin kann im Rahmen der Palliativmedizin die NIV hilfreich bei der Reduktion von Dyspnoe und Verbesserung von Lebensqualitat sein. Ziel des Updates dieser Leitlinie ist es, unter Berucksichtigung der zunehmenden aktuellen wissenschaftlichen Evidenz, sowohl die Vorteile als auch die Limitationen der NIV in der Behandlung der akuten respiratorischen Insuffizienz in der taglichen klinischen Praxis und bei verschiedenen Indikationen aufzuzeigen.

Aim Choking in children is a feared condition, which potentially can deteriorate to hypoxic cardiac arrest and death. Fast recognition and immediate initiation of basic life support (BLS)1, primary back blows and abdominal thrusts given by bystanders and secondary activation of the Emergency Medical System (EMS) are vital for the survival. Methods The Region of Southern Denmark has a tiered response with prehospital emergency physicians to supplement the ambulance service. EMS physicians register all contacts in a database. We reviewed the database for all children below the age of 5 years who suffered from choking in 2009 to 2014. Results From 70.289 total contacts 4.857 contacts was with children less than 5 years. In this group 98 children suffered from choking. In 78% BLS had resolved the obstructing foreign body before arrival of EMS services. Seventeen children had successful treatment with BLS by ambulance personal. Five children required advanced airway management and one child required cardiopulmonary resuscitation. No deaths were registered. None of the children with near fatal choking had any comorbidity prior to incident. Conclusion Choking in children is an uncommon emergency with only 0,14% of all contacts. We found like others2 that BLS solves most cases before arrival of EMS. This demonstrates the importance of immediate initiation of BLS and keeping the chain of survival as a concept. Death to choking is rare among small children. Near fatal choking resolves with skills and routine in advanced airway management and advanced life support. References Maconochie IK, Bingham R, Eich C, Lopez-Herce J4, Rodriguez-Nunez A, Rajka T, Van de Voorde P, Zideman DA, Biarent D: European Resuscitation Council Guidelines for Resuscitation 2015: Section 6. Paediatric life support. Resuscitation. 2015Oct;95:223–48. Vilke GM, Smith AM, Ray LU, Steen PJ, Murrin PA, Chan TC: Airway obstruction in children aged less than 5 years: the prehospital experience. Prehosp Emerg Care2004, 8:196–199. Conflict of interest None declared. Funding None declared.

Summary Body plethysmography allows to assess functional residual capacity ( FRC pleth ) and specific airway resistance ( sRaw ) as primary measures. In combination with deep expirations and inspirations, total lung capacity (TLC) and residual volume (RV) can be determined. Airway resistance ( Raw ) is calculated as the ratio of sRaw to FRC pleth . Raw is a measure of airway obstruction and indicates the alveolar pressure needed to establish a flow rate of 1 L s −1 . In contrast, sRaw can be interpreted as the work to be performed by volume displacement to establish this flow rate. These measures represent different functional aspects and should both be considered. The measurement relies on the fact that generation of airflow needs generation of pressure. Pressure generation means that a mass of air is compressed or decompressed relative to its equilibrium volume. This difference is called "shift volume". As the body box is sealed and has rigid walls, its free volume experiences the same, mirror image-like shift volume as the lung. This shift volume can be measured via the variation of box pressure. The relationship between shift volume and alveolar pressure is assessed in a shutter maneuver, by identifying mouth and alveolar pressure under zero-flow conditions. These variables are combined to obtain FRC pleth , sRaw and Raw . This presentation aims at providing the reader with a thorough and precise but non-technical understanding of the working principle of body plethysmography. It also aims at showing that this method yields significant additional information compared to spirometry and even bears a potential for further development.

The rising prevalence of type 2 diabetes is having an impact on limited medical and economic resources making increased efficiency and effectiveness of medical care and preventative strategies imperative. Quality management indicators that are fit for purpose will permit improvements and shortcomings to be identified in the strategies being employed and may provide information on how to better achieve objectives. This article considers two approaches to how indicators, which were developed by the Implementation of A European Guideline and training standards for diabetes prevention project, can be used in clinically applicable quality management, including benchmarking, in order to compare the quality of work among prevention managers and to develop an overall benchmark for preventive intervention. Br J Diabetes Vasc Dis 2011;11:217-222

Executive SummaryWhen we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: Prevention is Better Than Cure.Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20–79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe.The Good News is That Diabetes is Preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society.A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play.Small Changes in Lifestyle Will Bring Big Changes in Health.Through Joint Efforts, More People Will be Reached.The Time to Act is Now. When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now.

Die Vielfalt der Beatmungsgerate und der Beatmungsmodi ist nahezu unuberschaubar geworden. Versuche zur Nomenklatur und Systematik blieben unvollstandig. Die hauptsachlichen Beatmungsformen bleiben die Beatmung mit Volumen- oder Druckvorgabe, wobei die Druckvorgabe die Volumenvorgabe abgelost hat, und sich beide in sog. Hybridmodi erganzen. Selbstlernende, kontrollierte Beatmungsmodi erweitern das Feld von assistierter, assistiert-kontrollierter und kontrollierter Beatmung. Die Auswahl des geeigneten Beatmungssystems und die optimale Einstellung erfordern ein grundlegendes Verstandnis der jeweils vorliegenden Erkrankung. Je nach Erkrankung bedarf es unterschiedlicher Einstellungen von Beatmungsmodus und Beatmungsparametern. Die individuelle Einstellung der Druckaufbau- und -abbaugeschwindigkeit kann die Effizienz und Akzeptanz fordern. Die Auswahl des Zubehors (Schlauch, Maske) inklusive einer optimalen Atemgasklimatisierung hat ebenfalls Einfluss auf die Beatmungsqualitat.

Die praktische Umsetzung einer wirksamen Pravention des Diabetes mellitus Typ 2 stellt fur das Gesundheitswesen der Bundesrepublik Deutschland eine zentrale Herausforderung dar. Die Evidenz fur die Effektivitat und Effizienz der Diabetespravention ist sehr hoch. Verschiedene gesundheitsokonomische und gesundheitspolitische Untersuchungen sehen in einer erfolgreichen Pravention des Diabetes die einzige Moglichkeit, die Gesundheit der Bevolkerung und die Finanzierung des Gesundheitswesens nachhaltig zu sichern. Die Evidenz in der Diabetespravention stammt vorwiegend aus klinisch kontrollierten Studien. Die Herausforderung, die sich stellt, besteht im Transfer des in den Studien betriebenen Aufwands in den konkreten klinischen Alltag und in der adaquaten strukturellen und inhaltlichen Implementierung dieser Masnahmen mit vergleichbaren Ergebnissen. Dazu ist das Verstandnis der pathophysiologischen Prozesse der Diabetesentstehung, aber auch der pathophysiologischen Grundlagen praventiver Prozesse entscheidend. Gleichzeitig sind regionale und nationale strukturelle Aspekte in der Gesundheitsversorgung und gesundheitsokonomische Gegebenheiten entscheidende Rahmenbedingungen fur die Implementierung eines neuartigen Praventionsprogramms. Eine effiziente und effektive Pravention des Diabetes mellitus Typ 2 ist realisierbar. Das fachliche „Know-how“ und die Basis fur eine Vernetzung der unterschiedlichen Akteure zur Pravention des Diabetes mellitus Typ 2 und des metabolischen Syndroms sind in Deutschland vorhanden. Eine flachendeckende und im Ergebnis erfolgreiche Pravention stellt ein realistisches Ziel dar und die Voraussetzungen in Deutschland und auch der Europaischen Union sind ausgesprochen gut.

BACKGROUND AND OBJECTIVE In severe "pink puffer" emphysema the patients' physical capacity is limited by dyspnoea despite maximal application of established treatment. This pilot study investigated the effect of retarded morphine, taken orally for 10 days, on ventilation, dyspnoea, walking capacity and wakefulness. PATIENTS AND METHODS Twenty clinically stable patients (11 men, 9 women, mean age 68.5 [50-81] years) with "pink puffer" emphysema were studied over a period of 10 days in a prospective, non-controlled trial of cross-over design. Criteria for inclusion in the study were: 1-second forced expiratory volume (FEV1) < 1 I, vital capacity < 50% and normocapnia. In addition to their existing therapy patients received either no further therapy or retarded morphine. Morphine dosage was increased to maximally 3 x 30 mg daily, depending on effectiveness and side effects, dyspnoea at rest and immediately after a 6-min walk (assessed with Borg's visual analog scale), maximal walking capacity were determined, as well as blood gases, respiratory minute volume and the respiratory drive (airway occlusion pressure [P0.1]), responsiveness of the respiratory pathways to CO2 and wakefulness (concentration, fatigue, interest in surroundings). RESULTS Twelve patients completed the study (group A). In the remaining patients (group B) the test had to be stopped prematurely because of undesirable side effects or an exacerbation of the underlying infection. In group A, morphine (mean dosage: 49.2 +/- 28.4 mg/d) caused a reduction of PaO2, dyspnoea on activity, the resting minute respiratory volume, respiratory drive and CO2 response, and an increase in PaCO2, HCO3- and the 6-min walking distance. Morphine did not produce a change in subjectively evaluated vigilance and the blood pH. CONCLUSION After strict patient selection oral morphine produced a reduction of exercise dyspnoea and an increase in walking capacity in half of the patients with severe pulmonary emphysema. There also occurred a slight rise in PaCO2 without any relevant respiratory acidosis or significant decrease in wakefulness.

Of 129 patients with an acute lumbar root compression syndrome due to disc herniation 21, who were symptom-free, were examined by computed tomography (CT) on average 276 days after a three-step regimen of conservative treatment. In no instance had there been a deterioration of the original findings. In 14 patients the CT picture continued to demonstrate disc herniation, although the patients were without symptoms. In two patients a moderate, in five a marked regression of herniation was demonstrated by CT. Clinical improvement without change in the CT picture points to the compression syndrome not being explainable solely in mechanical terms. As a matter of fact, a possible cause may be a disturbance of radicular blood supply resulting in oedematous root swelling which is usually masked in the CT by prolapsed disc tissue. There is as yet no easy explanation for regression in case of prolapsed, perhaps even sequestered, disc tissue. It is possible that there have been reparative processes, such as have been described histopathologically in form of ingrown vessels. More plausibly would be a separation of the herniated and/or sequestered disc tissue in form of an asymptomatic sliding into the terminal caudal region.

Cough clears off foreign bodies from the airways and maintains bronchial clearance when mucociliary transport is defective. Cough requires intact inspiratory muscles to inflate the lung up to 80 % of vital capacity and sound expiratory muscles to generate pressure against a closed glottis. Two mechanisms are required to facilitate proximal mucus transport: 1. Constriction of the cartilage containing airways caused by anterior bulging of the pars membranacea due to high air-flow velocity. 2. Thixotropia of the sputum. This feature changes mechanical properties in a way that sputum viscosity decreases with motion. Thixotropia is caused by the complex mucin-structure of the mucus.

Invasiveness of interventions, complexity of diseases and patients' age are increasing in intensive care medicine. Ethical and legal issues are particularly challenging at the end of life of critically ill patients. At the borderline between intensive care and palliative medicine a significant amount of patients suffer from respiratory failure. Modern modes of mechanical ventilation may be able to improve ventilation and quality of life. On the other hand they may oppose a dignified death at the end of a long lasting chronic disease and e. g. prolong the suffering. In contrast to endotracheal intubation and invasive mechanical ventilation NIV enables patients to participate in the decision making process. While under normal circumstances, ethical standards dictate that patients themselves participate in the medical decision making process. For several reasons this is not always possible in intensive care medicine. However, chronically ill patients should get information from experts already at an early stage of the disease, go through a shared decision process and declare their will concerning interventions of intensive care medicine, e. g. mechanical ventilation. With respect to ethical and legal aspects of end of life this paper deals with chances of mechanical ventilation, including its withdrawal and withholding.

Mechanical ventilation is required if ventilatory insufficiency is present. This is typically indicated by hypercapnea. Hypoxemia occurs secondary to hypoventilation. Usually overload of the respiratory muscles (ventilatory pump) will be the underlying mechanism, for the most part caused by acute or chronic disease. In case of sole hypoxemia mechanical ventilation will only be indicated if the oxygen-content (equals oxygen saturation x haemoglobin x 1.39) drops below a critical threshold or if ventilatory pump failure is imminent on account of the underlying disease (eg. pneumonia). The background of our recommendations is to avoid potential damage caused by mechanical ventilation. Especially high inspiratory pressures and oxygen concentrations can be harmful to the lung. Therefore every case has to evaluated for individual target parameters of ventilation. The use of the oxygen-content instead of the arterial oxygen pressure as the target parameter will usually lead to a more careful ventilation. Cardiogenic pulmonary oedema is an exception to this rule since inspiratory positive pressure and PEEP will result in improved diffusion as well as reduction of preload and work of breathing. In recent years progress has been made on the field of ventilation access especially in severe and acute cases. Non-invasive ventilation is superior to invasive ventilation in patients with exacerbated COPD since it improves outcome effectively. This is being caused by a decline in ventilator associated pneumonias, most likely because non-invasive ventilation allows patients to clear their secretions by coughing, resulting in improved lung clearance. Controlled ventilation allows optimal unloading of the respiratory muscles which have been overloaded by the underlying disease. Application of a controlled ventilation mode in acute disease will usually require some kind of sedation. Assisted ventilation will result in improved gas exchange but only incomplete unloading of respiratory muscles and therefore delayed restitution. Permanent controlled ventilation under sedation for a prolonged period (days) requires intermittent periods of assisted- or spontaneous breathing in order to avoid atrophy of the respiratory muscles. This review summarizes background information on the nature of the derangement, the relation between oxygen supply and consumption under special consideration of respiratory muscle insufficiency and impact of different ventilation modes.

Developing more effective and convenient inhalation devices for the treatment of obstructive pulmonary diseases is at least as important as designing new drugs. In recent years, existing inhalation systems have undergone many technical modifications and there have also been many new developments. All of these systems have their own particular attributes and characteristics. Two fundamentally different modes of operation are represented by propellant-driven metered-dose inhalers (pMDI) on the one hand and dry powder inhalers (DPI) on the other. However, none of the systems developed so far can be considered ideal. The Respimat Soft Inhaler (Respimat SI) was developed in the light of experience with previous systems and was launched in Germany at the beginning of 2004. The aim in developing this new type of inhaler was to avoid the well-known drawbacks typically associated with pMDI and DPI. The Respimat SI requires neither a chemical propellant nor batteries. The active ingredients are dissolved in water and the solution is atomised using mechanical energy only imparted by a spring which, when released, provides the power to force the solution through an extremely fine nozzle system. Two fine jets of liquid are produced. They converge at an optimised angle and the resulting impact generates a fine mist which is slow-moving and lasts for about 1.5 seconds; moreover, a high proportion of the droplets fall into the fine particle fraction. All of these features allow excellent lung deposition and reduced oropharyngeal deposition. Coordination between actuation and inhalation is less critical as compared with pMDI due to the fact that the mist is both slow-moving and long-lasting. A further advantage is that the mist is generated independently of the patient's inspiratory flow. The Respimat SI meets the requirements for an ideal inhaler better than any other previous device and must therefore be regarded as a significant new development.

Background: Auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) may be central to the pathogenesis of adult sporadic pulmonary alveolar proteinosis (PAP). The role of anti-GM-CSF auto-antibodies in paediatric forms of PAP is as yet unclear. Methods: Anti-GM-CSF auto-antibodies were determined with the help of an antigen capture assay using serum and/or bronchoalveolar lavage (BAL) fluid from 27 patients with PAP (nine adults, 15 children, three neonates) and from 185 children with different diseases as disease controls (various pulmonary conditions and patients with malignancies). Results: Anti-GM-CSF auto-antibodies were detected in the serum of five of seven adult PAP patients. They were not found in the serum of any of the children or neonates with PAP nor in any of the disease control patients. Raised anti-GM-CSF titres were found in BAL fluid from three of four adult patients with PAP. Anti-GM-CSF auto-antibodies were detected in BAL fluid of only one of the 15 children (age at diagnosis 11 years, age at BAL 24 years) and in none of the neonates with PAP, nor in any of the disease control patients. Conclusions: The presence of anti-GM-CSF auto-antibodies seems to define an autoimmune disease underlying most of the adult sporadic type of PAP, but age at diagnosis may cause an overlap with children in some rare instances. In most of the children and all of the neonates the anti-GM-CSF titres were not significantly increased, indicating that alternative explanations are needed for the pathogenesis of the disease in these patients.

One of the main requirements of the current animal welfare legislation in Europe is to prove the necessity of performing a given experiment with animals. Thus, a study using animals should not proceed, if another scientifically reliable method is available to obtain the desired results that either avoids animal experiments altogether, minimises pain and suffering of animals or reduces the number of animals needed. Scientists are legally required to search the literature and other relevant sources for alternatives prior to any experimental study with animals. Access to information has become much easier since the introduction of the Internet as a standard tool. Today, a variety of online sources is available, e.g. web-based bibliographic databases and specialised web sites providing details about alternatives to animal studies. However, scientists still need to determine the most appropriate searching strategies, depending on the objectives of the relevant web sites and their own line of research. A critical discussion of this issue takes into account the objectives of both the information providers and the information retrieval systems.

Background: Leukotrienes are potent bronchoconstrictive and proinflammatory mediators in bronchial asthma. In a previous study on 16 subjects with bronchial asthma (two randomized groups) we showed that montelukast (10 mgdaily) significantly suppressed allergen provocation with specific allergens (mites and pollen) (p = 0.0005). In a follow-up study we addressed the question as to when montelukast should be discontinued in order to avoid a relevant effect on inhalational bronchial allergen provocation. Method: At the end of the first study montelukast (10 mg daily) was given again to both groups (2 × 8 asthma patients) for 21 days. After a montelukast-free period of one and three days allergen provocation was repeated in the same manner and the results were compared with the historic baseline values without montelukast. Results: The provocation dose for allergens was reduced by 39% after a montelukast-free period of one day and by 67% after three days. Only after three days was the difference significant (p=0.017), at which time the control value was nearly reached again. Conclusion: We recommend that montelukast be discontinued at least three days prior to inhalational allergen provocation.

ZusammenfassungDurch zahlreiche Studien ist belegt, dass inhalative, langwirksame Beta-2-Mimetika (LABA) und Anticholinergika (LAMA) sowie Steroide (ICS) die Exazerbationsrate bei COPD signifikant reduzieren. Allerdings konnte auch in aufwendigen und länger dauernden Studien nicht gezeigt werden, dass diese Reduktion der Exazerbation auch die Lebenserwartung reduziert. Im Gegensatz dazu zeigen zahlreiche Studien, dass die Lebenserwartung mit zunehmender Schwere und Häufigkeit der Exazerbation vermindert wird.In dieser Übersicht werden diese Studien gegenübergestellt und die Relevanz der Reduktion der Exazerbationsraten durch LABA, LAMA und ICS durch Bewertung ihrer Effektstärke mittels Cohen’s d bewertet. Dabei zeigt sich in den Studien ein gleiches Muster. Die Reduktion der Exazerbationsrate zeigt nur bei den geringen Schweregraden einen kleinen Effekt (Cohen’s d max. 0,21). Bei Exazerbation mit höherem Schweregrad und bei Vergleich der Substanzen untereinander fällt Cohen’s d unter 0,1, was zeigt, dass die Wirkung der Medikamente klinisch praktisch bedeutungslos ist. Die Wirkung von LABA, LAMA und ICS auf die Exazerbationsrate bei COPD ist deutlich überschätzt.

Backgmund: Leukotrienes are potent bronchoconstrictive and proinflammatory mediators in bronchial asthma. A randomized, cross-over study on 16 subjects assigned to two groups investigated whether premedication with the leukotriene antagonist montelukast (10 mg daily for 21 days) has a relevant effect on inhalational bronchial allergen provocation. Method: Allergens were inhaled by atomizing commercial provocation solutions in dilutions of 1 : 1000, 1 : 100, 1 : 50, 1 : 10 and 1 : 5 with a nebulizer (Pari). The allergen dose was escalated every 20 minutes until the positive criteria (20% fall in FEV1, doubling of oscillatory resistance) were met. The provocation tests were performed on days 1, 21 and 42 of the study. Results: An allergen protective effect of variable magnitude (PD20 increased by a factor of 1.6 to 21) was observed in 12 of the 16 subjects following provocation with pollen and mite allergens. The mean for all 16 patients showed a highly significant increase (p = 0.0005) by a factor of 4.3. The extent of allergen protection cannot be predicted in individual cases and is independent of the chosen allergen and the PD20 without montelukast. However, a significant correlation (p = 0.0016) was found between unspecific bronchial hyperreactivity (histamine) and the PD20. The allergen protective effect of montelukast decreases with increasing unspecific hyperreactivity. Conclusion: We recommend that medication with montelukast be discontinued before allergen provocation because it cannot be predicted in individual cases whether and to what extent montelukast suppresses the immediate reaction following inhalational bronchial allergen provocation.

Extreme mountain climbers and patients with stable but severe ventilatory insufficiency (e.g. obesitas hypoventilation-syndrome, scoliosis) sometimes experience a state of severe hypoxemia without any or only mild subjective disturbances. Organ failure is never observed in these periods. On the other hand there are two well documented studies concerning long term oxygen therapy (LTOT) that have shown in hypoxemic COPD-patients (pO 2 lower then 55 mm Hg) a doubling the life expectancy under oxygen. This contradiction can be elucidated if the influence of oxygen on the ventilation is taken into account. These study patients treated with LTOT all had more or less hypercapnia (hypoventilation) due to an overload of their respiratory pump. Oxygen reduces the ventilation (seen as hypercapnia) which leads to an unloading of the respiratory muscles. Later studies to LTOT found a positive correlation between the extent of stable hypercapnia and life expectancy. In this article the physiopathologic background of this findings are discussed. The main parameter of the regulator for the oxygen transport is not pO 2 but the oxygen content. The oxygen content multiplied by cardiac output determines the extent of oxygen delivery. Many regulatory systems (e.g. polyglobuly or expression of oxygen resistant isoenzymes of the respiratory chain) are involved to compensate the hypoxemia associated with hypoventilation which prevents an organ threatening hypoxia. This pathophysiologic finding has important impact on intensive care medicine, which usually takes only pO 2 into account for therapeutic decisions (e. g. high FiO 2 and high pressure support). This sometimes leads to "overtreatment", with possible harm to the patient.

Objective. Hospital mortality and survival rates of long-term ventilated patients. Design. Retrospective cohort study. Setting. Specialised national weaning centre. Intervention. Protocol-directed liberation from ventilator. Patients. Four hundred three of 640 patients with prolonged mechanical ventilation (MV) who were admitted to our respiratory intensive care unit (RICU) were studied. MV lasted longer than 2 weeks and patients had failed more than two weaning trials in the referring ICUs. The majority of patients (59.3%) had chronic obstructive pulmonary disease (COPD). Results. After a mean duration of 41 days of MV prior to transfer, 68% of patients were liberated from the ventilator. In total, 98 of 403 patients (24.3%) died during the stay in our hospital, 305 patients (75.7%) were discharged. Compared to the non-survivors, the survivors were characterised by younger age, longer length of stay in our RICU, lower severity of illness scores at admission, fewer cardiac illnesses and a higher rate of weaning success. In 31.5% of the discharged patients non-invasive MV (NIV) was initiated during the stay at our unit. We gathered follow-up data on 293 patients (96.1%). Post-discharge survival rates were 67.6% at 3 months, 49.4% at 1 year and 38.1% at 3 years. Length of survival was significantly dependent on age, weaning success and main diagnosis (i.e., prognosis in COPD is worse compared to thoracic restriction, neuromuscular disease and others) in the multivariate analysis. Conclusions. Difficult-to-wean patients have a high hospital mortality rate and poor long-term prognosis. Age, main diagnosis, severity of illness, weaning success and institution of NIV predict survival.

In der Behandlung von Patienten mit chronischer Ateminsuffizienz unterschiedlicher Genese hat sich in den letzten Jahrzehnten zunachst die Sauerstofflangzeittherapie und, mit stets verbesserter und vereinfachter Apparatetechnik, die Uberdruckbeatmung mit und ohne Sauerstoff etabliert. Wer diese Entwicklung uber einen langen Zeitraum uberblickt, weis zugleich, was dies – abgesehen von den objektivierbaren Ergebnissen dieser erfolgreichen Behandlung – an Lebensqualitat fur die oft von panischer Erstickungsangst geplagten Patienten bedeutet. Das diese Therapieform hierzulande nicht allen Patienten zugute kommt, die davon profitieren konnten, mus leider vermutet werden. Das mag verschiedene Ursachen haben, von denen die meisten in der Praxis leicht widerlegt werden durften. So informiert die vorliegende Arbeit nicht nur uber die Voraussetzungen und die Formen der Heimbeatmung, sondern kann zugleich auch als Pladoyer aufgefast werden, sich die Methoden der hauslichen Sauerstofflangzeittherapie und Sauerstoffbeatmung zu eigen zu machen. Des weiteren gibt die vorliegende Arbeit auch eine Ubersicht daruber, wie ineffektiv leider die medikamentosen Masnahmen zur Drucksenkung im Pulmonalkreislauf und zur Stimulation des Atemzentrums sind.

Die Spatphase der amyotrophen Lateralsklerose (ALS) ist wesentlich durch die respiratorische Globalinsuffizienz gekennzeichnet. Der Leidensdruck infolge pulmonaler Symptome ist bei der Mehrzahl der Patienten infolge einer sich allmahlich einstellenden Hyperkapnie-assoziierten Vigilanzminderung nur gering ausgepragt. Dennoch kann es im Einzelfall zu einer massiven Beeintrachtigung des Patienten durch schwergradige Dyspnoe und tracheobronchiale Schleimretention bei insuffizientem Hustenstos und schwacher Atemmuskulatur kommen. Der ALS-Patient und seine Angehorigen sollten daher fruhzeitig nach Diagnosestellung von einem Spezialisten uber den moglichen Verlauf, die Symptome der Spatphase der Erkrankung sowie die verfugbaren therapeutischen Masnahmen informiert werden. Bei unzureichender Aufklarung droht eine unbedachte Notfallsituation mit nachfolgender Intubation und irreversibler Langzeitbeatmung. Bei dominierender Dyspnoe bestehen Palliativmasnahmen in der Sauerstoffgabe und Morphiumtherapie. Bei starker tracheobronchialer Verschleimung stehen Sekretolytika, physikalische Masnahmen und die bronchoskopische Sekretabsaugung zur Verfugung. Die Indikation zur elektiven Beatmung sollte nur nach ausfuhrlicher Beratung des Patienten und bei ausdrucklichem Therapiewunsch gestellt werden. ALS-Patienten profitieren von der Maskenbeatmung, wenn die Dyspnoe bereits im fruhen Krankheitsverlauf auftritt, bei gleichzeitig fehlender oder nur geringer bulbarer Symptomatik und weitgehend erhaltener Funktion der oberen Extremitaten.

Long-term mechanical ventilation implies a significant number of weaning failures. The basis of this unweanability is chronic fatigue of the inspiratory muscles which is due to depletion of energy store (e.g. glycogen). Considering this pathophysiological principle, the decisive therapeutic option during weaning from long-term mechanical ventilation consists of resting the respiratory muscles. The commonly used assisted ventilation modes only partially relieve the respiratory muscles because the work of breathing is done both during the trigger phase and during the inspiratory cycle. The essential characteristic of our weaning concept includes the repeated determination of the spontaneous breathing frequency in awake patients, which is followed by controlled intermittent positive pressure ventilation with a slightly higher respiratory rate. Ideally, this results in total suppression of the activity of the breathing centre, and in subsequent relief and recovery of the respiratory muscles by replenishing the energy stores. The close succession of relief and training periods avoids inactivity-induced atrophy of the respiratory muscles and permits regeneration. Additionally, our weaning concept avoids increases in inspiratory work during the phases of spontaneous breathing. This means that high-resistance small-caliber endotracheal tubes have to be replaced by large tubes. Moreover, transtracheal oxygen insufflation during spontaneous breathing decreases anatomic dead space. This reduces minute ventilation and, therefore, the work of breathing. In patients still exhibiting chronic fatigue of the respiratory muscle pump after successful weaning, intermittent home ventilation is initiated via a breathing mask. Apart from the concept described above, successful weaning from the respirator after long-term ventilation is based upon dedicated patient care and depends on the architectural characteristics of the intensive care unit.

We report on a 56-year-old renal allograft recipient receiving cyclosporin A immunosuppression. During this therapy he subsequently developed the following cutaneous neoplasms: squamous cell carcinomas, basal cell carcinomas, Bowen's disease, actinic keratosis, sebaceous hyperplasia, a dysplastic naevus and, finally a nodular malignant melanoma. Adverse effects of the cyclosporin A therapy are discussed, with special reference to dermatologic effects and the implications for patient and doctor.

Background: The marked increase of type 2 diabetes necessitates active development and implementation of efficient prevention programs. A European level action has been taken by launching the IMAGE project to unify and improve the various prevention management concepts, which currently exist within the EU. This report describes the background and the methods used in the development of the IMAGE project quality indicators for diabetes primary prevention programs. It is targeted to the persons responsible for diabetes prevention at different levels of the health care systems. Methods: Development of the quality indicators was conducted by a group of specialists representing different professional groups from several European countries. Indicators and measurement recommendations were produced by the expert group in consensus meetings and further developed by combining evidence and expert opinion. Results: The quality indicators were developed for different prevention strategies: population level prevention strategy, screening for high risk, and high risk prevention strategy. Totally, 22 quality indicators were generated. They constitute the minimum level of quality assurance recommended for diabetes prevention programs. In addition, 20 scientific evaluation indicators with measurement standards were produced. These micro level indicators describe measurements, which should be used if evaluation, reporting, and scientific analysis are planned. Conclusions: We hope that these quality tools together with the IMAGE guidelines will provide a useful tool for improving the quality of diabetes prevention in Europe and make different prevention approaches comparable. BACKGROUND: The marked increase of type 2 diabetes necessitates active development and implementation of efficient prevention programs. A European level action has been taken by launching the IMAGE project to unify and improve the various prevention management concepts, which currently exist within the EU. This report describes the background and the methods used in the development of the IMAGE project quality indicators for diabetes primary prevention programs. It is targeted to the persons responsible for diabetes prevention at different levels of the health care systems. METHODS: Development of the quality indicators was conducted by a group of specialists representing different professional groups from several European countries. Indicators and measurement recommendations were produced by the expert group in consensus meetings and further developed by combining evidence and expert opinion. RESULTS: The quality indicators were developed for different prevention strategies: population level prevention strategy, screening for high risk, and high risk prevention strategy. Totally, 22 quality indicators were generated. They constitute the minimum level of quality assurance recommended for diabetes prevention programs. In addition, 20 scientific evaluation indicators with measurement standards were produced. These micro level indicators describe measurements, which should be used if evaluation, reporting, and scientific analysis are planned. CONCLUSIONS: We hope that these quality tools together with the IMAGE guidelines will provide a useful tool for improving the quality of diabetes prevention in Europe and make different prevention approaches comparable.

Background: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. Aims: This guideline provides evidence-based recommendations for preventing T2DM. Methods: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. Results: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8–4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by ≥ 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. Conclusions: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication. BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

A microscopic theory is presented for the Coulomb-interacting electron-hole system in an optically excited semiconductor that is probed by weak THz radiation. The relevant equations for the THz response are summarized and numerically evaluated for different optical excitation conditions. Experimental results are presented for a high-quality InGaAs/GaAs quantum-well system under resonant excitation. Formation and decay of excitonic populations are investigated.