[Victor Khrisanfovich Kandinsky (1849-1889) : Contributions of a Russian psychiatrist to the concepts of pseudohallucination and schizophrenias]. / Viktor Chrisanfovic Kandinskij (1849­1889) : Beiträge eines russischen Psychiaters zu den Konzepten der Pseudohalluzination und der Schizophrenien.

The article highlights the important work of the Russian psychiatrist Victor Khrisanfovich Kandinsky. His merits, in particular those in the fields of hallucinations and schizophrenias, have hitherto been neglected despite the fact that several of his articles have been published in German medical journals. He defined the term pseudohallucination in a way which is still common today. For him the criterion which separates it from real hallucinations was that the patient is aware of the fallacy of the phenomena perceived. Furthermore, his concept of ideophrenia can be regarded as a one of the precursors to today's concept of schizophrenias.

[First description of Schilder's disease : Paul Ferdinand Schilder and his struggle for the delimitation of a new entity]. / Die Erstbeschreibung der Schilder-Krankheit : Paul Ferdinand Schilder und sein Ringen um die Abgrenzung einer neuen Entität.

Paul Ferdinand Schilder was born in Vienna in 1886 and died in New York in 1940. He is nowadays remembered predominantly for his contributions to modern psychiatry and psychotherapy; however, he was also a neurologist and neuroscientist and in particular in his early years, he researched and published on neuropathological topics. This paper focuses on his scientific work during his years in Middle Germany (1909-1914), where he worked with Gabriel Anton in Halle and Paul Flechsig in Leipzig. During those years, he laid the foundations for his definition, clinical classification and differentiation of encephalitis periaxialis diffusa. Today, this inflammatory brain disease is known as Schilder's disease and is of some importance as a rare differential diagnosis of multiple sclerosis (MS), especially in children. Schilder's reflections and findings were based on his scrupulous and detailed analysis of only a few medical histories, which also comprised histological neuropathological examinations, as well as on his extensive and critical review of the relevant literature of the time. His aim was to differentiate encephalitis periaxialis diffusa from brain tumors, MS and Heubner's diffuse sclerosis. Schilder's scientific achievement, made in relatively young years, is still impressive even to the present day due do its thoroughness and accuracy as well as the enormous workload and ambition it required. Even though ambitious, Schilder was always prepared to critically review his own ideas.

[The career of the psychiatrist Dietfried Müller-Hegemann (1910-1989) : Example of a politically motivated rise and fall in the German Democratic Republic]. / Die Karriere des Psychiaters Dietfried Müller-Hegemann (1910­1989) : Beispiel eines politisch gewollten Auf- und Abstiegs in der DDR.

Dietfried Müller-Hegemann was one of the prominent figures in East German psychiatry and psychotherapy of the 1950s and 1960s. Having been a communist prior to 1933, a resistance fighter during the National Socialist regime and having gone through political training during his exile in Soviet Russia, he proved to be a committed member of the new ruling SED socialist party in Eastern Germany. As such both governmental and party organs regarded him as a promising and reliable party member to be supported and implemented as executive staff within the new, socialist scientific system. Also, due to the fact that he supported the Pavlovian school of thought for modern psychiatry, Müller-Hegemann was installed as the new head of the Department of Neurology and Psychiatry at Leipzig University by the state secretary for higher education, notably against the clear opposition of the university medical faculty. Soon thereafter however Müller-Hegemann fell from favor due to the fact that he supported views that did not follow the strict ideological guidelines, e. g. with regard to the emergence of fascism. Moreover, he strongly opposed the separation of neurology from psychiatry as ruled by the ministry. An attempt in 1963 by junior party members and ministerial staff to remove him from office failed, but still managed to make Müller-Hegemann resign from his Leipzig post and take over that of director of the Griesinger hospital for the mentally ill in East Berlin. In May 1971, after new conflicts with party officials, he did not return from a business trip to Essen in West Germany. This study does not review the scientific and medical merits of Müller-Hegemann, but concentrates on how his career as a leading psychiatrist was manipulated, both supported and sabotaged, and ideologically controlled by the German Democratic Republic (GDR) system. His development is documented proof that party officials did not tolerate opposition, neither in ideological nor in professional questions, even if the opponent was a committed Marxist. The example of his career shows that political and ideological dissent soon melted into personal animosity and drives, as a result of which Müller-Hegemann's promising career as professor in Leipzig was terminated.

[From boxing to geriatric psychiatry : Facets from the work of East German social psychiatrist Bernhard Schwarz (1918-1991)]. / Vom Boxsport bis zur Gerontopsychiatrie : Facetten des Schaffens des DDR-Sozialpsychiaters Bernhard Schwarz (1918­1991).

For the first time, this study presents publications representative for the work of the neurologist and sports physician Bernhard Schwarz, whose career spans from the 1950s to the 1970s. His work is characterized by exceptional originality. Schwarz acted as the physician of the GDR national boxing team and conducted a systematic long-term study of 800 boxers. He found increased occurrences of depression, Alzheimer's and Parkinson's diseases and suggested that these were linked to recurring craniocerebral injury. He was concerned about avoiding such long-term health effects in boxers and suggested a range of preventive measures that were later reflected in the guidelines of international boxing associations. Schwarz was distinguished by his drive to directly implement social psychiatric approaches in the hospital. As head of the psychiatric clinic at Leipzig University, he initiated a club for geriatric patients to help older patients with the problematic transition from hospitalization to outpatient assistance at home. Influenced by holistic anthropological thinking, he regarded geriatric mental illness as a consequence of social isolation. In addition, Schwarz was involved in a model project that assessed the work resilience of patients in the hospital with the goal of optimizing psychiatric rehabilitation. Both projects were successes, according to his published accounts.

[Suicidality in German-speaking school psychiatry : Thematization in textbooks from 1803 until the present]. / Suizidalität in der deutschsprachigen Schulpsychiatrie : Thematisierung in Lehrbüchern von 1803 bis heute.

BACKGROUND: This chronology gives an overview about continuities and changes in the perception of suicidality in German-speaking school psychiatry over the past 200+ years. QUESTIONS: This study was guided by the following questions: has suicidality been perceived as regularly being connected to certain mental illnesses? Which other possible causes have been discussed by psychiatrists from the nineteenth century to the beginning of the twenty-first century? What approaches have major psychiatrists adopted towards suicidal patients and threatened suicide? What treatment and preventive strategies have been suggested? METHODOLOGY: First, we compiled a list of the, in our view, most influential textbooks on psychiatry of German-speaking school psychiatry from 1803 until the present. These textbooks were then skim-read for relevant passages on suicidality. The material gained was elicited, classified and analyzed in relation to the questions at hand. Futhermore, an attempt was made to arrive at contextual estimations. RESULTS: Several authors named a certain set of psychiatric illnesses that are assumed to involve or increase the risk of suicide. These illnesses include depression, schizophrenia and also physical illnesses. In nineteenth century textbooks heredity, anatomical anomalies and nationality were discussed as potential influencing factors. In contrast, more recent books discuss models of how suicidal behavior emerges and often refer to the Werther effect. With respect to therapy there is a trend towards therapeutic discussions and modern psychopharmacotherapy. DISCUSSION: Over time, there have been continuities and changes in psychiatrists' approach to suicidality not only as far as clinical aspects are concerned but also the general approach to and management of suicidal patients.

[25 years after re-unification of Germany: An overview on Eastern German psychiatry. Part 2: Pluralistic approaches and the collapse in the 1980s]. / 25 Jahre nach der "Wiedervereinigung": Der Versuch einer Übersicht über die Psychiatrie in der DDR. Teil 2: Von pluralistischen Betrachtungsweisen und dem Zusammenbruch in den 1980er Jahren.

This is the second part of a 2-part study of the history of psychiatry in East Germany, i. e. the Soviet Occupied Zone and later German Democratic Republic. This part primarily covers the 1970 s and 1980 s. Starting from the 1970 s, pluralistic views on and approaches to mental illness and its treatment gained ground, which was especially visible in psychotherapy. The exacerbating economic crisis of the 1970 s and 1980 s led to a steadily worsening collapse of the building infrastructure of clinics and any reformation that would have led to significant financial investment became impossible. Despite attempts from party and state, psychiatric institutions successfully resisted being systematically misused against their patients.In the discussion part, the study supports the notion that East German psychiatry was neither totally isolated nor communist in nature. Even though communism had an influence, it did not have a decisively modifying impact on psychiatry, so that one can characterize psychiatry in East Germany as a medical discipline with a certain specific typology.

[25 Years After Re-Unification of Germany: An Overview on Eastern German Psychiatry. Part 1: Post-War Era, Pavlovization, Psychopharmacological Era and Social Psychiatric Reform Movement]. / 25 Jahre nach der "Wiedervereinigung": Versuch einer Übersicht über die Psychiatrie in der DDR. Teil 1: Nachkriegszeit, Pawlowisierung, psychopharmakologische Ära und sozialpsychiatrische Bewegung.

This is the first of a 2-part study on the history of psychiatry in Eastern Germany, i. e. the Soviet Occupied Zone and later German Democratic Republic. It mainly covers the years post World War II up until the beginning of the 1970s. The first post-war years were determined by the new power holders' attempts to overcome National Socialist (Nazi) heritage and to re-organize mental health and care in general. The doctrine of a strict denazifization in East Germany must, however, be regarded as a myth. Promoted by centralized organization, there was an increase in communist party-ideological influence and harassment as well as aligning scientific views and research with Soviet paradigms (Pavlovization) during the 1950s and early 1960s. This, however, led to an enormous rise in exodus of skilled labor to West Germany, which in turn further increased the notorious lack of staff. After the erection of the inner-German wall, this problem was mitigated, yet never fully solved over the 40 years of the existence of the GDR. Despite adverse conditions, East German psychiatrists made major original contributions to the development of psychiatry in general, at least up until the 1960s. Academic psychiatry was mainly based on biological concepts that were further promoted by new somatic and psychopharmacological therapeutic options. In the 1960s, social psychiatric reformist forces emerged, primarily in the large psychiatric hospitals. The improvements achieved by these forces, however, were not implemented on a nation-wide scale, but mainly restricted to one particular or several institutions.

[Müller-Hegemann's classification of depressions of 1964 as a proposal for a conceptualization of affective disorders: A critical review]. / Müller-Hegemanns Systematik der Depressionen von 1964 als Vorschlag zur Konzeptualisierung der affektiven Störungen. Eine kritische Analyse.

Against the background of current discussions on the classification of psychiatric disorders, this study analyses and discusses the East-German psychiatrist Dietfried Müller-Hegemann's concept of a clinical classification of depressions of 1964.In his paper, Müller-Hegemann differentiated between two main forms of depression, namely the "vitally tinged depression" (= melancholy), found mainly in the depressive phases of the manic-depressive disorder, and the "depressive disgruntlement" (= dysthymia) seen in "reactive and neurotic depression", "involutional depression", and in the depressive states in psychopathic personalities. Due to a lack of sufficient biological evidence, Müller-Hegemann refrained from a purely etiological differentiation.His proposal is significant in so far as it provided a classification that could easily be used in clinical practice, and at the same time, by pointing to the traditional concept of melancholy and by calling for a differentiated psychopathology, anticipated aspects of topical interest.

[Are the current concepts of obsessive disorders a novelty? From Westphal (1877) and Thomsen (1895) to ICD-10 and DSM-5]. / Sind die aktuellen Konzepte der Zwangsstörung ein Novum? Von Westphal (1877) und Thomsen (1895) zur ICD-10 und zum DSM-5.

In German-speaking countries it was Carl Westphal who in 1877 offered the first precise definition of obsessive ideas and distinguished obsessive compulsive disorder (OCD) as an independent disorder in its own right. The criteria mentioned by him for establishing OCD gave rise to a debate on the character and classification of OCD but were not fully acknowledged by his colleagues at the time. In 1895 Westphal's student Robert Thomsen tried to substantiate all points in his teacher's theory that had raised criticism. Thus the works by Westphal and Thomsen are most relevant for the current conceptualization and definition of OCD, for they laid the basis for the present phenomenology, definition and classification of OCD according to ICD-10 and DSM-5. Apart from phenomenologically differentiating between obsessions (i.e. obsessive thoughts and impulses) and compulsions (i.e. compulsive actions and inhibitions), Westphal and Thomsen also laid the basis for most of the current diagnostic criteria. Thomsen led the way to current classifications by subdifferentiating OCD as an illness on its own on the one hand and obsessions and compulsions as symptoms accompanying other conditions on the other.

[The contributions by Emil Kraepelin to the knowledge on sleep disorders and their treatment]. / Die Beiträge von Emil Kraepelin zum Wissen über Schlafstörungen und deren Behandlung.

While Emil Kraepelin's comprehensive psychiatric oeuvre has attracted researchers' attention, his studies on sleep disorders and their treatment as well as on the interconnections between sleep and mental disorders so far seem to have been neglected.This article identifies and analyzes Kraepelin's sporadic contributions on the pathology of sleep, the comorbidities and treatment made between 1883 and 1924 in textbooks and isolated papers as well as in a presentation that was also published and compares them with current opinions in sleep research.Kraepelin never published a dedicated work on sleep, apart from a summary of the different narcotics; however, his occasional statements reveal astonishing insights and in particular his clear etiologically oriented classification of sleep disorders is captivating. Similar to the current classification, Kraepelin conceptualized sleep disorders as symptoms or rather a complex of symptoms and also identified associated diseases which once again are very near to current opinion. Apart from this his recommendations on sleep hygiene and, in a second step, pharmacological treatment of pathological sleep patterns are still clinically relevant. As early as the end of the nineteenth century Kraepelin laid down an algorithm of treatment which is very similar to the current clinical guidelines. At Kraepelin's time it seemed impossible to reach an agreement on classification and treatment issues of sleep disturbances and even though there has been an ongoing discussion until the present day, an agreement at least about guidelines could be reached. Against this background Kraepelin's contributions can still be regarded as a proposal for best practice.

[Differential diagnosis of bipolar disorder: historical and clinical implications and perspectives]. / Differenzialdiagnostik der Bipolaren Störung: historische und klinische Implikationen und Perspektiven.

In DSM-5, bipolar disorder (BS) is no longer conceptualised as a pure mood disorder together with unipolar depression, but as a bridge between schizophrenia and depressive disorders. This nosological classification is founded on the historical context of the 19th century. In addition to unipolar depression and schizophrenia, schizoaffective disorder, borderline personality disorder and attention-deficit hyperactivity disorder (ADHD) overlap with BS symptomatology. Overlap also exists with somatic diseases such as multiple sclerosis, Cushing's syndrome and syphilis as well as iatrogenic affective syndromes.

Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone--a factorial study.

AIM: To evaluate the efficacy and safety of initial combination therapy of sitagliptin 100 mg/day coadministered with all marketed doses of pioglitazone in patients with type 2 diabetes. METHODS: Patients with A1c ≥7.5 and ≤11.0% were randomized among seven arms that received, once daily, 100 mg sitagliptin alone; 15, 30 or 45 mg pioglitazone alone, or 100 mg sitagliptin plus 15, 30 or 45 mg pioglitazone for 54 weeks. The primary endpoint was change from baseline in A1c at week 24. Protocol-specified analyses compared combination therapies with monotherapies at respective dose-strengths and combination of sitagliptin plus pioglitazone 30 mg with pioglitazone 45 mg monotherapy. Post-hoc analyses compared sitagliptin plus pioglitazone 15 mg with pioglitazone monotherapy at the two higher doses. RESULTS: Initial combination therapy with sitagliptin and pioglitazone provided significantly greater reductions in A1c (0.4-0.7% differences) and other glycaemic endpoints than either monotherapy at the same doses. Combining sitagliptin with low-dose pioglitazone generally produced greater glycaemic improvements than higher doses of pioglitazone monotherapy (0.3-0.4% differences in A1c). Combination therapy was generally well tolerated; adverse events (AEs) of hypoglycaemia were reported with similar incidence (7.8-11.1%) in all treatment groups over the 54 weeks of study; oedema was reported in 0.5% of patients in the sitagliptin monotherapy group and 2.7-5.3% among pioglitazone-treated groups. Significant weight gain was observed in all combination-treated groups compared with the sitagliptin monotherapy group. CONCLUSIONS: Initial combination therapy with sitagliptin and pioglitazone provided better glycaemic control than either monotherapy and was generally well tolerated.

Visceral smooth muscle α-actin deficiency associated with chronic intestinal pseudo-obstruction in a Bengal cat (Felis catus x Prionailurus bengalensis).

An adult Bengal cat (Felis catus × Prionailurus bengalensis) with a prolonged history of partial anorexia, regurgitation, and weight loss and a clinical, radiographic, and ultrasonographic diagnosis of persistent megaesophagus and gastrointestinal ileus was submitted for necropsy. The intestinal tract was diffusely distended by gas and fluid with appreciable loss of muscle tone and an absence of luminal obstruction, consistent with the clinical history of chronic intestinal pseudo-obstruction. Histologically, the autonomic nervous system was intact, but the smooth muscle within the gastrointestinal wall exhibited a marked basophilia that was most pronounced in the jejunum. Immunohistochemistry for neurofilament, synaptophysin, CD117, and desmin demonstrated that the number of myenteric ganglia, number of interstitial cells, and leiomyocyte desmin content were similar when compared with the unaffected age- and species-matched control. Immunohistochemistry for smooth muscle α-actin demonstrated a striking loss of immunoreactivity, predominantly in the circular layer of the jejunum, that corresponded with the tinctorial change in leiomyocytes. Transmission electron microscopy revealed loss of myofibrils, loss of organelle polarity, and significantly larger central mitochondria (megamitochondria) in affected leiomyocytes, as well as nonspecific degenerative changes. Although the presence of a primary leiomyopathy and a causal relationship could not be confirmed in this case, leiomyopathies are considered a cause of chronic intestinal pseudo-obstruction in human medicine, and loss of smooth muscle α-actin immunoreactivity is one recognized marker for intestinal dysmotility.

[Introduction and transformation of the psychiatric term "anancasm". From Gyula (Julius) Donáth via Kurt Schneider to ICD-10]. / Einführung und Wandlung des psychiatrischen Terminus "Anankasmus". Von Gyula (Julius) Donáth über Kurt Schneider bis zur ICD-10.

The conceptual history of "anancasm" in psychiatry remains almost unexplored and this article will help to remove this deficit. It was the Budapest-based neuropsychiatrist Gyula Donáth (1849-1944) who first proposed this Greek-rooted term in 1897 as an international term for compulsive symptoms and as an independent mental illness similar to present-day obsessive compulsive disorders (ICD-10). By suggesting this term Donáth wanted to extend the concept of compulsion as proposed by his teacher Carl Westphal to other compulsive phenomena, psychomotor impulses and restrictions including echolalia, coprolalia, echokinesis, echopraxia, contemporary maladie des tics (present day Tourette's syndrome) and even intermittent dipsomania (craving for alcohol), paraphilias, sexual fetishes and homosexuality. In 1923 Kurt Schneider used this term for a subgroup of psychopathic personalities, the so-called insecure anancastic psychopaths. His concept was much different to that suggested by Donáth, with the only thing in common being the compulsory component. Schneider's anancasts suffered from feelings of insecurity and insufficiency and were forced to try to overcompensate by being excessively careful, meticulous and hyper-correct. Based on Schneider's concept anancasm has survived as a name for a subdivision of compulsive personality disorders in ICD-10; however, these rather complex personality defects were not what Donáth had in mind when he first suggested the term anancasm. The paper discusses further discrepancies between Donáth, Schneider and ICD-10.

["Even electricity cannot work wonders!". Neglected achievements by German psychiatrists around 1880 in the treatment of depressions and psychoses]. / "Auch die Electricität leistet keine Wunder!". Die vergessenen Beiträge deutscher Psychiater um 1880 zur Therapie von Depressionen und Psychosen.

Parallel to the recent reneurobiologization of psychiatry as a subject, therapies based on electricity and elektrcomagnetism are returning to mental health care. Around 1880, the application of brain stimulating treatment on patients was particularly popular among German psychiatrists. This fact has largely been ignored in historical psychiatric research as present day practices, in particular deep brain stimulation (DBS), have frequently been seen solely within the tradition of brain surgery. Against this background the present study aims to revive the first trials of non-surgical electrical brain stimulation on depressive and psychotic patients, highlighting a 2-part study published by Wilhelm Tigges. It was Tigges along with Rudolph Gottfried Arndt and Wilhelm Erb who tried to establish clear rules on the most beneficial application methods and doses. Interestingly, Tigges's therapy was successful in cases of severe depression with chronification potential, i.e. precisely the clinical picture for which brain stimulation therapies are reserved today as a last option and ascribed an easing and even curing potential. Trigges also found that electricity produced almost no positive effect whatsoever with madly insane patients and hence anticipated the current non-application of DBS on these patients. After 1890 electrotherapeutic approaches in psychiatry were marginalized, first and foremost as no clear and reliable rules could be verified for their application, nor could their mode of action be fully explained. The success of electrotherapy in psychiatry was also restricted due to limitations of the time, namely (1) electrophysiology only emerging as a discipline, (2) the electrophysical medical apparatus industry only beginning to be established and (3) the lack of generally accepted guidelines and electrotherapy restriction to individual, barely generalizable experience (eclecticism). Present day applications of electricity, mainly DBS, have overcome these problems.

[The impartiality of ignorance? - A controversy between Paul Julius Möbius and Julius Wagner-Jauregg on the symptoms of reanimated persons after a suicide attempt through self-hanging]. / Die Unbefangenheit der Unwissenheit? - Ein Richtungsstreit zwischen Paul Julius Möbius und Julius Wagner-Jauregg über die Symptome wiederbelebter Erhängter.

INTRODUCTION: Between 1891 and 1893 the famous Austrian and German neuropsychiatrists Julius Wagner-Jauregg and Paul Julius Möbius disputed in leading German and Austrian medical journals about mental and physiological changes and symptoms in people who after strangulation could be revived in time to survive. Their dispute even touched personal issues. METHODS: For the study, the original sources were studied and contrasted with relevant secondary sources. RESULTS: The dispute was mainly about two opposing concepts: On the one hand, Wagner-Jauregg supported an organic, neurological concept; on the other hand a psychoreactive-symptoms concept represented by Möbius and elaborated by him first in his concept of hysteria. DISCUSSION: The study elaborates these factual differences in completely different approaches to psychiatry and - at least in the case of Möbius - how a medical theory was embedded into a pre-existing philosophical system. CONSEQUENCES: The dispute studied discusses a philosophical problem which has remained incompletely understood until the present day - the relationship of body and mind. Hence the study on this dispute is more than just an interesting aspect in the history of sciences, but rather the illustration of a meeting of two opponents in a still relevant discussion.

[Research on Depression in the GDR - Historical Lines of Development and Therapeutic Approaches]. / Depressionsforschung in der DDR - historische Entwicklungslinien und Therapieansätze.

BACKGROUND: Historical research has raised the issue of whether GDR psychiatry was isolated from Western influences to such an extent that an autonomous East German psychiatry developed. Taking a chronological approach and being based on a clearly defined range of topics, the objective of this paper is to identify specific contributions made by GDR psychiatry to academic research as well as the degree of its international orientation by focusing on the treatment and research on depression. METHODS: We have performed a systematic review of the East German psychiatric journal "Psychiatrie, Neurologie und medizinische Psychologie" and a screening of all psychiatric textbooks that appeared in the GDR. RESULTS: Although East German psychiatry was oriented towards Soviet as well as Western developments, some internationally used therapeutic or conceptual innovations reached East German clinics only with some delay. Yet, East German psychiatrists have also contributed their own, independent nosological and therapeutic concepts to research on depression. Pivotal figures included, among others, R. Lemke (Jena), D. Müller-Hegemann (Leipzig) or K. Leonhard (Berlin). CONCLUSION: With regard to research on depression one cannot truly speak of an autonomous East German psychiatry. Developments in East and West were largely running in parallel.

Efficacy and safety over 26 weeks of an oral treatment strategy including sitagliptin compared with an injectable treatment strategy with liraglutide in patients with type 2 diabetes mellitus inadequately controlled on metformin: a randomised clinical trial.

AIMS/HYPOTHESIS: The aim of this work was to compare treatment intensification strategies based on orally administered vs injectable incretin-based antihyperglycaemic agents in patients with type 2 diabetes mellitus on metformin monotherapy. METHODS: In a 26 week, open-label study, 653 patients (baseline HbA1c = 8.2% [66 mmol/mol]) were randomised at 111 sites in 21 countries in a 1:1 ratio to a strategy using oral agents (starting with sitagliptin 100 mg/day) or a strategy using the injectable drug liraglutide starting at a dose of 0.6 mg/day, up-titrated to 1.2 mg/day after 1 week. The following patients with type 2 diabetes mellitus were recruited for the study: those aged 18-79 years, on a stable dose of metformin monotherapy ≥1,500 mg/day for ≥12 weeks, with an HbA1c ≥7.0% (53 mmol/mol) and ≤11.0% (97 mmol/mol) and a fasting fingerstick glucose (FFG) <15 mmol/l (<270 mg/dl) at the randomisation visit, deemed capable by the investigator of using a Victoza pen injection device (containing 6 mg/ml liraglutide; Novo Nordisk, Bagsværd, Denmark). Women taking part in the study agreed to remain abstinent or use an acceptable method of birth control during the study. Randomisation was performed via a computer-generated allocation schedule using an interactive voice response system. After 12 weeks, patients on sitagliptin with HbA1c ≥ 7.0% (53 mmol/mol) and fasting glucose >6.1 mmol/l had their treatment intensified with glimepiride; patients on liraglutide with HbA1c ≥ 7.0% (53 mmol/mol) had the dose up-titrated to 1.8 mg/day. The primary analysis assessed whether the strategy using oral drugs was non-inferior to that using an injectable drug regarding HbA1c change from baseline at week 26 using a per-protocol (PP) population and a non-inferiority margin of 0.4%. RESULTS: In the PP population (522 patients included: oral strategy, n = 269; injectable strategy, n = 253) antihyperglycaemic therapy was intensified at week 12 in 50.2% and 28.5%, respectively. HbA1c decreased over 26 weeks in both treatment strategy groups, with a larger initial reduction at week 12 in the injectable strategy group. The LS mean change in HbA1c at week 26 was -1.3% (95% CI -1.4, -1.2) in the oral strategy group and -1.4% (95% CI -1.5, -1.3) in the injectable strategy group; the study met the non-inferiority criterion. Both treatment regimens were generally well tolerated; hypoglycaemia was reported more often with the oral strategy, while nausea, vomiting, diarrhoea and abdominal pain were reported more often with the injectable strategy. CONCLUSIONS/INTERPRETATION: An oral, incretin-based treatment strategy with sitagliptin and, if needed, glimepiride may be a good approach in many patients with type 2 diabetes mellitus for managing inadequate glycaemic control on metformin monotherapy, as compared with an injectable treatment strategy with liraglutide. The oral and injectable strategies had similar effects on HbA1c and had good overall tolerability. Trial registration ClinicalTrials.gov NCT01296412 Funding The study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck and Co., Inc., Whitehouse Station, NJ, USA.

[Knowledge of German neurologists on migraine around 1890. Paul Julius Möbius and his 1894 monograph Die Migräne]. / Das Wissen der deutschen Neurologen über die Migräne um 1890. Paul Julius Möbius und seine Monographie Die Migräne 1894.

Paul Julius Möbius (1853-1907), a Leipzig-based author and editor on a vast majority of subjects, has often been acknowledged as a leading 19th-century German neurologist. His impact on the development of knowledge on migraine has likewise been pointed to. This study compares the monograph published by Möbius on the illness in 1894 with contemporary publications and with present day best practice to establish if the author really made an essential contribution to the problem of migraine. As a representative of the central theory Möbius assumed that migraine was caused by aberrations in the brain. At the same time he made it clear that due to very limited diagnostic options this was only a hypothesis. Apart from a genetic factor and these cerebral changes, for Möbius the general state of health was a decisive factor and prevention and change in lifestyle therefore played a crucial role in his therapeutic recommendations. Basically there were only few differences between the views of Möbius and his colleagues, the major dissimilarity being that Möbius postulated a merely suggestive impact but no physical effect of electrotherapy. Although Möbius's monograph on migraine lacks originality, it provides a concise, easy to understand and stylistically impressive overview on the state of knowledge at that time. Therefore, the book can be considered as a benchmark publication of German speaking neurology around 1890 on migraine and it is highly recommended to present day headache and migraine researchers as well as historians of psychiatry and neurology.

[The discussion about the application and impact of music on depressive diseases throughout history and at present]. / Die Diskussion um die Anwendung und die Wirksamkeit von Musik bei depressiven Störungen in Geschichte und Gegenwart.

Music therapy is the customised application of music for therapeutic use. For the treatment of depression it is mostly applied within a multimodal therapeutic approach. Since music was already used in prehistoric societies to cure diseases, it can be considered as a traditional therapy. As early as the antiquity physicians discussed the kind of music, the duration and frequency of its application. In the 19th century the pioneers of modern scientific psychiatry began to follow these questions with empirical experimental research. Since the 20th century, research has been investigating the influence of music on biological and psychological parameters. Current studies show that music therapy appears to improve symptoms of depression, especially in combination with antidepressants. Due to the limited number of randomised studies, the validity of its efficiency is limited. Further research is necessary to provide evidence-based recommendations regarding music therapy for the treatment of depression.