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To explore factors associated with work impairment at 2 years following an acute episode.
European Mania in Bipolar disorder Longitudinal Evaluation of Medication (EMBLEM) is a prospective, observational study on the outcomes of patients with a manic/mixed episode. Work impairment was measured using a Longitudinal Interval Follow-up Evaluation (slice of LIFE) item and patients were categorised with either low or high work impairment at each observation. Baseline factors associated with work impairment at 2 years were assessed using multivariate modelling.
At baseline (n = 2289), 69% of patients had high work impairment. At 2 years (n = 1393), high impairment reduced to 41%. Modelling identified rapid cycling as the strongest disease-related factor associated with high work impairment at 2 years, although high work impairment at baseline had the strongest association overall. Lower levels of education, recent admissions, CGI-BP overall severity in the 12 months prior to baseline and CGI-BP mania at baseline all predicted higher work impairment. Living together in a relationship and independent housing were both significantly associated with having low work impairment at 2 years.
Work impairment in bipolar disorder is maintained over long periods, and is strongly associated with relationship status, living conditions and various disease-related factors.
To contrast the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a RCT assessing the same treatments (Tohen et al., 2002).
EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2-year, prospective, observational study of health outcomes associated with treatment of mania. Severity of mania and depression was assessed at baseline and 6 weeks using the YMRS and 5-item version of the HAMD, respectively. The RCT was a 3-week, randomised, double-blind comparison of olanzapine (n=125) and divalproate-treated (n=123) patients hospitalised for acute manic or mixed episodes. The YMRS and HAMD were used to quantify manic and depressive symptoms, respectively.
621 EMBLEM patients were analysed (n=107 valproate, n=514 olanzapine). Both observed groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with significantly greater mean improvements in the olanzapine compared with the valproate group using linear regression to adjust for baseline differences. The RCT reported significantly greater mean YMRS improvement (but not HAMD) in the olanzapine-treated group. EMBLEM patients treated with olanzapine experienced significantly greater weight gain than patients treated with valproate, similar to RCT results. There was a significantly greater incidence of treatment-emergent gastrointestinal adverse events in EMBLEM patients treated with valproate.
The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy may be more effective than valproate monotherapy in the treatment of acute mania. Contrasting observational and RCT results present methodological challenges but can provide important complementary information.
Use of ketamine in the prehospital setting may be advantageous due to its potent analgesic and sedative properties and favorable risk profile. Use in the military setting has demonstrated both efficacy and safety for pain relief. The purpose of this study was to assess ketamine training, use, and perceptions in the civilian setting among nationally certified paramedics (NRPs) in the United States.
A cross-sectional survey of NRPs was performed. The electronic questionnaire assessed paramedic training, authorization, use, and perceptions of ketamine. Included in the analysis were completed surveys of paramedics who held one or more state paramedic credentials, indicated “patient care provider” as their primary role, and worked in non-military settings. Descriptive statistics were calculated.
A total of 14,739 responses were obtained (response rate=23%), of which 10,737 (73%) met inclusion criteria and constituted the study cohort. Over one-half (53%) of paramedics reported learning about ketamine during their initial paramedic training. Meanwhile, 42% reported seeking ketamine-related education on their own. Of all respondents, only 33% (3,421/10,737) were authorized by protocol to use ketamine. Most commonly authorized uses included pain management (55%), rapid sequence intubation (RSI; 72%), and chemical restraint/sedation (72%). One-third of authorized providers (1,107/3,350) had never administered ketamine, with another 32% (1,070/3,350) having administered ketamine less than five times in their career. Ketamine was perceived to be safe and effective as the vast majority reported that they were comfortable with the use of ketamine (94%) and would, in similar situations (95%), use it again.
This was the first large, national survey to assess ketamine training, use, and perceptions among paramedics in the civilian prehospital setting. While training related to ketamine use was commonly reported among paramedics, few were authorized to administer the drug by their agency’s protocols. Of those authorized to use ketamine, most paramedics had limited experience administering the drug. Future research is needed to determine why the prevalence of ketamine use is low and to assess the safety and efficacy of ketamine use in the prehospital setting.
BucklandDM, CroweRP, CashRE, GondekS, MalusoP, SirajuddinS, SmithER, DangerfieldP, ShapiroG, WankaC, PanchalAR, SaraniB. Ketamine in the Prehospital Environment: A National Survey of Paramedics in the United States. Prehosp Disaster Med. 2018;33(1):23–28.
The use of psychoactive, potentially dependence-producing substances is highly prevalent around the world, and contributes substantially to global disease burden. There is a major gap between the need for treatment for substance use disorders. Changes proposed for the classification of substance use disorders in the Eleventh Revision of the International Classification of Diseases and Related Health Problems, based on a public health approach, have important implications for the conceptualisation, structure and availability of services. These include: (1) an updated and expanded range of substance classes; (2) greater specification of different harmful patterns of substance use, which may be continuous or episodic and recurrent; (3) a new category to denote single episodes of harmful use; (4) a category describing hazardous use of substances; and (5) simplification of diagnostic guidelines for substance dependence. This paper describes these changes and the opportunities they present for improved prevention, treatment, monitoring and health policy.
Aberrant emotional biases have been reported in bipolar disorder (BD), but results are inconsistent. Despite the clinical relevance of chronic mood variability in BD, there is no previous research investigating how the extent of symptom fluctuations in bipolar disorder might relate to emotional biases. This exploratory study investigated, in a large cohort of bipolar patients, whether instability in weekly mood episode symptoms and other clinical and demographic factors were related to emotional bias as measured in a simple laboratory task.
Participants (N = 271, BDI = 206, BDII = 121) completed an ‘emotional categorization and memory’ task. Weekly self-reported symptoms of depression and mania were collected prospectively. In linear regression analyses, associations between cognitive bias and mood variability were explored together with the influence of demographic and clinical factors, including current medication.
Greater accuracy in the classification of negative words relative to positive words was associated with greater instability in depressive symptoms. Furthermore, greater negative bias in free recall was associated with higher instability in manic symptoms. Participants diagnosed with BDII, compared with BDI, showed overall better word recognition and recall. Current antipsychotic use was associated with reduced instability in manic symptoms but this did not impact on emotional processing performance.
Emotional processing biases in bipolar disorder are related to instability in mood. These findings prompt further investigation into the underpinnings as well as clinical significance of mood instability.
Poor maternal nutrition inhibits muscle development and postnatal muscle growth. Satellite cells are myogenic precursor cells that contribute to postnatal muscle growth, and their activity can be evaluated by the expression of several transcription factors. Paired-box (Pax)7 is expressed in quiescent and active satellite cells. MyoD is expressed in activated and proliferating satellite cells and myogenin is expressed in terminally differentiating cells. Disruption in the expression pattern or timing of expression of myogenic regulatory factors negatively affects muscle development and growth. We hypothesized that poor maternal nutrition during gestation would alter the in vitro temporal expression of MyoD and myogenin in satellite cells from offspring at birth and 3 months of age. Ewes were fed 100% or 60% of NRC requirements from day 31±1.3 of gestation. Lambs from control-fed (CON) or restricted-fed (RES) ewes were euthanized within 24 h of birth (birth; n=5) or were fed a control diet until 3 months of age (n=5). Satellite cells isolated from the semitendinosus muscle were used for gene expression analysis or cultured for 24, 48 or 72 h and immunostained for Pax7, MyoD or myogenin. Fusion index was calculated from a subset of cells allowed to differentiate. Compared with CON, temporal expression of MyoD and myogenin was altered in cultured satellite cells isolated from RES lambs at birth. The percent of cells expressing MyoD was greater in RES than CON (P=0.03) after 24 h in culture. After 48 h of culture, there was a greater percent of cells expressing myogenin in RES compared with CON (P<0.001). After 72 h of culture the percent of satellite cells expressing myogenin in RES was less than CON (P<0.01). There were no differences in the gene expression of Pax7, Myf5 or MyoD in isolated satellite cells at birth (P>0.05). In satellite cells from RES lambs at 3 months of age, the percent of cells expressing MyoD and myogenin were greater than CON after 72 h in culture (P<0.05). Fusion index was reduced in RES lambs at 3 months of age compared with CON (P<0.001). Restricted nutrition during gestation alters the temporal expression of myogenic regulatory factors in satellite cells of the offspring, which may reduce the pool of myoblasts, decrease myoblast fusion and contribute to the poor postnatal muscle growth previously observed in these animals.
Background: There are no disease modifying agents for the treatment of Alzheimer’s disease (AD). Pathologically, AD is associated with the misfolding of two peptides: beta-amyloid (plaques) and tau (tangles). Methods: Using large-scale computer simulations, we modelled the misfolding of both beta-amyloid and tau, identifying a common conformational motif (CCM; i.e. an abnormal peptide shape), present in both beta-amyloid and tau, that promotes their misfolding. We screened a library of 11.8 million compounds against this in silico model of protein misfolding, identifying three novel molecular classes of putative therapeutics as anti-protein misfolding agents. We synthesized approximately 400 new chemical entity drug-like molecules in each of these three classes (i.e. 1200 potential drug candidates). These were comprehensively screened in a battery of five in vitro protein oligomerization assays. Selected compounds were next evaluated in the APP/PS1 doubly transgenic mouse model of AD. Results: Two new classes of molecules were identified with the ability to block the oligomerization of both beta-amyloid and tau. These compounds are drug-like with good pharmacokinetic properties and are brain-penetrant. They exhibit excellent efficacy in transgenic mouse models. Conclusion: Computer aided drug design has enabled the discovery of novel drug-like molecules able to inhibit both tau and beta-amyloid misfolding.
The fall of the Berlin Wall in 1989 and the unification of Germany in 1990 allowed East Germans to finally travel freely to western countries. This new freedom to travel to the West not only impacted the worldview of many former GDR citizens, but also found its way into the writings of East German authors throughout the 1990s and into the present. In her study on contemporary German literature around the turn of the twenty-first century, the literary critic Christine Cosentino examines several tendencies by which contemporary German authors deal with America in their texts. One tendency she describes is “die Reise in die USA als Topos für die Suche nach Identität, die den politischen Hintergrund weitgehend ausspart” (the journey to the USA as a symbol for the search for identity, which largely leaves out the political background). This tendency—finding one's identity by traveling to America—is noticeable in literature by East German authors from the 1990s, one of whom is Angela Krauß. In many of her works, particularly in her novels Die Überfliegerin (1995) and Milliarden neuer Sterne (1999), travel to America is a catalyst for the narrator experiencing her own identity in relation to past experiences, specifically her life in East German society. The exploration of the new world manifests itself in these texts as a discovery of the narrator's inner self.
Sophie von La Roche's America novel, Erscheinungen am See Oneida (Phenomena at Lake Oneida, 1798), centers on a French aristocratic couple from Flanders who go to live on a remote island in upstate New York. Carl and Emilie von Wattines have fled to the United States from the French revolutionary Terror, in which several of their relatives lost their lives. On advice from a Quaker friend in Philadelphia, they find their way to an island in Oneida Lake. There they live without contact with other Europeans for four years, producing two children and making a modest life for themselves, before moving to a new town founded by Dutch and German settlers on the lakeshore. A narrator traveling in the region pieces their story together from what he learns from them and their friends. At the crux of the tale is how the Wattineses, Crusoe-like, manage to survive in their isolation.
Three factors play a role. First, in spite of being aristocrats, they possess a bourgeois ethic, demonstrating qualities like modesty, hard work, and resourcefulness that help them to thrive. Second, they have brought a whole library of reference books with them, including the entire Encyclopédie and Buffon's Histoire naturelle, to which they frequently refer for how-to information. Finally and most interestingly, Emilie Wattines decides to reach out and make contact with the local indigenous people, the Oneidas, when she is about to give birth.
In recent years, the works by the German-Jewish poet Gertrud Kolmar (1894–1943) have found renewed interest among scholars. Raised in the upper middle class of Berlin and fully acculturated in the German cultural heritage, Gertrud Kolmar was persecuted, under the pressure of the National Socialist regime, because of her Jewish roots. Unlike many of her contemporaries, she chose to remain in Nazi Berlin and continued to write until her death in Auschwitz in 1943. Even though her published work spanned the innovative period between 1917 and 1937, Kolmar's poetic oeuvre from the years 1927 to 1937 has received the most attention. Though neglected by scholars, Kolmar's earlier work is fascinating precisely because it gives prescient insight into her poetic adaptations of questions concerning place, power, and gender at the end of the First World War.
My essay investigates an early poem in Kolmar's work: “Die Aztekin” (The Aztec Woman), written around 1920 and published in Früher Zyklus I. In memoriam 1918. Kolmar's “Aztekin” illustrates a testing ground for colonial fantasies and gendered mappings in its imaginary space of a poetic “Aztec empire.” The poem responds not only to preestablished writings on gendered conquests in the New World but also, more specifically, rewrites them in the perceived context of an imperial apocalypse in and after 1918, between megalomaniacal power struggles and the collapse of the Wilhelmine empire.
Swiss photojournalist and author Annemarie Schwarzenbach was born in 1908 into the family of the wealthy Swiss silk manufacturer Alfred Schwarzenbach and his wife Renée Schwarzenbach-Wille and died under tragic circumstances in 1942. Schwarzenbach's life was marked by her travels to the United States, the Orient, Africa, and through Europe. In this context, during her lifetime Schwarzenbach gained recognition for her travel writing and journalism within Switzerland. For example, her work was regularly published in Zürcher Illustrierte, National-Zeitung, Luzerner Tagblatt, Thurgauer Zeitung, and the journal ABC. As recent scholarship has emphasized, “her travel writings consist of a wide range of genres: from journalistic reportages and feuilletons to stories, novels, and also poems. In addition to her journalistic and travel writing, Schwarzenbach also produced several novels and novellas that thematize same-sex relationships as well as the blurring of gender lines, such as Eine Frau zu sehen (written in 1929, published in 2008), Pariser Novelle (written in 1929, published in 2003), Freunde um Bernhard (1931), and Tod in Persien (1936), among others. This last work also reflects her travels to the Near East. Schwarzenbach's androgynous and striking physical beauty, her homosexuality, travels, and drug abuse, as well as her encounters, friendships, and liaisons with famous contemporaries, made her in public and scholarly discourses into something of an icon. This icon status and the “clear autobiographical dimension” in her work fueled biographical scholarly approaches to Schwarzenbach's oeuvre after its rediscovery in 1987 (Schwelle, 404) after “her name [had] faded into obscurity” following her death.
November 5, 1853. Ida Pfeiffer, an Austrian traveler, is on her way to a village north of Crescent City in California, and the main purpose of her visit to this region is, as she claims, to see Indians. What she finds instead are ethnically hybrid Native Americans:
Nichts erschien mir komischer als die sonderbaren Anzüge, denn auch hier lasen sie alle von den Weißen weggeworfenen Kleidungsstücke auf. So sah ich einen Indianer, welcher ein Beinkleid, eine sehr schadhafte Mantille und einen zerknitterten Frauenhut trug. Ein anderer hatte weiter nichts als einen Frack an, den er nach eigenem Geschmacke auf der Rückseite ganz mit Glasperlen benäht hatte. Ein dritter trug wieder nur eine Weste, dazu einen Männerhut, in welchen er oben ein Loch geschnitten und viele Vogelfedern aufgesteckt hatte. Ebenso geschmackvoll waren die Weiber gekleidet.
[Nothing seemed more comical to me than their strange outfits, for here too they collected all the garments discarded by the whites. I saw an Indian wearing a pair of breeches, a very ragged mantilla, and a crumpled lady's hat. Another one wore nothing but a frock coat, the back of which he had adorned with glass beads according to his own taste. A third one wore only a waistcoat and a man's hat to go with it. On its top he had cut a hole and stuck many feathers into it. The women were dressed in equally good taste.]