bluuebunny/crossref_metadata_2025 huggingface dataset:
Disaster and Emergency Preparedness and the Impact of the COVID-19 Pandemic on Child Care Programs in Michigan: A Mixed-Methods Analysis
Authors: Budnik Elizabeth M. , Hashikawa Andrew N. , Cator Allison , Bradin Stuart , Mangus Courtney W.
Published: April 2023

Background:

Historically, the child care industry has been unprepared for emergencies. A previous study identified gaps in Michigan’s child care programs’ emergency plans. Study objectives were to reassess programs’ preparedness plans after introduction of state-mandated emergency plans and to examine the effect of the coronavirus disease 2019 (COVID-19) pandemic on programs’ operations.

Methods:

A 29-question survey was sent to ∼500 child care programs across Michigan in 2020 to assess emergency plans and response to COVID-19. Data were analyzed using descriptive statistics and qualitative methods.

Results:

A total of 346 programs (70%) responded. Most (92%) reported having a written plan, but one-third reported having no infectious outbreak plan pre-pandemic. One-third of programs lacked plans for special needs children (vs 40% in 2014); 62% lacked plans for child reunification (vs 60% in 2014); 46% reported staff received no preparedness training. COVID-19 impacted programs substantially: 59% closed, 20% decreased capacity, 27% changed disinfecting protocols. Several themes related to the pandemic’s effect on programs were identified: (1) changes in learning, (2) changes in socialization, (3) increased family burden, (4) financial challenges, (5) lack of guidance.

Conclusions:

Significant preparedness gaps remain among Michigan’s child care programs, suggesting the need for increased support and addition of emergency preparedness to programs’ quality ratings.
Political theories of money and the politics of contextualisation
Authors: Trivellato Francesca
Published: April 2023

This essay engages with Stephan Eich’s The Currency of Politics. It finds that the book pursues two goals at once: a minimalist goal of bringing money as a subject of inquiry back into the fold of political theory and a maximalist goal consisting in the stated ambition to ‘articulate more democratic visions of the future of money’. It interrogates Eich’s effort to harnesses a historical perspective to normative claims from the standpoint of a historian of pre-modern Europe. More specifically, it asks what role close reading, intertextuality and contextualisation play in Eich’s approach; why he recognises certain episodes from the (distant) past rather than others as relevant to current predicaments and potential future scenarios; and why he singles out the English financial revolution of the 1690s as the first relevant moment of crisis after the monetary reforms undertaken in Athens in the sixth century BCE.
Towards a constitutional theory of money: opening Europe’s money up to public discourse
Authors: Losada Fernando
Published: April 2023

Stefan Eich’s The Currency of Politics reconstructs and contextualises the monetary understanding of some of the most renowned political thinkers in history. By contextualising each author’s conceptualisation (subjective perception) against their respective contemporary monetary frameworks (objective institutional dimension), Eich elaborates a narrative composed of cumulative layers leading to a double conclusion: that money is political at its core, and that current policies are actively de-politicizing money. These relevant findings are the point of departure of a reflection on the role that law, and constitutional theory in particular, must play in the configuration of Europe’s common currency to overcome some of the most acute difficulties the process of integration is currently experiencing. If the triad law, money and public discourse is supposed to articulate social life in the polity, European monetary integration has neutralised them by neglecting the relevance of one of their key features: civic reciprocity. Reactivating the three mechanisms of social integration requires an exercise of constitutional imagination able to integrate interdisciplinary knowledge about money within an institutional framework able to prevent the concentration of unlimited power in unaccountable institutions and to promote and fully exploit the democratic potential of money.
Why European legal scholarship should become aware of Karl Polanyi: The Great Transformation and the integration project
Authors: Joerges Christian
Published: April 2023

As the Second World War was drawing to a close in 1944, two great works of political economy were published. One of them was Friedrich August von Hayek’s The Road to Serfdom,1 inspiring the defenders of free market movements ever since and up to the present. The other was Karl Polanyi’s The Great Transformation.2 This essay will focus on Polanyi but also pay tribute to Hayek. Contrasting the two helps to understand both of them better. Of the two, Hayek, the Nobel prize winner, is of course more widely known and by far more influential. But Polanyi’s work, too, has achieved and has been attracting as of recently such attention that one of the Directors of the Max Planck Institute for the Study of Societies in Cologne proclaimed that ‘we are all Polanyian now’,3 not only in economic sociology, but also in related disciplines, including, of course, political economy and political theory. A plethora of aspects of The Great Transformation are very widely discussed. This essay will be concerned with the not-so-well explored importance of Polanyi’s work for European Law and legal scholarship in general, including his theorems on the ‘embedded economy’, his conceptualisation of labour as a ‘fictitious commodity’ as well as the notion of counter-movements. It will then juxtapose Polanyi’s expectation of a new international order with the development of the European integration project and sketch out the contours of the democracy-enhancing conflicts law and its affinities with Polanyian core normative principles.
Property, corporations, and constitutionalisation in a global political economy
Authors: Robé Jean-Philippe
Published: April 2023

In the Law of Political Economy perspective, private property is the corner stone right. Constitutionally, it amounts to a right of decision-making as a matter of principle towards the object of property. It is a decentralisation of the State’s sovereignty. This feature entitles owners to set rules in connection with the use of their property to which users of their property must submit. This is the origin of the authority relationships within business firms. Within liberal constitutional orders, this strong enabling characteristic of property was originally designed for individuals only. But business corporations, subsequently introduced in the legal system, have found the way to have access to these same rights. Concentrating productive assets, they have in effect concentrated rights of decision-making as a matter if principle. And the global firms (or enterprises) using corporations to structure their activities now make use of their prerogatives in a global legal space in which the Law of Political Economy is unable to reconnect economic and political issues. One way out of this major issue raised by globalisation is to constitutionalise world private governments. Recent court cases addressing climate change demonstrate that this is a viable solution.1
The communicative turn in money production and central banking
Authors: Goldoni Marco
Published: April 2023

This intervention expands Stefan Eich’s analysis of the parallel between language and money in The Currency of Politics by emphasising the increasing importance of linguistic communication within processes of production. This expansion has had an impact on monetary policy and on the communicative strategies of central banks. The suggestion is to integrate Eich’s call for the politicisation of monetary design with an appraisal of post-fordiist productive processes and the importance of money creation for the valorisation of those processes. If this reading of the expansion of the logic of economic value to linguistic communication is correct, then any call for a monetary design of money that works like public speech ought to be carry forward cautiously, in light of the colonisation of the latter (speech) by market forces
Rigid continuation paths II. structured polynomial systems
Authors: Bürgisser Peter , Cucker Felipe , Lairez Pierre
Published: April 2023

This work studies the average complexity of solving structured polynomial systems that are characterised by a low evaluation cost, as opposed to the dense random model previously used. Firstly, we design a continuation algorithm that computes, with high probability, an approximate zero of a polynomial system given only as black-box evaluation program. Secondly, we introduce a universal model of random polynomial systems with prescribed evaluation complexityL. Combining both, we show that we can compute an approximate zero of a random structured polynomial system withnequations of degree at most${D}$innvariables with only$\operatorname {poly}(n, {D}) L$operations with high probability. This exceeds the expectations implicit in Smale’s 17th problem.
Bordered Floer homology and contact structures
Authors: Alishahi Akram , Földvári Viktória , Hendricks Kristen , Licata Joan , Petkova Ina , Vértesi Vera
Published: April 2023

We introduce a contact invariant in the bordered sutured Heegaard Floer homology of a three-manifold with boundary. The input for the invariant is a contact manifold

$(M, \xi , \mathcal {F})$

whose convex boundary is equipped with a signed singular foliation

$\mathcal {F}$

closely related to the characteristic foliation. Such a manifold admits a family of foliated open book decompositions classified by a Giroux correspondence, as described in [LV20]. We use a special class of foliated open books to construct admissible bordered sutured Heegaard diagrams and identify well-defined classes

$c_D$

and

$c_A$

in the corresponding bordered sutured modules.

Foliated open books exhibit user-friendly gluing behavior, and we show that the pairing on invariants induced by gluing compatible foliated open books recovers the Heegaard Floer contact invariant for closed contact manifolds. We also consider a natural map associated to forgetting the foliation

$\mathcal {F}$

in favor of the dividing set and show that it maps the bordered sutured invariant to the contact invariant of a sutured manifold defined by Honda–Kazez–Matić.
Disparities in central line-associated bloodstream infection and catheter-associated urinary tract infection rates: An exploratory analysis
Authors: Gettler Erin B. , Kalu Ibukunoluwa C. , Okeke Nwora L. , Lewis Sarah S. , Anderson Deverick J. , Smith Becky A. , Advani Sonali D.
Published: April 2023

This retrospective review of 4-year surveillance data revealed a higher central line-associated bloodstream infection (CLABSI) rate in non-Hispanic Black patients and higher catheter-associated urinary tract infection (CAUTI) rates in Asian and non-Hispanic Black patients compared with White patients despite similar catheter utilization between the groups.
Richardson and Reynolds number effects on the near field of buoyant plumes: flow statistics and fluxes
Authors: Meehan Michael A. , Hamlington Peter E.
Published: April 2023

The near-field characteristics of highly buoyant plumes, commonly referred to as lazy plumes, remain relatively poorly understood across a range of flow conditions, particularly compared with our understanding of far-field characteristics. Here, we perform fully resolved three-dimensional numerical simulations of round helium plumes to characterize the effects of different inlet Richardson,

${Ri}_0$

, and Reynolds,

${Re}_0$

, numbers on first- and second-order statistical moments as well as average vertical fluxes in the near field. For sufficiently high

${Re}_0$

at a particular

${Ri}_0$

, heavy air can penetrate the core of the plume, reminiscent of spikes in the classical Rayleigh–Taylor instability. In the most turbulent simulation, this penetration becomes so strong that a recirculation zone forms along the centreline of the plume. Vertical fluxes are found to scale linearly with vertical distance from the plume inlet, consistent with experimental and numerical observations (Jiang & Luo, Flow Turbul. Combust., vol. 64, 2000, pp. 43–69; Kaye & Hunt, Intl J. Heat Fluid Flow, vol. 30, 2009, pp. 1099–1105). We analytically derive this linear scaling from the governing equations by making a radial entrainment hypothesis whereby ambient fluid is entrained, on average, only in the radial direction at a finite distance from the inlet. Through this derivation, we identify physical mechanisms that can cause these relationships to remain only approximately valid for the present simulations. Lastly, we identify near-field power-law scaling relations for the flux magnitudes based on

${Ri}_0$

, and also examine vertical profiles of the non-dimensional Richardson number flux. Ultimately, insights from the present simulations are used to define near-, intermediate- and far-field regions in buoyant plumes.
Relationship between overweight and obesity and insufficient micronutrient intake: a nationwide study in Taiwan
Authors: Lin Shih-Pi , Fang Hsin-Yu , Li Ming-Chieh
Published: April 2023

The aim of the present study is to examine whether overweight or obese people in Taiwan have an inadequate intake of selected micronutrients. A population-based study was conducted using data from the Nutrition and Health Survey in Taiwan (NAHSIT) 2013–2016. We evaluated fourteen nutrient intakes using the 24 h dietary recall method. The dietary reference intake (DRI) adherence was estimated by the prevalence of participants whose intake was lower than the recommended dietary allowance (RDA) or adequate intakes (AIs) for selected micronutrients. Body mass index (BMI) ≥ 27 kg/m2 and waist circumference (WC), with men having WC ≥ 90 cm or women having WC ≥ 80 cm, were defined as obesity. A total of 3075 participants aged 19 years and above were included. After adjusting for confounders, we found that obese women have a lower DRI adherence of vitamin C (odds ratio (OR) 0⋅73, 95 % confidence interval (CI) 0⋅56, 0⋅95) and magnesium (OR 0⋅72, 95 % CI 0⋅54, 0⋅95), compared with normal-weight women. Obese men have a higher DRI adherence of vitamin B3 (OR 1⋅70, 95 % CI 1⋅29, 2⋅23), iron (OR 1⋅46, 95 % CI 1⋅06, 2⋅00) and zinc (OR 1⋅41, 95 % CI 1⋅07, 1⋅85), compared with normal-weight men. Similar findings were found using WC to define obesity. We conclude that obese women may have insufficient intakes of vitamin A, vitamin C and magnesium.
Retourner sa veste au Québec : une étude des défections transpartisanes politiques de 1980 à 2018
Authors: Lalancette Mireille , Marland Alex , Wesley Jared
Published: April 2023

Cet article aborde le phénomène des défections dans les partis politiques grâce à une étude du cas des députés québécois. Les entrevues avec les anciens parlementaires et une analyse des discours médiatiques à propos de leur départ documentent les motivations à quitter ou à rejoindre un autre parti. Cette recherche propose deux typologies novatrices : la première identifie les types de défections et la seconde explore les motivations à quitter. Les analyses montrent que les députés québécois partent surtout en raison de conflits liés aux valeurs et aux politiques, mais très peu pour le prestige. En ouvrant un dialogue avec les travaux d'Hirshman, l'article illustre aussi le rôle de la prise de parole et de l’écoute dans la décision pour un député de quitter un parti ou de rester dans celui-ci.
Writing in Arabic in Gujarat and the Hijaz: Some Reflections from the Early Modern Period
Authors: Balachandran Jyoti Gulati
Published: April 2023

As a region with a long coastline by the Arabian Sea in northwestern India, Gujarat has historically been connected to the maritime rhythms of the Indian Ocean and inter-regional developments in north India and the Deccan. These connections—commercial, but also political, cultural, and intellectual—remain central to the history of Gujarat as an independent sultanate in the fifteenth century and during the time of Mughal control from the late sixteenth century.1 The circulation of Muslim scholars and intellectuals between the urban centers of Gujarat and cities of the Hijaz, Hadramawt, and Egypt, shaped the intellectual enterprise of several prominent scholars in Gujarat (and more broadly South Asia) who wrote in Arabic—from al-Damamini (d. 1424) and ‘Ali Muttaqi (d. 1567) to Shah Wajih al-Din ‘Alawi (d. 1590) and ‘Abd al-Qadir al-‘Aydarus (d.1628). While these scholars’ works have received attention from modern scholars to varying degrees, this essay emphasizes the importance of foregrounding the early modern oceanic context in order to recover the transregional social and scholarly ties central to the lives and oeuvre of these intellectuals. Recovering transregional oceanic connections in turn calls for greater engagement with scholarly writings produced in Arabic, a language that has remained peripheral to South Asian historiography.
Of Echoes and Utterances: A Brief Sketch of Arabic Hauntings in Hindi Cinema and Song
Authors: Petiwala Ada
Published: April 2023

On a Saturday afternoon in January 2017, Shah Rukh Khan—Hindi cinema's reigning star of the last thirty years—arrived at Bollywood Parks Dubai to promote his latest film release, Raees (2017). To the crowd of adoring Arab and South Asian fans and journalists who had flocked to the theme park to catch a glimpse of the “Badshah of Bollywood” and brand ambassador of Dubai, SRK unveiled the much-anticipated Arabic version of “Zaalima” (Cruel One), the film's breakout hit song. Rendered in Darija by Moroccan pop artists Abdelfettah Grini and Jamila El Badaoui, this version of “Zaalima” proved an awkward copy of the original, its unwieldy Arabic lyrics molded to fit as tightly within the blueprint melody as possible. “Dīrī fiya al-thiqa, al-gharām hā howa” (Put your confidence in me, for love is here) did not have quite the same ring or seamlessness as the Hindi-Urdu “Main sau martaba dīwāna hua” (I fell in love a hundred times over), with the Arabic line painstakingly crafted to echo the “hua” ending of the Hindi-Urdu.
The Effects of Antitrust Laws on Horizontal Mergers: International Evidence
Authors: Chung Chune Young , Hasan Iftekhar , Hwang JiHoon , Kim Incheol
Published: April 2023

This study examines how antitrust law adoptions affect horizontal merger and acquisition outcomes. Using the staggered introduction of competition laws in 20 countries, we find antitrust regulation decreases acquirers’ 5-day cumulative abnormal returns surrounding horizontal merger announcements. A decrease in deal value, target book assets, and industry peers’ announcement returns are consistent with the market power hypothesis. Exploiting antitrust law adoptions addresses a downward bias to an estimated effect of antitrust enforcement. The potential bias from heterogeneous treatment effects does not nullify our results. Overall, antitrust policies seem to deter post-merger monopolistic gains, potentially improving customer welfare.
Settler cities in the Dutch Indies: Race, class and the emergence of settler colonialism
Authors: Fakih Farabi
Published: April 2023

This article explores the colonial land tenure system which evolved in the municipalities of the Dutch Indies in the early twentieth century, resulting in structural differences in urban property ownership. The development of a formal and informal property regime during this period created the logic of racialised capitalism that underpinned settler colonialism. By looking at the actions of the Indo-Europeesche Verbond (IEV), the main Indo-European political party, this article seeks to understand why settler colonialism failed in the Dutch Indies. It finds that the success of the settler colonialism project depended on its relationship with global capitalism and imperial support. This study also finds that structural differences in property ownership have continued in postcolonial Indonesia.
Wild meat consumption in urban Sierra Leone during the Covid-19 pandemic
Authors: Sainge Moses N. , Wusha-Conteh Fartimah , Fa Julia E. , Sullivan Martin J.P. , Cuni-Sanchez Aida
Published: April 2023

Wild meat is associated with an increased risk of zoonotic diseases. In some West African countries wild meat consumption declined as the result of official restrictions following Ebola outbreaks during 2013–2016, and was also affected by the current Covid-19 pandemic. In Sierra Leone, a country affected by these diseases, we documented wild meat use in four markets in the capital, Freetown. From a total of 197 interviews, we analysed the influence of age and gender on the types of wild meat eaten and the reasons for their consumption. We found that more men than women consumed wild meat, and for both genders taste was the main reason for eating wild meat. Age did not affect wild meat consumption amongst women. Evidence for changes in consumer behaviour in response to zoonotic disease risk was mixed. Although some consumers avoided wild meat because of disease risk, none stated this was the primary reason for not eating wild meat, and monkeys (presumed to carry a high zoonotic disease risk) were amongst the species cited as being consumed often. More work is needed to identify the best pathway towards safe and sustainable consumption of wild meat in urban Sierra Leone.
Mysticism and scholasticism
Authors: Cross Richard
Published: April 2023

This article offers some reflections on Christina Van Dyke's Hidden Wisdom, using the opportunity to make some suggestions as to possible lines of influence between the world of scholastic theology and that of the female medieval mystics in what Van Dyke considers their ‘annihilationist’ mode: that the goal of the spiritual life is transformation into God in some sense.
Behavioural and heuristic models are as-if models too – and that’s ok
Authors: Moscati Ivan
Published: April 2023

I examine some behavioural and heuristic models of individual decision-making and argue that the diverse psychological mechanisms these models posit are too demanding to be implemented, either consciously or unconsciously, by actual decision makers. Accordingly, and contrary to what their advocates typically claim, behavioural and heuristic models are best understood as ‘as-if’ models. I then sketch a version of scientific antirealism that justifies the practice of as-if modelling in decision theory but goes beyond traditional instrumentalism. Finally, I relate my account of decision models to the recent controversy about mentalism versus behaviourism, reject both positions, and offer an alternative view.
Beyond replication: An exact replication study of Łodzikowski (2021)
Authors: Foung Dennis , Kohnke Lucas
Published: April 2023

Replication studies have become an emerging line of research in recent decades, including in computer-assisted language learning (CALL). Exact replication, which closely follows a study’s protocol, is rare as it is hard to recreate results without establishing a highly controlled environment. However, using data available online, we were able to conduct an exact replication of Łodzikowski’s (2021) study, which reported on the use of an allophonic transcription tool by 55 Polish learners of English. Allophonic features are used by native speakers to produce acoustic variants of the same phoneme. The original study offered learners an allophonic transcription tool, examined how they used it and considered its association with phonological awareness. This study extended the original research by addressing the limitations of its regression and transcription analyses. Our findings allowed us to offer several suggestions on (1) how an allophonic transcription tool can be better designed to help learners, (2) how CALL researchers can acquire more data for more useful research and (3) why more replication studies are needed in CALL.
Patient and Staff Attitudes Toward Clothing Restrictions on a Pediatric Psychiatric Unit
Authors: Schmidt Scott C.
Published: April 2023

Introduction

Pediatric psychiatric inpatients are among the most vulnerable individuals in society. While the use of seclusion and restraint is well chronicled in the field of research in this population, there is limited literature describing the effects, meaning, and attitudes of mandating the wear of clothing in hospital settings. This research explores the phenomenon of the practice of mandatory wear of hospital-issued clothing and its meaning to patients and the awareness and attitudes of this practice among staff caring for this population. This research aims to improve understanding of the experiences of patients regarding this practice at a large, urban hospital providing care for children using a mixed methods design. A qualitative, descriptive phenomenological analysis was conducted through individual interviews with adolescent patients (N = 5) on an inpatient psychiatric unit. Additionally, a cross-sectional self-reported questionnaire examined the awareness and attitudes toward this practice among unit staff (N = 41). The patients’ attitudes toward clothing restrictions was predominantly negative, noting a lack of self-expression, feeling like a mental health patient, desires to wear ones’ personal clothing, and feelings of shame and punishment. Among the staff there was a modest correlation between age, number of years practicing as a health professional, and years practicing in a pediatric setting with feelings of a need for a change in the clothing policy to allow patients to wear their own clothing on admission. Staff age and number of years working at the institution demonstrated a modest correlation between awareness of legal statutes regarding patients’ rights to their own clothing. This research found a readiness among staff to adopt a clothing policy that would permit patients to wear their own clothing on admission, which would improve the negative experiences described among the patients in the sample.

Funding

No Funding
Number Needed to Treat and Number Needed to Harm From Two Phase 3 Studies of Sublingual Dexmedetomidine for Treating Acute Agitation in Patients With Schizophrenia and Bipolar Disorder
Authors: L Citrome , R Risinger , L Rajachandran , E Patton , H Robison
Published: April 2023

Background

Episodes of acute agitation can occur in individuals who suffer from schizophrenia or bipolar disorder and these can be a significant challenge for patients and for those who provide care to them. Sublingual dexmedetomidine is a selective alpha2-adrenergic receptor agonist that was recently approved by the US Food and Drug Administration for the treatment of agitation in adults with schizophrenia or bipolar disorder. The sublingual form of dexmedetomidine does not undergo first-pass hepatic metabolism, thus resulting in greater absorption than when ingested. In two Phase 3 studies of adults with schizophrenia or bipolar disorder, sublingual dexmedetomidine significantly reduced acute agitation at 2 hours, as measured by the five-item Positive and Negative Syndrome Scale-Excited Component (PEC). When initially appraising the potential utility of a new medication, number needed to treat (NNT) and needed to harm (NNH) can be helpful to assess the size of the treatment effect and, hence, clinical relevance.

Objective

Calculation of NNT and NNH through post hoc analysis of Phase 3 data.

Methods

Post hoc analysis of data were performed on data from two double-blind, randomized, placebo-controlled studies of sublingual dexmedetomidine in adults with schizophrenia or bipolar disorder experiencing acute agitation. Patients were randomized to a single dose of sublingual dexmedetomidine 180 μg, 120 μg, or placebo. The primary endpoint was mean change from baseline in the PEC total score. A therapeutic response was defined as a ≥40% reduction from baseline in PEC total score at 2 hours. NNT was calculated for PEC response rate for sublingual dexmedetomidine versus placebo. NNH was calculated using the incidence of adverse events for sublingual dexmedetomidine versus placebo. Likelihood to be helped or harmed (LHH) was calculated as the ratio of NNH to NNT.

Results

NNT (95% CI) was 3 (2, 3) for 180 mcg and 3 (3, 4) for 120 ug in patients with schizophrenia and 3 (2, 3) for 180 mcg and 4 (3, 6) for 120 ug in patients with bipolar disorder. NNH was greater than 10 for all AEs except somnolence, where NNH was 7 (5, 10) for all doses pooled from both studies. LLH values were greater than 1 for efficacy versus applicable tolerability outcomes in all cases.

Conclusions

This post hoc analysis demonstrated favorable NNT and NNH values for sublingual dexmedetomidine. In all instances therapeutic response was encountered more frequently than any adverse event. These values compare favorably to similar analyses for other approved agents for the treatment of agitation associated with schizophrenia or bipolar disorder, including intramuscular and inhaled formulations.

Funding

BioXcel Therapeutics, Inc.
Comorbidities and Presenting Symptoms in a Real-World Population With Obstructive Sleep Apnea
Authors: Parthasarathy Sairam , Zhang Jerry , Hyman Danielle , Doherty James , Saad Ragy , Fox Benjamin , Marshall Nell J. , Parks Gregory
Published: April 2023

Background

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is often associated with numerous medical and psychiatric comorbidities. Patients with OSA experience a variety of symptoms that can be burdensome and affect their quality of life and satisfaction with care. Excessive daytime sleepiness (EDS) is a common symptom of OSA, and can persist despite primary airway therapy (e.g., positive airway pressure [PAP]). This analysis aimed to characterize common comorbidities, as well as symptoms present at OSA diagnosis and their burden in a real-world population of participants with OSA.

Methods

US residents (≥18 years of age, self-reported clinician diagnosis of OSA [from 1/1/2015 to 3/31/2020]) completed a survey in Evidation Health’s Achievement app that assessed self-reported sleepiness (Epworth Sleepiness Scale [ESS]), self-reported PAP usage, self-reported physician-diagnosed comorbidities, and information on their symptoms at time of OSA diagnosis. Self-reported PAP use was categorized as nonuse (no PAP use), nonadherent (<4 h/night or <5 d/wk), intermediate (4–6 h/night, ≥5 d/wk), or highly adherent (≥6 h/night, ≥5 d/wk). EDS was defined as ESS score >10. All data were summarized descriptively.

Results

In total, 2289 participants completed the survey (50.3% female; 82.5% White; mean ± standard deviation [SD] age, 44.8 ± 11.1 years; mean ± SD age at OSA diagnosis, 40.7 ± 11.4 years; mean ± SD body mass index, 35.4 ± 8.7 kg/m2); 42.5% had EDS. Among the total population, 30.6% were PAP non-users, 6.7% were nonadherent, 9.8% were intermediate adherent, and 52.9% were highly adherent. Across the study population, the most common self-reported physician-diagnosed comorbidities were anxiety (44%) and depression (42%) followed by hypertension (39%), dyslipidemia (26%), and asthma (21%). Among the symptoms participants reported having had at the time of OSA diagnosis, the most common were EDS (79%), fatigue (79%), snoring (75%), and awakening with a dry mouth or sore throat (63%). Concentration/Memory problems (48%) and mood changes (46%) were also common. In the overall population, the symptoms present at the time of OSA diagnosis that were most likely to be highly burdensome were fatigue (53%), EDS (46%), snoring (35%), difficulty concentrating/memory issues (31%), and mood changes (25%).

Conclusions

These real-world survey data identify anxiety and depression as the most frequently reported comorbidities in a population of participants with OSA, each affecting over 40% of participants. In addition to classic OSA symptoms (e.g., EDS, fatigue, snoring, and awakening with dry mouth/sore throat), concentration/memory problems and mood changes were also common at the time of OSA diagnosis and were among the presenting symptoms most frequently reported as highly burdensome, along with fatigue, EDS, and snoring.

Funding

Axsome Therapeutics and Jazz Pharmaceuticals
Safety And Tolerability of Aripiprazole 2-Month Ready-to-Use 960 mg in Adult Patients With Schizophrenia or Bipolar I Disorder
Authors: Harlin Matthew , Yildirim Murat , Such Pedro , Madera-McDonough Jessica , Jan Michael , Larsen Frank
Published: April 2023

Introduction

Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months, intended for the treatment of schizophrenia and maintenance monotherapy treatment of bipolar I disorder (BP-I). This 32-week trial evaluated the safety, tolerability, and pharmacokinetic profile of multiple-dose gluteal administration of Ari 2MRTU 960 in clinically stable adult patients with a diagnosis of schizophrenia or BP-I, versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the treatment of schizophrenia and maintenance monotherapy treatment of BP-I).

Methods

This was an open-label, multiple-dose, randomized, parallel-arm trial conducted at 16 sites in the US. Eligible patients (N=266) were randomized to receive Ari 2MRTU 960 every 56±2 days (n=132; 4 injections in total) or AOM 400 every 28±2 days (n=134; 8 injections in total). Safety and tolerability were evaluated throughout the study; assessments included adverse event reporting, patient reporting of injection site pain, and monitoring of extrapyramidal symptoms.

Results

In the Ari 2MRTU group, 102 patients (77.3%) completed the study; in the AOM 400 group, 92 patients (68.7%) completed the study. The overall incidence of treatment-emergent adverse events (TEAEs) was similar between Ari 2MRTU 960 and AOM 400 (71.2% versus 70.9%, respectively). The most frequently reported TEAEs were increased weight (22.7% for Ari 2MRTU 960 versus 20.9% for AOM 400) and injection site pain (18.2% for Ari 2MRTU 960 versus 9.0% for AOM 400), none of which were assessed as serious or severe by the investigators. All injection site pain events in the Ari 2MRTU 960 group were assessed as mild or moderate in severity; most (15.9%) coincided with the first injection and resolved within 5 days. Extrapyramidal symptom scores remained unchanged in both treatment groups.

Conclusions

Multiple-dose administration of Ari 2MRTU 960 was generally well tolerated in patients with schizophrenia or BP-I and did not show any new safety concerns.

Funding

Otsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark)
Increasing Awareness of Naloxone-Induced Noncardiogenic Pulmonary and Peripheral Edema
Authors: Conley Kimberly D. , Murphy-Parker Dana , Conley Virginia M.
Published: April 2023

Introduction

Naloxone use has increased in recent years in response to the nation’s opioid crisis. Once only available to health care professionals, it is now obtainable by prescription for persons at risk for substance overdose and their families. Increasing its availability is seen by some as an “over-the-counter solution” to the opioid problem. However, while naloxone has been viewed as relatively safe, with a low side effect profile when appropriately dosed and monitored, it is not without safety concerns that may go unrecognized or misattributed to other causes.

Methods

Here we present a case study of a 41-year-old female who presented to our medication-assisted treatment (MAT) clinic complaining of sudden onset weight gain, shortness of breath, upper and lower extremity peripheral edema, tachycardia, insomnia, and nocturnal enuresis. These symptoms made it difficult for her to work at her housekeeping job, resulting in missed workdays. She had seen a primary care provider for her symptoms and been prescribed a rescue inhaler for her shortness of breath. This patient had previously been treated for opioid use disorder with buprenorphine/naloxone and experienced similar symptoms, which disappeared when she relapsed on opioids. However, symptoms reappeared upon resuming her prescribed treatment.

Results

The patient was identified as experiencing side effects to naloxone, causing noncardiogenic edema. Her MAT medication was switched to buprenorphine. Within two weeks her heart rate had returned to normal, she had lost weight, and she no longer had nocturnal enuresis or needed the rescue inhaler. Her peripheral edema resolved so she was able to walk better and resume work. At the same time, buprenorphine continued to relieve her cravings.

There is a dearth of information related to naloxone-induced edema. Our patient had not received a formal evaluation of pulmonary edema, but her pulmonary and cardiac symptoms were consistent with that diagnosis. Although pulmonary edema is mentioned in the product literature, peripheral edema is not. A literature search indicates that the number of case studies on naloxone-induced pulmonary edema have increased since 2018, but only one other case of naloxone-induced peripheral edema was discovered.

Conclusions/Importance

Naloxone is used in a variety of settings by differing types of health care providers. As the number of persons treated with naloxone increases, there will likely be a corresponding increase in incidences of pulmonary and/or peripheral edema as side effects. Providers and patients who are not aware of these manifestations and their relationship to naloxone treatment may easily attribute presenting symptoms to cardiogenic or other causes, as this case illustrates. It is important for providers in all settings to consider new onset shortness of breath and edema within the context of the person’s whole health and to be aware of their implications for mental as well as physical health.

Funding

No Funding
Metabolic Syndrome in Bipolar Depression with Lumateperone (ITI-007): A Post Hoc Analysis of 2 Randomized, Placebo-Controlled Trials
Authors: Correll Christoph U , Kozauer Susan G , Lands Micah , Huo Jason , Durgam Suresh
Published: April 2023

Introduction

Treatments for bipolar disorder are often associated with increased rates of metabolic syndrome (MetSy). MetSy is defined as meeting 3 of the following 5 criteria: waist circumference >40in (men) or >35in (women), triglycerides ≥150mg/dL, high density lipoprotein cholesterol <40mg/dL (men) or <50mg/dL (women), systolic blood pressure (BP) ≥130mmHg or diastolic BP ≥85mmHg, fasting glucose ≥100mg/dL.

MetSy elevates the risk of developing type II diabetes, cardiovascular disease, and premature morbidity. Lumateperone (LUMA), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. This distinct pharmacological profile has been associated with favorable tolerability and a low risk of adverse metabolic effects in clinical trials.

LUMA 42-mg monotherapy was evaluated in 2 randomized, double-blind, placebo (PBO)-controlled studies (Study 401 [NCT02600494]; Study 404 [NCT03249376]) in patients with a major depressive episode (MDE) associated with bipolar I or bipolar II disorder. This post hoc pooled analysis of these studies compares rates of MetSy with LUMA 42 mg and PBO in the treatment of bipolar depression.

Methods

The incidence and shift in MetSy were analyzed in data pooled from 2 studies that recruited patients aged 18–75 years with a confirmed diagnosis of bipolar I or bipolar II disorder who were experiencing an MDE (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score ≥4). Patients in these studies were randomized 1:1 to LUMA or PBO and treated for 6 weeks.

Results

The safety population comprised 746 patients (LUMA, 372; PBO, 374). Rates of MetSy were similar between groups at baseline (LUMA, 20.7%; PBO, 22.2%) and at the end of treatment (EOT, LUMA, 21.8%; PBO, 23.8%). More LUMA patients (36.4%) compared with PBO patients (30.1%) improved from having MetSy at baseline to no longer meeting MetSy criteria at EOT. The individual criteria that shifted the most from meeting MetSy criteria at baseline to no longer meeting criteria at EOT was BP for LUMA (46.8%) and glucose for PBO (43.2%). The rate of MetSy developed during treatment was similar for LUMA (10.8%) and PBO (10.7%) with approximately half of these patients (LUMA, 43.8%; PBO, 45.2%) shifting due to a change in ≥2 criteria.

Conclusion

In this post hoc analysis of 2 randomized, PBO-controlled trials in patients with a MDE associated with bipolar I or bipolar II disorder, LUMA 42 mg had similar rates of MetSy compared with PBO. These results suggest that LUMA 42 mg is a promising new treatment for bipolar depression with a favorable metabolic profile.

Funding

Intra-Cellular Therapies, Inc.
IVIG for Treatment-Resistant Psychosis For a Child with Turner Syndrome
Authors: Perdomo Monica , Silverman Daniel , Hamilton Celine
Published: April 2023

Psychosis is defined as the presence of false beliefs or false perceptions. In children some causes of psychosis include psychiatric diagnosis such as schizophrenia and autism. However, it may also be secondary to medical conditions like various forms of encephalitis. Studies have shown that IVIG has been efficacious in the treatment of psychosis in the setting of autoimmune encephalitis.

A 9-year-old girl with a past medical history of Turner Syndrome, developmental delay, epilepsy, growth hormone deficiency, metabolic bone disease, and autism (ASD) presented with auditory and visual hallucinations that began June 2020. She began with her hearing voices that repeated the word “dead” and told her that she would not live. The hallucination later took the form of a man that would mock her, laugh about her parents dying, and tell her to kill them. The patient had associated symptoms of insomnia, anxiety, sadness, and increased anger. On her initial admission, CSF studies including culture and gram strain were unremarkable. NMDA, VHKC, and GAD65 antibodies were negative. At this time the hallucinations were thought to be due to ASD and she was prescribed Risperdal 0.25mg twice a day. Unfortunately, this did not improve her symptoms and from the time period of June 2020 to May 2021 she subsequently underwent trials of Risperdal, Zyprexa, Invega, Abilify, Thorazine, Haldol, and Clozaril. However, the symptoms persisted. Zoloft was prescribed, which was efficacious for anger and dysphoria. Trazodone, melatonin, and Remeron were tried for the treatment of insomnia, but did not cause enough improvement to continue the medications. Due to progression of command hallucinations with “the man” instructing her to hurt others, the patient was admitted July 2021 for administration of IVIG. Repeat CSF studies and brain MRI were unremarkable. From July 29, 2021 to August 1, 2021 she received three doses of IVIG which resulted in improvement of psychosis. Prior to administration, she was seeing “the man” throughout the day every single day, was sleeping only 3–4 hours a night, and having nightmares everyday. On evaluation 2 weeks after IVIG, she was only seeing “the man” 1–2 time a day, sleeping 6–8 hours a night, having nightmares 1–2 times a week, and her mood had improved.

This case illustrates the potential use of IVIG for the treatment of treatment-resistant psychosis. Although the cause of this patient’s symptoms remains unclear, there were clear benefits from the administration of IVIG that were not seen with trials of antipsychotics.

Funding

No Funding
Health-Related Quality of Life and Healthcare Resource Use: Comparison of Patients with Bipolar I Disorder and Potentially Misdiagnosed Depression
Authors: Culpepper Larry , Higa Sara , Martin Ashley , Parikh Mousam , Harrington Amanda
Published: April 2023

Background

Bipolar I disorder (BP-I) is associated with a high humanistic and economic burden. Evidence suggests that BP-I is often misdiagnosed as major depressive disorder (MDD), but the unmet needs associated with BP-I misdiagnosis are unknown. This study compares socioeconomic, healthcare-related quality of life (HRQoL), and healthcare resource utilization (HRU) burdens of participants diagnosed with BP-I vs participants who screened as probable for BP-I but were diagnosed only with MDD.

Methods

Using responses to the 2020 National Health and Wellness Survey, respondents were categorized into cohorts of potentially misdiagnosed BP-I (i.e., self-reported physician diagnosis of MDD but screened as probable BP-I [mBP-I]) or BP-I (i.e., self-reported physician diagnosis of BP-I, stratified by BP-I severity). Baseline characteristics were evaluated using bivariate analyses. HRQoL (Short Form-36v2 Health Survey [SF36v2] mental and physical component scores, EuroQol Five-Dimension Visual Analogue Scale [EQ-5D VAS]), HRU, were evaluated using multivariable analyses adjusting for key baseline differences.

Results

There were 302 respondents in the mBP-I cohort and 818 in the BP-I cohort (mild=336, moderate=285, severe=197). Adults with mBP-I were similar in age and level of depression and anxiety to those with moderate and severe BP-I. With respect to HRQoL, the mBP-I cohort had significantly worse SF36v2 mental component scores and EQ-5D VAS scores vs the mild BP-I cohort (31.3 vs 40.3 [P<.001] and 60.6 vs 69.4 [P=.01], respectively) and statistically similar scores vs the moderate BP-I cohort. SF36v2 physical component scores were statistically similar to those of the mild BP-I cohort. Respondents with mBP-I reported similar rates of provider (5.5 vs 6.1 [P=.63]) and ER visits (.34 vs .40 [P=.59]) to patients with mild BP-I (but significantly fewer hospitalizations: .08 vs .19 [P=.03]).

Conclusions

Respondents with mBP-I exhibited similar HRQoL scores to those with mild to moderate BP-I. As expected for patients without a formal BP-I diagnosis, HRU was lower for mBP-I patients than moderate or severe BP-I, but comparable with mild BP-I. These results suggest that patients with potentially misdiagnosed BP-I may experience considerable HRQoL and HRU burdens akin to those of patients with mild to moderate BP-I.

Funding

AbbVie