bluuebunny/crossref_metadata_2025 huggingface dataset:
Premature Myocardial Infarction in the Middle East and North Africa: Rationale for the Gulf PREVENT Study
Authors: Dugani Sagar B. , Murad Waheed , Damilig Karisamae , Atos Jean , Mohamed Eshraga , Callachan Edward , Farukhi Zareen , Shaikh Arshia , Elfatih Abubaker , Yusef Salwa , Hydoub Yousif M. , Moorthy M. Vinayaga , Mora Bassem , Alawadhi Ahlam , Issac Robin , Saleh Abdulkarim , Al-Mulla Arif , Mora Samia , Alsheikh-Ali Alawi A.
Published: May 2019

The Middle East and North Africa (MENA) region has a high burden of morbidity and mortality due to premature (≤55 years in men; ≤65 years in women) myocardial infarction (MI) and acute coronary syndrome (ACS). Despite this, the prevalence of risk factors in patients presenting with premature MI or ACS is incompletely described. We compared lifestyle, clinical risk factors, and biomarkers associated with premature MI/ACS in the MENA region with selected non-MENA high-income countries. We identified English-language, peer-reviewed publications through PubMed (up to March 2018). We used the World Bank classification system to categorize countries. Patients with premature MI/ACS in the MENA region had a higher prevalence of smoking than older patients with MI/ACS but a lower prevalence of diabetes, hypertension, and dyslipidemia. Men with premature MI/ACS had a higher prevalence of smoking than women but a lower prevalence of diabetes and hypertension. The MENA region had sparse data on lifestyle, diet, psychological stress, and physical activity. To address these knowledge gaps, we initiated the ongoing Gulf Population Risks and Epidemiology of Vascular Events and Treatment (Gulf PREVENT) case–control study to improve primary and secondary prevention of premature MI in the United Arab Emirates, a high-income country in the MENA region.
Depression in migrant workers and nationals of Qatar: An exploratory cross-cultural study
Authors: Khaled Salma M , Gray Richard
Published: May 2019

Background:

The aim of this study was to compare the prevalence of depressive symptoms among migrants and non-migrants living in Qatar and identify variables associated with depressive symptomology in these groups, including culture of origin, time living in country and perceived quality of life. In addition, we tested if the latter two variables moderated the effect of culture of origin on depressive symptomology in the migrant groups.

Subject and Methods:

A telephone survey of a probability-based sample of 2,520 participants was conducted in February 2016. The sample was divided into three groups based on nationality and income: labour migrants (LMs), white-collar migrants (WCMs) and non-migrants or Qatari nationals (QNs). Participants completed the Whooley two-question test for depression.

Results:

The odds of depression were significantly increased in LMs (OR = 3.31, 95% CI = 2.36–4.65) and WCMs (OR = 1.40, 95% CI = 1.04–1.90) compared with non-migrants. Among LMs, having a problem with current employer in the last 3 months was also associated with depressive symptoms (OR = 2.10, 95% CI = 1.14–3.84). Culture of origin was significantly associated with depressive symptoms including South Asians (OR = 3.12, p < .001), East Asians (OR = 0.52, p = .013) and Westerners (OR = 0.45, p = .044) relative to Arabs. LM status remained strongly associated with depressive symptoms independent of culture of origin (OR = 2.02, p < .001).

Conclusion:

Perceived quality of life, but not length of stay, appears to be an important variable in explaining differences in symptoms between some cultural groups. Findings from this study highlight the importance of the context of migration and culture of origin as potential determinants of depressive symptomology in the host country.
“We’re Being Released to a Jungle”: The State of Prisoner Reentry and the Resilience of Women of Color
Authors: Garcia-Hallett Janet
Published: May 2019

The punitive carceral system is expected to tame people of color into docile bodies through their imprisonment. Furthermore, the oppressive and punitive U.S. context embodies patriarchy and injustice in which women of color endure unique obstacles at the intersection of race and gender. Given the power structures built to destabilize women of color before and after incarceration, this study uses interview data to examine their perseverance through carceral systems. The findings illustrate how oppressive regimes shape postincarceration obstacles and explore how women of color combat social-structural inequalities after incarceration.
School Choice and Conflict Narratives: Representative Bureaucracy at the Street Level in East Jerusalem
Authors: O’Connor Karl , Larkin Craig , Nasasra Mansour , Shanks Kelsey
Published: May 2019

In representative bureaucracy research, the dominant view holds that passive representation leads to active representation. Much of the research to date has focused on the conditions that influence this process. In this research, we argue that more attention needs to be paid to the manifestation of active representation, rather than simply its presence. We find that although passive representation may indeed lead to active representation, the nature of this active representation is interpreted differently by those sharing a primary identity. We use the lens of representative bureaucracy theory, and Q Methodology, to understand how street-level bureaucrats in East Jerusalem use their discretion within the education system of a contested society.
Trends and Patterns of Homicides Arising From Interpersonal Violence in Nigeria (2006-2016)
Authors: Ojedokun Usman A. , Tade Oludayo , Aderinto Adeyinka A.
Published: May 2019

Despite the considerable shift that has been recorded in the dimension and patterns of violence involving individuals in primary group relationships in Nigeria, available scholarly research on the phenomenon has been largely narrow with the majority concentrating on spousal abuse. To fill this gap, this study examined the incidence of homicides arising from interpersonal violence between 2006 and 2016. The descriptive design was employed, and social disorganization theory was adopted for its conceptual framework. Data were generated from the content review of a corpus of some Nigerian newspapers’ coverage on cases of interpersonal violence that resulted into fatalities. Findings revealed that 516 cases of homicide occurring in a wide range of contexts were recorded in Nigeria between 2006 and 2016. Although instances of violent deaths due to interpersonal violence were recorded in all years considered, we found that the highest share (37%) of the fatalities occurred in 2012. Also, the majority of homicides (58%) due to interpersonal violence occurred in the South–West region. A multilayered approach involving relevant stakeholders is advocated as way of successfully containing the problem.
The Change in the Composition of Trichoderma reesei Carbohydrases Complex as a Result of Gamma Mutagenesis
Authors: Kostyleva Elena V , Sereda Anna S , Osipov Dmitrii O , Velikoretskaya Irina A , Tsurikova Nina V
Published: May 2019

The filamentous fungus Trichoderma reesei is traditionally used as the main industrial producer of cellulases and hemicellulases. Recently, the relevance of carbohydrases hydrolyzing nonstarch polysaccharides of cereals has significantly increased in feed production. In processing of grain raw materials, endodepolymerases, mainly xylanases and endoglucanases, play a key role. Earlier, we carried out gamma mutagenesis of an industrial strain T. reesei BCM18.2/KK to increase the proportion of endodepolymerases in its enzyme complex. Endoglucanase activity of the strain was increased 5-fold, while xylanase activity increased more than 8-fold. It was interesting to determine the carbohydrases composition in enzyme preparations obtained from the original and mutant T. reesei strains. So, the strains were cultured in laboratory fermenters; concentrated preparations were obtained using freeze dryer. It was established that gamma mutagenesis resulted in significant changes in the carbohydrases complex of the strain. Cellobiohydrolase I being the major carbohydrase in the original strain was absent in the enzyme complex of the mutant. The share of xylanases and endoglucanases in the preparation from the mutant strain increased by 6% and 6.5%, respectively, compared with the preparation from the original strain. The obtained data show the ability of gamma irradiation to affect the component composition of T. reesei carbohydrase complex.
The Prevalence and Forecast Prevalence of Overactive Bladder in the Medicare Population
Authors: Puckrein Gary , Walker David , Xu Liou , Congdon Peter , Gooch Katherine
Published: May 2019

Objectives:

To determine current and future prevalence of overactive bladder (OAB) among Medicare fee-for-service beneficiaries in the United States.

Methods:

Prevalence of OAB in US adults ⩾ 65 years was determined using the 2013 Medicare Beneficiary Part B Carrier Claims File, Part D Drug Event File, and Medicare Beneficiary Annual Summary File. Prevalence for 2027 was forecasted with US Census population projections. Regional projections were based on applying national OAB rates by age, sex, and race/ethnicity to zip code tabulation area beneficiary populations.

Results:

In the 2013 dataset, the prevalence of OAB was 7.2% (male: 7.7%; female: 6.7%). Across demographic categories, prevalence was the highest among those aged more than 74 years (9.3%), identifying as White (7.4%), and residing in urban areas (7.5%). By 2027, OAB is projected to increase by 48.1%.

Discussion:

OAB affects a substantial proportion of the US fee-for-service beneficiary population, with the prevalent population projected to rise substantially by 2027.
Explaining legislative party switching in advanced and new democracies
Authors: Klein Elad
Published: May 2019

The phenomenon of legislative party switching has attracted considerable attention among scholars. Studies show that parties are likely to experience defections if they are unable to offer their legislators electoral, office and policy benefits. While often deemed a symptom of a weakly institutionalized party system, switching may also be frequent in established democracies. Yet, surprisingly, we have no empirical evidence to help us understand whether party benefits that drive switchers are different in established democracies and new democracies. I argue that parties that fail to provide their members with re-election prospects or government access are likely to witness switching only in new democracies. In advanced democracies, switching is likely to be associated with ideological identity and policy motives. The statistical analysis of party switching across 25 European advanced and post-communist democracies confirms my expectations.
A worked example of initial theory-building: PARTNERS2 collaborative care for people who have experienced psychosis in England
Authors: Gwernan-Jones Ruth , Britten Nicky , Allard Jon , Baker Elina , Gill Laura , Lloyd Helen , Rawcliffe Tim , Sayers Ruth , Plappert Humera , Gibson John , Clark Michael , Birchwood Maximillian , Pinfold Vanessa , Reilly Siobhan , Gask Linda , Byng Richard
Published: May 2019

In this article, we present an exemplar of the initial theory-building phase of theory-driven evaluation for the PARTNERS2 project, a collaborative care intervention for people with experience of psychosis in England. Initial theory-building involved analysis of the literature, interviews with key leaders and focus groups with service users. The initial programme theory was developed from these sources in an iterative process between researchers and stakeholders (service users, practitioners, commissioners) involving four activities: articulation of 442 explanatory statements systematically developed using realist methods; debate and consensus; communication; and interrogation. We refute two criticisms of theory-driven evaluation of complex interventions. We demonstrate how the process of initial theory-building made a meaningful contribution to our complex intervention in five ways. Although time-consuming, it allowed us to develop an internally coherent and well-documented intervention. This study and the lessons learnt provide a detailed resource for other researchers wishing to build theory for theory-driven evaluation.
Standard tools for non-standard care: The values and scripts of a person-centred assessment protocol
Authors: Lydahl Doris
Published: May 2019

This article uses a material semiotic perspective to study a highly influential model of healthcare policy and practice today: person-centred care. While person-centred care is often regarded as implying a turn away from technology and standardization towards more humanistic values in care, this article shows that mundane standardization technologies, such as an assessment protocol, are integral components of person-centred care. Building on interviews and observational studies at a Swedish hospital introducing person-centred care, the article analyses the person-centred protocol in situ. The article teases out three core concerns inscribed in the protocol: a concern for the patient experience and perspective, a valuing of evidence-based knowledge and a managerial imperative. The article illustrates how these contrasting values were rendered compatible through the continuous tinkering of healthcare professionals. Finally, it shows how users modified the script of the protocol under analysis and how relations between the three core concerns were adjusted in the process. The article concludes that tinkering and user–technology relations are of significance for the fate of person-centred care at large.
Cross-cultural adaptation of the Arabic Positive and Negative Syndrome Scale in schizophrenia: Qualitative analysis of a focus group
Authors: Amro Iman , Ghuloum Suhaila , Mahfoud Ziyad , Opler Mark , Khan Anzalee , Hammoudeh Samer , Hani Yahya , Yehya Arij , Al-Amin Hassen
Published: May 2019

As part of a project to translate and validate scales used in the diagnosis and treatment of Arab patients with schizophrenia, this study aimed to explore the experience of clinical research coordinators (CRCs) while administering the Arabic version of the Positive and Negative Syndrome Scale (PANSS) on Arab schizophrenia patients. We previously reported that the Arabic version of PANSS is a valid and reliable tool to assess Arab patients with schizophrenia. Five CRCs and the principal investigator attended focus group discussions on cultural issues in administering the PANSS. A thematic analysis approach was utilized for data coding and analysis. The results identified issues related to the translation of the instrument, the structure of the interview, the cultural sensitivity of some questions, and the procedures for rating items of the PANSS. Qualitative analysis also identified four main themes relevant to clinical assessment of patients from Middle Eastern cultures: religion, beliefs and values, gender, and semantic expressions. In conclusion, researchers or clinicians administering the PANSS scale interview in Arabic should be trained to consider the roles of local dialects, familiarity with abstract thinking, religion, and social constructs when assessing psychosis.
The practices of modern criminal defence lawyers: Alienation and its implications for access to justice
Authors: Newman Daniel , Welsh Lucy
Published: May 2019

This article marries two sets of independently gathered empirical data (observation and interviews) to argue that English criminal defence lawyers currently present as alienated workers. We seek to revive and revisit theories of alienation that are grounded in Marxism and use them as a lens through which lawyers’ behaviour can be viewed and understood. Building on a Marxist application of alienation, we offer a refined analysis premised upon a contemporary understanding of how alienation plays out in criminal defence work during the neoliberal era. We highlight that the way lawyers talk about their roles suggests that they have lost a sense of purpose, and feel powerless and undervalued. We argue that those feelings appear to have developed as a result of structural change—most notably funding cuts and demands for efficiency—which seem to be grounded in what can broadly be understood as neoliberal political ideology and austerity measures. We further suggest that such structural change and resultant feelings of alienation have implications for the quality of service that defendants receive.
From Confrontation to Mediation: Cambodian Farmers Expelled by a Vietnamese Company
Authors: Bourdier Frédéric
Published: May 2019

Concessions granted to investors in Cambodia have generated a deep sense of insecurity in rural forested areas. Villagers are not confined to a passive “everyday resistance of the poor,” as mentioned by James Scott, insofar as they frequently engage in frontal strategies for recovering land. Such has been the case in the northeastern provinces, where indigenous livelihoods are recurrently threatened by foreign and national companies. But what happens when a land conflict ends up in a stakeholder dialogue? The article intends to follow such a story that occurred for the first time in Ratanakiri, in a vast territory inhabited by several ethnic groups. After gruelling hostilities with the encroacher, dispossessed farmers finally accepted, encouraged by international/national NGOs, to comply with existing mechanisms associated with international law regulations and World Bank procedures. It ends up in an institutionalised mediation, technical and apolitical, which turned to the disadvantage of the people, with evident power imbalance. Our analysis, while portraying the trajectories of national/international actors involved in the mediation process, reveals the effects on this mediation on local sociopolitical organisations.
Religion, Mass Violence, and Illiberal Regimes: Recent Research on the Rohingya in Myanmar
Authors: Zakaria Faizah Binte
Published: May 2019

The plight of the Rohingya in Myanmar has drawn considerable international attention in recent years but a solution to the crisis remains elusive. This article gathers pertinent research from key books on Myanmar's politics and society published during the last five years and synthesizes their contributions to our understanding of the issue. It argues that the picture emerging from these works highlights how legal infrastructure for dealing with mass violence fails to deal adequately with the realities of an illiberal state. It further shows how the conflict's religious dimension - amplified through public discourse - obscures a competition between historically oppressed peoples to be heard. Rather than a conflict between Buddhists and Muslims, the nested dynamics of Rakhine State's regional politics shaped a situation where minorities turn on other minorities. This critical reading of the issue thus implies that international intervention in the form of labeling victims to save and perpetrators to sanction would likely be unproductive.
Vascular injury in tubular lumbar microdiscectomy, case report and literature review
Authors: Hasan Ghazwan Abdulla , Qatran Raheem Hayder , Yuser Akeel , Al-Naser Luay M , Sheta Reda Ali
Published: May 2019

Vascular injury in lumbar disk disease is a common complication reviewed in the literature. In our study, we reviewed the rare complication of vascular injury that occurs during lumbar microscopic tubular discectomy. The patient is a 46-year-old male, diabetic, hypertensive and a smoker who presented with a history of backache and right-sided radiculopathy to S1 dermatome for 6 weeks. Conservative measures failed, and we planned and performed microscopic tubular discectomy at the level of L5-S1. Immediately postoperatively, the patient developed acute, sharp, burning pain in the left leg, partially relieved on hip flexion, with diminished distal pulsation of dorsalis pedis, popliteal and femoral. Urgent consultation with a vascular surgeon included a computed tomography angiography which confirmed a vascular injury of the left iliac artery and vein near the bifurcation. The plan involved urgent retroperitoneal exploration of the left iliac vessels, and primary repair with synthetic graft was done with distal embolectomy to regain distal pulsation postoperatively. Further follow-up revealed that the repair was successful.
Non-Hispanic Black Adolescents’ Self-Reported Health Behaviors Associated With Childhood Obesity in an Urban Clinic
Authors: Lam Suet Kam , Cheng Allison , Li Hong , Lazebnik Rina
Published: May 2019

Background: The prevalence of children with overweight or obese weight status in the United States is ~30%. Limited data exist on urban adolescents’ self-reported health behaviors and their perceptions to healthy living. Objectives: To examine adolescents’ self-reported health behaviors and perceived barriers and their associations with weight status. Methods: In 2014, patients (ages 9+ years) were enrolled and completed health behavior surveys. Measurements were categorized into body mass index (BMI)-for-age percentiles. Adolescents without obesity (including underweight, healthy weight, and overweight) were compared against adolescents with obesity. Results: A total of 132 adolescents were enrolled. The only factor that was statistically significant between the 2 weight groups was frequent exercise, which decreased odds of obesity by 0.34 (95% CI 0.13-0.93). Surprisingly, the odds of being obese increased significantly by 11.1 (95% CI 4.2-33.3) in those reporting trying to lose weight. Conclusions: To combat obesity, we reiterate the need for frequent exercise. Health care professionals should consider highlighting increased frequency of exercise and explore why adolescents with obesity were more inclined to report weight loss methods.
“Look Like You Have It Together”: Examining Mental Illness Stigma and Help Seeking Among Diverse Emerging Adults
Authors: Crumb Loni , Crowe Allison , Averett Paige , Harris Janee’ Avent , Dart Courtney
Published: May 2019

Individuals transitioning through emerging adulthood endure various challenges that impact their mental health and well-being. Mental illness stigma interferes with the willingness to seek professional mental health services during this transition period. We must fully understand the influence of mental illness stigma and ways to increase the utilization of mental health services for emerging adults. Using content analysis, the researchers examined responses to open-ended survey questions and identified themes that captured beliefs about mental illness stigma and help seeking, desired characteristics of mental health providers, and support preferences for mental health concerns in a diverse group of emerging adults. The three core themes of (1) public stigma, (2) mental health provider traits, and (3) supports for mental health concerns provide insight into the understudied area of emerging adulthood. Study findings have important implications to combat stigma, increase mental health service utilization, and improve mental health service delivery for emerging adults.
A Narrative Literature Review Considering the Development and Implementation of Longitudinal Integrated Clerkships, Including a Practical Guide for Application
Authors: Brown Megan EL , Anderson Kevin , Finn Gabrielle M
Published: May 2019

Hailed by supporters as the answer to many challenges facing medical schools and the wider health care system, longitudinal integrated clerkships (LICs) offer a practical and sustainable alternative to more traditional block rotational models. Given this, their popularity as a curricular measure is increasing, although such clerkships remain relatively novel within the United Kingdom. This narrative literature review of international work provides a comprehensive introduction to developing and implementing LICs within medical education. This review generates a practical guide for medical educators with a focus on the development and implementation of LICs within the United Kingdom, on which there is little work. Using illustrated examples and with reference to contemporary literature, it outlines the rationale for considering an LIC within a curriculum, the different types of LIC, barriers and enabling factors to LIC implementation and considers the contemporary application of LIC models within the United Kingdom. The practical guide details key questions educators must consider when developing and implementing an LIC, particularly within the landscape of UK medical education.
Structural factors affecting the crystal-chemical variability in Al-rich K-dioctahedral 2M1 micas
Authors: Zviagina Bella B. , Drits Victor A.
Published: May 2019

To reveal the factors that determine the different ranges of compositional variations in high- and low-temperature Al-rich K-dioctahedral micas, relationships between structural parameters and cation composition were analysed for: (1) a series of synthetic 2M1 muscovite–phengite–aluminoceladonite samples; and (2) Al-rich, K-dioctahedral 2M1 micas with previously published refined structural data. The dependences of the unit-cell parameters on cation composition and the variations in tetrahedral and octahedral lateral dimensions and sheet thicknesses, interlayer distances and tetrahedral rotation angles were analysed and compared with those found previously for the series 1M trans-vacant (tv) illite–1M aluminoceladonite. The similarities in the variations of unit-cell parameters with cation composition observed in 2M1 and 1M natural and synthetic K-dioctahedral micas imply that these variations are controlled by similar – albeit not identical – structural factors. A major structural factor is the readjustment of the differently sized tetrahedral and octahedral sheets, which is realized in a different manner in micas formed under different pressure and temperature conditions.
NMR structure determination of Ixolaris and factor X(a) interaction reveals a noncanonical mechanism of Kunitz inhibition
Authors: De Paula Viviane S. , Sgourakis Nikolaos G. , Francischetti Ivo M. B. , Almeida Fabio C. L. , Monteiro Robson Q. , Valente Ana Paula
Published: May 2019

Ixolaris is a potent tick salivary anticoagulant that binds coagulation factor Xa (FXa) and zymogen FX, with formation of a quaternary tissue factor (TF)/FVIIa/ FX(a)/Ixolaris inhibitory complex. Ixolaris blocks TF-induced coagulation and PAR2 signaling and prevents thrombosis, tumor growth, and immune activation. We present a high-resolution structure and dynamics of Ixolaris and describe the structural basis for recognition of FX. Ixolaris consists of 2 Kunitz domains (K1 and K2) in which K2 is strikingly dynamic and encompasses several residues involved in FX binding. This indicates that the backbone plasticity of K2 is critical for Ixolaris biological activity. Notably, a nuclear magnetic resonance–derived model reveals a mechanism for an electrostatically guided, high-affinity interaction between Ixolaris and FX heparin-binding (pro)exosite, resulting in an allosteric switch in the catalytic site. This is the first report revealing the structure-function relationship of an anticoagulant targeting a zymogen serving as a scaffold for TF inhibition.
Can evolutionary thinking shed light on gender diversity?
Authors: Wren Bernadette , Launer John , Reiss Michael J. , Swanepoel Annie , Music Graham
Published: May 2019

Issues of sexual reproduction lie at the core of evolutionary thinking, which often places an emphasis on how individuals attempt to maximise the number of successful offspring that they can produce. At first sight, it may therefore appear that individuals who opt for gender-affirming medical interventions are acting in ways that are evolutionarily disadvantageous. However, there are persuasive hypotheses that might make sense of such choices in evolutionary terms and we explore these here. It is premature to claim knowledge of the extent to which evolutionary arguments can usefully be applied to issues of gender identity, although worth reflecting on the extent to which nature tends towards diversity in matters of sex and gender. The importance of acknowledging and respecting different views in this domain, as well as recognising both the uncertainty and likely multiplicity of causal pathways, has implications for clinicians. We make some suggestions about how clinicians might best respond when faced with requests from patients in this area.

LEARNING OBJECTIVES

After reading this article you will be able to:

•

understand evolutionary arguments about diversity in human gender identity

•

identify strengths and weaknesses in evolutionary arguments applied to transgender issues

•

appreciate the range and diversity of gender experience and gender expression among people who present to specialist gender services, as well as the likely complexities of their reasons for requesting medical intervention.
The History of Psychiatry
Authors: Birley J. L. T.
Published: May 2019

I am not a historian, a mere dabbler in history, but the figures of the past have always intrigued me. Psychiatry lives in the shadow of the 19th century, both in terms of its architecture and of its theories. It is not too difficult to give oneself déjà vu feelings about psychiatry, and to see its ‘progress' as a circular tour. But what of it ? In that way we revisit all sorts of old friends, provided we meet them as they really were, and not as dusty images, mouldering statues, ancient deities or foolish fond old men.
Drugs and Delinquency: A Four Year Follow-up of Drug Clinic Patients
Authors: Gordon Alistair M.
Published: May 2019

The addiction and conviction status of 60 male patients, examined at a London drug clinic in 1970 was reassessed at four-year follow-up. Forty-three per cent had become abstinent, 23 per cent remained dependent and 15 per cent had died. Ninety-seven per cent had received a court conviction and 73 per cent were convicted during follow-up. A prognostic assessment was determined in combined terms of continued addiction and continued delinquency. Poor outcome related to a lack of educational attainment, earlier first conviction and regular opiate use on arrival, and was associated during follow-up with an irregular clinic attendance beyond one year, drug conviction and death. Good outcome related to an absence of parental loss and later first conviction, and was associated during follow-up with discharge within one year without hospital admission. Analysis of the data indicates the value of combining forensic information with drug history in prognostic assessment.
The Senior Registrar Survey: The Second Year Follow-up
Authors: Brook Peter
Published: May 2019

A two-year follow-up inquiry was made of the residuum of a cohort formed by all senior registrars in general psychiatry in post in late 1974. Of the original 155, nearly half are in permanent posts, but only three-quarters of these are in general psychiatry in the United Kingdom. Twelve have already emigrated.
Psychiatric Out-patients in a Geographically Delimited Area
Authors: Kastrup Marianne
Published: May 2019

A three-month long study was undertaken of the utilization of the local psychiatric out-patient clinic by the geographically delimited population of Århus, Denmark.

Of the 307 males and 580 females contacting the clinics, 107 males and 148 females were new referrals, corresponding to 1·25 males and 1·48 females per 1,000 inhabitants 15 years or more, respectively. The ratio of treated females to males increased from 0·87 in the 15–24–year age group to 2·22 for patients 55 years or above.

Manic-depressive psychosis accounted for 43 per cent, followed by schizophrenia and other functional psychoses in males, and neuroses and other functional psychoses in females. The clinics collaborated closely with the in-patient facilities. Thus about 75 per cent were referrals from the in-patient clinics and 70 per cent of the discharged out-patients admitted.
Suicide Reporting: Information or Entertainment?
Authors: Shepherd Daphne , Barraclough B. M.
Published: May 2019

The reporting of suicide inquests by a provincial evening paper has been examined. Inquests on violent and youthful suicides were given more reports, larger reports and more eye-catching headlines.
The Patient and the First Psychiatric Interview
Authors: Michaels Ruth M. , Sevitt Michael A.
Published: May 2019

This paper presents work that formed the basis of a fourth-year project at Southampton University Medical School. Thirty patients were seen prior to their first psychiatric consultation and asked about their hopes, fears and expectations. Twenty-five were seen subsequently.

The study, which is largely descriptive, shows that many patients have unrealistic expectations about various aspects of the interview, and afterwards many are dissatisfied with its outcome. The paper discusses these findings and makes some tentative recommendations.
AAML 1421, a phase I/II study of CPX-351 followed by fludarabine, cytarabine, and G-CSF (FLAG) for children with relapsed acute myeloid leukemia (AML): A Report from the Children’s Oncology Group.
Authors: Cooper Todd Michael , Absalon Michael , Alonzo Todd Allen , Gerbing Robert B , Leger Kasey Joanne , Hirsch Betsy A , Pollard Jessica Anne , Razzouk Bassem I. , Aplenc Richard , Kolb E. Anders
Published: May 2019

10003

Background: Effective regimens with favorable toxicity profiles are needed for heavily pre-treated children with relapsed AML. AAML1421 is a Phase I/II study of CPX-351, a liposomal preparation of cytarabine and daunorubicin demonstrating efficacy in adults. AAML1421 sought to determine the recommended Phase 2 Dose (RPD2) of CPX-351 and the response rate (complete response (CR) + complete response without platelet recovery (CRp)) after up to 2 cycles of therapy. Methods: Children > 1 and ≤ 21 years of age with relapsed/refractory AML were eligible for dose finding, and those in first relapse were eligible for efficacy. A modified rolling six design was used for dose-limiting toxicity (DLT) assessment which occurred in Cycle 1. Dose level 1 (DL1) was 135 units/m2 on days 1, 3, and 5 with a single dose de-escalation to 100 units/m2 if DL1 was intolerable. The Efficacy Phase used a Simon-two stage design. The response rate was determined after up to 2 cycles of therapy (Cycle 1: CPX-351; Cycle 2: FLAG). The Overall Response Rate (ORR) was defined as CR+CRp+CRi (CRi = CR with incomplete hematologic recovery). Results: Thirty-eight patients (pts) enrolled: 6 in dose-finding and 32 in the efficacy phase. DLT occurred in 1/6 patients and was a grade 3 decrease in ejection fraction(EF). This was the only Grade 3 cardiac toxicity. Therefore, 135 units/m2 on days 1, 3, 5 was the RP2D. All dose finding pts were eligible for efficacy determination. One pt in the efficacy phase was unevaluable. The most common ≥ Grade 3 toxicities in Cycle 1 included fever/neutropenia (45%), infection (47%), and rash (40%). There was no toxic mortality. Best responses included 20 CR (54%), 5 CRp (14%), and 5 CRi (14%). Seventy percent achieved best response after cycle 1. Twenty-one of 25 patients with CR/CRp had no detectable residual disease (RD) (84%) by flow cytometry. HSCT was used as consolidation in 23/29 responders (79%); 18 of 23 (78%) had no detectable RD prior to HSCT. Conclusions: The RP2D of CPX-351 is 135 units/m2/dose on days 1, 3, 5. CPX-351 was well tolerated and protocol therapy was effective with CR+CRp rates of 68.3% (90% CI 52.9% to 78.0%) and ORR (CR+CRp+CRi) of 81.1% (90% CI 67.4% to 88.8%). AAML1421 response rates are superior to any published North American cooperative group clinical trial for children with AML in first relapse. Clinical trial information: NCT02642965.
Safety and activity of venetoclax in combination with high-dose cytarabine in children with relapsed or refractory acute myeloid leukemia.
Authors: Karol Seth E , Alexander Thomas , Das Gupta Soumyasri , Pounds Stanley B. , Canavera Kristin , Klco Jeffery M , Lacayo Norman James , Pui Ching-Hon , Opferman Joseph T , Rubnitz Jeffrey E
Published: May 2019

10004

Background: Venetoclax is an orally available BCL-2 antagonist with demonstrated activity in adults with newly diagnosed or relapsed acute myeloid leukemia (AML). Here, we describe the first use of venetoclax 1) in combination with high-dose cytarabine and idarubicin 2) in patients 2-22 years old with relapsed AML. Methods: Patients with relapsed AML or AML refractory to at least two courses of induction therapy were enrolled in this Phase 1 study with a rolling-six design. All patients received venetoclax (240 or 360 mg/m2) on days 1-28 and low-dose (LD: 100 mg/m2 every 12 hours x 20 doses) or high-dose (HD: 1000 mg/m2 every 12 hours x 8 doses) cytarabine beginning on day 8 (Table). Patients who had previously received < 270 mg/m2 of doxorubicin equivalents also received idarubicin 12 mg/m2 on day 8 in dose level 4; other patients were enrolled on the expansion cohort at dose level 3. Non-hematologic CTCAE grade 3 or higher toxicities were intensity limiting (ILT), excluding those anticipated with HD cytarabine. Results: Among 18 evaluable patients, a single ILT (prolonged hematological suppression beyond day 50) was observed (Table). Toxicities were consistent with the underlying cytotoxic chemotherapy, with 14 patients experiencing a total of 40 grade 3 toxicities including 6 documented infections and 23 episodes of febrile neutropenia. There was 1 grade 4 fungal sepsis. The recommended phase 2 dose of venetoclax was 360 mg/m2 (max 600 mg) when combined with HD cytarabine or HD cytarabine/idarubicin. Of the 12 patients with > 50% reduction in blasts following the 7-day venetoclax window therapy, end-of-cycle marrow responses included 7 CR/CRi and 3 PR. Minimal residual disease negative remissions occurred in 4 patients. BH3 profiling of samples and a phase 2 expansion of both dose levels 3 and 4 to further characterize the promising activity of these combinations are underway. Conclusions: Venetoclax combined with cytarabine or cytarabine/idarubicin is active and well tolerated in pediatric patients with relapsed/ refractory AML. Clinical trial information: NCT03194932. [Table: see text]
Randomized use of anti-GD2 antibody dinutuximab beta (DB) long-term infusion with and without subcutaneous interleukin-2 (scIL-2) in high-risk neuroblastoma patients with relapsed and refractory disease: Results from the SIOPEN LTI-trial.
Authors: Lode Holger N. , Valteau-Couanet Dominique , Gray Juliet , Luksch Roberto , Wieczorek Aleksandra , Castel Victoria , Ash Shifra , Laureys Genevieve , Papadakis Vassilios , Owens Cormac , Garaventa Alberto , Manzitti Carla , Siebert Nikolai , Troschke-Meurer Sascha , Glogova Evgenia , Poetschger Ulrike , Ladenstein Ruth Lydia
Published: May 2019

10014

Background: We determined the role of scIL-2 combined with long term infusion (LTI) of DB in patients (pts) with high-risk relapsed/refractory neuroblastoma. Methods: 160 pts were enrolled into an open label SIOPEN Phase II clinical trial (EudraCT 2009-018077-31). Pts were randomly assigned to receive up to 5 cycles of 100 mg/m2 DB-LTI (d8-17) and 160 mg/m2 oral isotretinoin (d19-32) (81 pts) with and without 6x106IU/m2 scIL-2 (d1-5; 8-12) (79 pts). Endpoints were toxicity, response rates and 2yrs-event free and -overall survival. Results: Between 07/2014 and 07/2017, 160 pts from 11 countries were randomised. Median follow-up is 2.6 years. Pts were well balanced between arms according to stage, age, MYCN amplification, patients with relapse and remission status. The 2yrs-EFS and -OS for DB (81 pts) vs. DB combined with scIL-2 (79 pts) was 59%±6% vs 65%±6% (p = 0.721) and 79%±5% vs 84%±4% (p = 0.904). In 97 pts with evaluable disease, a response rate of 49% (9% CR, 40% PR) vs 52% (26% CR, 26% PR) after treatment with DB vs DB and scIL-2 was observed. Grade 3&4 fever (16% vs 46%, P = 0.000), allergic reaction (1% vs 14%, P = 0.004), hematological toxicity (46% vs 66%, P = 0.013) and neurotoxicity (0% vs 8%, p = 0.003) were significantly worse in the combination arm, but no difference was seen for capillary leak, gastrointestinal, liver enzyme elevation and pain. Paraplegia possibly related to the treatment was observed in 2 pts in the combination arm, none in the arm without scIL-2, and one resolved to baseline. A subgroup of 34 pts who had a relapse and measurable disease at treatment start, showed a 2yrs-EFS and -OS in DB (17 pts) vs DB combined with scIL-2 (17 pts) of 35%±12% vs 69%±12% (p = 0.116) and 59%±12% vs 81%±10% (p = 0.167). However, this trend was statistically not significant. Pharmacokinetic and HACA response between both arms was not different with overlapping antibody concentration-time curves and a HACA response of 15/81 (19%) (DB) vs 16/79 (20%) (DB and scIL-2). Conclusions: No significant difference in efficacy of DB combined with scIL-2 and increased toxicity in this arm suggests that this schedule of scIL-2 is of no additional benefit. Clinical trial information: 2009-018077-31.
Outcomes of adolescent males with extracranial malignant germ cell tumors compared with children and young adults: A report from the Malignant Germ Cell Tumors International Consortium (MaGIC) group.
Authors: Shaikh Furqan , Stark Daniel P. , Dang Ha , Xia Caihong , Krailo Mark D. , Stenning Sally Patricia , Pashankar Farzana D. , Rodriguez-Galindo Carlos , Olson Thomas Arthur , Hale Juliet , Depani Sarita , Stoneham Sara , Nicholson James , Murray Matthew , Amatruda James F. , Billmire Deborah F , Fonseca Adriana , Frazier A. Lindsay
Published: May 2019

10022

Background: Adolescents with extracranial malignant germ cell tumors (GCTs) are often treated on the same regimens developed for children, but more closely resemble the clinical characteristics of young adult patients. We sought to determine whether event-free survival (EFS) for adolescents with GCTs was more like that of children or young adults. Methods: We assembled an individual patient database of ten GCT trials: seven conducted by pediatric cooperative groups and three by an adult group. We selected male patients aged 0-30 years old treated with platinum-based chemotherapy for non-seminomatous malignant GCTs of the testis, retroperitoneum, or mediastinum. We categorized age-group as children (0 to < 11 years), adolescents (11 to < 18 years), or young adults (18 to < 30 years old). We compared EFS among age groups, and adjusted for calculated IGCCCG risk-group using Cox proportional hazards analysis. Results: 593 patients met inclusion criteria, of whom 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS for adolescents (72%; CI = 62-79%) was significantly lower than for children (90%; CI = 81-95%, p = 0.003) and for young adults (88%; CI = 84-91%, p < 0.001). Risk-group was significantly associated with EFS in the adolescent age-group (p = 0.002). In a Cox multivariable analysis, the difference between adolescents and children remained statistically significant (HR = 0.30, p = 0.001), but the difference between adolescents and young adults did not (HR 0.66, p = 0.114). Conclusions: EFS for adolescent patients with extracranial malignant GCTs was similar to young adults but significantly worse than children. This finding may have important implications for how adolescent patients are treated.
Outcome of children with malignant germ cell tumors by response status at the end of induction chemotherapy.
Authors: Fonseca Adriana , Villaluna Doojduen , Krailo Mark D. , Frazier A. Lindsay , Shaikh Furqan
Published: May 2019

10023

Background: The management of pediatric malignant germ cell tumors (MGCTs) includes induction therapy with 3-4 cycles cisplatin, etoposide, bleomycin (PEb). The current practice recommends 2-3 cycles of PEb (total 6 cycles) as consolidation therapy if response is not complete at the end of induction, a significantly different approach than that used in adult patients who receive a standard number of cycles. Furthermore, there is no evidence supporting the addition of a consolidation phase with PEb in pediatric patients with MGCTs. Methods: We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs (AGCT0132). All patients received 3 cycles of PEb and underwent response assessment at the end of induction. Complete Response (CR) was defined as negative tumor markers and no viable residual lesion. Patients in CR were not to receive any further chemotherapy. Patients not in CR were prescribed 3 additional cycles of PEb as consolidation. Event-free survival (EFS) and Overall survival (OS) was calculated using the Kaplan-Meier method. Results: Among 210 patients enrolled, 193 patients had CR after 3 cycles of induction chemotherapy, and their post-induction 4yr-EFS and OS was 93% and 99%. Fifteen patients were not in CR at the end of the first 3 cycles and received additional chemotherapy, and their 4yr-EFS and OS was 51% and 60%. Conclusions: Children with MGCTs who have a partial response after the first 3 cycles of chemotherapy had an inferior outcome compared to those with a CR, despite receiving additional cycles of PEb chemotherapy. Thus, we conclude that consolidation is of unclear benefit. Although our results are limited by small sample size and lack of comparator, we propose that pediatric MGCT patients who fail to achieve a CR after standard induction chemotherapy should receive a salvage regimen with different agents rather than consolidation with more cycles of the same chemotherapy.
High-dose naxitamab plus stepped-up dosing of GM-CSF for high-risk neuroblastoma (HR-NB): Efficacy against histologically-evident primary refractory metastases in bone marrow (BM).
Authors: Kushner Brian H. , Modak Shakeel , Basu Ellen M. , Roberts Stephen S. , Cheung Nai-Kong V.
Published: May 2019

10024

Background: Cure of HR-NB often requires ablating BM metastases that are chemoresistant and survive 131I-metaiodobenzylguanidine (MIBG) therapy. BM is ideal for immunotherapy with anti-GD2 antibodies including naxitamab (humanized-3F8; granted FDA’s breakthrough designation in 2018) because of excellent accessibility to antibody, complement, and effector cells. GM-CSF exerts a dose-response effect in antibody-dependent cellular cytotoxicity and significantly improves outcome with murine-3F8 ( JCO 2012;30:426). Methods: We evaluated HR-NB patients with histologically-evident chemoresistant disease in BM, but no soft tissue or prior progressive disease, for response to naxitamab+GM-CSF on protocol (NCT01757626). Cycles comprised naxitamab infused intravenously (30 minutes) x3 (Mon-Wed-Fri) and subcutaneously-administered GM-CSF starting 5 days pre-naxitamab in priming doses of 250µg/m2/day, then stepped-up to 500µg/m2/day beginning with antibody. Naxitamab was dose-escalated in the phase I portion and 9mg/kg/cycle (~270mg/m2/cycle, i.e., > 2.5x dosage of ch14.18) in the phase I/II expansion. BM was assessed post-cycle 2 in aspirates+biopsies from bilateral posterior and anterior iliac crests. Cycles were monthly but were deferred if human anti-human antibody (HAHA) developed. Results: The 19 patients enrolled through 5/2018 were 5m-to-19m (median 7.5m) post-diagnosis and age 2y10m-to-10y1m (median 5y2m). Included were 5 phase I and 14 phase I/II patients. Histology showed primitive NB in 12 and ganglioneuromatous cells in 7 patients. All (100%) patients achieved complete response (CR) in BM. 16 patients also had NB in bone/BM by 123I-MIBG scan; the latter showed CR in 12 (75%). 11 patients remained progression-free 20+-to-54+ (median 27+) months from enrollment, including 10 treated with anti-NB vaccine. HAHA developed in 2 patients post-cycle 2. Toxicities were as expected ( JAMA Oncol 2018;4:1729). Conclusions: Naxitamab+GM-CSF is effective against chemoresistant NB in BM, supporting further development of naxitamab which is proceeding in a pivotal international trial (NCT02502786). Clinical trial information: NCT01757626.