Publications by authors named "Claudia Lang"

46 Publications

Reply to "Benralizumab: A potential tailored treatment for life-threatening DRESS in the COVID-19 era".

J Allergy Clin Immunol Pract 2021 Jul 15. Epub 2021 Jul 15.

Faculty of Medicine, University of Zurich, Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Christine Kühne Center for Allergy Research and Education CK-CARE, Davos, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2021.06.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299284PMC
July 2021

Comprehensive Approach: Current Status on Patient Education in Atopic Dermatitis and Other Allergic Diseases.

Handb Exp Pharmacol 2021 Jul 5. Epub 2021 Jul 5.

Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany.

Allergic diseases are characterized by a complex complex chronic pathophysiology. Therapeutic patient education (TPE) programs are an important part of health care for allergic patients. These programs aim to increase the patient's adherence to evidence-based treatment and improve their ability to cope with the disease. TPE led by a multiprofessional team covers the complex pathogenesis of the disease, trigger factors, nursing and dietary issues, and the broad variety of treatment options available including psychological and behavioral aspects.Regarding atopic dermatitis (AD), randomized, controlled studies have demonstrated the beneficial effects of delivering structured group training to children, their caregivers, and adult patients with AD. Such intervention achieved substantial improvements in quality of life and objective clinical disease parameters. Besides AD, training programs have also been developed and evaluated for patients with anaphylaxis and asthma. This article provides an overview of the multitude of TPE concepts and their impact on subjective and objective outcomes. It focuses on AD but also sheds light on other allergic diseases such as anaphylaxis and asthma.
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http://dx.doi.org/10.1007/164_2021_488DOI Listing
July 2021

Allergens in permanent tattoo ink - first results of the Information Network of Departments of Dermatology (IVDK).

J Dtsch Dermatol Ges 2021 Jun 29. Epub 2021 Jun 29.

Information Network of Departments of Dermatology (IVDK), Institute at the University Medical Center Göttingen, Göttingen, Germany.

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http://dx.doi.org/10.1111/ddg.14530DOI Listing
June 2021

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID-19 patients.

Allergy 2021 Jun 22. Epub 2021 Jun 22.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Background: Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR.

Methods: Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19-related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed.

Results: IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8 T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features.

Conclusion: A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8 T cells in severe COVID-19 patients, which in turn may impact the development of MDR.
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http://dx.doi.org/10.1111/all.14983DOI Listing
June 2021

Immune and barrier characterization of atopic dermatitis skin phenotype in Tanzanian patients.

Ann Allergy Asthma Immunol 2021 May 9. Epub 2021 May 9.

Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background: Atopic dermatitis (AD) is a common disease, with particularly high prevalence found in Africa. It is increasingly recognized that patients with AD of different ethnic backgrounds have unique molecular signatures in the skin, potentially accounting for treatment response variations. Nevertheless, the skin profile of patients with AD from Africa is unknown, hindering development of new treatments targeted to this patient population.

Objective: To characterize the skin profile of patients with AD from Africa.

Methods: Gene expression studies, including RNA sequencing (using threshold of fold change of >2 and false discovery rate of <0.05) and real-time polymerase chain reaction, were performed on skin biopsies of Tanzanian patients with moderate-to-severe AD and controls.

Results: Tanzanian AD skin presented robust up-regulations of multiple key mediators of both T helper 2 (T2) (interleukin 13 [IL-13], IL-10, IL-4R, CCL13,CCL17,CCL18,CCL26) and T22 (IL22, S100As) pathways. Markers related to T17 and IL-23 (IL-17A, IL-23A, IL-12, PI3, DEFB4B) and T1 (interferon gamma, CXCL9,CXCL10,CXCL11) were also significantly overexpressed in AD tissues (FDR<.05), albeit to a lesser extent. IL-36 isoforms revealed substantial up-regulations in African skin. The barrier fingerprint of Tanzanian AD revealed no suppression of hallmark epidermal barrier differentiation genes, such as filaggrin, loricrin, and periplakin, with robust attenuation of lipid metabolism genes (ie, AWAT1).

Conclusion: The skin phenotype of Tanzanian patients with AD is consistent with that of African Americans, exhibiting dominant T2 and T22 skewing, minimal dysregulation of terminal differentiation, and even broader attenuation of lipid metabolism-related products. These data highlight the unique characteristic of AD in Black individuals and the need to develop unique treatments targeting patients with AD from these underrepresented populations.
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http://dx.doi.org/10.1016/j.anai.2021.04.023DOI Listing
May 2021

Patch-test results in patients with suspected contact allergy to shoes: Retrospective IVDK data analysis 2009-2018.

Contact Dermatitis 2021 Apr 21. Epub 2021 Apr 21.

Information Network of Departments of Dermatology, University Medical Centre Göttingen, Göttingen, Germany.

Background: Allergic contact dermatitis caused by shoes is common and new relevant allergens have been identified.

Objectives: To investigate the pattern of type IV sensitization in patients with suspected allergic contact dermatitis of the feet related to shoes as a presumed culprit trigger.

Methods: Retrospective analysis of data of the Information Network of Departments of Dermatology (IVDK), 2009-2018.

Results: Six hundred twenty-five patients with presumed shoe dermatitis were identified in a cohort of 119 417 patients. Compared to patients with suspected contact sensitization from other allergen sources (n = 118 792), study group patients were more frequently sensitized to potassium dichromate (10.8% vs 3.5%), colophony (7.2% vs 3.7%), mercaptobenzothiazole (MBT; 4.0% vs 0.6%), mercapto mix (4.6% vs 0.6%), and p-tert-butylphenol formaldehyde resin (1.6% vs 0.5%). Sensitizations to urea formaldehyde resin, melamine formaldehyde resin, glutaraldehyde, tricresyl phosphate, and phenyl glycidylether were rare. Moreover, reactions to compounds in the leather or textile dyes test series were scarce.

Conclusion: A distinct sensitization pattern was observed in patients with suspected allergy to shoe materials. Although substances with low sensitization rates should be removed from the leather and shoe patch-test series, novel potential allergens should be added.
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http://dx.doi.org/10.1111/cod.13868DOI Listing
April 2021

Obsessive compulsive symptoms severity among children and adolescents during COVID-19 first wave in Israel‏.

J Obsessive Compuls Relat Disord 2021 Jan 2;28:100610. Epub 2020 Dec 2.

Child and Adolescent Psychiatry Division, Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Several current publications have considered persons with obsessive compulsive disorder (OCD) as particularly vulnerable during the COVID-19 period, and to require more frequent symptom monitoring. The purpose of this study was to evaluate whether OCD exacerbated during the first wave of COVID-19 in children and adolescents. Twenty-nine children and adolescents with OCD were evaluated in the midst of the first outbreak of the COVID-19 pandemic in Israel (April-May 2020). Obsessive-compulsive symptoms (OCS) were assessed using the Clinical Global Impression Scale (CGI), by means of a functional questionnaire and by the Obsessive-Compulsive Inventory-child version (OCI-CV) questionnaires. Obsessive-compulsive symptoms were not found to have exacerbated during the period investigated, as evident by a lack of change in CGI severity scores and by improvement rather than deterioration among more participants, based on the CGI improvement scores. Additionally, the children and adolescents reported better general functioning during the COVID-19 period and had relatively low scores on the OCI-CV scale. Our findings indicate that Israeli children and adolescents with OCD coped well with COVID-19 during the first two months of the pandemic and mostly did not experience exacerbation of OCS. However, due to the short duration of exposure to the pandemic at the time of the study, social isolation and lockdown might have masked OCS; thus, further longitudinal studies are needed.
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http://dx.doi.org/10.1016/j.jocrd.2020.100610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709811PMC
January 2021

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

Allergy 2021 03 29;76(3):816-830. Epub 2020 Dec 29.

Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.

Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19.

Materials And Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.

Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19.

Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
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http://dx.doi.org/10.1111/all.14687DOI Listing
March 2021

Embodied Belonging: In/exclusion, Health Care, and Well-Being in a World in Motion.

Cult Med Psychiatry 2021 Mar;45(1):2-21

Institute of Anthropology, University of Leipzig, Leipzig, Germany.

In this introduction, we propose the notion of 'embodied belonging' as a fruitful analytical heuristic for scholars in medical and psychological anthropology. We envision this notion to help us gain a more nuanced understanding of the entanglements of the political, social, and affective dimensions of belonging and their effects on health, illness, and healing. A focus on embodied belonging, we argue, reveals how displacement, exclusion, and marginalization cause existential and health-related ruptures in people's lives and bodies, and how affected people, in the struggle for re/emplacement and re/integration, may regain health and sustain their well-being. Covering a variety of regional contexts (Germany/Vietnam, Norway, the UK, Japan), the contributions to this special issue examine how embodied non/belonging is experienced, re/imagined, negotiated, practiced, disrupted, contested, and achieved (or not) by their protagonists, who are excluded and marginalized in diverse ways. Each article highlights the intricate trajectories of how dynamics of non/belonging inscribe themselves in human bodies. They also reveal how belonging can be utilized and drawn on as a forceful means and resource of social resilience, if not (self-)therapy and healing.
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http://dx.doi.org/10.1007/s11013-020-09693-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679788PMC
March 2021

Eosinophil-mast cell interaction: Mepolizumab leads to a reduction of clinical symptoms and serum tryptase in a patient with eosinophilic asthma and idiopathic mast cell activation.

J Allergy Clin Immunol Pract 2021 03 20;9(3):1393-1395.e1. Epub 2020 Oct 20.

Allergy Unit, Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

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http://dx.doi.org/10.1016/j.jaip.2020.10.020DOI Listing
March 2021

The Feasibility of a Parent Group Treatment for Youth with Anxiety Disorders and Obsessive Compulsive Disorder.

Child Psychiatry Hum Dev 2020 Oct 17. Epub 2020 Oct 17.

The Child Psychiatry Division, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

Cognitive behavioral therapy (CBT) is an effective treatment for children and adolescents with anxiety disorders and obsessive-compulsive disorder (OCD). Yet CBT is insufficiently effective in approximately half of cases in clinical trials and in a substantial number of cases children refuse to participate in CBT sessions altogether. Parent training offers a promising alternative to direct child therapy. The present study examined the feasibility of a group implementation of SPACE (Supportive Parenting for Anxious Childhood Emotions), a novel parent training approach aimed at reducing parent's accommodation of children's anxiety symptoms. Based on parent reports (N = 25), following treatment there was a significant decrease in parental accommodation, in family power struggles and in parental sense of helplessness, as well as a significant reduction in anxiety and OCD symptom severity. Results support the promise of group SPACE treatment and underscore the need for additional clinical trial research.
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http://dx.doi.org/10.1007/s10578-020-01082-6DOI Listing
October 2020

Benralizumab for severe DRESS in two COVID-19 patients.

J Allergy Clin Immunol Pract 2021 01 8;9(1):481-483.e2. Epub 2020 Oct 8.

Faculty of Medicine, University of Zurich, Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Department of Dermatology, Hochgebirgsklinik Davos, Davos, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.09.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543785PMC
January 2021

Innovative Therapeutic Approaches in Primary Cutaneous B Cell Lymphoma.

Front Oncol 2020 7;10:1163. Epub 2020 Aug 7.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Primary cutaneous B-cell lymphomas (pCBCL) include an infrequent group of non-Hodgkin lymphomas that are limited to skin sites at the time of diagnosis. They comprise roughly 20-25% of all cutaneous lymphomas and are subdivided into primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large cell B cell lymphoma, leg type (PCDLCBCL, LT). The first two show a rather indolent course while PCDLCBCL, LT carries a worse prognosis. Intravascular large cell B-cell lymphoma is the most infrequent subtype, and its therapy is not covered in this review. For solitary, single-site PCMZL and PCFCL, several topical treatment options exist. They include, but are not limited to, excision, radiotherapy, and intralesional therapies, discussed in this review. However, in selected cases, even "watchful waiting" is reasonable. Indolent types of pCBCL rarely require systemic treatment. However, in extended cases and more importantly DLCBCL, LT, systemic treatment is the first choice. Monoclonal anti-CD20-antibody rituximab is often used as monotherapy in PCMZL and PCFCL or combined with chemotherapy in PCDLBCL, LT. Newer options are monoclonal anti-CD40 antibody dacetuzumab, anti-PD-1 and anti-PD-L1 checkpoint inhibitors, and Bruton tyrosine kinase inhibitors. Indolent pCBCL are treated with a risk-adapted strategy using intralesional steroids, RT, and interferon-α as first-line treatments. Relapsing cases may profit from rituximab. In aggressive PCDLCBCL, LT, rituximab with polychemotherapy is recommended. Innovative therapies include intralesional oncolytic virotherapy, systemic monoclonal antibodies, and small molecules.
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http://dx.doi.org/10.3389/fonc.2020.01163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426470PMC
August 2020

Canakinumab Lacks Efficacy in Treating Adult Patients with Moderate to Severe Chronic Spontaneous Urticaria in a Phase II Randomized Double-Blind Placebo-Controlled Single-Center Study.

J Allergy Clin Immunol Pract 2021 01 20;9(1):463-468.e3. Epub 2020 Aug 20.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Christine Kühne Center for Allergy Research and Education CK-CARE Davos, Davos, Switzerland.

Background: Chronic idiopathic/spontaneous urticaria (CSU) is a common disease with a significant proportion of patients who do not respond to standard therapy with antihistamines and optionally corticosteroids/immunosuppressants.

Objective: The IL-1β antagonist canakinumab is effective in cryopyrin-associated periodic syndromes associated with urticarial symptoms and urticarial vasculitis, and so it was suspected that it could also be effective in patients with CSU.

Methods: The effect of canakinumab was investigated in 20 patients with moderate to severe CSU in a 1:1 randomization to either canakinumab or placebo in a double-blind single-dose crossover design. The verum group received 150 mg canakinumab subcutaneously once at baseline. Patients who had received placebo were able to switch to canakinumab at week 4 if they did not improve. The primary end point was clinical improvement at week 4 compared with baseline in sum of urticaria activity scores over 7 consecutive days. Secondary end points were the clinical improvement at week 8 compared with baseline in sum of urticaria activity scores over 7 consecutive days and the clinical improvement measured by the Physician Score and Dermatology Life Quality Index at week 1, 2, 4, and 8.

Results: At week 4, 2 patients with canakinumab and 3 with placebo met the primary end point, and so canakinumab failed the significant superiority to the placebo (P = 1.0). An inclusion of the patients who switched to canakinumab after 4 weeks did not alter the result. There was also no significant difference between the verum and placebo groups for all secondary end points. The therapy was well tolerated, and mild adverse events were equally distributed between verum and placebo groups.

Conclusions: Because of this clinical trial with 20 patients, it must be assumed that canakinumab has no effect on lesions of CSU. This suggests that IL-1β may not play a crucial role in pathology of patients with CSU, unlike, for example, in hereditary fevers or urticarial vasculitis, where targeting IL-1 is a main treatment option. However, the good tolerability of canakinumab could be confirmed.
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http://dx.doi.org/10.1016/j.jaip.2020.07.058DOI Listing
January 2021

Enabling Agile Clinical and Translational Data Warehousing: Platform Development and Evaluation.

JMIR Med Inform 2020 Jul 21;8(7):e15918. Epub 2020 Jul 21.

Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: Modern data-driven medical research provides new insights into the development and course of diseases and enables novel methods of clinical decision support. Clinical and translational data warehouses, such as Informatics for Integrating Biology and the Bedside (i2b2) and tranSMART, are important infrastructure components that provide users with unified access to the large heterogeneous data sets needed to realize this and support use cases such as cohort selection, hypothesis generation, and ad hoc data analysis.

Objective: Often, different warehousing platforms are needed to support different use cases and different types of data. Moreover, to achieve an optimal data representation within the target systems, specific domain knowledge is needed when designing data-loading processes. Consequently, informaticians need to work closely with clinicians and researchers in short iterations. This is a challenging task as installing and maintaining warehousing platforms can be complex and time consuming. Furthermore, data loading typically requires significant effort in terms of data preprocessing, cleansing, and restructuring. The platform described in this study aims to address these challenges.

Methods: We formulated system requirements to achieve agility in terms of platform management and data loading. The derived system architecture includes a cloud infrastructure with unified management interfaces for multiple warehouse platforms and a data-loading pipeline with a declarative configuration paradigm and meta-loading approach. The latter compiles data and configuration files into forms required by existing loading tools, thereby automating a wide range of data restructuring and cleansing tasks. We demonstrated the fulfillment of the requirements and the originality of our approach by an experimental evaluation and a comparison with previous work.

Results: The platform supports both i2b2 and tranSMART with built-in security. Our experiments showed that the loading pipeline accepts input data that cannot be loaded with existing tools without preprocessing. Moreover, it lowered efforts significantly, reducing the size of configuration files required by factors of up to 22 for tranSMART and 1135 for i2b2. The time required to perform the compilation process was roughly equivalent to the time required for actual data loading. Comparison with other tools showed that our solution was the only tool fulfilling all requirements.

Conclusions: Our platform significantly reduces the efforts required for managing clinical and translational warehouses and for loading data in various formats and structures, such as complex entity-attribute-value structures often found in laboratory data. Moreover, it facilitates the iterative refinement of data representations in the target platforms, as the required configuration files are very compact. The quantitative measurements presented are consistent with our experiences of significantly reduced efforts for building warehousing platforms in close cooperation with medical researchers. Both the cloud-based hosting infrastructure and the data-loading pipeline are available to the community as open source software with comprehensive documentation.
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http://dx.doi.org/10.2196/15918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404007PMC
July 2020

Neurochemistry and subjunctivities of depression in Kerala, South India.

Authors:
Claudia Lang

Anthropol Med 2020 Mar 30:1-15. Epub 2020 Mar 30.

Cermes3, Site CNRS, Villejuif, France.

The narrative of depression as a neurochemical imbalance in the brain or, more precisely, a deficiency of the neurotransmitters serotonin and norepinephrine - largely produced by commercial interests of the international and national pharmaceutical industry and spread globally by international diagnostic systems - has found its way into the offices of mainstream psychiatrists in Kerala. In the clinical encounters, social, economic and existential suffering is thus transformed into a medical condition, treatable with pharmacological means. On the one hand, the setting of a psychiatric outpatient department largely shapes the way depressive patients express their subjectivities. On the other hand, the diagnosis (and explanation) of depression as neurochemical imbalance and the prescription of drugs influences the way patients experience their suffering. Using two ethnographic examples, the aim of this paper is to analyze how subjectivities are construed and shaped in the process of negotiating depression in clinical encounters in mainstream psychiatric institutions in Kerala and how multiple framings and ontologies of affliction are assembled in them. Subjectivities of depression are, it will be argued, less coherent than ambigious and fractured, unstable and fragile. They engage, accentuate and sometimes merge different, often contradictory discourses. They should therefore better be referred to as 'subjunctivities'. The idiom of depression often becomes a rhetorical device to emphasize affiliation to a scientific medical discourse or citizenship and is often a statement to emphasize 'scientific temper' and modernity and to demarcate oneself from backwardness and superstition.
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http://dx.doi.org/10.1080/13648470.2019.1651585DOI Listing
March 2020

Neurochemistry and subjunctivities of depression in Kerala, South India.

Authors:
Claudia Lang

Anthropol Med 2020 Mar 30:1-15. Epub 2020 Mar 30.

Cermes3, Site CNRS, Villejuif, France.

The narrative of depression as a neurochemical imbalance in the brain or, more precisely, a deficiency of the neurotransmitters serotonin and norepinephrine - largely produced by commercial interests of the international and national pharmaceutical industry and spread globally by international diagnostic systems - has found its way into the offices of mainstream psychiatrists in Kerala. In the clinical encounters, social, economic and existential suffering is thus transformed into a medical condition, treatable with pharmacological means. On the one hand, the setting of a psychiatric outpatient department largely shapes the way depressive patients express their subjectivities. On the other hand, the diagnosis (and explanation) of depression as neurochemical imbalance and the prescription of drugs influences the way patients experience their suffering. Using two ethnographic examples, the aim of this paper is to analyze how subjectivities are construed and shaped in the process of negotiating depression in clinical encounters in mainstream psychiatric institutions in Kerala and how multiple framings and ontologies of affliction are assembled in them. Subjectivities of depression are, it will be argued, less coherent than ambigious and fractured, unstable and fragile. They engage, accentuate and sometimes merge different, often contradictory discourses. They should therefore better be referred to as 'subjunctivities'. The idiom of depression often becomes a rhetorical device to emphasize affiliation to a scientific medical discourse or citizenship and is often a statement to emphasize 'scientific temper' and modernity and to demarcate oneself from backwardness and superstition.
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http://dx.doi.org/10.1080/13648470.2019.1651585DOI Listing
March 2020

Genealogies and Anthropologies of Global Mental Health.

Cult Med Psychiatry 2019 Dec;43(4):519-547

Department of Anthropology, University of Leipzig, Leipzig, Germany.

Within the proliferation of studies identified with global mental health, anthropologists rarely take global mental health itself as their object of inquiry. The papers in this special issue were selected specifically to problematize global mental health. To contextualize them, this introduction critically weighs three possible genealogies through which the emergence of global health can be explored: (1) as a divergent thread in the qualitative turn of global health away from earlier international health and development; (2) as the product of networks and social movements; and (3) as a diagnostically- and metrics-driven psychiatric imperialism, reinforced by pharmaceutical markets. Each paper tackles a different component of the assemblage of global mental health: knowledge production and circulation, global mental health principles enacted in situ, and subaltern modalities of healing through which global mental health can be questioned. Pluralizing anthropology, the articles include research sites in meeting rooms, universities, research laboratories, clinics, healers and health screening camps, households, and the public spaces of everyday life, in India, Ghana, Brazil, Senegal, South Africa, Kosovo and Palestine, as well as in US and European institutions that constitute nodes in the global network through which scientific knowledge and certain models of mental health circulate.
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http://dx.doi.org/10.1007/s11013-019-09660-7DOI Listing
December 2019

Management of allergy transfer upon solid organ transplantation.

Am J Transplant 2020 03 19;20(3):834-843. Epub 2019 Oct 19.

Division of Immunology and Allergy, Department of Medicine, University Hospitals and University of Geneva, Geneva, Switzerland.

Allergy transfer upon solid organ transplantation has been reported in the literature, although only few data are available as to the frequency, significance, and management of these cases. Based on a review of 577 consecutive deceased donors from the Swisstransplant Donor-Registry, 3 cases (0.5%) of fatal anaphylaxis were identified, 2 because of peanut and 1 of wasp allergy. The sera of all 3 donors and their 10 paired recipients, prospectively collected before and after transplantation for the Swiss Transplant Cohort Study, were retrospectively processed using a commercial protein microarray fluorescent test. As early as 5 days posttransplantation, newly acquired peanut-specific IgE were transiently detected from 1 donor to 3 recipients, of whom 1 liver and lung recipients developed grade III anaphylaxis. Yet, to define how allergy testing should be performed in transplant recipients and to better understand the impact of immunosuppressive therapy on IgE sensitization, we prospectively studied 5 atopic living-donor kidney recipients. All pollen-specific IgE and >90% of skin prick tests remained positive 7 days and 3 months after transplantation, indicating that early diagnosis of donor-derived IgE sensitization is possible. Importantly, we propose recommendations with respect to safety for recipients undergoing solid-organ transplantation from donors with a history of fatal anaphylaxis.
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http://dx.doi.org/10.1111/ajt.15601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065229PMC
March 2020

How I treat metastatic melanoma.

ESMO Open 2019 21;4(Suppl 2):e000509. Epub 2019 Jul 21.

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

Tremendous progress in basic and clinical research has completely revolutionised the management of advanced melanoma, and this dramatic development is still ongoing. In this environment, state-of-the-art patient care is a major challenge. We describe how patient-centred medicine is organised in a leading referral centre that is also involved in early and late clinical trials and is part of a worldwide network for translational research.
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http://dx.doi.org/10.1136/esmoopen-2019-000509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677980PMC
July 2019

Phenotypic and Genomic Analyses of Burkholderia stabilis Clinical Contamination, Switzerland.

Emerg Infect Dis 2019 06;25(6):1084-1092

A recent hospital outbreak related to premoistened gloves used to wash patients exposed the difficulties of defining Burkholderia species in clinical settings. The outbreak strain displayed key B. stabilis phenotypes, including the inability to grow at 42°C; we used whole-genome sequencing to confirm the pathogen was B. stabilis. The outbreak strain genome comprises 3 chromosomes and a plasmid, sharing an average nucleotide identity of 98.4% with B. stabilis ATCC27515 BAA-67, but with 13% novel coding sequences. The genome lacks identifiable virulence factors and has no apparent increase in encoded antimicrobial drug resistance, few insertion sequences, and few pseudogenes, suggesting this outbreak was an opportunistic infection by an environmental strain not adapted to human pathogenicity. The diversity among outbreak isolates (22 from patients and 16 from washing gloves) is only 6 single-nucleotide polymorphisms, although the genome remains plastic, with large elements stochastically lost from outbreak isolates.
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http://dx.doi.org/10.3201/eid2506.172119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537712PMC
June 2019

Population Pharmacokinetics with Monte Carlo Simulations of Gentamicin in a Population of Severely Ill Adult Patients from Sub-Saharan Africa.

Antimicrob Agents Chemother 2019 04 27;63(4). Epub 2019 Mar 27.

Amsterdam UMC, University of Amsterdam, Department of Hospital Pharmacy, Division of Clinical Pharmacology, Amsterdam, the Netherlands.

In sub-Saharan Africa (SSA), gentamicin is commonly used for severe infections in non-intensive-care-unit (ICU) settings, but pharmacokinetic and pharmacodynamic data for this specific population are lacking. We performed a population pharmacokinetic study in an adult Mozambican non-ICU hospital population treated with gentamicin ( = 48) and developed a pharmacokinetic model using nonlinear mixed-effects modeling. Simulations showed that non-ICU patient populations in SSA may be at substantial risk for underexposure to gentamicin during routine once-daily dosing.
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http://dx.doi.org/10.1128/AAC.02328-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437512PMC
April 2019

Allergen Recognition Patterns in Walnut Allergy Are Age Dependent and Correlate with the Severity of Allergic Reactions.

J Allergy Clin Immunol Pract 2019 May - Jun;7(5):1560-1567.e6. Epub 2019 Jan 30.

Paul-Ehrlich-Institut, Langen, Germany.

Background: Walnut is an important elicitor of food allergy in children and adults with a high rate of severe reactions. Multicenter studies using a common clinical protocol and a comprehensive allergen are lacking.

Objective: To investigate potential correlations between molecular sensitization patterns and clinical characteristics of walnut-allergic patients.

Methods: A total of 91 walnut-allergic subjects and 24 tolerant controls from Switzerland, Germany, and Spain were included. Walnut allergy was established by food challenge in all but anaphylactic subjects. Specific IgE (sIgE) to walnut extract, rJug r 1 (2S albumin), rJug r 3 (nonspecific lipid transfer protein 1), nJug r 4 (11S globulin), rJug r 5 (PR-10 protein), 2 vicilin fractions, profiling, and cross-reactive carbohydrate determinant was determined by ImmunoCAP. A threshold of 0.10 kU/L was used for positivity.

Results: Sensitivity of sIgE to walnut extract was 87% and increased to 96% for the sum of all walnut components. sIgE to walnut extract and all walnut components, except rJug r 5, was significantly higher in patients younger than 14 years at inclusion. Stratification by age at onset of walnut allergy led to similar results. All patients younger than 14 years had severe reactions, whereas 38% of patients 14 years or older were mild reactors. Severe reactors (n = 70) had higher sIgE levels than did mild reactors (n = 21) to walnut extract (P < .0001), rJug r 1 (P < .0001), nJug r 4 (P = .0003), and both vicilin fractions (P < .0001), but not to Jug r 3 and Jug r 5.

Conclusions: Sensitization to walnut storage proteins is acquired in childhood and correlates with severe reactions. sIgE levels to storage proteins Jug r 1 and Jug r 4 and vicilin fractions, but not to nonspecific lipid transfer protein and PR-10 proteins, correlate with systemic reactions to walnut.
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http://dx.doi.org/10.1016/j.jaip.2019.01.029DOI Listing
August 2020

Common Variants of the Plant microRNA-168a Exhibit Differing Silencing Efficacy for Human Low-Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1).

Microrna 2019 ;8(2):166-170

The New Zealand Institute for Plant & Food Research Ltd., Auckland 1142, New Zealand.

Background: The discovery that a plant microRNA (miRNAs) from rice (Oryza sativa miR168a) can modify post-transcriptional expression of the mammalian. Low-Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) gene highlights the potential for cross-kingdom miRNAmRNA interactions.

Objective: To investigate whether common variants of the conserved miR168a family have the capability for similar cross-kingdom regulatory functions, we selected sequences from three dietary plant sources: rice (Oryza sativa), tomato (Solanum lycopersicum), apple (Malus domestica) and compared their ability to regulate human LDLRAP1 expression.

Methods: Target prediction software intaRNA and RNAhybrid were used to analyze and calculate the energy and alignment score between the miR168a variants and human LDLRAP1 mRNA. An in vitro cell-based Dual-Luciferase® Reporter Assay (pmirGLO, Promega), was then used to validate the miRNA-mRNA interaction experimentally.

Results: Computational analyses revealed that a single nucleotide difference at position 14 (from the 5' end of the miRNA) creates a G:U wobble in the miRNA-mRNA duplex formed by tomato and apple miR168a variants. This G:U wobble had only a small effect on the free energy score (-33.8-34.7 kcal/mol). However, despite reasonable hybridization energy scores (<-20 kcal/mol) for all miR168a variants, only the rice miR168a variant lacking a G:U wobble significantly reduced LDLRAP1 transcript expression by 25.8 + 7.3% (p<0.05), as measured by relative luciferase activity.

Conclusion: In summary, single nucleotide differences at key positions can have a marked influence on regulatory function despite similar predicted energy scores and miRNA-mRNA duplex structures.
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http://dx.doi.org/10.2174/2211536608666181203103233DOI Listing
April 2019

Pharmacokinetics and pharmacodynamic target attainment of ceftriaxone in adult severely ill sub-Saharan African patients: a population pharmacokinetic modelling study.

J Antimicrob Chemother 2018 06;73(6):1620-1629

Academic Medical Centre (AMC), University of Amsterdam, Department of Hospital Pharmacy, Division of Clinical Pharmacology, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Background: In sub-Saharan Africa (SSA), the highly albumin-bound β-lactam ceftriaxone is frequently used for the empirical treatment of severe bacterial infections. Systemic drug exposure of β-lactams can be altered in critically ill ICU patients, but pharmacokinetic and pharmacodynamic data for non-ICU SSA populations are lacking.

Methods: We performed a population pharmacokinetic study in an adult hospital population in Mozambique, treated with ceftriaxone for presumptive severe bacterial infection from October 2014 to November 2015. Four blood samples per patient were collected for total ceftriaxone (CEFt) and unbound ceftriaxone (CEFu) concentration measurement. We developed a population pharmacokinetic model through non-linear mixed effect analysis and performed simulations for different patient variable, dosing and pharmacodynamic target scenarios.

Results: Eighty-eight participants yielded 277 CEFt and 276 CEFu concentrations. The median BMI was 18.9 kg/m2 and the median albumin concentration was 29 g/L. In a one-compartment model with non-linear protein binding, creatinine clearance was positively correlated with CEFu clearance. For microorganisms with an MIC of 1 mg/L, simulations demonstrated that with a 1 g twice-daily regimen and a 2 g once-daily regimen, 95.1% and 74.8% would have a CEFu concentration > MIC during half of the dosing interval (fT>MIC = 50%), respectively, whereas this was only 58.2% and 16.5% for the fT>MIC = 100% target.

Conclusions: Severely ill adult non-ICU SSA patients may be at substantial risk for underexposure to CEFu during routine intermittent bolus dosing, especially when their renal function is intact.
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http://dx.doi.org/10.1093/jac/dky071DOI Listing
June 2018

The association between sleep disturbances of children with anxiety disorders and those of their mothers.

Sleep Med 2018 03 14;43:77-82. Epub 2017 Nov 14.

The Child Psychiatry Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel; Department of Psychology, The Interdisciplinary Center, Herzliya, Israel. Electronic address:

Objective: Previous research has demonstrated a link between childhood anxiety and sleep problems, but little is known about the link between these difficulties and parental sleep disturbances. The purpose of the current study was to explore the association between anxious children's sleep difficulties and those of their mothers.

Method: A total of 101 children aged 8-18 years and their mothers participated in this study. The clinical group included 66 children (mean age = 11.45 years, standard deviation = 2.79 years) diagnosed with anxiety disorders, and the control group included 35 age- and sex-matched normal healthy controls. Mothers completed questionnaires assessing their child's anxiety and sleep, as well as their own sleep. Children completed questionnaires assessing anxiety, sleep, depression, and obsessive symptoms.

Results: Both children and mothers in the clinical group exhibited more sleep difficulties compared to controls. A regression analysis revealed that pre-sleep arousal negatively predicted children's sleep. Furthermore, children's anxiety level was associated with parental levels of sleep disturbances. This link was fully mediated by the children's sleep disturbances score.

Conclusion: Mothers of children with anxiety disorders exhibit higher levels of sleep disturbances than controls. These difficulties are linked to children's anxiety and sleep problems. When treating children with anxiety, it is therefore important to assess their overall sleep disturbances, as well as parental sleep difficulties, and when appropriate to add a specific sleep intervention component.
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http://dx.doi.org/10.1016/j.sleep.2017.10.009DOI Listing
March 2018

Diagnostic criteria and contributors to Gilbert's syndrome.

Crit Rev Clin Lab Sci 2018 03 1;55(2):129-139. Epub 2018 Feb 1.

b School of Medical Science and Menzies Health Institute Queensland , Griffith University , Gold Coast , Australia.

Hyperbilirubinemia is a well-known condition in the clinical setting; however, the causes of elevated serum bilirubin are diverse, as are the clinical ramifications of this condition. For example, diagnoses of individuals vary depending on whether they exhibit an unconjugated or conjugated hyperbilirubinemia. Diagnoses can include conditions of disordered bilirubin metabolism (Gilbert's, Crigler-Najjar, Rotor, or Dubin-Johnson syndromes) or an acquired disease, including alcoholic/non-alcoholic fatty liver disease, hepatotropic hepatitis, cirrhosis, or hepato-biliary malignancy. Assessment of bilirubin concentrations is typically conducted as part of routine liver function testing. Mildly elevated total bilirubin with normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts, however, may indicate the presence of Gilbert's syndrome (GS), a benign condition that is present in ∼5-10% of the population. In this case, mildly elevated unconjugated bilirubin in GS is strongly associated with "reduced" prevalence of chronic diseases, particularly cardiovascular diseases (CVD) and type 2 diabetes mellitus (and associated risk factors), as well as CVD-related and all-cause mortality. These reports challenge the dogma that bilirubin is simply a potentially neurotoxic by-product of heme catabolism and emphasize the importance of understanding its potential beneficial physiologic and detrimental pathophysiologic effects, in order to appropriately consider bilirubin test results within the clinical laboratory setting. With this information, we hope to improve the understanding of disorders of bilirubin metabolism, emphasize the diagnostic importance of these conditions, and outline the potential impact GS may have on resistance to disease.
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http://dx.doi.org/10.1080/10408363.2018.1428526DOI Listing
March 2018

Evaluation of Nickel Release from Endobronchial Valves as a Possible Cause of Hypersensitivity Pneumonitis in a Patient Treated with Bronchoscopic Lung Volume Reduction.

Int Arch Allergy Immunol 2017 15;174(3-4):144-150. Epub 2017 Nov 15.

Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.

Background: Endobronchial valve (EBV) placement is an established lung volume reduction procedure aiming to improve lung function and exercise capacity in patients with severe emphysema. As EBVs consist of silicone and nitinol (a metal alloy of nickel and titanium), there are concerns that nickel ions might be released and could have a clinical impact in patients with a contact allergy to nickel. Based on a case with hypersensitivity pneumonitis (HP) after treatment with EBVs, we aimed to evaluate the in vitro nickel release from EBVs using inductively coupled plasma mass spectrometry (ICP-MS) and scanning electron microscopy (SEM).

Methods: Six EBVs were immersed in artificial saliva for a period of 7 days. At 24-h intervals, the nickel ion concentration was measured using ICP-MS.

Results: There was evidence of a significant nickel release from EBV during the first 48 h, which is possibly due to an incomplete silicone layer detected by SEM. The concentration of released nickel was below the toxic limit.

Conclusions: To the best of our knowledge, we report the first case of HP after EBV treatment. Our finding of in vitro release of nickel ions from EBVs may contribute to the current understanding on hypersensitivity reactions after nitinol implants in patients with nickel contact allergy. However, it did not confirm a causative relationship.
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http://dx.doi.org/10.1159/000481986DOI Listing
December 2017

Pharmacokinetics and Pharmacodynamic Target Attainment of Benzylpenicillin in an Adult Severely Ill Sub-Saharan African Patient Population.

Clin Infect Dis 2018 04;66(8):1261-1269

Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, The Netherlands.

Background: In intensive care (ICU) patients, systemic exposure of β-lactam antibiotics can be altered, and positive clinical outcome is associated with increasing fT > MIC ratios. In sub-Saharan African hospitals, benzylpenicillin (PEN) is frequently used for the empiric treatment of severe pneumococcal infections. Pharmacokinetic data for non-ICU hospitalized populations are lacking.

Methods: We performed a population pharmacokinetic (PPK) study in an adult Mozambican hospital population treated intravenously with PEN from October 2014 through November 2015. Four blood samples/patient were collected for total PEN (PENt) and unbound PEN (PENu) concentration measurement. We developed a PPK model through nonlinear mixed-effects analysis and performed simulations for different patient variable, dosing, and pharmacodynamic target scenarios.

Results: One hundred twelve participants yielded 387 PENt and 53 PENu concentrations. The median body mass index was 18.3 (range, 10.5-31.3) kg/m2 and the median albumin concentration and creatinine clearance (CrCl) were 29 (range, 12-44) g/L and 80 (range, 3-195) mL/minute, respectively. In a 1-compartment model, CrCl was positively correlated with PENt clearance. For infections with a microorganism with a minimum inhibitory concentration (MIC) of 1 mg/L, simulations demonstrated that with 3 million IU (1.8 g) every 6 hours, 74.1% would have a PENu concentration greater than the MIC during half of the dosing interval (fT > MIC = 50%), whereas this was 24.8% for the fT > MIC = 100% target. For pathogens with an MIC of 0.06 mg/L, these percentages were 98.2% and 72.3%, respectively.

Conclusions: Severely ill adult sub-Saharan African patients may be at high risk for underexposure to PENu during routine intermittent bolus dosing, especially when their renal function is intact and when infected with pathogens with intermediate susceptibility.
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http://dx.doi.org/10.1093/cid/cix961DOI Listing
April 2018

Translation and purification: Ayurvedic psychiatry, allopathic psychiatry, spirits and occult violence in Kerala, South India.

Authors:
Claudia Lang

Anthropol Med 2018 Aug 8;25(2):141-161. Epub 2017 May 8.

a Department of Social and Cultural Anthropology , Ludwig-Maximilians-Universitat Munchen , Munchen , Germany.

In this paper, the author traces two parallel movements of institutionalized Ayurvedic psychiatry, an emergent field of specialization in Kerala, India: the 'work of purification' and the 'work of translation' that Latour has described as characteristic of the 'modern constitution.' The author delineates these processes in terms of the relationship of Ayurvedic psychiatry to (1) allopathic psychiatry, (2) bhutavidya, a branch of textual Ayurveda dealing with spirits, and (3) occult violence. The aim is to offer a model of these open and hidden processes and of Ayurvedic psychiatry's positioning within a hierarchical mental health field characterized simultaneously by biopsychiatric hegemony and a persistent vernacular healing tradition. Through these processes, Ayurvedic psychiatry emerges as a relevant actor. It demarcates itself from both allopathic and vernacular epistemologies and ontologies while simultaneously drawing upon aspects of each, and, in this way, shows itself to be both deeply modern and highly pragmatic.
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http://dx.doi.org/10.1080/13648470.2017.1285001DOI Listing
August 2018
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