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  1. Article ; Online: Real-World Implementation and Outcomes of Adalimumab Therapeutic Drug Monitoring in Psoriasis: A National Specialized Center Experience.

    Raharja, Antony / Arkir, Zehra / Rinaldi, Giulia / Tsakok, Teresa / Dasandi, Tejus / Guard, Sarah / McGuire, Arlene / Pink, Andrew E / Woolf, Richard / Barker, Jonathan N / Smith, Catherine H / Mahil, Satveer K

    The Journal of investigative dermatology

    2023  Volume 143, Issue 9, Page(s) 1708–1716.e4

    Abstract: Serum adalimumab concentration is a biomarker of treatment response but therapeutic drug monitoring (TDM) is yet to be implemented in routine psoriasis care. We incorporated adalimumab TDM in a national specialized psoriasis service and evaluated it ... ...

    Abstract Serum adalimumab concentration is a biomarker of treatment response but therapeutic drug monitoring (TDM) is yet to be implemented in routine psoriasis care. We incorporated adalimumab TDM in a national specialized psoriasis service and evaluated it using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) implementation science framework. We undertook pre-implementation planning (validating local assays) and implementation interventions targeted to patients (pragmatic sampling at routine reviews), clinicians (introduction of a TDM protocol), and healthcare systems (adalimumab TDM as a key performance indicator). Over 5 months, 170 of 229 (74%) individuals treated with adalimumab received TDM. Clinical improvement after TDM-guided dose escalation occurred in 13 of 15 (87%) nonresponders with serum drug concentrations <8.3 μg/ml (median PASI reduction of 3.2 [interquartile range = 2.2-8.2] after 23.4 weeks) and in all nonresponders who had TDM-guided switch in biologic due to supratherapeutic drug concentrations (>8.3 μg/ml; n = 2) or positive antidrug antibody (n = 2) (PASI reduction of 7.8 [interquartile range = 7.5-12.9] after 20.0 weeks). Proactive TDM led to dose reduction in five individuals with clear skin and subtherapeutic or supratherapeutic drug concentrations; four (80%) sustained clear skin after 50 weeks (range = 42-52). Adalimumab TDM based on pragmatic serum sampling is clinically viable and may lead to patient benefit. Context-specific implementation interventions and systematic implementation assessment may bridge the biomarker research-to-practice gap.
    MeSH term(s) Humans ; Adalimumab/therapeutic use ; Drug Monitoring/methods ; Psoriasis/diagnosis ; Psoriasis/drug therapy ; Remission Induction ; Treatment Outcome
    Chemical Substances Adalimumab (FYS6T7F842)
    Language English
    Publishing date 2023-03-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2023.01.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Systematic review of deep learning image analyses for the diagnosis and monitoring of skin disease.

    Choy, Shern Ping / Kim, Byung Jin / Paolino, Alexandra / Tan, Wei Ren / Lim, Sarah Man Lin / Seo, Jessica / Tan, Sze Ping / Francis, Luc / Tsakok, Teresa / Simpson, Michael / Barker, Jonathan N W N / Lynch, Magnus D / Corbett, Mark S / Smith, Catherine H / Mahil, Satveer K

    NPJ digital medicine

    2023  Volume 6, Issue 1, Page(s) 180

    Abstract: Skin diseases affect one-third of the global population, posing a major healthcare burden. Deep learning may optimise healthcare workflows through processing skin images via neural networks to make predictions. A focus of deep learning research is skin ... ...

    Abstract Skin diseases affect one-third of the global population, posing a major healthcare burden. Deep learning may optimise healthcare workflows through processing skin images via neural networks to make predictions. A focus of deep learning research is skin lesion triage to detect cancer, but this may not translate to the wider scope of >2000 other skin diseases. We searched for studies applying deep learning to skin images, excluding benign/malignant lesions (1/1/2000-23/6/2022, PROSPERO CRD42022309935). The primary outcome was accuracy of deep learning algorithms in disease diagnosis or severity assessment. We modified QUADAS-2 for quality assessment. Of 13,857 references identified, 64 were included. The most studied diseases were acne, psoriasis, eczema, rosacea, vitiligo, urticaria. Deep learning algorithms had high specificity and variable sensitivity in diagnosing these conditions. Accuracy of algorithms in diagnosing acne (median 94%, IQR 86-98; n = 11), rosacea (94%, 90-97; n = 4), eczema (93%, 90-99; n = 9) and psoriasis (89%, 78-92; n = 8) was high. Accuracy for grading severity was highest for psoriasis (range 93-100%, n = 2), eczema (88%, n = 1), and acne (67-86%, n = 4). However, 59 (92%) studies had high risk-of-bias judgements and 62 (97%) had high-level applicability concerns. Only 12 (19%) reported participant ethnicity/skin type. Twenty-four (37.5%) evaluated the algorithm in an independent dataset, clinical setting or prospectively. These data indicate potential of deep learning image analysis in diagnosing and monitoring common skin diseases. Current research has important methodological/reporting limitations. Real-world, prospectively-acquired image datasets with external validation/testing will advance deep learning beyond the current experimental phase towards clinically-useful tools to mitigate rising health and cost impacts of skin disease.
    Language English
    Publishing date 2023-09-27
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2398-6352
    ISSN (online) 2398-6352
    DOI 10.1038/s41746-023-00914-8
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  3. Article ; Online: Prevention of food allergy.

    Tsakok, Teresa / Du Toit, George / Lack, Gideon

    Chemical immunology and allergy

    2015  Volume 101, Page(s) 253–262

    Abstract: Despite a trend towards delayed weaning, food allergies (FAs) have increased in the past few decades and are now considered a public health concern, resulting in significant morbidity as well as occasional mortality. Whilst genetic factors are clearly ... ...

    Abstract Despite a trend towards delayed weaning, food allergies (FAs) have increased in the past few decades and are now considered a public health concern, resulting in significant morbidity as well as occasional mortality. Whilst genetic factors are clearly important in the development of FA, a rise in FAs has occurred over a short period of time and is therefore unlikely to be due to germ-line genetic changes alone. Thus, it seems plausible that one or more environmental exposures may, via epigenetic changes, result in the interruption of the 'default immunologic state' of tolerance to foods. Strategies are therefore required for the prevention of FA: primary prevention seeks to prevent the onset of IgE-sensitisation; secondary prevention seeks to interrupt the development of FA in IgE-sensitised children; and tertiary prevention seeks to reduce the expression of 'end-organ' allergic disease in children with established FA. This chapter will outline the major findings in this field, with the aim of equipping the clinician with an evidence-based approach to a burgeoning yet poorly understood clinical problem. We also highlight the methodological challenges hindering the interpretation of existing FA studies. Fortunately, there are now robust studies underway, the results of which are expected to guide public health recommendations with respect to how and when to introduce major allergenic foods to children, regardless of allergic risk.
    MeSH term(s) Diet ; Diet Therapy ; Dietary Supplements ; Female ; Food Hypersensitivity/diet therapy ; Food Hypersensitivity/epidemiology ; Food Hypersensitivity/prevention & control ; Humans ; Infant ; Infant Food ; Pregnancy ; Prenatal Nutritional Physiological Phenomena
    Language English
    Publishing date 2015
    Publishing country Switzerland
    Document type Journal Article
    ISSN 1662-2898 ; 1660-2242
    ISSN (online) 1662-2898
    ISSN 1660-2242
    DOI 10.1159/000373911
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  4. Article ; Online: Does prophylactic inhaled nitric oxide reduce morbidity and mortality after lung transplantation?

    Tavare, Aniket N / Tsakok, Teresa

    Interactive cardiovascular and thoracic surgery

    2011  Volume 13, Issue 5, Page(s) 516–520

    Abstract: A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was does prophylactic inhaled nitric oxide (NO) reduce morbidity and mortality after lung transplantation? Altogether 232 papers were found ... ...

    Abstract A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was does prophylactic inhaled nitric oxide (NO) reduce morbidity and mortality after lung transplantation? Altogether 232 papers were found using the reported search, of which six represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Primary graft dysfunction and failure are serious complications in the first few days following lung transplantation. These phenomena are characterised by bilateral infiltrates on chest radiographs, reduced lung compliance and increased FiO(2) requirements and alveolar-arterial gradients; thus necessitating prolonged mechanical ventilation and often leading to significant mortality. The process known as ischaemic-reperfusion injury is thought to underlie primary graft failure. The studies conducted examining the role of inhaled NO in preventing morbidity and mortality after orthotropic lung transplant tend to focus on potential reductions in the incidence of ischaemic-reperfusion injury as the determinant of clinical outcomes. The majority of these are unfortunately non-randomised and/or uncontrolled studies. All the studies discussed, including the two prospective randomised controlled trials, suffer from small sample sizes. Nonetheless, despite their limitations, there are currently, no randomised controlled studies that demonstrate a reduction in morbidity [time to extubation, length of intensive care unit (ICU) or hospital stay] or mortality. As such it is difficult to currently, recommend the routine use of prophylactic inhaled NO in lung transplant surgery. Further studies may outline a benefit in certain types of surgeries, e.g. single-lung transplants or double-lung requiring cardiopulmonary bypass.
    MeSH term(s) Administration, Inhalation ; Adult ; Benchmarking ; Evidence-Based Medicine ; Female ; Graft Survival/drug effects ; Humans ; Lung Transplantation/adverse effects ; Lung Transplantation/mortality ; Male ; Nitric Oxide/administration & dosage ; Patient Selection ; Premedication ; Primary Graft Dysfunction/etiology ; Primary Graft Dysfunction/mortality ; Primary Graft Dysfunction/prevention & control ; Respiration, Artificial ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome
    Chemical Substances Nitric Oxide (31C4KY9ESH)
    Language English
    Publishing date 2011-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2095298-3
    ISSN 1569-9285 ; 1569-9293
    ISSN (online) 1569-9285
    ISSN 1569-9293
    DOI 10.1510/icvts.2011.274365
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    Zs.A 5730: Show issues Location:
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  5. Article ; Online: Prevention of food allergy.

    du Toit, George / Tsakok, Teresa / Lack, Simon / Lack, Gideon

    The Journal of allergy and clinical immunology

    2016  Volume 137, Issue 4, Page(s) 998–1010

    Abstract: The past few decades have witnessed an increase in the prevalence of IgE-mediated food allergy (FA). For prevention strategies to be effective, we need to understand the causative factors underpinning this rise. Genetic factors are clearly important in ... ...

    Abstract The past few decades have witnessed an increase in the prevalence of IgE-mediated food allergy (FA). For prevention strategies to be effective, we need to understand the causative factors underpinning this rise. Genetic factors are clearly important in the development of FA, but given the dramatic increase in prevalence over a short period of human evolution, it is unlikely that FA arises through germline genetic changes alone. A plausible hypothesis is that 1 or more environmental exposures, or lack thereof, induce epigenetic changes that result in interruption of the default immunologic state of tolerance. Strategies for the prevention of FA might include primary prevention, which seeks to prevent the onset of IgE sensitization; secondary prevention, which seeks to interrupt the development of FA in IgE-sensitized children; and tertiary prevention, which seeks to reduce the expression of end-organ allergic disease in children with established FA. This review emphasizes the prevention of IgE-mediated FA through dietary manipulation, among other strategies; in particular, we focus on recent interventional studies in this field.
    MeSH term(s) Diet Therapy/methods ; Epigenesis, Genetic ; Female ; Food Hypersensitivity/genetics ; Food Hypersensitivity/immunology ; Food Hypersensitivity/prevention & control ; Humans ; Immune Tolerance ; Immunoglobulin E ; Pregnancy ; Prenatal Exposure Delayed Effects/immunology ; Risk Factors
    Chemical Substances Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2016-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2016.02.005
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  6. Article ; Online: Pediatric urticaria.

    Tsakok, Teresa / Du Toit, George / Flohr, Carsten

    Immunology and allergy clinics of North America

    2014  Volume 34, Issue 1, Page(s) 117–139

    Abstract: Although urticaria is not a life-threatening disease, its impact on quality of life in children should not be overlooked. A systematic search of online databases, including Medline, was performed to inform a review aiming to equip clinicians with an ... ...

    Abstract Although urticaria is not a life-threatening disease, its impact on quality of life in children should not be overlooked. A systematic search of online databases, including Medline, was performed to inform a review aiming to equip clinicians with an evidence-based approach to all aspects of pediatric urticaria. This review hinges on an illustrative case and includes a summary table of studies pertaining to disease management in children. The multiple issues faced by patients, their families, and treating clinicians are highlighted, and the current literature on the presentation, natural history, investigation, and management of this poorly understood condition is assessed.
    MeSH term(s) Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Urticaria/diagnosis ; Urticaria/epidemiology ; Urticaria/etiology ; Urticaria/therapy
    Language English
    Publishing date 2014-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 92606-1
    ISSN 1557-8607 ; 0889-8561
    ISSN (online) 1557-8607
    ISSN 0889-8561
    DOI 10.1016/j.iac.2013.09.008
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  7. Article ; Online: The association between atopic dermatitis and food allergy in adults.

    Manam, Seshi / Tsakok, Teresa / Till, Stephen / Flohr, Carsten

    Current opinion in allergy and clinical immunology

    2014  Volume 14, Issue 5, Page(s) 423–429

    Abstract: Purpose of review: We conducted a systematic literature search for studies investigating the link between atopic dermatitis and food sensitization or clinically significant allergy (FA) in adults, to assess the strength of the association between the ... ...

    Abstract Purpose of review: We conducted a systematic literature search for studies investigating the link between atopic dermatitis and food sensitization or clinically significant allergy (FA) in adults, to assess the strength of the association between the two diseases in both general and selected populations.
    Recent findings: Around 10% of adults with FA have concomitant atopic dermatitis at the population level. Adult atopic dermatitis patients show much higher rates of sensitization to foods than healthy individuals, in particular to food proteins cross-reactive with airborne allergens, rather than the food allergens that typically predominate amongst children with atopic dermatitis. When food challenges have been performed, rather than relying on questionnaire information and specific IgE testing alone, they often do not confirm eczematous reactions. Only half of patients who have challenge-proven FA improve on a strict elimination diet.
    Summary: Challenge-proven FA in adults with atopic dermatitis is uncommon. The incidence of new-onset FA in adult atopic dermatitis patients is currently unknown, as are the main routes of sensitization. There is increasing evidence from studies in infants that sensitization to food protein can occur across the skin barrier, in particular in the presence of eczematous skin inflammation. Carefully conducted large longitudinal studies amongst adults that take into account skin barrier function and genetics are required.
    MeSH term(s) Adult ; Allergens/adverse effects ; Allergens/immunology ; Child ; Cross Reactions ; Dermatitis, Atopic/diagnosis ; Dermatitis, Atopic/epidemiology ; Dermatitis, Atopic/immunology ; Food/adverse effects ; Food Hypersensitivity/diagnosis ; Food Hypersensitivity/epidemiology ; Food Hypersensitivity/immunology ; Humans ; Immunization ; Infant ; Particulate Matter/immunology ; Population Groups
    Chemical Substances Allergens ; Particulate Matter
    Language English
    Publishing date 2014-06-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2088710-3
    ISSN 1473-6322 ; 1528-4050
    ISSN (online) 1473-6322
    ISSN 1528-4050
    DOI 10.1097/ACI.0000000000000095
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  8. Article ; Online: Choosing drugs for UK COVID-19 treatment trials.

    Chinnery, Patrick F / Bonnet, Marion / Cave, Alison / Hofer, Matthias P / Lamb, Alastair / McConkey, Glenn A / Medcalf, Nicholas / Smith, Stephen P / Tsakok, Teresa / Watson, Robert / Webster, Steve / You, Tao

    Nature reviews. Drug discovery

    2021  Volume 21, Issue 2, Page(s) 81–82

    MeSH term(s) Clinical Trials as Topic/economics ; Clinical Trials as Topic/methods ; Drug Development/economics ; Drug Development/methods ; Financing, Government ; Humans ; Research Support as Topic ; United Kingdom ; COVID-19 Drug Treatment
    Language English
    Publishing date 2021-12-07
    Publishing country England
    Document type News ; Research Support, Non-U.S. Gov't
    ZDB-ID 2062954-0
    ISSN 1474-1784 ; 1474-1776
    ISSN (online) 1474-1784
    ISSN 1474-1776
    DOI 10.1038/d41573-021-00203-7
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    Zs.A 5564: Show issues Location:
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  9. Article ; Online: Storage of saphenous vein grafts prior to coronary artery bypass grafting: is autologous whole blood more effective than saline in preserving graft function?

    Tsakok, Maria / Montgomery-Taylor, Sarah / Tsakok, Teresa

    Interactive cardiovascular and thoracic surgery

    2012  Volume 15, Issue 4, Page(s) 720–725

    Abstract: A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: 'Is storage of saphenous vein grafts in autologous whole blood prior to coronary artery bypass grafting (CABG) more effective than ... ...

    Abstract A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: 'Is storage of saphenous vein grafts in autologous whole blood prior to coronary artery bypass grafting (CABG) more effective than storage in saline in preserving graft function?' Altogether more than 580 papers were found using the reported search, of which, 10 represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Preservation of the vein graft endothelium during graft preparation is of well-recognized importance in forestalling graft occlusion and saphenous vein graft disease following CABG, however, the different preservation capabilities of saline vs autologous whole blood are not well validated. Although there is a complete lack of randomized clinical trials addressing this issue, some studies using basic in vitro techniques and animal models can be extrapolated to answer the clinical question in hand. All are consistent in demonstrating the detrimental effects of saline on vascular endothelium and therefore graft patency, but there is some disagreement in the literature as to whether autologous whole blood is superior as a storage medium. Though three well-designed studies suggest preserved endothelial function when saphenous vein grafts are stored in saline compared with storage in autologous whole blood, data from other studies are unimpressive, with two studies showing no difference. Furthermore, two elegant experiments that seek to mimic in vivo conditions by comparing outcomes postarterialization show no benefit of prior storage in autologous whole blood, despite the initial better-preserved endothelium. Instead, some notice should be taken of alternative storage solutions such as the University of Wisconsin solution, as some early studies suggest that it may be advantageous over both blood and crystalloid solution.
    MeSH term(s) Animals ; Benchmarking ; Blood ; Coronary Artery Bypass/adverse effects ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/pathology ; Endothelium, Vascular/physiopathology ; Endothelium, Vascular/transplantation ; Evidence-Based Medicine ; Graft Occlusion, Vascular/etiology ; Graft Occlusion, Vascular/physiopathology ; Graft Occlusion, Vascular/prevention & control ; Humans ; Organ Preservation/adverse effects ; Organ Preservation/methods ; Organ Preservation Solutions/adverse effects ; Organ Preservation Solutions/therapeutic use ; Saphenous Vein/drug effects ; Saphenous Vein/pathology ; Saphenous Vein/physiopathology ; Saphenous Vein/transplantation ; Sodium Chloride/therapeutic use ; Tissue and Organ Harvesting ; Treatment Outcome ; Vascular Patency
    Chemical Substances Organ Preservation Solutions ; Sodium Chloride (451W47IQ8X)
    Language English
    Publishing date 2012-06-29
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2095298-3
    ISSN 1569-9285 ; 1569-9293
    ISSN (online) 1569-9285
    ISSN 1569-9293
    DOI 10.1093/icvts/ivs275
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  10. Article: Lentigo maligna mimicking invasive melanoma in Mohs surgery: a case report.

    Tsakok, Teresa / Sheth, Nisith / Robson, Alistair / Gleeson, Catherine / Mallipeddi, Raj

    F1000Research

    2014  Volume 3, Page(s) 25

    Abstract: Lentigo maligna is a lentiginous proliferation of atypical melanocytes confined to the epidermis, typically on chronically sun-damaged skin. Following biopsy and exclusion of invasive disease, therapy may involve Mohs surgery, topical treatment or ... ...

    Abstract Lentigo maligna is a lentiginous proliferation of atypical melanocytes confined to the epidermis, typically on chronically sun-damaged skin. Following biopsy and exclusion of invasive disease, therapy may involve Mohs surgery, topical treatment or radiotherapy. However, lentigo maligna often involves adnexal structures, creating histological difficulty in distinguishing these foci from invasive melanoma. We present a case in which, during Mohs excision, a nodule of severely atypical melanocytes appeared to lie within the dermis, potentially altering treatment and prognosis. The use of laminin-5 provided a means of resolving this diagnostic dilemma, facilitating continuation of Mohs surgery until tumour clearance was achieved.
    Language English
    Publishing date 2014-01-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 2699932-8
    ISSN 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.3-25.v1
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