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  1. Article ; Online: Female paediatric patients with epilepsy who continue to receive valproate in the UK.

    Lang, Lilly / Dunbar-Creasey, Neisha / Kneen, Rachel / Neely, Laura / Hawcutt, Daniel B

    Archives of disease in childhood

    2024  Volume 109, Issue 2, Page(s) 174–175

    MeSH term(s) Humans ; Female ; Child ; Valproic Acid/adverse effects ; Epilepsy/drug therapy ; Anticonvulsants/adverse effects ; United Kingdom/epidemiology
    Chemical Substances Valproic Acid (614OI1Z5WI) ; Anticonvulsants
    Language English
    Publishing date 2024-01-22
    Publishing country England
    Document type Letter
    ZDB-ID 524-1
    ISSN 1468-2044 ; 0003-9888 ; 1359-2998
    ISSN (online) 1468-2044
    ISSN 0003-9888 ; 1359-2998
    DOI 10.1136/archdischild-2023-326591
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Baló's concentric sclerosis presenting asymptomatically in a child: clinico-radiological-pathological correlation.

    Southin, Justine-Clair / Avula, Shivaram / du Plessis, Daniel / Kumar, Ram / Kneen, Rachel

    BMJ case reports

    2023  Volume 16, Issue 11

    MeSH term(s) Humans ; Child ; Diffuse Cerebral Sclerosis of Schilder/diagnostic imaging ; Diffuse Cerebral Sclerosis of Schilder/pathology ; Magnetic Resonance Imaging ; Radiography ; Radiology ; Brain/pathology ; Multiple Sclerosis
    Language English
    Publishing date 2023-11-27
    Publishing country England
    Document type Case Reports ; Journal Article
    ISSN 1757-790X
    ISSN (online) 1757-790X
    DOI 10.1136/bcr-2023-256185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Characterization of a multidisciplinary team's role in hospital discharge for patients receiving hypomethylating agents with venetoclax as induction therapy for acute myeloid leukemia.

    Pervitsky, Vera / Guglielmo, Julie / Moskoff, Benjamin / Kneen, Roxie / Leija, Carol / Sawicky, Deborah / Krackeler, Margaret Li / Jonas, Brian A / Beechinor, Ryan

    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

    2023  Volume 31, Issue 4, Page(s) 224

    Abstract: Purpose: Venetoclax combined with a hypomethylating agent (HMA) has become the standard of care for elderly/unfit patients with newly diagnosed acute myeloid leukemia (AML). This study is aimed at characterizing the impact of an interdisciplinary team ... ...

    Abstract Purpose: Venetoclax combined with a hypomethylating agent (HMA) has become the standard of care for elderly/unfit patients with newly diagnosed acute myeloid leukemia (AML). This study is aimed at characterizing the impact of an interdisciplinary team on the length of stay (LOS) of patients with newly diagnosed AML receiving venetoclax with an HMA.
    Methods: This retrospective observational study included patients with AML who received HMA with venetoclax as an initial treatment between December 2015 and July 2021. The primary outcome was the median LOS during induction stratified by HMA. Secondary outcomes included barriers to hospital discharge, incidence of tumor lysis syndrome (TLS), response rates, and utilization of the institution's prescription assistance program (PAP).
    Results: Seventy-eight patients were included in our analysis: 51 received azacitidine/venetoclax, and 27 received decitabine/venetoclax. The median LOS from therapy initiation was eight days (range 7-38) for the azacitidine group and six days (range 5-26) for the decitabine group. The most common barriers to discharge were transfusion dependence (33 patients, 42.3%) and insurance coverage (12 patients, 15.4%). Twelve patients (15.3%) had tumor lysis syndrome during hospital admission, and 20 (25.6%) were readmitted during induction. Twenty-three patients (29.5%) required financial assistance for AML care, and a pharmacy-led PAP generated approximately $342,646 in cost savings.
    Conclusion: The utilization of an interdisciplinary AML team to target early hospital discharge proved to be safe and effective and led to a reduction in costs for the health system. Future research may identify select patients who may be suitable for earlier discharge or outpatient induction.
    MeSH term(s) Humans ; Aged ; Decitabine/pharmacology ; Decitabine/therapeutic use ; Treatment Outcome ; Tumor Lysis Syndrome/etiology ; Patient Discharge ; Induction Chemotherapy ; Azacitidine/therapeutic use ; Leukemia, Myeloid, Acute/pathology ; Patient Care Team ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
    Chemical Substances Decitabine (776B62CQ27) ; venetoclax (N54AIC43PW) ; Azacitidine (M801H13NRU)
    Language English
    Publishing date 2023-03-21
    Publishing country Germany
    Document type Observational Study ; Journal Article
    ZDB-ID 1134446-5
    ISSN 1433-7339 ; 0941-4355
    ISSN (online) 1433-7339
    ISSN 0941-4355
    DOI 10.1007/s00520-023-07664-z
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  4. Article ; Online: Leigh syndrome mimicking neuromyelitis optica spectrum disorder (NMOSD).

    Kim, Nee Na / Abdel-Mannan, Omar / Davidson, James / Du Pre, Pascale / Kneen, Rachel / Mankad, Kshitij / Hacohen, Yael

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2023  Volume 29, Issue 7, Page(s) 889–892

    Abstract: We report two children with molecularly confirmed mitochondrial disease mimicking Neuromyelitis Optica Spectrum Disorder (NMOSD). The first patient presented at the age of 15 months with acute deterioration following a pyrexial illness with clinical ... ...

    Abstract We report two children with molecularly confirmed mitochondrial disease mimicking Neuromyelitis Optica Spectrum Disorder (NMOSD). The first patient presented at the age of 15 months with acute deterioration following a pyrexial illness with clinical features localising to the brainstem and spinal cord. The second patient presented at 5 years with acute bilateral visual loss. In both cases, MOG and AQP4 antibodies were negative. Both patients died within a year of symptoms onset from respiratory failure. Arriving at an early genetic diagnosis is important for redirection of care and avoiding potentially harmful immunosuppressant therapies.
    MeSH term(s) Child ; Humans ; Infant ; Neuromyelitis Optica/diagnosis ; Aquaporin 4 ; Leigh Disease/diagnosis ; Myelin-Oligodendrocyte Glycoprotein ; Autoantibodies ; Syndrome
    Chemical Substances Aquaporin 4 ; Myelin-Oligodendrocyte Glycoprotein ; Autoantibodies
    Language English
    Publishing date 2023-05-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/13524585231172950
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  5. Article ; Online: Raised Intracranial Pressure in Three Children with Cystic Fibrosis Receiving Elexacaftor-Tezacaftor-Ivacaftor Modulator Therapy.

    Southern, Kevin W / Barben, Jürg / Goldring, Stephen / Kneen, Rachel / Southward, Suzanne / Rajeev, Yashasvi / Davies, Jane C / Bush, Andrew

    American journal of respiratory and critical care medicine

    2023  Volume 208, Issue 1, Page(s) 103–105

    MeSH term(s) Humans ; Child ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis/genetics ; Intracranial Pressure ; Cystic Fibrosis Transmembrane Conductance Regulator ; Aminophenols/therapeutic use ; Benzodioxoles/therapeutic use ; Mutation
    Chemical Substances elexacaftor (RRN67GMB0V) ; ivacaftor (1Y740ILL1Z) ; tezacaftor ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Aminophenols ; Benzodioxoles
    Language English
    Publishing date 2023-05-25
    Publishing country United States
    Document type Letter
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202303-0380LE
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  6. Article ; Online: Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology.

    Martin, N G / Defres, S / Willis, L / Beckley, R / Hardwick, H / Coxon, A / Kadambari, S / Yu, L-M / Liu, X / Galal, U / Conlin, K / Griffiths, M J / Kneen, R / Nadel, S / Heath, P T / Kelly, D E / Solomon, T / Sadarangani, M / Pollard, A J

    The Journal of infection

    2024  Volume 88, Issue 5, Page(s) 106145

    Abstract: Objectives: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes.: Methods: Children aged < ... ...

    Abstract Objectives: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes.
    Methods: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology.
    Results: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis.
    Conclusions: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis.
    Funding: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.
    Language English
    Publishing date 2024-03-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 424417-5
    ISSN 1532-2742 ; 0163-4453
    ISSN (online) 1532-2742
    ISSN 0163-4453
    DOI 10.1016/j.jinf.2024.106145
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  7. Article ; Online: Endemic erythromycin resistant

    Nguyen Thi Nguyen, To / Parry, Christopher M / Campbell, James I / Vinh, Phat Voong / Kneen, Rachel / Baker, Stephen

    Microbial genomics

    2022  Volume 8, Issue 10

    Abstract: Diphtheria is a potentially fatal respiratory disease caused by toxigenic forms of the Gram-positive ... ...

    Abstract Diphtheria is a potentially fatal respiratory disease caused by toxigenic forms of the Gram-positive bacterium
    MeSH term(s) Humans ; Corynebacterium diphtheriae/genetics ; Diphtheria/epidemiology ; Diphtheria/microbiology ; Erythromycin/pharmacology ; Vietnam/epidemiology ; Corynebacterium ; Diphtheria Toxoid ; Antitoxins
    Chemical Substances Erythromycin (63937KV33D) ; Diphtheria Toxoid ; Antitoxins
    Language English
    Publishing date 2022-10-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2835258-0
    ISSN 2057-5858 ; 2057-5858
    ISSN (online) 2057-5858
    ISSN 2057-5858
    DOI 10.1099/mgen.0.000861
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  8. Article: Second generation "peptoid" CCK-B receptor antagonists: identification and development of N-(adamantyloxycarbonyl)-alpha-methyl-(R)-tryptophan derivative (CI-1015) with an improved pharmacokinetic profile.

    Trivedi, B K / Padia, J K / Holmes, A / Rose, S / Wright, D S / Hinton, J P / Pritchard, M C / Eden, J M / Kneen, C / Webdale, L / Suman-Chauhan, N / Boden, P / Singh, L / Field, M J / Hill, D

    Journal of medicinal chemistry

    1998  Volume 41, Issue 1, Page(s) 38–45

    Abstract: We have previously described the design and development of CI-988, a peptoid analogue of CCK-4 with excellent binding affinity and selectivity for the CCK-B receptor. Due to its anxiolytic profile in animal models of anxiety, this compound was developed ... ...

    Abstract We have previously described the design and development of CI-988, a peptoid analogue of CCK-4 with excellent binding affinity and selectivity for the CCK-B receptor. Due to its anxiolytic profile in animal models of anxiety, this compound was developed as a clinical candidate. However, during its development, it was determined that CI-988 had low bioavailability in both rodent and nonrodent species. In the clinic, it was further established that CI-988 had poor bioavailability. Thus, there was a need to identify an analogue with an improved pharmacokinetic (PK) profile. The poor bioavailability was attributed to poor absorption and efficient hepatic extraction. We envisaged that reducing the molecular weight of the parent compound (5, MW = 614) would lead to better absorption. Thus, we synthesized a series of analogues in which the key alpha-methyltryptophan and adamantyloxycarbonyl moieties, required for receptor binding, were kept intact and the C-terminus was extensively modified. This SAR study led to the identification of tricyclo[3.3.1.1(3,7)]dec-2-yl [1S-[1 alpha(S*)2 beta]-[2-[(2-hydroxycyclohexyl)amino]-1-(1H-indol-3- ylmethyl)-1-methyl-2-oxoethyl]carbamate (CI-1015, 31) with binding affinities of 3.0 and 2900 nM for the CCK-B and CCK-A receptors, respectively. The compound showed CCK-B antagonist profile in the rat ventromedial hypothalamus assay with a Ke of 34 nM. It also showed an anxiolytic like profile orally in a standard anxiety paradigm (X-maze) with a minimum effective dose (MED) of 0.1 microgram/kg. Although the compound is less water soluble than CI-988, oral bioavailability in rat was improved nearly 10 times relative to CI-988 when dosed in HP beta CD. The blood-brain permeability of CI-1015 (31) was also enhanced relative to CI-988 (5). On the basis of the overall improved pharmacokinetic profile as well as enhanced brain penetration, CI-1015 (31) was chosen as a development candidate.
    MeSH term(s) Adamantane/analogs & derivatives ; Adamantane/chemical synthesis ; Adamantane/chemistry ; Adamantane/pharmacokinetics ; Animals ; Anti-Anxiety Agents/chemical synthesis ; Anti-Anxiety Agents/chemistry ; Anti-Anxiety Agents/pharmacokinetics ; Anti-Anxiety Agents/pharmacology ; Biological Availability ; Blood-Brain Barrier ; Maze Learning/drug effects ; Mice ; Models, Molecular ; Molecular Structure ; Peptoids ; Rats ; Rats, Wistar ; Receptor, Cholecystokinin A ; Receptor, Cholecystokinin B ; Receptors, Cholecystokinin/antagonists & inhibitors ; Receptors, Cholecystokinin/metabolism ; Tetragastrin/analogs & derivatives ; Tryptophan/analogs & derivatives ; Tryptophan/chemical synthesis ; Tryptophan/chemistry ; Tryptophan/pharmacokinetics
    Chemical Substances Anti-Anxiety Agents ; Peptoids ; Receptor, Cholecystokinin A ; Receptor, Cholecystokinin B ; Receptors, Cholecystokinin ; Tetragastrin (0OL293AV80) ; CI 1015 (6RYQ64Z587) ; Tryptophan (8DUH1N11BX) ; Adamantane (PJY633525U)
    Language English
    Publishing date 1998-01-01
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm970065l
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Acquired torticollis due to primary pyomyositis of the paraspinal muscles in an 11-year-old boy.

    Ray, S / Iyer, A / Avula, S / Kneen, R

    BMJ case reports

    2016  Volume 2016

    Abstract: Torticollis is characterised by tilting and rotation of the cervical spine in opposite directions. Causes can be congenital or acquired. Primary pyomyositis is a rare subacute deep bacterial infection of skeletal muscles that typically affects ... ...

    Abstract Torticollis is characterised by tilting and rotation of the cervical spine in opposite directions. Causes can be congenital or acquired. Primary pyomyositis is a rare subacute deep bacterial infection of skeletal muscles that typically affects individuals under 20 years of age from tropical countries. Infrequently, pyomyositis occurs in individuals from temperate regions, usually in immunocompromised adults, and this is defined as secondary pyomyositis. We report a case of acquired torticollis due to primary pyomyositis of the paraspinal muscles in a previously healthy boy from the UK. A prolonged course of antibiotics and physiotherapy led to a complete resolution of his illness. We review how to differentiate pyomyositis from focal myositis, a more common inflammatory muscular cause of acquired torticollis.
    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Child ; Diagnosis, Differential ; Fever/etiology ; Humans ; Male ; Paraspinal Muscles/diagnostic imaging ; Physical Therapy Modalities ; Pyomyositis/complications ; Pyomyositis/diagnosis ; Pyomyositis/therapy ; Torticollis/etiology ; United Kingdom
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2016-03-18
    Publishing country England
    Document type Case Reports ; Journal Article
    ISSN 1757-790X
    ISSN (online) 1757-790X
    DOI 10.1136/bcr-2015-213409
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Evolution of brain MRI lesions in paediatric myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and its relevance to disease course.

    Abdel-Mannan, Omar / Champsas, Dimitrios / Tur, Carmen / Lee, Vanessa / Manivannan, Sharmila / Usman, Haroon / Skippen, Alison / Desai, Ishita / Chitre, Manali / Forsyth, Rob / Kneen, Rachel / Ram, Dipak / Ramdas, Sithara / Rossor, Thomas / West, Siobhan / Wright, Sukhvir / Palace, Jacqueline / Wassmer, Evangeline / Hemingway, Cheryl /
    Lim, Ming J / Mankad, Kshitij / Ciccarelli, Olga / Hacohen, Yael

    Journal of neurology, neurosurgery, and psychiatry

    2024  Volume 95, Issue 5, Page(s) 426–433

    Abstract: Background: Lesion resolution is often observed in children with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and asymptomatic lesions are less commonly reported in MOGAD than in multiple sclerosis (MS).: Objective: We ... ...

    Abstract Background: Lesion resolution is often observed in children with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and asymptomatic lesions are less commonly reported in MOGAD than in multiple sclerosis (MS).
    Objective: We aimed to evaluate brain MRI changes over time in paediatric MOGAD.
    Methods: Retrospective study in eight UK paediatric neuroscience centres. Acute brain MRI and available follow-up MRIs were reviewed. Predictors for lesion dynamic were evaluated using multivariable regression and Kaplan-Meier survival analyses were used to predict risk of relapse, disability and MOG-Ab status.
    Results: 200 children were included (MOGAD 97; MS 103). At first MRI post attack, new symptomatic and asymptomatic lesions were seen more often in MS versus MOGAD (52/103 vs 28/97; p=0.002 and 37/103 vs 11/97; p<0.001); 83% of patients with MOGAD showed at least one lesion's resolution at first follow-up scan, and 23% had normal MRI. Only 1 patient with MS had single lesion resolution; none had normal MRI. Disappearing lesions in MOGAD were seen in 40% after the second attack, 21% after third attack and none after the fourth attack.New lesions at first follow-up scan were associated with increased likelihood of relapse (p=0.02) and persistent MOG-Ab serostatus (p=0.0016) compared with those with no new lesions. Plasma exchange was associated with increased likelihood of lesion resolution (p=0.01). Longer time from symptom onset to steroids was associated with increased likelihood of new lesions; 50% increase at 20 days (p=0.01).
    Conclusions: These striking differences in lesion dynamics between MOGAD and MS suggest greater potential to repair. Early treatment with steroids and plasma exchange is associated with reduced likelihood of new lesions.
    MeSH term(s) Child ; Humans ; Autoantibodies ; Brain/diagnostic imaging ; Disease Progression ; Magnetic Resonance Imaging ; Multiple Sclerosis/diagnostic imaging ; Myelin-Oligodendrocyte Glycoprotein ; Recurrence ; Retrospective Studies ; Steroids
    Chemical Substances Autoantibodies ; Myelin-Oligodendrocyte Glycoprotein ; Steroids
    Language English
    Publishing date 2024-04-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 3087-9
    ISSN 1468-330X ; 0022-3050
    ISSN (online) 1468-330X
    ISSN 0022-3050
    DOI 10.1136/jnnp-2023-332542
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