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1. A new functional method to choose the target lobe for lung volume reduction in emphysema – comparison with the conventional densitometric method

Author

Hetzel J, Boeckeler M, Horger M, Ehab A, Kloth C, Wagner R, Freitag L, Slebos DJ, Lewis RA, and Haentschel M

Subjects
Emphysema - Chronic obstructive pulmonary disease – High-resolution computed tomography – Lung volume reduction, Diseases of the respiratory system, RC705-779
Abstract

Juergen Hetzel,1 Michael Boeckeler,1 Marius Horger,2 Ahmed Ehab,1 Christopher Kloth,2 Robert Wagner,3 Lutz Freitag,4 Dirk-Jan Slebos,5 Richard Alexander Lewis,6 Maik Haentschel1 1Division of Haematology, Oncology, Rheumatology, Immunology and Pulmonology, Department of Internal Medicine, 2Department of Diagnostic and Interventional Radiology, 3Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tuebingen, Tuebingen, Germany; 4Division of Pulmonology, University Hospital Zurich, Zurich, Switzerland; 5Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 6National Pollen and Aerobiology Research Unit, Institute of Science and the Environment, University of Worcester, Worcester, UK Background: Lung volume reduction (LVR) improves breathing mechanics by reducing hyperinflation. Lobar selection usually focuses on choosing the most destroyed emphysematous lobes as seen on an inspiratory CT scan. However, it has never been shown to what extent these densitometric CT parameters predict the least deflation of an individual lobe during expiration. The addition of expiratory CT analysis allows measurement of the extent of lobar air trapping and could therefore provide additional functional information for choice of potential treatment targets. Objectives: To determine lobar vital capacity/lobar total capacity (LVC/LTC) as a functional parameter for lobar air trapping using on an inspiratory and expiratory CT scan. To compare lobar selection by LVC/LTC with the established morphological CT density parameters. Methods: 36 patients referred for endoscopic LVR were studied. LVC/LTC, defined as delta volume over maximum volume of a lobe, was calculated using inspiratory and expiratory CT scans. The CT morphological parameters of mean lung density (MLD), low attenuation volume (LAV), and 15th percentile of Hounsfield units (15%P) were determined on an inspiratory CT scan for each lobe. We compared and correlated LVC/LTC with MLD, LAV, and 15%P. Results: There was a weak correlation between the functional parameter LVC/LTC and all inspiratory densitometric parameters. Target lobe selection using lowest lobar deflation (lowest LVC/LTC) correlated with target lobe selection based on lowest MLD in 18 patients (50.0%), with the highest LAV in 13 patients (36.1%), and with the lowest 15%P in 12 patients (33.3%). Conclusion: CT-based measurement of deflation (LVC/LTC) as a functional parameter correlates weakly with all densitometric CT parameters on a lobar level. Therefore, morphological criteria based on inspiratory CT densitometry partially reflect the deflation of particular lung lobes, and may be of limited value as a sole predictor for target lobe selection in LVR. Keywords: emphysema, chronic obstructive pulmonary disease, high-resolution computed tomography, lung volume reduction

Published
2017

2. D.1 Efficacy, safety, and tolerability of subcutaneous efgartigimod in chronic inflammatory demyelinating polyneuropathy: results from the ADHERE trial

Author

Siddiqi, Z, primary, Allen, JA, additional, Basta, I, additional, Eggers, C, additional, Guptill, J, additional, Gwathmey, K, additional, Hewamadduma, C, additional, Hofman, E, additional, Hussain, Y, additional, Kuwabara, S, additional, Leypoldt, F, additional, Lin, J, additional, Lipowska, M, additional, Lowe, M, additional, Lauria Pinter, G, additional, Querol, L, additional, Suresh, N, additional, Chang, T, additional, Tse, A, additional, Ulrichts, P, additional, van Doorn, PA, additional, Van Hoorick, B, additional, Yamasaki, R, additional, and Lewis, RA, additional

Published
2024
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3. S90 Right ventricular remodelling assessed using cardiac magnetic resonance predicts survival and treatment response in pulmonary arterial hypertension

Author

Goh, ZM, primary, Balasubramanian, N, additional, Alabed, S, additional, Dwivedi, K, additional, Shahin, Y, additional, Rothman, AMK, additional, Garg, P, additional, Lawrie, A, additional, Capener, D, additional, Thompson, AAR, additional, Alandejani, F, additional, Wild, JM, additional, Johns, CS, additional, Lewis, RA, additional, Gosling, R, additional, Sharkey, M, additional, Condliffe, R, additional, Kiely, DG, additional, and Swift, AJ, additional

Published
2022
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4. S93 Systematic follow-up of patients following acute pulmonary embolism is associated with an increased incidence of chronic thromboembolic pulmonary hypertension and less severe disease

Author

Durrington, C, primary, Armstrong, I, additional, Charalampopoulos, A, additional, Condliffe, R, additional, Devey, T, additional, Elliot, C, additional, Hameed, A, additional, Hamilton, N, additional, Hill, C, additional, Hurdman, J, additional, Lewis, RA, additional, Maclean, R, additional, Rajaram, S, additional, Rothman, AMK, additional, Saccullo, G, additional, Swift, AJ, additional, Thomas, S, additional, Thompson, AAR, additional, Van Veen, JJ, additional, Wild, JM, additional, and Kiely, DG, additional

Published
2022
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5. P38 Assessing the repeatability of NT-proBNP testing using laboratory and point of care testing in PAH (REPEAT-PAH)

Author

Durrington, C, primary, Battersby, C, additional, Holt, L, additional, Fairman, A, additional, Salisbury, T, additional, Turton, H, additional, Watson, L, additional, Hameed, AG, additional, Charalampopoulos, A, additional, Elliot, CA, additional, Rothman, AMK, additional, Middleton, J, additional, Zafar, H, additional, Condliffe, R, additional, Lewis, RA, additional, Kiely, DG, additional, and Thompson, AAR, additional

Published
2022
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7. Fluctuations of an omega-type killed process in discrete time

Author

Meral Şimşek, Lewis Ramsden, and Apostolos D. Papaioannou

Subjects
Fluctuation theory in discrete time, exit problems, upwards skip-free killed random walks, potential measures, one-step analysis, probability of bankruptcy, Applied mathematics. Quantitative methods, T57-57.97, Mathematics, QA1-939
Abstract

The theory of the so-called ${\mathcal{W}_{q}}$ and ${\mathcal{Z}_{q}}$ scale functions is developped for the fluctuations of right-continuous discrete time and space killed random walks. Explicit expressions are derived for the resolvents and two-sided exit problem when killing depends on the present level of the process. Similar results in the reflected case are also considered. All the expressions are given in terms of new generalisations of the scale functions, which are obtained using arguments different from the continuous case (spectrally negative Lévy processes). Hence, the connections between the two cases are spelled out. For a specific form of the killing function, the probability of bankruptcy is obtained for the model known as omega model in the actuarial literature.

Published
2024
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9. 24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients.

Author

Craven, ER, Walters, T, Christie, WC, Day, DG, Lewis, RA, Goodkin, ML, Chen, M, Wangsadipura, V, Robinson, MR, Bejanian, M, Bimatoprost SR Study Group, Craven, ER, Walters, T, Christie, WC, Day, DG, Lewis, RA, Goodkin, ML, Chen, M, Wangsadipura, V, Robinson, MR, Bejanian, M, and Bimatoprost SR Study Group

Abstract

OBJECTIVE: The objective of this study was to evaluate the safety and intraocular pressure (IOP)-lowering effects over 24 months of biodegradable bimatoprost sustained-release implant (Bimatoprost SR) administration versus topical bimatoprost 0.03% in patients with open-angle glaucoma (OAG). METHODS: This was a phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial. At baseline following washout, adult patients with OAG (N = 75) received Bimatoprost SR (6, 10, 15, or 20 µg) intracamerally in the study eye; the fellow eye received topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or single repeat administration with implant was permitted. The primary endpoint was IOP change from baseline. Safety measures included adverse events (AEs). RESULTS: At month 24, mean IOP reduction from baseline was 7.5, 7.3, 7.3, and 8.9 mmHg in eyes treated with Bimatoprost SR 6, 10, 15, and 20 µg, respectively, versus 8.2 mmHg in pooled fellow eyes; 68, 40, and 28% of pooled study eyes had not been rescued/retreated at months 6, 12, and 24, respectively. AEs in study eyes that occurred ≤ 2 days post-procedure typically were transient. After 2 days post-procedure, overall AE incidence was similar between study and fellow eyes, with some events typically associated with topical prostaglandin analogs having lower incidence in study eyes. CONCLUSIONS: Bimatoprost SR showed favorable efficacy and safety profiles up to 24 months, with all evaluated dose strengths demonstrating overall IOP-reducing effects comparable to those of topical bimatoprost. Targeted and sustained delivery of bimatoprost resulted in protracted IOP lowering, suggesting that Bimatoprost SR may represent a transformational new approach to glaucoma therapy. Clinicaltrials.gov identifier: NCT01157364.

Published
2020

10. Placebo effect in chronic inflammatory demyelinating polyneuropathy: ThePATHstudy and a systematic review

Author

Lewis, RA, Cornblath, DR, Hartung, H-P, Sobue, G, Lawo, J-P, Mielke, O, Durn, BL, Bril, V, Merkies, ISJ, Bassett, P, Cleasby, A, van Schaik, IN, Lewis, RA, Cornblath, DR, Hartung, H-P, Sobue, G, Lawo, J-P, Mielke, O, Durn, BL, Bril, V, Merkies, ISJ, Bassett, P, Cleasby, A, and van Schaik, IN

Abstract

The Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post-hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo-controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non-deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration.

Published
2020

12. Functional characterization of synthetic leukotriene B and its stereochemical isomers.

Author

Lewis, RA, Goetzl, EJ, Drazen, JM, Soter, NA, Austen, KF, and Corey, EJ

Subjects
Biomedical and Clinical Sciences, Animals, Arachidonic Acids, Chemical Phenomena, Chemistry, Chemotaxis, Leukocyte, Guinea Pigs, Humans, Leukotriene B4, Macaca mulatta, Muscle, Smooth, Neutrophils, Skin Tests, Spasm, Stereoisomerism, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Leukotriene B (LTB), a potent lipid chemotactic factor for neutrophils, is 5S,12R-dihydroxy-6,14-cis,8,10-trans-eicosatetraenoic acid (Fig 1), based upon direct comparison of natural LTB with synthetic 5S,12R-dihydroxy-6,8,10,14-eicosatetraenoic acid (5,12-di-HETE) stereoisomers in three biological assays. Of the six synthetic stereoisomers evaluated, only the 5S,12R,6,14-cis,8,10-trans compound had chemotactic potency for human neutrophils in vitro that was comparable to that of natural LTB, with a concentration of 3 X 10(9-9) M eliciting a one-half maximum response. In contrast, the racemic mixture of 5R,12R- and 5S,12S-6,10-trans,8,14-cis, the racemic mixture of 5S,12R- and 5R,12S-6,10-trans,8,14-cis, the 5S,12R-6,8-trans,10,14-cis, the 5S,12R-6,8,10-trans,14-cis, and the 5S,12S-6,8,10-trans,14-cis stereoisomers required concentrations of 3 X 10(-7) to 1 X 10(-6) M to elicit comparable responses. Only natural LTB and its synthetic counterpart elicited a local neutrophil infiltration when injected into the skin of the rhesus monkey at 10 ng and 100 ng per site. Natural and synthetic LTB at a concentration of 3 X 10(-8) M each provoked an EC25 contractile response of guinea pig pulmonary parenchymal strips in vitro, whereas the other four tested stereoisomers of 5,12-di-HETE were inactive at this concentration. Structure-function analyses suggest that the neutrophil chemotactic activity depends critically upon the C-1 to C-12 domain, including the stereochemistry of the 6-,8-,and 10-olefinic bonds and the presence of both hydroxyl groups.

Published
1981

13. Formation of slow-reacting substance of anaphylaxis in human lung tissue and cells before release.

Author

Lewis, RA, Wasserman, SI, Goetzi, EJ, and Austen, KF

Subjects
Lung, Animals, Humans, Guinea Pigs, Rats, Anaphylaxis, SRS-A, Immunoglobulin E, Immunoglobulin G, Cyclic AMP, Bucladesine, Cyclic GMP, Tissue Extracts, Antigens, Immunization, Biological Assay, Rare Diseases, Immunology, Medical and Health Sciences
Abstract

The capacity to extract slow-reacting substance of anaphylaxis (SRS-A) from human lung tissue or cells after immunologic activation, together with the measurement of SRS-A in both the extract and the surrounding fluid, permits study of total SRS-A generation. That the material extracted is SRS-A was established by both differential bioassay and purification. SRS-A accumulation was entirely intracellular after limited IgE-dependent direct or reversed anaphylactic activation. Intracellular accumulation also generally preceded release, with generation of SRS-A continuing well beyond a plateau in the cellular SRS-A level and the release of preformed mediators. The quantity of SRS-A generated after immunologic activation was modulated by the introduction of exogenous cyclic nucleotides, revealing a site of cyclic nucleotide action distinct from that on mediator release. The capacity to determine not only the release of preformed mediators but also the generation of a newly formed mediator, the sum of SRS-A in cells and supernate, adds an additional dimension to the analysis of the cellular events of immediate hypersensitivity.

Published
1974

15. Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies

Author

Merkies, ISJ, van Schaik, IN, Leger, J-M, Bril, V, van Geloven, N, Hartung, H-P, Lewis, RA, Sobue, G, Lawo, J-P, Durn, BL, Cornblath, DR, De Bleecker, JL, Sommer, C, Robberecht, W, Saarela, M, Kamienowski, J, Stelmasiak, Z, Tackenberg, B, Mielke, O, Sabet, A, George, K, Roberts, L, Carne, R, Blum, S, Henderson, R, Van Damme, P, Demeestere, J, Larue, S, D'Amour, C, Kunc, P, Valis, M, Sussova, J, Kalous, T, Talab, R, Bednar, M, Toomsoo, T, Rubanovits, I, Gross-Paju, K, Sorro, U, Auranen, M, Pouget, J, Attarian, S, Le Masson, G, Wielanek-Bachelet, A, Desnuelle, C, Delmont, E, Clavelou, P, Aufauvre, D, Schmidt, J, Zschuentzsch, J, Kramer, D, Hoffmann, O, Goerlitz, C, Haas, J, Chatzopoulos, M, Yoon, R, Gold, R, Berlit, P, Jaspert-Grehl, A, Liebetanz, D, Kutschenko, A, Stangel, M, Trebst, C, Baum, P, Bergh, F, Klehmet, J, Meisel, A, Klostermann, F, Oechtering, J, Lehmann, H, Schroeter, M, Hagenacker, T, Mueller, D, Sperfeld, A, Bethke, F, Drory, V, Algom, A, Yarnitsky, D, Murinson, B, Di Muzio, A, Ciccocioppo, F, Sorbi, S, Mata, S, Schenone, A, Grandis, M, Lauria, G, Cazzato, D, Antonini, G, Morino, S, Cocito, D, Zibetti, M, Yokota, T, Ohkubo, T, Kanda, T, Kawai, M, Kaida, K, Onoue, H, Kuwabara, S, Mori, M, Iijima, M, Ohyama, K, Baba, M, Tomiyama, M, Nishiyama, K, Akutsu, T, Yokoyama, K, Kanai, K, Eftimov, F, Notermans, NC, Visser, N, Faber, C, Hoeijmakers, J, Rejdak, K, Chyrchel-Paszkiewicz, U, Casanovas Pons, C, Antonia, M, Gamez, J, Salvado, M, Marquez Infante, C, Benitez, S, Lunn, M, Morrow, J, Gosal, D, Lavin, T, Melamed, I, Testori, A, Ajroud-Driss, S, Menichella, D, Simpson, Lai, EC-H, Dimachkie, M, Barohn, RJ, Beydoun, S, Johl, H, Lange, D, Shtilbans, A, Muley, S, Ladha, S, Freimer, M, Kissel, J, Latov, N, Chin, R, Ubogu, E, Mumfrey, S, Rao, T, MacDonald, P, Sharma, K, Gonzalez, G, Allen, J, Walk, D, Hobson-Webb, L, Gable, K, Franques, J, Morales, RJ, Nguento, A, Schrey, C, Zwolinska, G, Merkies, ISJ, van Schaik, IN, Leger, J-M, Bril, V, van Geloven, N, Hartung, H-P, Lewis, RA, Sobue, G, Lawo, J-P, Durn, BL, Cornblath, DR, De Bleecker, JL, Sommer, C, Robberecht, W, Saarela, M, Kamienowski, J, Stelmasiak, Z, Tackenberg, B, Mielke, O, Sabet, A, George, K, Roberts, L, Carne, R, Blum, S, Henderson, R, Van Damme, P, Demeestere, J, Larue, S, D'Amour, C, Kunc, P, Valis, M, Sussova, J, Kalous, T, Talab, R, Bednar, M, Toomsoo, T, Rubanovits, I, Gross-Paju, K, Sorro, U, Auranen, M, Pouget, J, Attarian, S, Le Masson, G, Wielanek-Bachelet, A, Desnuelle, C, Delmont, E, Clavelou, P, Aufauvre, D, Schmidt, J, Zschuentzsch, J, Kramer, D, Hoffmann, O, Goerlitz, C, Haas, J, Chatzopoulos, M, Yoon, R, Gold, R, Berlit, P, Jaspert-Grehl, A, Liebetanz, D, Kutschenko, A, Stangel, M, Trebst, C, Baum, P, Bergh, F, Klehmet, J, Meisel, A, Klostermann, F, Oechtering, J, Lehmann, H, Schroeter, M, Hagenacker, T, Mueller, D, Sperfeld, A, Bethke, F, Drory, V, Algom, A, Yarnitsky, D, Murinson, B, Di Muzio, A, Ciccocioppo, F, Sorbi, S, Mata, S, Schenone, A, Grandis, M, Lauria, G, Cazzato, D, Antonini, G, Morino, S, Cocito, D, Zibetti, M, Yokota, T, Ohkubo, T, Kanda, T, Kawai, M, Kaida, K, Onoue, H, Kuwabara, S, Mori, M, Iijima, M, Ohyama, K, Baba, M, Tomiyama, M, Nishiyama, K, Akutsu, T, Yokoyama, K, Kanai, K, Eftimov, F, Notermans, NC, Visser, N, Faber, C, Hoeijmakers, J, Rejdak, K, Chyrchel-Paszkiewicz, U, Casanovas Pons, C, Antonia, M, Gamez, J, Salvado, M, Marquez Infante, C, Benitez, S, Lunn, M, Morrow, J, Gosal, D, Lavin, T, Melamed, I, Testori, A, Ajroud-Driss, S, Menichella, D, Simpson, Lai, EC-H, Dimachkie, M, Barohn, RJ, Beydoun, S, Johl, H, Lange, D, Shtilbans, A, Muley, S, Ladha, S, Freimer, M, Kissel, J, Latov, N, Chin, R, Ubogu, E, Mumfrey, S, Rao, T, MacDonald, P, Sharma, K, Gonzalez, G, Allen, J, Walk, D, Hobson-Webb, L, Gable, K, Franques, J, Morales, RJ, Nguento, A, Schrey, C, and Zwolinska, G

Abstract

Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open-label, single-arm study of IVIG in immunoglobulin (Ig)-naïve or IVIG pre-treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double-blind, randomized study including an open-label, single-arm IVIG phase in IVIG pre-treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre-treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was -1.0 (interquartile range -2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA-approved IVIG for CIDP, in a population of mainly pre-treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].

Published
2019

16. Spectrum of neurodevelopmental disease associated with the GNAO1 guanosine triphosphate-binding region

Author

Kelly, M, Park, M, Mihalek, I, Rochtus, A, Gramm, M, Perez-Palma, E, Axeen, ET, Hung, CY, Olson, H, Swanson, L, Anselm, I, Briere, LC, High, FA, Sweetser, DA, Kayani, S, Snyder, M, Calvert, S, Scheffer, IE, Yang, E, Waugh, JL, Lal, D, Bodamer, O, Poduri, A, Adams, DR, Aday, A, Alejandro, ME, Allard, P, Ashley, EA, Azamian, MS, Bacino, CA, Baker, E, Balasubramanyam, A, Barseghyan, H, Batzli, GF, Beggs, AH, Behnam, B, Bellen, HJ, Bernstein, JA, Bican, A, Bick, DP, Birch, CL, Bonner, D, Boone, BE, Bostwick, BL, Brokamp, E, Brown, DM, Brush, M, Burke, EA, Burrage, LC, Butte, MJ, Chen, S, Clark, GD, Coakley, TR, Cogan, JD, Colley, HA, Cooper, CM, Cope, H, Craigen, WJ, D'Souza, P, Davids, M, Davidson, JM, Dayal, JG, Dell'Angelica, EC, Dhar, SU, Dipple, KM, Donnell-Fink, LA, Dorrani, N, Dorset, DC, Douine, ED, Draper, DD, Dries, AM, Eckstein, DJ, Emrick, LT, Eng, CM, Enns, G-GM, Eskin, A, Esteves, C, Estwick, T, Fairbrother, L, Fernandez, L, Ferreira, C, Fieg, EL, Fisher, PG, Fogel, BL, Friedman, ND, Gahl, WA, Glanton, E, Godfrey, RA, Goldman, AM, Goldstein, DB, Gould, SE, Gourdine, J-PF, Groden, CA, Gropman, AL, Haendel, M, Hamid, R, Hanchard, NA, High, F, Holm, IA, Horn, J, Howerton, EM, Huang, Y, Jamal, F, Jiang, Y-H, Johnston, JM, Jones, AL, Karaviti, L, Koeller, DM, Kohane, IS, Kohler, JN, Konick, S, Koziura, M, Krasnewich, DM, Krier, JB, Kyle, JE, Lalani, SR, Lau, CC, Lazar, J, LeBlanc, K, Lee, BH, Lee, H, Levy, SE, Lewis, RA, Lincoln, SA, Loo, SK, Loscalzo, J, Maas, RL, Macnamara, EF, MacRae, CA, Maduro, VV, Majch-erska, MM, Malicdan, MC, Mamounas, LA, Manolio, TA, Markello, TC, Marom, R, Martin, MG, Martinez-Agosto, JA, Mar-waha, S, May, T, McConkie-Rosell, A, McCormack, CE, McCray, AF, Merker, JD, Metz, TO, Might, M, Moretti, PM, Morimoto, M, Mulvihill, JJ, Murdock, DR, Murphy, JL, Muzny, DM, Nehrebecky, ME, Nelson, SF, Newberry, JS, Newman, JH, Nicholas, SK, Novacic, D, Orange, JS, Orengo, JP, Pallais, JC, Palmer, CGS, Papp, JC, Parker, NH, Pena, LDM, Phillips, JA, Posey, JE, Postlethwait, JH, Potocki, L, Pusey, BN, Reuter, CM, Rives, L, Robertson, AK, Rodan, LH, Rosenfeld, JA, Sampson, JB, Samson, SL, Schoch, K, Scott, DA, Shakachite, L, Sharma, P, Shashi, V, Signer, R, Silverman, EK, Sinsheimer, JS, Smith, KS, Spillmann, RC, Stoler, JM, Stong, N, Sullivan, JA, Tan, QK-G, Tifft, CJ, Toro, C, Tran, AA, Urv, TK, Vilain, E, Vogel, TP, Waggott, DM, Wahl, CE, Walker, M, Walley, NM, Walsh, CA, Wan, J, Wangler, MF, Ward, PA, Waters, KM, Webb-Robertson, B-JM, Westerfield, M, Wheeler, MT, Wise, AL, Wolfe, LA, Worthey, EA, Yamamoto, S, Yang, Y, Yoon, AJ, Yu, G, Zastrow, DB, Zhao, C, Zheng, A, Kelly, M, Park, M, Mihalek, I, Rochtus, A, Gramm, M, Perez-Palma, E, Axeen, ET, Hung, CY, Olson, H, Swanson, L, Anselm, I, Briere, LC, High, FA, Sweetser, DA, Kayani, S, Snyder, M, Calvert, S, Scheffer, IE, Yang, E, Waugh, JL, Lal, D, Bodamer, O, Poduri, A, Adams, DR, Aday, A, Alejandro, ME, Allard, P, Ashley, EA, Azamian, MS, Bacino, CA, Baker, E, Balasubramanyam, A, Barseghyan, H, Batzli, GF, Beggs, AH, Behnam, B, Bellen, HJ, Bernstein, JA, Bican, A, Bick, DP, Birch, CL, Bonner, D, Boone, BE, Bostwick, BL, Brokamp, E, Brown, DM, Brush, M, Burke, EA, Burrage, LC, Butte, MJ, Chen, S, Clark, GD, Coakley, TR, Cogan, JD, Colley, HA, Cooper, CM, Cope, H, Craigen, WJ, D'Souza, P, Davids, M, Davidson, JM, Dayal, JG, Dell'Angelica, EC, Dhar, SU, Dipple, KM, Donnell-Fink, LA, Dorrani, N, Dorset, DC, Douine, ED, Draper, DD, Dries, AM, Eckstein, DJ, Emrick, LT, Eng, CM, Enns, G-GM, Eskin, A, Esteves, C, Estwick, T, Fairbrother, L, Fernandez, L, Ferreira, C, Fieg, EL, Fisher, PG, Fogel, BL, Friedman, ND, Gahl, WA, Glanton, E, Godfrey, RA, Goldman, AM, Goldstein, DB, Gould, SE, Gourdine, J-PF, Groden, CA, Gropman, AL, Haendel, M, Hamid, R, Hanchard, NA, High, F, Holm, IA, Horn, J, Howerton, EM, Huang, Y, Jamal, F, Jiang, Y-H, Johnston, JM, Jones, AL, Karaviti, L, Koeller, DM, Kohane, IS, Kohler, JN, Konick, S, Koziura, M, Krasnewich, DM, Krier, JB, Kyle, JE, Lalani, SR, Lau, CC, Lazar, J, LeBlanc, K, Lee, BH, Lee, H, Levy, SE, Lewis, RA, Lincoln, SA, Loo, SK, Loscalzo, J, Maas, RL, Macnamara, EF, MacRae, CA, Maduro, VV, Majch-erska, MM, Malicdan, MC, Mamounas, LA, Manolio, TA, Markello, TC, Marom, R, Martin, MG, Martinez-Agosto, JA, Mar-waha, S, May, T, McConkie-Rosell, A, McCormack, CE, McCray, AF, Merker, JD, Metz, TO, Might, M, Moretti, PM, Morimoto, M, Mulvihill, JJ, Murdock, DR, Murphy, JL, Muzny, DM, Nehrebecky, ME, Nelson, SF, Newberry, JS, Newman, JH, Nicholas, SK, Novacic, D, Orange, JS, Orengo, JP, Pallais, JC, Palmer, CGS, Papp, JC, Parker, NH, Pena, LDM, Phillips, JA, Posey, JE, Postlethwait, JH, Potocki, L, Pusey, BN, Reuter, CM, Rives, L, Robertson, AK, Rodan, LH, Rosenfeld, JA, Sampson, JB, Samson, SL, Schoch, K, Scott, DA, Shakachite, L, Sharma, P, Shashi, V, Signer, R, Silverman, EK, Sinsheimer, JS, Smith, KS, Spillmann, RC, Stoler, JM, Stong, N, Sullivan, JA, Tan, QK-G, Tifft, CJ, Toro, C, Tran, AA, Urv, TK, Vilain, E, Vogel, TP, Waggott, DM, Wahl, CE, Walker, M, Walley, NM, Walsh, CA, Wan, J, Wangler, MF, Ward, PA, Waters, KM, Webb-Robertson, B-JM, Westerfield, M, Wheeler, MT, Wise, AL, Wolfe, LA, Worthey, EA, Yamamoto, S, Yang, Y, Yoon, AJ, Yu, G, Zastrow, DB, Zhao, C, and Zheng, A

Abstract

OBJECTIVE: To characterize the phenotypic spectrum associated with GNAO1 variants and establish genotype-protein structure-phenotype relationships. METHODS: We evaluated the phenotypes of 14 patients with GNAO1 variants, analyzed their variants for potential pathogenicity, and mapped them, along with those in the literature, on a three-dimensional structural protein model. RESULTS: The 14 patients in our cohort, including one sibling pair, had 13 distinct, heterozygous GNAO1 variants classified as pathogenic or likely pathogenic. We attributed the same variant in two siblings to parental mosaicism. Patients initially presented with seizures beginning in the first 3 months of life (8/14), developmental delay (4/14), hypotonia (1/14), or movement disorder (1/14). All patients had hypotonia and developmental delay ranging from mild to severe. Nine had epilepsy, and nine had movement disorders, including dystonia, ataxia, chorea, and dyskinesia. The 13 GNAO1 variants in our patients are predicted to result in amino acid substitutions or deletions in the GNAO1 guanosine triphosphate (GTP)-binding region, analogous to those in previous publications. Patients with variants affecting amino acids 207-221 had only movement disorder and hypotonia. Patients with variants affecting the C-terminal region had the mildest phenotypes. SIGNIFICANCE: GNAO1 encephalopathy most frequently presents with seizures beginning in the first 3 months of life. Concurrent movement disorders are also a prominent feature in the spectrum of GNAO1 encephalopathy. All variants affected the GTP-binding domain of GNAO1, highlighting the importance of this region for G-protein signaling and neurodevelopment.

Published
2019

17. Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study

Author

Mielke, O, Bril, V, Cornblath, DR, Lawo, J-P, van Geloven, N, Hartung, H-P, Lewis, RA, Merkies, ISJ, Sobue, G, Durn, B, Shebl, A, van Schaik, IN, Sabet, A, George, K, Roberts, L, Carne, R, Blum, S, Henderson, R, Van Damme, P, Demeestere, J, Larue, S, D'Amour, C, Kunc, P, Valis, M, Sussova, J, Kalous, T, Talab, R, Bednar, M, Toomsoo, T, Rubanovits, I, Gross-Paju, K, Sorro, U, Saarela, M, Auranen, M, Pouget, J, Attarian, S, Le Masson, G, Wielanek-Bachelet, A, Desnuelle, C, Delmont, E, Clavelou, P, Aufauvre, D, Schmidt, J, Zschuentzsch, J, Sommer, C, Kramer, D, Hoffmann, O, Goerlitz, C, Haas, J, Chatzopoulos, M, Yoon, R, Gold, R, Berlit, P, Jaspert-Grehl, A, Liebetanz, D, Kutschenko, A, Stangel, M, Trebst, C, Baum, P, Bergh, F, Klehmet, J, Meisel, A, Klostermann, F, Oechtering, J, Lehmann, H, Schroeter, M, Hagenacker, T, Mueller, D, Sperfeld, A, Bethke, F, Drory, V, Algom, A, Yarnitsky, D, Murinson, B, Di Muzio, A, Ciccocioppo, F, Sorbi, S, Mata, S, Schenone, A, Grandis, M, Lauria, G, Cazzato, D, Antonini, G, Morino, S, Cocito, D, Zibetti, M, Yokota, T, Ohkubo, T, Kanda, T, Kawai, M, Kaida, K, Onoue, H, Kuwabara, S, Mori, M, Iijima, M, Ohyama, K, Baba, M, Tomiyama, M, Nishiyama, K, Akutsu, T, Yokoyama, K, Kanai, K, Eftimov, F, Notermans, NC, Visser, N, Faber, C, Hoeijmakers, J, Rejdak, K, Chyrchel-Paszkiewicz, U, Casanovas Pons, C, Antonia, M, Gamez, J, Salvado, M, Marquez Infante, C, Benitez, S, Lunn, M, Morrow, J, Gosal, D, Lavin, T, Melamed, I, Testori, A, Ajroud-Driss, S, Menichella, D, Simpson, E, Lai, EC-H, Dimachkie, M, Barohn, RJ, Beydoun, S, Johl, H, Lange, D, Shtilbans, A, Muley, S, Ladha, S, Freimer, M, Kissel, J, Latov, N, Chin, R, Ubogu, E, Mumfrey, S, Rao, T, MacDonald, P, Sharma, K, Gonzalez, G, Allen, J, Walk, D, Hobson-Webb, L, Gable, K, Mielke, O, Bril, V, Cornblath, DR, Lawo, J-P, van Geloven, N, Hartung, H-P, Lewis, RA, Merkies, ISJ, Sobue, G, Durn, B, Shebl, A, van Schaik, IN, Sabet, A, George, K, Roberts, L, Carne, R, Blum, S, Henderson, R, Van Damme, P, Demeestere, J, Larue, S, D'Amour, C, Kunc, P, Valis, M, Sussova, J, Kalous, T, Talab, R, Bednar, M, Toomsoo, T, Rubanovits, I, Gross-Paju, K, Sorro, U, Saarela, M, Auranen, M, Pouget, J, Attarian, S, Le Masson, G, Wielanek-Bachelet, A, Desnuelle, C, Delmont, E, Clavelou, P, Aufauvre, D, Schmidt, J, Zschuentzsch, J, Sommer, C, Kramer, D, Hoffmann, O, Goerlitz, C, Haas, J, Chatzopoulos, M, Yoon, R, Gold, R, Berlit, P, Jaspert-Grehl, A, Liebetanz, D, Kutschenko, A, Stangel, M, Trebst, C, Baum, P, Bergh, F, Klehmet, J, Meisel, A, Klostermann, F, Oechtering, J, Lehmann, H, Schroeter, M, Hagenacker, T, Mueller, D, Sperfeld, A, Bethke, F, Drory, V, Algom, A, Yarnitsky, D, Murinson, B, Di Muzio, A, Ciccocioppo, F, Sorbi, S, Mata, S, Schenone, A, Grandis, M, Lauria, G, Cazzato, D, Antonini, G, Morino, S, Cocito, D, Zibetti, M, Yokota, T, Ohkubo, T, Kanda, T, Kawai, M, Kaida, K, Onoue, H, Kuwabara, S, Mori, M, Iijima, M, Ohyama, K, Baba, M, Tomiyama, M, Nishiyama, K, Akutsu, T, Yokoyama, K, Kanai, K, Eftimov, F, Notermans, NC, Visser, N, Faber, C, Hoeijmakers, J, Rejdak, K, Chyrchel-Paszkiewicz, U, Casanovas Pons, C, Antonia, M, Gamez, J, Salvado, M, Marquez Infante, C, Benitez, S, Lunn, M, Morrow, J, Gosal, D, Lavin, T, Melamed, I, Testori, A, Ajroud-Driss, S, Menichella, D, Simpson, E, Lai, EC-H, Dimachkie, M, Barohn, RJ, Beydoun, S, Johl, H, Lange, D, Shtilbans, A, Muley, S, Ladha, S, Freimer, M, Kissel, J, Latov, N, Chin, R, Ubogu, E, Mumfrey, S, Rao, T, MacDonald, P, Sharma, K, Gonzalez, G, Allen, J, Walk, D, Hobson-Webb, L, and Gable, K

Abstract

In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre-randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow-up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post-study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal.

Published
2019

20. Utilising a non-surgical intervention in the knee osteoarthritis care pathway: a 6-year retrospective audit on NHS patients

Author

Robyn Benn, Lewis Rawson, and Amanda Phillips

Subjects
Diseases of the musculoskeletal system, RC925-935
Abstract

Background: Knee osteoarthritis (OA) is a chronic, debilitating, musculoskeletal condition that affects millions. The increase in prevalence and its economic impact on healthcare and society raise the need for additional non-surgical interventions. Objective: To assess the referral rates to secondary care consultation and clinical outcomes in patients with severe knee OA treated with a home-based, non-surgical intervention. Design: This was a retrospective audit on 571 patients with knee OA who met the clinical criteria for total knee replacement (TKR) and received the service between October 2015 and March 2020. Methods: Patients were treated with a non-surgical, home-based, biomechanical intervention that aims to reduce pain and improve function, involving a foot-worn device for gait rehabilitation. The device is adjusted to the patient based on their gait patterns and clinical symptoms. Patients are advised to use the device at home or work and continue their routine. Patients are also advised to return to follow-up appointments to readjust the device and treatment plan. The primary outcome measure was the referral rates to secondary care consultation. Secondary outcomes included patient-reported outcome measures to assess pain and function and a computerised gait test. Follow-up time was between 1 and 6 years post-treatment initiation with a mean follow-up time of 1308.1 (SD = 473.4) days (i.e. 3.5 years.). Results: There were 65 (11.4%) referrals for secondary consultation with an average follow-up of 3.5 years. The mean days to referral was 480.9 (SD = 399.2) days. Of all referrals, 48% ( n = 31) occurred during the first year of treatment, and 32% ( n = 21) occurred during the second year. The rest were after more than 2 years of treatment. Significant improvements were seen in all clinical outcomes, including a reduction in pain and an improvement in function and gait patterns ( p

Published
2023
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21. P183 Impact of patient choice on survival in patients with chronic thromboembolic pulmonary hypertension offered pulmonary endarterectomy

Author

Quadery, SR, primary, Swift, AJ, additional, Billings, C, additional, Thompson, AAR, additional, Elliot, CA, additional, Hurdman, J, additional, Garrod, S, additional, Charalampopolous, A, additional, Sabroe, I, additional, Armstrong, I, additional, Hamilton, N, additional, Sephton, P, additional, Lewis, RA, additional, Prasannan, P, additional, Jenkins, DP, additional, Pepke-Zaba, J, additional, Screaton, N, additional, Lawrie, A, additional, Johns, CS, additional, Rajaram, S, additional, Hill, C, additional, Wild, JM, additional, Condliffe, R, additional, and Kiely, DG, additional

Published
2017
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23. Quantifying the Electron Donor and Acceptor Abilities of the Ketimide Ligands in M(N=CtBu2)4(M = V, Nb, Ta)

Author

Damon, PL, Liss, CJ, Lewis, RA, Morochnik, S, Szpunar, DE, Telser, J, and Hayton, TW

Abstract

© 2015 American Chemical Society. Addition of 4 equiv of Li(N=CtBu2) to VCl3in THF, followed by addition of 0.5 equiv of I2, generates the homoleptic V(IV) ketimide complex, V(N=CtBu2)4(1), in 42% yield. Similarly, reaction of 4 equiv of Li(N=CtBu2) with NbCl4(THF)2in THF affords the homoleptic Nb(IV) ketimide complex, Nb(N=CtBu2)4(2), in 55% yield. Seeking to extend the series to the tantalum congener, a new Ta(IV) starting material, TaCl4(TMEDA) (3), was prepared via reduction of TaCl5with Et3SiH, followed by addition of TMEDA. Reaction of 3 with 4 equiv of Li(N=CtBu2) in THF results in the isolation of a Ta(V) ketimide complex, Ta(Cl)(N=CtBu2)4(5), which can be isolated in 32% yield. Reaction of 5 with Tl(OTf) yields Ta(OTf)(N=CtBu2)4(6) in 44% yield. Subsequent reduction of 6 with Cp∗2Co in toluene generates the homoleptic Ta(IV) congener Ta(N=CtBu2)4(7), although the yields are poor. All three homoleptic group 5 ketimide complexes exhibit squashed tetrahedral geometries in the solid state, as determined by X-ray crystallography. This geometry leads to a dx2-y21(2B1in D2d) ground state, as supported by DFT calculations. EPR spectroscopic analysis of 1 and 2, performed at X- and Q-band frequencies (∼9 and 35 GHz, respectively), further supports the2B1ground-state assignment, whereas comparison of 1, 2, and 7 with related group 5 tetra(aryl), tetra(amido), and tetra(alkoxo) complexes shows a higher M-L covalency in the ketimide-metal interaction. In addition, a ligand field analysis of 1 and 2 demonstrates that the ketimide ligand is both a strong π-donor and strong π-acceptor, an unusual combination found in very few organometallic ligands.

Published
2015
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24. Grip strength comparison in immune-mediated neuropathies: Vigorimeter vs. Jamar

Author

Draak, THP, Pruppers, MHJ, Nes, Sonja, Vanhoutte, EK, Bakkers, M (Mayienne), Gorson, KC, van der Pol, WL, Lewis, RA, Notermans, NC, Nobile-Orazio, E, Leger, JM, Van den Bergh, PYK, Lauria, G, Bril, V, Katzberg, H, Lunn, MPT, Pouget, J, van der Kooi, AJ, van den Berg, LH, van Doorn, Pieter, Cornblath, DR, Hahn, AF, Faber, CG, Merkies, ISJ (Ingemar), Amsterdam Neuroscience, Neurology, Amsterdam institute for Infection and Immunity, 05 Neurology and psychiatry, MUMC+: DA KG Polikliniek (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Klinische Neurowetenschappen

Subjects
grip strength, Jamar dynamometer, responsiveness comparison, Vigorimeter
Abstract

The Jamar dynamometer and Vigorimeter have been used to assess grip strength in immune-mediated neuropathies, but have never been compared to each other. Therefore, we performed a comparison study between these two devices in patients with immune-mediated neuropathies. Grip strength data were collected in 102 cross-sectional stable and 163 longitudinal (new diagnoses or changing condition) patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), gammopathy-related polyneuropathy (MGUSP), and multifocal motor neuropathy (MMN). Stable patients were assessed twice (validity/reliability studies). Longitudinal patients were assessed 3-5 times during 1 year. Responsiveness comparison between the two tools was examined using combined anchor-/distribution-based minimum clinically important difference (MCID) techniques. Patients were asked to indicate their preference for the Jamar or Vigorimeter. Both tools correlated highly with each other (ρ = 0.86, p

Published
2015

25. Impairment measures versus inflammatory RODS in GBS and CIDP: a responsiveness comparison

Author

Vanhoutte, EK, Draak, THP, Gorson, KC, van Nes, SI, Hoeijmakers, JGJ, Van der Pol, WL, Notermans, NC, Lewis, RA, Nobile-Orazio, E, Leger, JM, Van den Bergh, PYK, Lauria, G, Bril, V, Katzberg, H, Lunn, MPT, Pouget, J, van der Kooi, AJ, Hahn, AF, van Doorn, PA, Cornblath, DR, van den Berg, LH, Faber, CG, Merkies, ISJ, Illa I., Querol, L., and PeriNomS Study Grp

Subjects
outcome measure, immune-mediated neuropathies, minimum clinically important difference, Rasch
Abstract

This study aimed to define responder' through the concept of minimum clinically important differences using the individually obtained standard errors (MCID-SE) and a heuristic external criterion' responsiveness method in patients with Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One hundred and fourteen newly diagnosed or relapsing patients (GBS: 55, CIDP: 59) were serially examined (1-year follow-up). The inflammatory Rasch-built overall disability scale (I-RODS), Rasch-transformed MRC sum score (RT-MRC), and Rasch-transformed modified-INCAT-sensory scale (RT-mISS) were assessed. Being-a-responder was defined as having a MCID-SE cut-off 1.96. Also, the correlations between patients' scores on each scale and the EuroQoL health-status thermometer' (external criterion) were determined (higher correlation indicated better responsiveness). In both diseases, the SEs showed a characteristic U'-shaped dynamic pattern across each scales' continuum. The number of patients showing a meaningful change were higher for the I-RODS>RT-MRC>RT-mISS and were in GBS higher than CIDP patients. The MCID-SE concept using Rasch-transformed data demonstrated an individual pattern of being-a-responder' in patients with immune-mediated neuropathies, and the findings were validated by the external criterion responsiveness method. The I-RODS showed greater responsiveness compared with the MRC and INCAT-sensory scales, and its use is therefore recommended in future trials in GBS and CIDP.

Published
2015

26. Outcome measures in MMN revisited: further improvement needed

Author

Pruppers, MHJ, Draak, THP, Vanhoutte, EK, Van der Pol, WL, Gorson, KC, Leger, JM, Nobile-Orazio, E, Lewis, RA, van den Berg, LH, Faber, CG, Merkies, ISJ, Illa I., Querol, L., and PeriNomS Study Grp

Subjects
MMN, outcome measure
Abstract

The objectives of this study were to provide an overview of the outcome measures (OMs) applied in clinical trials in multifocal motor neuropathy (MMN) and to determine the responsiveness of a core set of selected OMs as part of the peripheral neuropathy outcome measures standardization (PeriNomS) study. The following OMs were serially applied in 26 patients with newly diagnosed or relapsing MMN, receiving intravenous immunoglobulin (assessments: T0/T3/T12months): 14 muscle pairs MRC (Medical Research Council) scale, the Neuropathy Impairment Scale motor-subset, a self-evaluation scale, grip strength, and MMN-RODS(C) (Rasch-built overall disability scale). All data, except the grip strength, were subjected to Rasch analyses before determining responsiveness. For grip strength, responsiveness was examined using a combined anchor- (SF-36 question-2) and distribution-based (1/2xSD) minimum clinically important difference (MCID) techniques, determining the proportion of patients exceeding both the identified cut-offs. For the remaining scales, the magnitude of change for each patient on each scale was determined using the MCID related to the individual SE (responder definition: MCID-SE1.96). Overall, a great assortment of measures has been used in MMN trials with different responsiveness definitions. For the selected OMs, responsiveness was poor and only seen in one fourth to one third of the patients, the grip strength being more responsive. Despite the efforts taken to standardize outcome assessment, further clinimetric responsiveness studies are needed in MMN.

Published
2015

27. Comparing the NIS vs. MRC and INCAT sensory scale through Rasch analyses

Author

Draak, THP, Vanhoutte, EK, van Nes, SI, Gorson, KC, Van der Pol, WL, Notermans, NC, Nobile-Orazio, E, Lewis, RA, Leger, JM, Van den Bergh, PYK, Lauria, G, Bril, V, Katzberg, H, Lunn, MPT, Pouget, J, van der Kooi, AJ, Hahn, AF, van den Berg, LH, van Doorn, PA, Cornblath, DR, Faber, CG, Merkies, ISJ, Illa I., Querol, L., and PeriNomS Study Grp

Subjects
mISS, MRC, responsiveness, NIS, Rasch
Abstract

We performed a comparison between Neuropathy Impairment Scale-sensory (NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale (mISS), and NIS-motor vs. the Medical Research Council sum score in patients with Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and IgM monoclonal gammopathy of undetermined significance-related polyneuropathy (MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch-transformed (RT)-intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients (GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2-4weeks later: one observer), and 137 newly diagnosed or relapsing patients (GBS: 55, CIDP: 59, and IgM-MGUSP: 23) were serially examined with 12months follow-up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT-mISS compared to RT-NISs. Responsiveness was equal for the RT-motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow-up in the latter group of patients.

Published
2015

28. GDNF AND CT-1 GENE THERAPY PROLONGES THE SURVIVAL OF SOD-1 MICE

Author

Acsadi, G., Anguelov, R., Yang, H., Toth, G., Jani, A., Lewis, RA., and Shy, ME.

Subjects
Genetic research -- Analysis, Human genetics -- Research, Sclerosis -- Genetic aspects, Spinal muscular atrophy -- Genetic aspects, Biological sciences
Published
2000

29. Cost–effectiveness of imipenem/cilastatin/relebactam for hospital-acquired and ventilator-associated bacterial pneumonia

Author

Jaesh Naik, Ryan Dillon, Matthew Massello, Lewis Ralph, and Zhuo Yang

Subjects
antimicrobial resistance, cost–effectiveness analysis, culture and susceptibility, habp/vabp, health economics, imipenem/cilastatin/relebactam, infectious diseases, Public aspects of medicine, RA1-1270
Abstract

Aim: This study evaluates the cost–effectiveness of imipenem/cilastatin/relebactam (IMI/REL) for treating hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in an ‘early adjustment prescribing scenario’. Methods: An economic model was constructed to compare two strategies: continuation of empiric piperacillin/tazobactam (PIP/TAZ) versus early adjustment to IMI/REL. A decision tree was used to depict the hospitalization period, and a Markov model used to capture longterm outcomes. Results: IMI/REL generated more quality-adjusted life years than PIP/TAZ, at an increased cost per patient. The incremental cost–effectiveness ratio of $17,529 per QALY is below the typical US willingness-to-pay threshold. Conclusion: IMI/RELmay represent a cost-effective treatment for payers and a valuable option for clinicians, when considered alongside patient risk factors, local epidemiology, and susceptibility data.

Published
2023
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30. Meta-synthesis of qualitative research on the barriers and facilitators to implementing workplace mental health interventions

Author

Yarker Joanna, Lewis Rachel, Sinclair Alice, Michlig Georgia, and Munir Fehmidah

Subjects
Systematic review, Meta-synthesis, Mental health, Intervention, Implementation, workplace, Mental healing, RZ400-408, Public aspects of medicine, RA1-1270
Abstract

Purpose: There has been a rapid increase in the number of mental health interventions implemented in the workplace. The efficacy of these interventions has been mixed. The factors influencing implementation may offer insights to why some interventions fail to be effective. Method: We conducted a meta-synthesis of qualitative research on the barriers and facilitators to implementing workplace mental health interventions. We evaluated the quality of evidence using CASP and CERQual and synthesized our data using thematic analysis. Results: 33 studies were included in the review. A broad range of interventions were reflected in the studies, a majority of which were implemented at the individual level and in health care settings. Facilitators included positive disclosure by line managers, completion of intervention in work time, scheduling flexibility and trainer credibility. Barriers included managers not prioritising interventions, lack of suitable training of facilitators, competing priorities, workload issues and staff shortages. No findings were judged to be very well supported (i.e., high confidence). Conclusion: Evidence surrounding the implementation of mental health interventions in the workplace is weak, and studies are limited to high income countries, with a bias towards healthcare and public sector settings. We call for a taxonomy of implementation issues specifically for workplace mental health to advance knowledge and practice.

Published
2022
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31. Generalized Metabolic Bone Disease in Neurofibromatosis Type I

Author

BRUNETTI PIERRI, NICOLA, Doty SB, Hicks J, Phan K, Mendoza Londono R, Blazo M, Tran A, Carter S, Lewis RA, Plon SE, Phillips WA, Smith EO, Ellis KJ, Lee B., BRUNETTI PIERRI, Nicola, Doty, Sb, Hicks, J, Phan, K, Mendoza Londono, R, Blazo, M, Tran, A, Carter, S, Lewis, Ra, Plon, Se, Phillips, Wa, Smith, Eo, Ellis, Kj, and Lee, B.

Published
2008

33. Modifying the Medical Research Council grading system through Rasch analyses

Author

Vanhoutte, Ek, Faber, Cg, Van Nes, Si, Jacobs, Bc, Van Doorn, Pa, Van Koningsveld, R, Cornblath, Dr, Van Der Kooi, Aj, Cats, Ea, Van Den Berg, Lh, Notermans, Nc, Van Der Pol, Wl, Hermans, Mc, Van Der Beek, Na, Gorson, Kc, Eurelings, M, Engelsman, J, Boot, H, Meijer, Rj, Lauria, G, Tennant, A, Merkies, Is, Barreira, Aa, Bennett, D, Van Den Bergh, Py, Bril, V, Devigili, G, Hadden, Rd, Hahn, Af, Hartung, Hp, Hughes, Ra, Illa, I, Katzberg, H, Léger, Jm, Lewis, Ra, Lunn, Mp, Nascimento, Oj, Nobile Orazio, E, Padua, Luca, Pouget, J, Reilly, Mm, Van Schaik, I, Smith, B, De Visser, M, Walk, D., Neurology, Immunology, MUMC+: DA KG Polikliniek (9), Klinische Neurowetenschappen, RS: MHeNs School for Mental Health and Neuroscience, ANS - Amsterdam Neuroscience, AII - Amsterdam institute for Infection and Immunity, and Faculteit der Geneeskunde

Subjects
Adult, Male, medicine.medical_specialty, Weakness, Biomedical Research, Adolescent, medicine.medical_treatment, Disease, neuromuscular disorders, Young Adult, Bias, Muscular Diseases, medicine, Humans, Muscle Strength, Occasional Paper, Child, Rasch, Rasch model, Rehabilitation, business.industry, manual muscle testing, Infant, Newborn, Infant, Polyradiculoneuropathy, Middle Aged, medicine.disease, Medical research, Settore MED/26 - NEUROLOGIA, MRC, PESQUISA (MÉTODOS), Child, Preschool, Cohort, Physical therapy, Female, Health Planning Councils, Neurology (clinical), medicine.symptom, business, Multifocal motor neuropathy
Abstract

The Medical Research Council grading system has served through decades for the evaluation of muscle strength and has been recognized as a cardinal feature of daily neurological, rehabilitation and general medicine examination of patients, despite being respectfully criticized due to the unequal width of its response options. No study has systematically examined, through modern psychometric approach, whether physicians are able to properly use the Medical Research Council grades. The objectives of this study were: (i) to investigate physicians' ability to discriminate among the Medical Research Council categories in patients with different neuromuscular disorders and with various degrees of weakness through thresholds examination using Rasch analysis as a modern psychometric method; (ii) to examine possible factors influencing physicians' ability to apply the Medical Research Council categories through differential item function analyses; and (iii) to examine whether the widely used Medical Research Council 12 muscles sum score in patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy would meet Rasch model's expectations. A total of 1065 patients were included from nine cohorts with the following diseases: Guillain-Barre syndrome (n = 480); myotonic dystrophy type-1 (n = 169); chronic inflammatory demyelinating polyradiculoneuropathy (n = 139); limb-girdle muscular dystrophy (n = 105); multifocal motor neuropathy (n = 102); Pompe's disease (n = 62) and monoclonal gammopathy of undetermined related polyneuropathy (n = 8). Medical Research Council data of 72 muscles were collected. Rasch analyses were performed on Medical Research Council data for each cohort separately and after pooling data at the muscle level to increase category frequencies, and on the Medical Research Council sum score in patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Disordered thresholds were demonstrated in 74-79% of the muscles examined, indicating physicians' inability to discriminate between most Medical Research Council categories. Factors such as physicians' experience or illness type did not influence these findings. Thresholds were restored after rescoring the Medical Research Council grades from six to four options (0, paralysis; 1, severe weakness; 2, slight weakness; 3, normal strength). The Medical Research Council sum score acceptably fulfilled Rasch model expectations after rescoring the response options and creating subsets to resolve local dependency and item bias on diagnosis. In conclusion, a modified, Rasch-built four response category Medical Research Council grading system is proposed, resolving clinicians' inability to differentiate among its original response categories and improving clinical applicability. A modified Medical Research Council sum score at the interval level is presented and is recommended for future studies in Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.

Published
2012

34. MRC sum-score in the ICU: good reliability does not necessarily reflect 'true reliability'

Author

Vanhoutte, Ek, Faber, Cg, Merkies, Is, Barreira, Aa, Bennett, D, Van Den Bergh, Py, Bril, V, Devigili, G, Hadden, Rd, Hahn, Af, Hartung, Hp, Hughes, Ra, Illa, I, Katzberg, H, Van Der Kooi, Aj, Léger, Jm, Lewis, Ra, Lunn, Mp, Nobile Orazio, E, Padua, Luca, Pouget, J, Reilly, Mm, Van Schaik, I, and De Visser, M.

Subjects
Settore MED/26 - NEUROLOGIA, polyneuropathies, critical illness, neuromuscular diseases, reproducibility of results, muscle weakness
Published
2012

35. Exploring the experiences of older adults living with asthma in the United Kingdom: A co-produced qualitative study

Author

Tracy Jackson, Flora Flinn, Lewis Rafferty, Elisabeth Ehrlich, and Monica Fletcher

Subjects
Aging, Asthma, Older adults, Qualitative methods, Geriatrics, RC952-954.6
Abstract

Background: Older adults are the fastest growing population in the UK, but asthma is often underdiagnosed, undertreated and poorly self-managed in this population. It is necessary to explore the experiences of older adults with asthma to identify areas of research that could improve quality of life. This study aimed to explore the perceptions of older adults in the UK living with asthma and how it impacts their lives. Methods: Telephone interviews were conducted with 15 adults with General Practitioner diagnosed asthma, aged 60 years and over, from across the UK. Interviews were audio-recorded, transcribed verbatim and thematically analysed. This study was co-produced with an Asthma UK Centre for Applied Research (AUKCAR) Patient and Public Involvement Lead and guided by the National Institute for Health Research UK standards for Public Involvement in Research to ensure meaningful public involvement. Results: Themes clustered around impact of asthma, managing asthma, interaction with healthcare and understanding of asthma. Participants experienced increased physical, psychological and social impacts of asthma management as they aged which led to feelings of isolation. Competing multimorbidities and polypharmacy complicate treatment and self-management of asthma. Ageism and a lack of empathy from health care providers were mentioned by the majority participants. Quality of care varied widely across the UK, however all participants had seen a healthcare professional for an asthma review in the previous 12 months. Conclusions: Older adults experience increased challenges in managing their asthma due to increased multimorbidities, polypharmacy and ageism from healthcare providers.

Published
2022
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36. Improving fatigue assessment in immune-mediated neuropathies: the modified Rasch-built fatigue severity scale

Author

Van Nes, Si, Vanhoutte, Ek, Faber, Cg, Garssen, M, Van Doorn, Pa, Merkies, Is, Bennett, D, Van Den Berg, Lh, Van Den Bergh, Py, Cornblath, Dr, Dalakas, M, Devigili, G, Gorson, Kc, Hadden, Rd, Hahn, Af, Hartung, Hp, Hughes, Ra, Lauria, Giuseppe, Léger, Jm, Lewis, Ra, Lunn, Mp, Nobile Orazio, E, Notermans, Nc, Padua, Luca, Reilly, Mm, and Smith, B.

Subjects
Settore MED/26 - NEUROLOGIA, fatigue, Rash analysis, immune-mediated neuropathy, fatigue severity scale
Published
2009

37. Revising two-point discrimination assessment in normal aging and in patients with polyneuropathies

Author

Van Nes, Si, Faber, Cg, Hamers, Rm, Harschnitz, O, Bakkers, M, Hermans, Mc, Meijer, Rj, Van Doorn, Pa, Merkies, Is, Bennett, D, Van Den Berg, Lh, Van Den Bergh, Py, Cornblath, Dr, Dalakas, M, Gorson, Kc, Hadden, Rd, Hahn, Af, Hughes, Ra, Lauria, G, Léger, Jm, Lewis, Ra, Lunn, Pt, Nobile Orazio, E, Notermans, Nc, Padua, Luca, and Reilly, Mm

Subjects
Settore MED/26 - NEUROLOGIA, polyneuropathies
Published
2008

40. Expired CO2 Levels Indicate Degree of Lung Aeration at Birth

Author

Szyld, E, Hooper, SB, Fouras, A, Siew, ML, Wallace, MJ, Kitchen, MJ, te Pas, AB, Klingenberg, C, Lewis, RA, Davis, PG, Morley, CJ, Schmoelzer, GM, Szyld, E, Hooper, SB, Fouras, A, Siew, ML, Wallace, MJ, Kitchen, MJ, te Pas, AB, Klingenberg, C, Lewis, RA, Davis, PG, Morley, CJ, and Schmoelzer, GM

Abstract

As neonatal resuscitation critically depends upon lung aeration at birth, knowledge of the progression of this process is required to guide ongoing care. We investigated whether expired CO2 (ECO2) levels indicate the degree of lung aeration immediately after birth in two animal models and in preterm infants. Lambs were delivered by caesarean section and ventilated from birth. In lambs, ECO2 levels were significantly (p<0.0001) related to tidal volumes and CO2 clearance/breath increased exponentially when tidal volumes were greater than 6 mL/kg. Preterm (28 days of gestation; term = 32 days) rabbits were also delivered by caesarean section and lung aeration was measured using phase contrast X-ray imaging. In rabbit kittens, ECO2 levels were closely related (p<0.001) to lung volumes at end-inflation and were first detected when ∼7% of the distal lung regions were aerated. ECO2 levels in preterm infants at birth also correlated with tidal volumes. In each infant, ECO2 levels increased to >10 mmHg 28 (median) (21-36) seconds before the heart rate increased above 100 beats per minute. These data demonstrate that ECO2 levels can indicate the relative degree of lung aeration after birth and can be used to clinically assess ventilation in the immediate newborn period.

Published
2013

41. Recursive Approaches for Multi-Layer Dividend Strategies in a Phase-Type Renewal Risk Model

Author

Apostolos D. Papaioannou and Lewis Ramsden

Subjects
two-classes of claim, renewal risk processes, multi-layer dividend strategy, phase-type distribution, Gerber–Shiu function, expected discounted dividend payments, Insurance, HG8011-9999
Abstract

In this paper we consider a risk model with two independent classes of insurance risks in the presence of a multi-layer dividend strategy. We assume that both of the claim number processes are renewal processes with phase-type inter-arrival times. By analysing the Markov chains associated with the two given phase-type distributions of the inter-arrival times, algorithmic schemes for the determination of explicit expressions for the Gerber–Shiu expected discounted penalty function, as well as the expected discounted dividend payments are derived, using two different approaches.

Published
2022
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46. MEASUREMENT OF THE J/PSI AND PSI' RESONANCE PARAMETERS IN (P)OVER-BAR ANNIHILATION RID C-5223-2009

Author

Armstrong, Ta, Bettoni, D, Bharadwaj, V, Biino, C, Borreani, G, Broemmelsiek, D, Buzzo, A, Calabrese, R, Ceccucci, A, Cester, R, Church, Md, Dalpiaz, P, Dalpiaz, Pf, Dibenedetto, R, Dimitroyannis, D, Fabbri, M, Fast, Je, Gianoli, A, Ginsburg, Cm, Gollwitzer, Ke, Hahn, Aa, Hasan, Ma, Hsueh, Sy, Lewis, Ra, Luppi, E, Macri, M, Majewska, A, Mandelkern, Ma, Marchetto, F, Marinelli, M, Marques, Jl, Marsh, W, Martini, M, Masuzawa, M, Menichetti, E, Migliori, A, Mussa, R, Palestini, S, Pallavicini, M, Passaggio, S, Pastrone, N, Patrignani, C, Peoples, J, Pesando, L, Petrucci, F, Pia, Mg, Pordes, S, Rapidis, Pa, Ray, Re, Reid, Jd, Rinaudo, G, Rocuzzo, B, Rosen, Jl, Santroni, A, Sarmiento, M, Savrie, M, Scalisi, A, Schultz, J, Seth, Kk, Smith, A, Smith, Ga, Sozzi, MARCO STANISLAO, Tecchio, L, Trokenheim, S, Weber, Mf, Werkema, Sj, Zhang, Y, Zhao, Jl, Zioulas, G, and Zito, M.

Published
1993

47. PROTON ELECTROMAGNETIC FORM-FACTORS IN THE TIME-LIKE REGION FROM 8.9 TO 13.0 GEV(2) RID C-5223-2009

Author

Armstrong, Ta, Bettoni, D, Bharadwaj, V, Biino, C, Borreani, G, Broemmelsiek, D, Buzzo, A, Calabrese, R, Ceccucci, A, Cester, R, Church, Md, Dalpiaz, P, Dalpiaz, Pf, Dibenedetto, R, Dimitroyannis, D, Fabbri, M, Fast, Je, Gianoli, A, Ginsburg, Cm, Gollwitzer, Ke, Hahn, Aa, Hasan, Ma, Hsueh, Sy, Lewis, Ra, Luppi, E, Macri, M, Majewska, A, Mandelkern, Ma, Marchetto, F, Marinelli, M, Marques, Jl, Marsh, W, Martini, M, Masuzawa, M, Menichetti, E, Migliori, A, Mussa, R, Palestini, S, Pallavicini, M, Pastrone, N, Patrignani, C, Peoples, J, Pesando, L, Petrucci, F, Pia, Mg, Pordes, S, Rapidis, Pa, Ray, Re, Reid, Jd, Rinaudo, G, Roccuzzo, B, Rosen, Jl, Santroni, A, Sarmiento, M, Savrie, M, Scalisi, A, Schultz, J, Seth, Kk, Smith, A, Smith, Ga, Sozzi, MARCO STANISLAO, Trokenheim, S, Weber, Mf, Werkema, Sj, Zhang, Y, Zhao, Jl, and Zioulas, G.

Published
1993

48. STUDY OF THE ANGULAR-DISTRIBUTION OF THE REACTION (P)OVER-BARP-]CHI-C2-]J/PSI-GAMMA-]E+E-GAMMA RID C-5223-2009

Author

Armstrong, Ta, Bettoni, D, Bharadwaj, V, Biino, C, Borreani, G, Broemmelsiek, D, Buzzo, A, Calabrese, R, Ceccucci, A, Cester, R, Church, Md, Dalpiaz, P, Dalpiaz, Pf, Dibenedetto, R, Dimitroyannis, D, Fabbri, Mg, Fast, Je, Gianoli, A, Ginsburg, Cm, Gollwitzer, Ke, Hahn, Aa, Hasan, Ma, Hsueh, Sy, Lewis, Ra, Luppi, E, Macri, M, Majewska, Am, Mandelkern, Ma, Marchetto, F, Marinelli, M, Marques, Jl, Marsh, W, Martini, M, Masuzawa, M, Menichetti, E, Migliori, A, Mussa, R, Palestini, S, Pallavicini, M, Pastrone, N, Patrignani, C, Peoples, J, Pesando, L, Petrucci, F, Pia, Mg, Pordes, S, Rapidis, Pa, Ray, Re, Reid, Jd, Rinaudo, G, Roccuzzo, B, Rosen, Jl, Santroni, A, Sarmiento, M, Savrie, M, Scalisi, A, Schultz, J, Seth, Kk, Smith, A, Smith, Ga, Sozzi, MARCO STANISLAO, Trokenheim, S, Weber, Mf, Werkema, Sj, Zhang, Y, Zhao, Jl, and Zioulas, G.

Published
1993

50. Primary signet ring cell carcinoma of the pancreatic head: A case report

Author

Dheeraj Alexander, Lewis Rashid, Michael Hollis, and Srinivas Kavuturu

Subjects
chemotherapy, pancreatic cancer, pancreaticoduodenectomy, Signet ring cell carcinoma, Medicine, Medicine (General), R5-920
Abstract

Abstract Pancreatic SRCC is a rare, aggressive tumor. Given limited evidence and the risk of side effects, physicians may elect to withhold chemotherapy in select patients, with the exception of neoadjuvant chemotherapy use to facilitate resectability.

Published
2019
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