Determination of adalimumab and etanercept trough levels and drug antibodies in long-term psoriasis treatment: a single-centre cohort study

Summary

Background

An algorithm based on measurement of a serum tumour necrosis factor antagonists (anti-TNF) and antidrug antibodies (ADA) has been proposed previously to guide dose escalation or therapy switching in the early (i.e. the first months of) treatment of psoriasis by anti-TNF. In long-term treatment of responding patients with psoriasis, it is usual to empirically reduce standard doses of anti-TNF to reduce exposure while maintaining clinical response. The relationship between serum anti-TNF, ADA levels and clinical efficacy in long-term treated patients with psoriasis has not yet been determined, so the potential role of these parameters in guiding dose escalation in this scenario is unknown.

Aims

To evaluate the relationship between drug/ADA levels and clinical efficacy in a group of patients with psoriasis undergoing long-term treatment with adalimumab or etanercept.

Methods

This was a single-centre, prospective, cohort study of patients with psoriasis receiving adalimumab or etanercept for a minimum of 48 weeks. All patients were started on the standard dose, but some adalimumab users had a reduced frequency of administration. Clinical efficacy was measured using the Psoriasis Area and Severity Index. Serum concentrations were measured by ELISA. Clinical assessment and blood sample collection were carried out simultaneously within 24 h before the next drug administration.

Results

In total, 21 patients were enrolled (67 simultaneous clinical and serum determinations: 38 receiving adalimumab, 29 receiving etanercept). We did not find any association between serum anti-TNF levels and clinical response. None of the patients developed ADA.

Conclusions

ADA and anti-TNF levels are not related to clinical effectiveness in patients with psoriasis undergoing long-term treatment with adalimumab or etanercept.

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Improving access to school based education for South African children in rural areas who have a tracheostomy: A case series and recommendations

Publication date: January 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 92
Author(s): Chengetai Mahomva, Sue Harris, Narvanie Seebran, Bridget Mudge, Brian Catlin, Louise Davies
ObjectivesCurrently few children with tracheostomies attend rural mainstreams schools in South Africa limiting their ability to gain an education. We sought to document the current school experience for the few children attending school who have tracheostomies and devise educational tools for teachers and administrators that will facilitate greater acceptance and safety in classrooms for this population.MethodsThe four patients that are currently attending school with a tracheostomy were identified from the patient records of a tertiary hospital with a pediatric tracheostomy home based care service. With the aid of a Zulu language translator, the mothers and classroom teachers completed a semi structured interview and closed item questionnaire in their home and school, respectively. Schools were visited to understand and describe the settings in which the children and their teachers were being asked to function. Tools for education were developed in conjunction with key stakeholders at schools already hosting such children.ResultsThe key teacher-identified barriers to enrollment were: teacher unfamiliarity with tracheostomies, uncertainty about the school's liability, and concerns about the response of other children. The safety barriers identified were: greater than 60 children per classroom - limiting teacher's ability to attend to the child with a tracheostomy, lack of running water, pit latrines separate from school threatening hygiene and isolating the child when they leave to use the latrines & sandy classrooms which can result in sand entering the airway. Identified needs for successful school placement include providing tracheostomy supplies and suctioning equipment, hand hygiene materials and training teachers in: identification of respiratory distress, performance of emergency tracheostomy changes, CPR.ConclusionsChildren with tracheostomies could likely successfully attend South African rural mainstream public schools with a training program for teachers. As a first step, an introductory booklet for teachers that explains tracheostomies and provides educational and safety suggestions was created. A list of recommendations for successful inclusion of students in the school system was developed together with and delivered to key stakeholders.



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Preferred parental method of post-operative tonsillectomy and adenoidectomy follow-up (phone call vs. clinic visit)

Publication date: January 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 92
Author(s): Martin E. Anderson, Brianna Brancazio, Deepak K. Mehta, Matthew Georg, Sukgi S. Choi, Noel Jabbour
IntroductionTonsillectomy is the second most common procedure performed in the United States. Over 530,000 tonsillectomies are performed on children under 15 years of age in the United States, accounting for 16% of surgeries in this age group, resulting in missed school for patients of school-age and also resulting in missed work for caregivers. This study compared parent preferences for in-clinic follow-up (CFU) to telephone interview follow-up (TFU) after tonsillectomy.Materials and methodsOne hundred twenty-one parents of children who underwent a tonsillectomy and/or adenoidectomy were recruited to complete a survey about their child's post-operative visit.ResultsStatistical analyses were performed using t-test, Wilcoxon rank-sum, and Fischer's exact tests where appropriate. 60.3% of the surveys were completed as a TFU and the remainder were completed as a CFU. There were no statistical differences in the children's age, the time to follow-up, satisfaction with their follow-up, or the frequency of unresolved symptoms. Of parents receiving TFU, 91.8% disagreed they would have preferred a CFU, with 86.3% strongly disagreeing, and only 5.5% expressing that they would have preferred a CFU. Of the parents with CFU, 47.9% expressed a preference for a TFU. For CFU, 43.9% of parents missed work and 58.1% of their school-age children missed school.ConclusionOur study results indicate that parents receiving phone follow-up strongly preferred this method to an in-clinic follow-up, and that nearly half of all parents receiving in-clinic follow-up would have preferred a telephone follow-up. In select patients, telephone follow-up after tonsillectomy may increase patient satisfaction and decrease days of missed work and school.



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Implementation of Ultraviolet Radiation Safety Measures for Outdoor Workers: A Canadian Perspective

Ultraviolet radiation (UVR) poses a major risk for outdoor workers, putting them at greater risk for skin cancer. In the general population, the incidence of both melanoma and nonmelanoma skin cancers is increasing. It is estimated that 90% of skin cancers in Canada are directly attributable to UVR exposure, making this cancer largely preventable with the appropriate precautions. A scoping review was conducted on the barriers and facilitators to UVR safety in outdoor workers to elucidate why these precautions are not in use currently. We discuss these results according to the Hierarchy of Controls as a means to outline effective and feasible prevention strategies for outdoor workers. In doing so, this review may be used to inform the design of future workplace interventions for UVR safety in outdoor workers to decrease the risk of skin cancer in this vulnerable population.

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Association Between Changes in Thyroid Hormones and Incident Type 2 Diabetes: A Seven-Year Longitudinal Study

Thyroid , Vol. 0, No. 0.


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In vivo Functional Consequences of Human THRA Variants Expressed in the Zebrafish

Thyroid , Vol. 0, No. 0.


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Predictions of the Contribution of HCN Half-Maximal Activation Potential Heterogeneity to Variability in Intrinsic Adaptation of Spiral Ganglion Neurons

Abstract

Spiral ganglion neurons (SGNs) exhibit a wide range in their strength of intrinsic adaptation on a timescale of 10s to 100s of milliseconds in response to electrical stimulation from a cochlear implant (CI). The purpose of this study was to determine how much of that variability could be caused by the heterogeneity in half-maximal activation potentials of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, which are known to produce intrinsic adaptation. In this study, a computational membrane model of cat type I SGN was developed based on the Hodgkin-Huxley model plus HCN and low-threshold potassium (KLT) conductances in which the half-maximal activation potential of the HCN channel was varied and the response of the SGN to pulse train and paired-pulse stimulation was simulated. Physiologically plausible variation of HCN half-maximal activation potentials could indeed determine the range of adaptation on the timescale of 10s to 100s of milliseconds and recovery from adaptation seen in the physiological data while maintaining refractoriness within physiological bounds. This computational model demonstrates that HCN channels may play an important role in regulating the degree of adaptation in response to pulse train stimulation and therefore contribute to variable constraints on acoustic information coding by CIs. This finding has broad implications for CI stimulation paradigms in that cell-to-cell variation of HCN channel properties are likely to significantly alter SGN excitability and therefore auditory perception.

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Tubulopapillary Hidradenoma-like Tumour of the Mandible: A Case Report and Literature Review

Abstract

Tubulopapillary hidradenoma is an uncommon benign sweat gland tumour which appears as a well-defined superficially located dermal nodule, most commonly occurring in the head or of the extremities. Its occurrence is extremely rare in the mandible, as there are only two cases of tubulopapillary hidradenoma-like tumour of the mandiblereported in the literature. Microscopically, the lesion appears as a well circumscribed but unencapsulated neoplasm composed of numerous irregularly shaped tubular structures that have a double to several layered epithelial lining. The outer layer consists of flat to cuboidal myoepithelial cells and inner layer contains cuboidal to columnar cells that demonstrate decapitation secretions. We report an unusual case of tubulopapillary hidradenoma-like tumour presented as a nodular growth in the right retromolar region of the mandible in a 67-year-old man. The light microscopic features along with immunohistochemical findings of this unusual neoplasm are discussed.

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Non-syndromic severe hypodontia caused by a novel frameshift insertion mutation in the homeobox of the MSX1 gene

Publication date: March 2017
Source:Archives of Oral Biology, Volume 75
Author(s): Mushriq F. Abid, M.A. Simpson, Christos Petridis, M.T. Cobourne, P.T. Sharpe
ObjectiveInherited congenital anomalies in tooth number, particularly hypodontia are relatively common. Although substantial progress has been made that permits a better understanding of the causes of tooth agenesis, overall knowledge of the phenotype:genotype correlations in this anomaly are still lacking. The aim in this study was to identify the causal gene mutation(s) in a family of two sisters with severe hypodontia (oligodontia) including 2nd premolars and 1st and 3rd molars, using whole exome sequencing (WES).MethodsWES was performed using in-solution hybridization, followed by massively parallel sequencing.ResultsA frameshift insertion of 7 basepairs (GCAAGTT) in the homebox of MSX1 gene located in the exon 2 in heterozygous state has been identified in both sisters (NM_002448:exon2:c.572_573ins GCAAGTT: p.F191fs).ConclusionWe conclude that this frameshift mutation in the homeodomain (which plays an essential role in DNA binding) of MSX1 gene is responsible for tooth agenesis in this family. This expands the phenotype-genotype correlation associated with MSX1 mutations.



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G6PD structure and activity: Potential for development of novel low-cost assays for field detection of G6PD deficiency for malaria management

Carbone, F; (2016) G6PD structure and activity: Potential for development of novel low-cost assays for field detection of G6PD deficiency for malaria management. Doctoral thesis, UCL (University College London). Green open access

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The timing performance of scintillator detectors

Brown, MS; (2016) The timing performance of scintillator detectors. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2hs4U6c

The potential role of stromal derived factor 1α in remote ischaemic conditioning

Bromage, DI; (2016) The potential role of stromal derived factor 1α in remote ischaemic conditioning. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2h3U4Gx

Reconstructing the Arsenical Copper Production Process in Early Bronze Age Southwest Asia

Boscher, LC; (2016) Reconstructing the Arsenical Copper Production Process in Early Bronze Age Southwest Asia. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2hrUxz4

The application of mass spectrometry-based techniques to full thickness skin tissue: method development and biochemical analysis in health and disease

Bliss, EJ; (2016) The application of mass spectrometry-based techniques to full thickness skin tissue: method development and biochemical analysis in health and disease. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2h3WapA

Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability

Camilloni, C; Sala, BM; Sormanni, P; Porcari, R; Corazza, A; De Rosa, M; Zanini, S; Camilloni, C; Sala, BM; Sormanni, P; Porcari, R; Corazza, A; De Rosa, M; Zanini, S; Barbiroli, A; Esposito, G; Bolognesi, M; Bellotti, V; Vendruscolo, M; Ricagno, S; - view fewer (2016) Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability. Scientific Reports , 6 , Article 25559. 10.1038/srep25559 . Green open access

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Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets

Bienczak, A; Denti, P; Cook, A; Wiesner, L; Mulenga, V; Kityo, C; Kekitiinwa, A; Bienczak, A; Denti, P; Cook, A; Wiesner, L; Mulenga, V; Kityo, C; Kekitiinwa, A; Gibb, DM; Walker, AS; McIlleron, H; - view fewer (2017) Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets. AIDS (In press).

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Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures

Peters, C; Rosch, RE; Hughes, E; Ruben, PC; (2016) Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures. Scientific Reports , 6 (31879) 10.1038/srep31879 . Green open access

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Monocular and Binocular Contributions to Oculomotor Plasticity

Maiello, G; Harrison, WJ; Bex, PJ; (2016) Monocular and Binocular Contributions to Oculomotor Plasticity. Scientific Reports , 6 (31861) 10.1038/srep31861 . Green open access

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Secrecy and Energy Efficiency in Massive MIMO Aided Heterogeneous C-RAN: A New Look at Interference

Wang, L; Wong, K-K; Elkashlan, M; Nallanathan, A; Lambotharan, S; (2016) Secrecy and Energy Efficiency in Massive MIMO Aided Heterogeneous C-RAN: A New Look at Interference. IEEE Journal of Selected Topics in Signal Processing , 10 (8) pp. 1375-1389. 10.1109/JSTSP.2016.2600520 . Green open access

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Human cancers and mammalian retroviruses: should we worry about bovine leukemia virus?

Munro, AC; Houldcroft, C; (2016) Human cancers and mammalian retroviruses: should we worry about bovine leukemia virus? Future Virology , 11 (3) pp. 163-166. 10.2217/fvl.16.5 .

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Stability of a spin-triplet nematic state near to a quantum critical point

Hannappel, G; Pedder, CJ; Krueger, F; Green, AG; (2016) Stability of a spin-triplet nematic state near to a quantum critical point. Physical Review B , 93 , Article 235105. 10.1103/PhysRevB.93.235105 . Green open access

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Understanding pneumococcal serotype 1 biology through population genomic analysis

Chaguza, C; Cornick, JE; Harris, SR; Andam, CP; Bricio-Moreno, L; Yang, M; Yalcin, F; Chaguza, C; Cornick, JE; Harris, SR; Andam, CP; Bricio-Moreno, L; Yang, M; Yalcin, F; Ousmane, S; Govindpersad, S; Senghore, M; Ebruke, C; Du Plessis, M; Kiran, AM; Pluschke, G; Sigauque, B; McGee, L; Klugman, KP; Turner, P; Corander, J; Parkhill, J; Collard, J-M; Antonio, M; von Gottberg, A; Heyderman, RS; French, N; Kadioglu, A; Hanage, WP; Everett, DB; Bentley, SD; - view fewer (2016) Understanding pneumococcal serotype 1 biology through population genomic analysis. BMC Infectious Diseases , 16 (649) 10.1186/s12879-016-1987-z . Green open access

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Image-based optical miniaturized three-axis force sensor for cardiac catheterization

Noh, Y; Liu, H; Sareh, S; Chathuranga, DS; Wurdemann, H; Rhode, K; Althoefer, K; (2016) Image-based optical miniaturized three-axis force sensor for cardiac catheterization. IEEE Sensors Journal , 16 (22) pp. 7924-7932. 10.1109/JSEN.2016.2600671 . Green open access

http://ift.tt/2hs124V

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule.

Chaguza, C; Andam, CP; Harris, SR; Cornick, JE; Yang, M; Bricio-Moreno, L; Kamng'ona, AW; Chaguza, C; Andam, CP; Harris, SR; Cornick, JE; Yang, M; Bricio-Moreno, L; Kamng'ona, AW; Parkhill, J; French, N; Heyderman, RS; Kadioglu, A; Everett, DB; Bentley, SD; Hanage, WP; - view fewer (2016) Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule. MBio , 7 (5) , Article e01053-16.. 10.1128/mBio.01053-16 . Green open access

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Respiratory Virus–Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition

Peterson, I; Bar-Zeev, N; Kennedy, N; Ho, A; Newberry, L; SanJoaquin, MA; Menyere, M; Peterson, I; Bar-Zeev, N; Kennedy, N; Ho, A; Newberry, L; SanJoaquin, MA; Menyere, M; Alaerts, M; Mapurisa, G; Chilombe, M; Mambule, I; Lalloo, DG; Anderson, ST; Katangwe, T; Cunliffe, N; Nagelkerke, N; McMorrow, M; Widdowson, M-A; French, N; Everett, D; Heyderman, RS; - view fewer (2016) Respiratory Virus–Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition. Journal of Infectious Diseases , 214 (11) pp. 1700-1711. 10.1093/infdis/jiw426 .

http://ift.tt/2hs6AMM

Energy-saving occupant behaviours in offices: change strategies

Mulville, M; Jones, K; Huebner, G; Powell-Greig, J; (2016) Energy-saving occupant behaviours in offices: change strategies. Building Research & Information 10.1080/09613218.2016.1212299 . (In press).

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Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis

Fogh, I; Lin, K; Tiloca, C; Rooney, J; Gellera, C; Diekstra, FP; Ratti, A; Fogh, I; Lin, K; Tiloca, C; Rooney, J; Gellera, C; Diekstra, FP; Ratti, A; Shatunov, A; van Es, MA; Proitsi, P; Jones, A; Sproviero, W; Chiò, A; McLaughlin, RL; Sorarù, G; Corrado, L; Stahl, D; Del Bo, R; Cereda, C; Castellotti, B; Glass, JD; Newhouse, S; Dobson, R; Smith, BN; Topp, S; van Rheenen, W; Meininger, V; Melki, J; Morrison, KE; Shaw, PJ; Leigh, PN; Andersen, PM; Comi, GP; Ticozzi, N; Mazzini, L; D'Alfonso, S; Traynor, BJ; Van Damme, P; Robberecht, W; Brown, RH; Landers, JE; Hardiman, O; Lewis, CM; van den Berg, LH; Shaw, CE; Veldink, JH; Silani, V; Al-Chalabi, A; Powell, J; - view fewer (2016) Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis. JAMA Neurology , 73 (7) pp. 812-820. 10.1001/jamaneurol.2016.1114 .

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Eéncellige waterbewoners: onzichtbaar maar onmisbaar

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Primaire productie op het kruispunt van estuarium en kustzone

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