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Transcript of KCH Dental ‘Fostering Research’ Seminar Series Tara Renton.
KCH Dental ‘Fostering Research’ Seminar Series
Tara Renton
New Government Strategy 2006
The NIHR Clinical Research Network
The National Institute for Health Research (NIHR) Clinical Research Network is an essential element in achieving the government’s vision “to create a health research system in which the NHS supports outstanding individuals, working in world-class facilities, conducting leading-edge research focused on the needs of patients and the public.”
NHS = largest clinical trial centre world wide
National Institute for Health Research - LCRN
Infrastructure
Clinical Research Facilities & Centres
Clinical Research Networks
Research
Research Projects & Programmes
Research Governance
Systems
Research Information
Systems
Systems
Patients&
Public
Universities
Investigators &Senior
InvestigatorsAssociates
Faculty
Trainees
Research Units & Schools
NHS Trusts
UK Health Research income 2008£7.4B spent on health research in UK
(75% industrial and 75% health specific)R&D levy £21m GSTT and £11m KCHFuture emphasis on Research funding
Best performing clinical academic partnerships in translational and applied research (AHSCs)
Continued focus on cancer / cardiac but also on high burden diseases (dental?)
Education and training MPET and HEFCE
NIHR Research Programmes Translating research evidence into NHS practice
Basic Research (Biomedical, population,Social Science& engineering & technology)
Experimental Medicine
Effectivenessand cost-effectiveness
Adoption into theservice
Proof of concept
Efficacy
Knowledge transfer for NHS
NICE
Research Centres
Programme Grants
Healthcare Technology Cooperatives
Health Technology Assessment
Service Delivery and Organisation
Research for Innovation, Speculation and
CreativityNew & Emerging Applications of
Tech. Health Technology
Devices
Research for Patient Benefit
Structure NIHR Clinical research network
Six “topic” Clinical Research Networks, which focus on specific disease areas: Cancer, Diabetes, Dementias and Neurodegenerative Diseases, Medicines for Children, Mental Health, and Stroke
A Primary Care Research NetworkThe CCRN is made up of 25 Comprehensive Local Research Networks (CLRNs) which cover
the whole of England by region. These locally based Research Networks coordinate and facilitate the conduct of clinical research and provide a wide range of support to the local research community.
18 health specialty groups
Map
Activity by health groupKCH portfolio
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Primary Topic
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Activity by health groupKCH portfolio
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What is a portfolio study?Studies eligible for NIHR Clinical Research Network support
include;National competitionCommercial Non-commercial studies including those that are
automatically make up the greatest proportion of studies on the NIHR
Adoption process You can opt into existing open recruiting studiesNRES tick section 59 a
How to get adoption of study
KCH Portfolio Activity117 portfolio studies:
76 Interventional (gain £1600 per pt)
41 Observational (gain £3-600 per pt)
Oral dental Specialty Group
Oral and dental
Supports portfolio studiesCovers wide range of conditions oral cancer – orthodonticDevelopment of prevention and management strategies
for all oral diseasesPromotion oral healthDesign and evaluation services of successful and cost
effective delivery of oral health care
Oral and Dental UK groupOur membership
CLRN
Northumberland, Tyne and Wear: CHAIR Professor Jimmy Steele
Birmingham and the Black Country Professor Thomas Dietrich
Central and East London Professor John Galloway
London (North West) Manolis Heliotis
London (South) Professor Tara Renton
Northumberland, Tyne and Wear Professor Jimmy Steele
South Yorkshire Professor Peter Robinson (Deputy Chair)
West Anglia Chi-Hwa Chan
Western Dr Anthony Ireland
West Yorkshire Dr James McCaul
Professor Paul Brunton
Scotland Professor Jeremy Bagg
Dr Jan Clarkson
Wales Professor Stephen Richmond
Oral and dental studiesLow dose intravenous immunoglobulin or 0.9 sodium chloride in the treatment of primary trigeminal neuralgia refractory to Carbamazepine. A randomised double blind parrallel placebo controlled
multicentre trial in an outpatient setting
Monitoring of Oral Cancer Patients Using Novel Lab-On-A-Chip Ensembles
Timing of Primary Surgery for Cleft Palate (TOPS) v1.1
The role of selective neck dissection in patients with early oral squamous cell carcinoma (1-3cm primary size) and no clinical evidence of lymph node metastases in the neck (N0)
Are microimplants as effective at providing orthodontic anchorage as conventional methods
Chewing gum and orthodontic pain
Development of technique to assist with culture of stem cells from oral mucosa & dental pulp
Treatment of Periodontitis and metabolic control in patients with Type 2 Diabetes Mellitus
Dielectrophoresis as a prognostic tool for potentially malignant and malignant disease of the mouth
A comparison of pre medication with oral paracetamol versus intravenous paracetamol given at time of induction for postoperative analgesia following wisdom tooth extraction
A study evaluating (selected) saliva biomarkers to validate their predictive capability in diagnosing clinical periodontal disease
Genetic and psychometric role in post surgical acute pain using ASL/regional cerebral blood (rCBF) flow
Analysis of the Saliva Proteome for Diagnostic Markers of Gingivitis and Periodontitis using FT-ICR-MS/MS.
An analysis of the effect of photographic intervention on medical dialogue within pain consultations. An exploration of photographic portraiture with patients and clinicians from oral and dental medicine
Human tonsil cellular response to infection
IMPROVDENT:Improving Dentures for Patient Benefit A cross over randomised clinical trial comparing impression materials for complete dentures
Eliminating periodontal infection in patients with type 2 diabetes.
X-ray microtomography study of carious teeth and comparison of its removal by various techniques
INTERVAL Dental Recalls Trial [Investigation of NICE Technologies for Enabling Risk-Variable-Adjusted-Length Dental Recall Trial]
Odontogenesis: a paradigm for mammalian biomineralisation and the role of extracellular matrix in the control of crystal deposition and growth
Effect of nitrite in saliva on gastro-oesophageal reflux
Seal or Varnish? A randomised trial to determine the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay
Filling Children’s Teeth: Indicated or Not? Pilot Rehearsal Trial
Preventing obesity in young people attending primary dental care settings: an exploratory randomised controlled trial
So what studies are happening at KCH Dental?
Mapping pain in man using fMRICulture of stem cells from human teethIntervention to assess drivers for Paedodontic
GA extractionsMore?
Trigeminal pain research in KHP
Trigeminal nerveVth cranial nerveSensory supply to
face, scalp and mouth
Homunculus
M3M surgery
Classification of Chronic orofacial pain
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The Team clinicalDental Institute Clinical Orofacial pain clinics at KCHFT
Professor Tara Renton Oral Surgery KCL / Hon Cons KCHFT / GSTFT Cathy Bryant NHS consultant Oral Surgery
Liaison staff at Oral surgery pain clinics Dr Sam Chong Neurology Consultant KCHFT Dr Tom Smith Pain management consultant Dr Lisa Page Liaison Psychiatrist Hon Cons Sarah Barker Liaison clinical Psychologist Nicky James Health psychologist Peter Bullock and Sinan Barazi Neurosurgeons
Other staff involved in orofacial pain Dr Michael Escudier Consultant Oral Medicine GSTFT Dr Tim Poate Consultant Oral Medicine KCHFT Dr Helen Mac Pharlane Staff Grade Oral Medicine GSTFT Professor Ray Chaudery Neurology Consultant KCHFT Prof Manjit Kothari Neurology Queens Square UCL Prof Mike Gleeson ENT KCL
The Team academic
ClinicalTara Renton
IAT PhDsNadine KhawajaKiran BenengNorazah Bakar
CollaborationsProf Manjit Kothari UCLProf Praveen Anand ICProf Vishal Aggrawal QMUL
Non ClinicalZehra Yilmaz Post Doc
PhDsObi Ebugnegwe KCL
WolfsonAndy Grant Post Doc
ImagingSteve Williams Prof IoPMatt Howard IoP Post DocKristina Krause IoP PhD
student
Work ongoingTrigeminal pain: an update
Inflammatory nociceptive pain Dental Pain Peripheral + genetics
Post surgical pain Genetics,Peripheral and central
Neuropathic painPost Traumatic Neuropathy Genetics,
Peripheral and central
Trigeminal autonomic cephalgias Genetics, Peripheral and central
Trigeminal neuralgia Genetics, Peripheral and central
Burning mouth Genetics, Peripheral and central
Unravelling toothache
Immortalised cell line of odontoblastic
+ve markers TRPA1, TRPV1 and TRPV4.
Microarray, RT-PCR, flow cytometry and
Calcium imaging studies
Obi Egbuniwe PhD St
Prof Lucy Di Silvio
Dr Andy Grant
P16/P53 expression and telomerase activity in immortalized human dental pulp cellsEgbuniwe O., Idowu BD, Funes JM, Grant AD, Renton T, Di Silvio L ( Tissue Engineering (IF = 4.5)
The microaaray data we got from painful and non painful teeth showed an up regulation of certain inflammatory markers and cytokines. We are looking at the effect of Substance P exposure on cellular activityWork with Prof Steve MacMahon & Dr Andy Grant
BMSDr Kiran Beneng PhD St
Prof Praveen Anand
Dr Michael EscudierOngoing work TRPM8CB1, P2X3 and GABA receptors Imaging central pathways (CNS)
Dr Matt Howard
NF Bar charts of the mean ± SEM of epithelial nerve fibres per papilla in control and BMS tongue. * P <0.0001.P =0.0006, Spearman r =0.55
Control BMS0.0
0.5
1.0
1.5
2.0 *
TRPV
1 % im
mun
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TRPV1
Control BMS0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5*
% N
GFim
mun
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fibr
es
NGF
NF
TRPV1
Third molar surgery
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Psychological featuresDepressionAngerPost traumatic stress disorderVictim of abuseLoss of ability to trust
36
Imaging central pathwaysPost surgical pain
Post PerfalgenPost dicolfenac
Burning mouth syndrome before and after RxMigrainesTrigeminal neuralgiaTrigeminal autonomic cephalgias
Cluster headacheSUNCTSUNA
Imaging post surgical pain
Prof Steve Williams IoP KCL Center Neuroscience imaging Matt Howard, Kristina Krause, Anbarasu Lourdusamy Gunter Schumann SGDP IoPNadine Khawaja IA PhD St
• TME most frequent model in acute pain trials
(Moore et al., 2005)
• 30-80% of patients suffer moderate to severe pain post-operatively (Popping 2008 & Apfelbaum 2003).
Significant increases in post-surgical regional CBF in brain regions previously associated with pain (pain neuromatrix)
•Additional amygdala, hippocampus, brainstem, and V5 ROIs
ACC
S1 S2
THAL INS
PCC
Results
Significant increases in post surgical rCBF observed in;S1, S2, Thalamus, Insula, Anterior cingulate cortexAlso in Amygdala and HippocampusBut NOT in control regionLargest change seen in ThalamusNo first or second order interaction of surgery for all ROIs
Presusrgery /post surgery Side (left or right) Hemisphere (left or right)
Post surgical painGene expression & VAS score relationships
Correlation between 38 genes and VAS scores
RED up regulatedGREEN down
regulatedLeft side correlation
with VAS score for all 6 cASL maps
Highest correlation reveals a gene BMX involved in regulation of IL6 in pts with RA
41
Clinical, imaging and genetic characterisation of Cluster headaches
Dr Norazah Bakar PhD StProf Manjit Matharu UCLMat Howard IoP KClSteve Williams IoP KCLDr Sam Chong KCH
Trigeminal autonomic cephalgiasCluster headachesSUNCT and SUNA
Grants Private donation Prevention trigeminal nerve injuries 2011 £50KKCH NHS Trust/KCL Joint Research Committee 2010 59K Functional MRI evaluation of brain response BMS
MRC translational project grants Shortlisted 2011 £388K Proof of concept studies on the development of a pain biomarker in man
Pfizer support for PhD students in lab based work 2011 £ 60K British Pain Society Mildred B Clulow 2010 £68K Proof of concept studies on the development of a pain biomarker in man
BRC Oral Health 2010 £8K Consumables For Odontoblast progenitor cell project
London central research fund 2009 10K Development of model to culture neural progenitor cells for human dental pulp.
PI Pfizer Pain / KCL Consortium 2007 £567K Mapping central, peripheral changes in response to acute post operative pain following third molar surgery -
Diabetic burning foot
David Bennett Dave Edmonds
STH Input
Neuromodulation
Back pain
Rheumatology Knee painErnest Choy
Dental
Acute /chronic V
Pain related Anxiety
IoP CNS
Clinical Neuroimaging
Biomarker for acute pain
Dental. RA, Back pain
Birth CNS Myelination of brain first 7 months
IOP
Palliative CareJoan HesterSt Christophers Hospice
Primary careSELDOCGMPs headaches
2y and 3y care
Neurology
42 neurologists
Sam Chong Headaches
Pain management
Joan Hester + Tom Smith Pain / Palliative care
Sue Peat Medical education
NeurosurgeryRichard Selway
Ashkan KeymoursPeter Bullock
Back painTN
Post surgical painbreast
Charlotte Wilson Jones
Primary Care
Leone Ridsdale
4 specialist GPSI in headaches
Prof Bjornsson
Gastroenterology
IBS
Psychosexual clinicVulvadynia
Sue Peat and Joan Hester
UG Medicine
Nursing
Emma Briggs
Nightingale Institute
Mick ThackerWolfson
Masters degree pain neurosciences
Tara RentonMike Escudier
UG dental
Masters Neuroscience
IoP
Publications Yilmaz Z, Renton T, Yiangou Y, Zakrzewska J, Chessell IP, Bountra C, Anand P. Burning mouth syndrome as a trigeminal small fibre neuropathy:
Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score. J Clin Neurosci. 2007 Sep;14(9):864-71. Renton T. An update on pain. Br Dent J. 2008 Mar 22;204(6):335-8. Renton T Summary of: Unexplained orofacial pain - is an early diagnosis possible? Br Dent J. 2008 Aug 9;205(3):140-141 Coulthard P, Esposito M, Renton T, Worthington HV. Surgical techniques for the removal of mandibular wisdom teeth (protocol). Cochrane Database
of Systematic Reviews 2003, Issue 3. Art. No: CD004345. www.cochrane.org Khawaja N, Renton T. Case studies on implant removal influencing the resolution of inferior alveolar nerve injury. Br Dent J. 2009 Apr 11;206(7):365-
70 Seymour RA, Moore U, Hawkesford J, Coulthard P, Jackson-Leech D, Thomas D, Hill M, Combs ML, Renton T, McGurk M. An investigation into the
efficacy of intravenous diclofenac in post-operative dental pain. Eur J Clin Pharmacol. 2000 Sep;56(6-7):447-52. Renton T. Prevention of iatrogenic inferior alveolar nerve injuries in relation to dental procedures. Dent Update. 2010 Jul-Aug;37(6):350-2, 354-6, 358-
60 Beneng K, Renton T, Yilmaz Z, Yiangou Y, Anand P. Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth
syndrome. BMC Neurosci. 2010 Jun 8;11(1):71. [Epub ahead of print]PMID: 20529324 Beneng K, Yilmaz Z, Yiangou Y, McPharland H, Anand P, Renton T. Sensory purinergic receptor P2X(3) is elevated in burning mouth syndrome. Int J
Oral Maxillofac Surg. 2010 Apr 24. [Epub ahead of print] Beneng K, Renton T, Yilmaz Z, Yiangou Y, Anand P. Cannabinoid receptor CB1-immunoreactive nerve fibres in painful and non-painful human tooth
pulp. J Clin Neurosci. 2010 Nov;17(11):1476-9. Epub 2010 Aug 11 Frafjord R & Renton T. Update on Coronectomy J Oral Surgery;2010:vol3 (1-2) 1-7 Renton T, Adey-Viscuso D, Meechan JG, Yilmaz Z. Trigeminal nerve injuries in relation to the local anaesthesia in mandibular injections. Br Dent J.
2010 Nov;209(9):E15 Renton T. Prevention of iatrogenic inferior alveolar nerve injuries in relation to dental procedures. SADJ. 2010 Sep;65(8):342-4, 346-8, 350-1 Renton T Summary of: Experience in third molar surgery: an update. Br Dent J. 2010 Jul 10;209(1):36-7. Howard M, Khawaja N, Krause K, Schumann G, Williams S, Renton T. ASL labeling or central pain pathways in post third molar surgical pain. A pilot
study. PLOS 1 accepted Feb 2011 Lourdusamy A, Krause K, Howard M, Khawaja N, Renton T, Schumann G, Williams S, Analysis of dental pain gene expression related to third molar
surgery. Submitted Am J Human Genetics N Khawaja, Renton T. Case Studies illustrating the management of trigeminal neuropathic pain using topical 5% Lidocaine patches. Accepted JOS
June 2010
Publications YILMAZ, Z, ZAKRZEWSKA, J, HARDING, L, RENTON, T. Identification of allodynia and hypoalgesia using quantitative thermal threshold
testing in burning mouth syndrome and lingual nerve injury. Accepted European Journal of Pain. Impact factor = 3.714 Renton T, Yilmaz Z. Experience of the management of trigeminal nerve injuries Accepted JOMS Nov 2010 Gaballah K, Khawaja N, Renton T. Factors contributing to needle stick injuries trainee dentists and nurses in a dental school. Submitted
J Dent Education Nov 2010 Renton T, Dawood A, Shah A, Yilmaz Z. Trigeminal nerve injuries in relation to dental implants. Accepted Clinical research in
Implantology Accepted Nov 2010 Renton T Frafjord R. Notes on coronectomy. Accepted BDJ RentonT . Coronectomy update. Accepted Dental Update Renton T. A systematic review of haematological screening for BMS. accepted Elsevier Renton T A systematic review of histological evaluation for BMS. accepted Elsevier T Renton, Z Yilmaz ‘Numb chin’ syndrome an update and case series Submitted J Oral Surgery June 2010 T Renton. Z Yilmaz S Chong. A series of medication over use orofacial pain Submitted Pain Jan 2011 T Renton. Z Yilmaz S Chong. Lacosamide for chronic oro-facial pain: a case series. Submitted Neurology Jan 2011 Mehdi I Yilmaz Z, Renton T, Page L The treatment goals of patients attending an orofacial pain clinic. Comparsion of psochological
morbidity of headaches and chronic orofacial pain. Submitted J Oral Surgery Dec 2010 Renton T, Z Yılmaz Profiling of patients with iatrogenic trigeminal nerve injuries Accepted J Orofacial Pain Jan 2011 Renton T Foot N, Yilmaz Z. Endodontic related trigeminal nerve injuries. J Endodontics submitted Jan 2011 Renton T Gabbalah K, Yilmaz Z Trigeminal nerve injuries in relation to third molar surgery. How do we minimize these? Submitted IJOMS
So how can you get involved?Collaborate ...whats happening locally?
KCH KCLGSTTPrimary care
Opportunities Local supportStaff Patients
Huge patient cohortKings College Hospital
Walk in acute pain 30K per annumDental extractions 1500 per weekSurgical extractions 1100 per weekThird molar surgery 600 per weekBiopsy 50 per week
Guys and St Thomas’Dental extractions 500 per weekSurgical extractions 350 per weekThird molar surgery 175 per weekBiopsy 15 per week
Local opportunitiesRelated AHSC health research
King’s PSSQ Research CentreJoint clinical trials officeEducation and trainingCentral BiomedSocial care workforceMedical law and ethics
Friendly R&D dental team!Tara Zehra & Sue
What dental research themes ‘dovetail’ in with KCH or AHSC?
Main themesPain neuroscienceMedically compromisedTrauma
Secondary themesCancerClinical trialsPrevention disease
Cardiac stroke DM Alcohol abuse / smoking
What’s the big question in your area?RestorativeOrthoPaedoSpec care dentistryOral surgeryPDCMaxFac
How can you improve?Service deliveryPatient accessHealth outomesTeachingTraining
Potential research areas for Dental? Clinical trials SD SW Facial trauma JC TN Medically compromised patient
ADC CHD DM risk study WB TR Liver disease in kids MTH Parkinsons / MS/ OFP TR Smoking alcohol cessation JG LZ Others
Oncology Improved oral health of KCH in patients Anxiety Sedation paedo / adult Bisphosphonate therapy
Potential areas Imaging US CBCT Dentoalveolar trauma Orthodontic RX Paedo dentoalveolar surgery Primary care movement of 40% services from 2dry to 1ry care TMJ pain
Potential strategy to increase NHS consultant research activity
Identify themes for dentalLink up KCL leads with NHS interested staffFree up time for KCH staffLocal grant applications Cochrane review topicsIA Trainee applications recommended for Encourage PhDs and masters (OSeas?)Updated information systems to assist research and
developmentDedicated staff to assist with review, papers, grants
What does this mean for the ‘jobbing’ NHS staff?
Increased recognised Research activityPAs for ResearchCochrane reviews –local supportWalport posts IATsMore funding for your trustCollaborative research activityMore satisfied patients
What does this mean for the ‘jobbing’ NHS staff?
MORE FUN!
All positiveBest research for best health
Current GOLD standard is not necessarily good enough!
Constant improvement of health services provision
DentalClinical
KCH > GSTT dental approx 200K pts / yearKCH > GSTT Dental, liver, gastrointestinal and
neurosciencesKCH 46% of clinical activity
ResearchResearch income for dental GSTT >KCHDental top seven KCL groups over £5m incomeMedical>IoP>BHS>dental>nursingDental dropping from 23-11% of income 2005-08
Clinical academic staffKCH 12 vs GSTT 29GSTT 60% AHSC overall income (more Research)