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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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

25

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

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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

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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)