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Research

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Evidence-based OMFS: Shifting the culture with MANTRA

Professor Panayiotis Kyzas

PhD, FRCS (OMFS) Ed

Consultant OMFS Head and Neck Surgeon

East Lancashire Hospitals Trust

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BJOMS

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Royal Blackburn Teaching Hospital

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Edge Hill University

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Handler of a 2M NIHR grant (NIHR152682) to run the MANTRA trial

MANdibular TRauma and Antibiotics

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What is evidence-based medicine?

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What is evidence-based medicine?

Combining:

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Research evidence

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with

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Robust clinical acumen

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AND

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Patient’s wishes

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Evidence pyramid

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OMFS evidence

  • RCTs < 1.5% of published papers

  • > 80% enroll less than 100 patients

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  • > 65% no power calculations

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  • > 70% no allocation concealment

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  • 60% no description of randomization details

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OMFS evidence

  • RCTs are rare and poor
  • H&N fairs better
  • Guidelines based on “best available”
  • NIHR portfolio under-representation
  • OMFS clinical academics a rarity

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  • RECRUITEMENT

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OMFS topics with “unclear” evidence

  • Steroid use in cervicofacial infections
  • Non-surgical management of dysplasia
  • ERAS impact in H&N surgery
  • Sentinel node v Neck Dissection
  • Antibiotic prophylaxis in major H&N surgery
  • Drains post-neck dissection
  • Medical management of ORN
  • Tranexamic acid in neck bleed post-free flap
  • Best time pathway to treat zygoma fractures
  • Oral diet post-intraoral resection (timing)
  • Margins and BCC and management
  • Lingual nerve exploration post wisdom tooth extraction
  • Sialolithiasis – stone size matters?
  • Prophylactic extraction of wisdom teeth
  • Composite flaps v soft tissue for lateral mandibular defects
  • The ideal surgical margin for oral cancer
  • Acetazolamide in orbital trauma
  • Steroids in post-zygomaticoorbital fractures treatment
  • …

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The evidence for a simple intervention

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The evidence for a simple intervention

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Antibiotics and mandible fractures: What do we know?

> 80% patients receive pre-operative IV antibiotics

> 50% receive two post-op IV doses and 5 days oral

Some receive just two post-op doses

Some receive no further antibiotics

Augmentin is the antibiotic of choice

Incidence of post-surgical infection is 10%

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Using antibiotics if not needed: Is it a bad thing?

Antibiotic resistance

>12.000 deaths in UK per year

Cost

Antibiotic-related complications

Clinical practice culture

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NOT using antibiotics if needed: Is it a bad thing?

Infected fractured mandible

Non-union

Malunion

Return to theatre

Osteomyelitis

Spreading cervicofacial infection

Prolonged hospitalization

Cost

QoL

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Antibiotics and mandible fractures

Clinically important question

It should be easy to address

Why don’t we have the answer?

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What can influence infection in mandible fractures? (confounders)

  • Time from injury to treatment?
  • Mechanism of injury?
  • Type and location of fracture?
  • Plating kit?
  • Operator?
  • Smoking?
  • Alcohol?
  • Oral/dental hygiene?
  • Chlorhexidine mouthwash?
  • Other injuries?
  • Co-morbidities (diabetes)?
  • Technical surgical issues?
  • The need of IMF?
  • Medications (i.e., long term steroids)?
  • Antibiotics???

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What can influence infection in mandible fractures? (confounders)

Observational studies or cohort studies will always be biased in these circumstances

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  • Can only generate equipoise

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Study design of choice when evaluating interventions

RCT

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Introducing the…

MANTRA

RCT

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Non-inferiority

Non blinded

RCT

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Non-inferiority design

Sample Size

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Based on the 5% NI cut-off:

775 patients per arm

2325 participants across the 3 arms

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Power: 90%, a:0.025%

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20% dropout rate

2907

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SAMLE SIZE…made simple

4 patients per unit per month

(based on rolling 25 UK units participating)

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MANTRA…

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…will be the largest UK OMFS RCT ever conducted

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THE INTERVENTION

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Primary endpoint

SSI as per CDC

Most infections are superficial

Deep space mandible infections (osteomyelitis) start as superficial

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The timeline…

Start of grant:                 1st July 2023

Start of RCT / pilot:             1st January 2024

End of pilot:                     30th June 2024

End of recruitment:         31st December 2026

End of follow-up:             30th June 2027

Completion:                31st December 2027

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The recruitment phase…

20-25 units (at any given time point)

Aim to enroll as many UK units as possible

ROLLING participation

Avoid postcode lottery

Include rural, urban, DGH, University Hospitals

Small and large units

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MANTRA trial key points

No change in local practice

Only intervention is post-op antibiotics

Pragmatic design

ALL patients receive IV abxs on induction

Objective Primary Outcome

Thinking ahead for implementation and change in practice – research culture

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Questions ?

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In summary

A very difficult task

We want to deliver and shift research culture in OMFS

More than enough units signed up thus far, but we want all on-board

Takes effort, sweat and tears

Rewarding

Patient-centered approach

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Thanks for listening

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+44(0)7505402640

Panayiotis.Kyzas@elht.nhs.uk

kyzasp@icloud.com