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Transcript
Prevention and personalized treatments in
knee osteoarthritis
Synthesis of evidence from systematic literature searches with focus on
implications for prevention and personalized treatment
WP4
Ewa Roos - Hans Lund
SDU
General background ESR8
Effectiveness of biomechanical therapies, examples:
 Effect of exercise on joint structure or Joint load
 Effect of bracing on pain/disability
Joint load is crucial in stimulating the cartilage cells and maintaining the homeostasis
of the cartilage. Thus physical activity is a potentially important part of maintaining
cartilage health, and exercise is indeed a corner stone of knee OA treatment. On the
other hand high-level physical activity such as elite sports and long-term knee bending
work are risk factors for knee OA development. In summary, a window of optimal knee
joint load seems to promote joint health.
General Background – ESR7
Evidence synthesis on biomechanical pathways in knee
OA, examples
 Effect of strengthening exercise on pain/disability
 Effect of improved hip abductor strength on knee adduction
moment
It is not known whether a poor muscle function leads to cartilage degradation / pain
and/or disability or cartilage changes lead to poor muscle function. In some situations
good muscle strength may diminish the load in the knee joint, while it in other
situations it may increase the load.
In the same way, muscles around the knee and hip joints may be of importance to
secure an even distribution of loads between the medial and lateral knee joint
compartment. It is however currently unknown how the muscle function is related to
the development and worsening of KOA.
Aim
ESR7
Overall aim: evidence synthesis on biomechanical pathways in knee OA
Specific aim: To identify the optimal muscle function for patients with KOA
both in daily activities and when performing exercise.
ESR8
Overall aim: compile the existing evidence on the effectiveness of
biomechanical therapies in knee OA
Specific aim: To provide guidelines for optimal knee joint load in preventing
and treating participants at high risk of developing OA and participants with
knee OA.
Example
Methodical background: optimal muscle function
 The expanding body of research reports increase the
danger of an increasing number of less than
meaningful observations are being reported in the
literature is a real possibility (Chow 2011)
 Fewer than 20% of the papers published in two
applied biomechanics serials could be rated highly on
rationale, theory and statistical analysis (Knudson
2005).
5
Theoretical assumption
By mapping the possible mechanisms it would
be possible to examine the evidence for each
mechanism.
By dividing each mechanism into deterministic
models it is possible to examine the evidence
for each part/step of the model
Beckwee et al. 2013
Qualitative analysis of the literature aims to
provide an overview of theoretical models
that are put forward to explain the beneficial
treatment effects of exercise in KOA
70 original papers identified from reviews and
guidelines
22 had a explanation for why exercise can help
diminishing pain in KOA
Beckwee 2013
Categories
Theoretical concepts
Neuromuscular components
Muscle
Proprioception
Energy absorption capacity
Stability
Peri-articular components
Connective tissue
Bone
Intra-articular components
Cartilage
Inflammation
Joint fluid
General fitness /health components
Comorbidity
Weight loss
Aerobic fitness
Psychosocial components
Increase of well-being
Decrease of depression
Placebo effect
Increase of self-efficacy
Deterministic models, muscle and KOA
(from Beckwee 2013)
Mikesky 2006:
Røgind 1998:
Better muscle strength
Better muscle strength
Better cartilage quality
Increased functional capacity
Hinmann 2007:
Better hip abductor muscle strength
Reduce knee adduction moment
Less load in medial compartment
What is the
evidence?
METHOD
STEP 1
Identify the primary goal / primary outcome.
Operationalised in KOA:
1. Less pain?
2. Less disability? – patient-reported OR observed
3. Structural changes?
10
METHOD
STEP 2
Identify the factors that could contribute to this
outcome
Operationalised in KOA
1. Beckwee's study from 2013 identifies 16 different
concepts/mechanisms focusing on reducing pain for
patients with KOA
2. Choice: MUSCLE (Neuromuscular components)
11
METHOD
STEP 3
For each concept/mechanism form a block diagram
(deterministic model). The links between each block
and the blocks should be all-inclusive and nonredundant.
Operationalised in KOA
Bradford Hill criteria should be used for each link in the
block diagram (deterministic model)
12
Bradford Hill criteria
In 1965 Austin Bradford Hill proposed a series of
considerations to help assess evidence of causation,[21]
which have come to be commonly known as the
"Bradford Hill criteria".
In contrast to the explicit intentions of their author, Hill's considerations are
now sometimes taught as a checklist to be implemented for assessing
causality.[22] Hill himself said "None of my nine viewpoints can bring
indisputable evidence for or against the cause-and-effect hypothesis and
none can be required sine qua non."[21]
13
Bradford Hill criteria
1.
2.
3.
4.
5.
6.
7.
8.
9.
Strength: A small association does not mean that there is not a causal effect, though the larger the
association, the more likely that it is causal.[21]
Consistency: Consistent findings observed by different persons in different places with different samples
strengthens the likelihood of an effect.[21]
Specificity: Causation is likely if a very specific population at a specific site and disease with no other
likely explanation. The more specific an association between a factor and an effect is, the bigger the
probability of a causal relationship.[21]
Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause
and expected effect, then the effect must occur after that delay).[21]
Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However,
in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse
proportion is observed: greater exposure leads to lower incidence.[21]
Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge
of the mechanism is limited by current knowledge).[21]
Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an
effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological
effect on associations".[21]
Experiment: "Occasionally it is possible to appeal to experimental evidence".[21]
Analogy: The effect of similar factors may be considered.[21]
14
Bradford Hill criteria
The consequence of using these criteria is a systematic search
for documentation for each link in the block
diagram/deterministic model.
A strong mechanism (block diagram) is one where every link is
supported by earlier studies / Bradford Hill criteria
A weak mechanism (block diagram) is one where the support for
hub links (i.e. crucial link) is absent or weak according to the
Bradford Hill criteria
15
Method
STEP 4
Comparing each deterministic model – which
models have the strongest evidence
Operationalized in KOA:
The strongest mechanism can show us:
1. The persons with high risk for KOA
2. The best exercise regimes for KOA
16
Method
STEP 5
A systematic search for all RCTs dealing with the
deterministic model(s) with the best evidence
PS
It would be relevant to search for RCTs for both the strong and
weak mechanisms. Sometimes the theoretical foundation is
lacking but clinical research indicates an effect
17