# A Data-Driven Approach At Characterizing Heterogeneity In Neuropathy Assessments
### Luke Johnston

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<div class="footer">
<img src="../../common/au_logo_black.png" alt="Aarhus University", width="160">
https://gitlab.com/lwjohnst/neuropathy.clusters
</div>

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## PURPOSE:

Get feedback, comments on two issues:

- Analysis implementation

- Extracting key results

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# BACKGROUND

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## Diabetic neuropathy: Major complication without strong definition

- Many assessments:
    - DN4, UENS, TCSS, mTCSS, Monofilament-based, MNSI, Heart rate variability,
    Sural nerve conduction

- No consensus on assessing neuropathy

---

## Study objectives

- Are there specific groups of people who share similar assessment responses?

- Are some assessment tools better at capturing features of neuropathy?

- Based on above, could we simplify what assessment items to give and use the
responses?

---

## Study and measurements

- Cohort: ~13 year followup of ADDITION-DK (n=526)

- Measures: 8 different neuropathy assessment tools (105 total items)

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## Rationale on statistical analysis

---

## Groups by row: Hierarchical cluster (HCA)

<table class="table table-striped table-condensed" style="margin-left: auto; margin-right: auto;">
 <thead>
  <tr>
   <th style="text-align:right;"> ID </th>
   <th style="text-align:left;"> A1 </th>
   <th style="text-align:left;"> A2 </th>
   <th style="text-align:left;"> A3 </th>
   <th style="text-align:left;"> A4 </th>
   <th style="text-align:left;"> A5 </th>
   <th style="text-align:left;"> A6 </th>
  </tr>
 </thead>
<tbody>
  <tr>
   <td style="text-align:right;font-weight: bold;background-color: lightblue !important;"> 1 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;background-color: lightblue !important;"> 2 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;background-color: lightblue !important;"> 3 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;background-color: lightblue !important;"> 4 </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;background-color: lightblue !important;"> 5 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;background-color: lightblue !important;"> 6 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;background-color: lightgreen !important;"> 7 </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;background-color: lightgreen !important;"> 8 </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
  </tr>
</tbody>
</table>

---

## "Groups" by variable: Factor analysis

<table class="table table-striped table-condensed" style="margin-left: auto; margin-right: auto;">
 <thead>
  <tr>
   <th style="text-align:right;"> ID </th>
   <th style="text-align:left;"> A1 </th>
   <th style="text-align:left;"> A2 </th>
   <th style="text-align:left;"> A3 </th>
   <th style="text-align:left;"> A4 </th>
   <th style="text-align:left;"> A5 </th>
   <th style="text-align:left;"> A6 </th>
  </tr>
 </thead>
<tbody>
  <tr>
   <td style="text-align:right;font-weight: bold;"> 1 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;"> 2 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;"> 3 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;"> 4 </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;"> 5 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;"> 6 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;"> 7 </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightblue !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
  </tr>
  <tr>
   <td style="text-align:right;font-weight: bold;"> 8 </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightblue !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> present </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
   <td style="text-align:left;background-color: lightgreen !important;"> absent </td>
  </tr>
</tbody>
</table>

---

# FIRST ISSUE:

### Both methods data-specific, with fixed groups.

### What is *likelihood* individual will be in group?

---

# My idea for implementation:

### Run methods on resampled sets (4-fold CV, x 25)

---

&nbsp;

---

## HCA results: Likelihood of group membership

---

# SECOND ISSUE:

### What are common responses by group?

---

### This is 50 rows of what results look like:

<div style="border: 1px solid #ddd; padding: 0px; overflow-y: scroll; height:350px; "><table class="table table-striped table-condensed" style="margin-left: auto; margin-right: auto;">
 <thead>
  <tr>
   <th style="text-align:left;position: sticky; top:0; background-color: #FFFFFF;"> ClusterNumber </th>
   <th style="text-align:left;position: sticky; top:0; background-color: #FFFFFF;"> Questionnaire </th>
   <th style="text-align:left;position: sticky; top:0; background-color: #FFFFFF;"> AssessmentResponse </th>
   <th style="text-align:right;position: sticky; top:0; background-color: #FFFFFF;"> MeanPercent </th>
  </tr>
 </thead>
<tbody>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Ankle reflex: Present with reinforcement </td>
   <td style="text-align:right;"> 0.8977778 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> TCSS </td>
   <td style="text-align:left;"> Ankle reflex: Decreased(present by reinforcement) </td>
   <td style="text-align:right;"> 0.8977778 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> HRV </td>
   <td style="text-align:left;"> E:i (expiration inspiration): High </td>
   <td style="text-align:right;"> 0.8107937 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> mTCSS </td>
   <td style="text-align:left;"> Tingling?: No </td>
   <td style="text-align:right;"> 0.7972152 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Neurotip section 1: Normal </td>
   <td style="text-align:right;"> 0.7894309 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Do you ever have any burning pain in your legs and/or feet?: No </td>
   <td style="text-align:right;"> 0.7872358 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> TCSS </td>
   <td style="text-align:left;"> Ataxia?: No </td>
   <td style="text-align:right;"> 0.7855172 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Do your legs hurt when you walk?: No </td>
   <td style="text-align:right;"> 0.7803376 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Ulceration foot?: Absent </td>
   <td style="text-align:right;"> 0.7726740 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Ulceration foot?: Absent </td>
   <td style="text-align:right;"> 0.7726740 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> mTCSS </td>
   <td style="text-align:left;"> Position sensation: Normal </td>
   <td style="text-align:right;"> 0.7721547 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Neurotip section 4: Decreased </td>
   <td style="text-align:right;"> 0.7600000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Neurotip section 2: Decreased </td>
   <td style="text-align:right;"> 0.7569231 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> TCSS </td>
   <td style="text-align:left;"> Temperature for foot: Abnormal </td>
   <td style="text-align:right;"> 0.7544304 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> TCSS </td>
   <td style="text-align:left;"> Upper limb symptoms?: Yes </td>
   <td style="text-align:right;"> 0.7446667 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> DPN </td>
   <td style="text-align:left;"> Amplitude: Low-mid </td>
   <td style="text-align:right;"> 0.7406803 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> DN4 </td>
   <td style="text-align:left;"> Pain in area may reveal hypoesthesia to touch?: No </td>
   <td style="text-align:right;"> 0.6948315 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Vibration on great toe: Decreased </td>
   <td style="text-align:right;"> 0.6471795 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Have you ever had an open sore on your foot?: Yes </td>
   <td style="text-align:right;"> 0.4088889 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> DN4 </td>
   <td style="text-align:left;"> Do you suffer from pain in your feet?: Yes </td>
   <td style="text-align:right;"> 0.2711111 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 1 </td>
   <td style="text-align:left;"> DN4 </td>
   <td style="text-align:left;"> Pain feels like painful cold?: No </td>
   <td style="text-align:right;"> 0.2320000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> mTCSS </td>
   <td style="text-align:left;"> Foot pain?: Yes </td>
   <td style="text-align:right;"> 0.5133333 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> DN4 </td>
   <td style="text-align:left;"> Pain feels like electric shocks?: Yes </td>
   <td style="text-align:right;"> 0.5093333 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> TCSS </td>
   <td style="text-align:left;"> Knee reflex: Decreased(present by reinforcement) </td>
   <td style="text-align:right;"> 0.4174359 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> TCSS </td>
   <td style="text-align:left;"> Ataxia?: Yes </td>
   <td style="text-align:right;"> 0.4150000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Do you ever have any burning pain in your legs and/or feet?: Yes </td>
   <td style="text-align:right;"> 0.3059259 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> DN4 </td>
   <td style="text-align:left;"> Pain caused or increased by brushing?: No </td>
   <td style="text-align:right;"> 0.2794203 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> DPN </td>
   <td style="text-align:left;"> Velocity: Low-mid </td>
   <td style="text-align:right;"> 0.2385185 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Do your legs hurt when you walk?: Yes </td>
   <td style="text-align:right;"> 0.2350000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> Monofilament </td>
   <td style="text-align:left;"> Light touch under foot, point 4: Abnormal(≤1/3) </td>
   <td style="text-align:right;"> 0.2112821 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> Monofilament </td>
   <td style="text-align:left;"> Light touch under foot, point 1: Normal(≥ 2/3) </td>
   <td style="text-align:right;"> 0.2088623 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Monofilament great toe: Normal(8-10) </td>
   <td style="text-align:right;"> 0.2086842 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Neurotip section 5: Normal </td>
   <td style="text-align:right;"> 0.2084291 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Do you ever have any burning pain in your legs and/or feet?: No </td>
   <td style="text-align:right;"> 0.2000000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Extension great toe: Normal </td>
   <td style="text-align:right;"> 0.1996101 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Neurotip section 3: Decreased </td>
   <td style="text-align:right;"> 0.1966667 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 2 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Neurotip section 1: Absent </td>
   <td style="text-align:right;"> 0.0333333 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Has your doctor ever told you that you have diabetic neuropathy?: Yes </td>
   <td style="text-align:right;"> 0.2966667 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> Monofilament </td>
   <td style="text-align:left;"> Light touch under foot, point 1: Abnormal(≤1/3) </td>
   <td style="text-align:right;"> 0.2555556 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> DN4 </td>
   <td style="text-align:left;"> Pain feels like electric shocks?: No </td>
   <td style="text-align:right;"> 0.1720000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> Monofilament </td>
   <td style="text-align:left;"> Light touch under foot, point 3: Abnormal(≤1/3) </td>
   <td style="text-align:right;"> 0.1293333 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> HRV </td>
   <td style="text-align:left;"> Root mean square of successive differences for hr: Mid-high </td>
   <td style="text-align:right;"> 0.0720000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> mTCSS </td>
   <td style="text-align:left;"> Upper limb symptoms?: No </td>
   <td style="text-align:right;"> 0.0525490 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> HRV </td>
   <td style="text-align:left;"> High frequency (?): Low </td>
   <td style="text-align:right;"> 0.0512000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> TCSS </td>
   <td style="text-align:left;"> Ataxia?: No </td>
   <td style="text-align:right;"> 0.0482270 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> TCSS </td>
   <td style="text-align:left;"> Ankle reflex: Normal </td>
   <td style="text-align:right;"> 0.0477778 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> UENS </td>
   <td style="text-align:left;"> Extension great toe: Normal </td>
   <td style="text-align:right;"> 0.0475789 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> Monofilament </td>
   <td style="text-align:left;"> Light touch under foot, point 1: Normal(≥ 2/3) </td>
   <td style="text-align:right;"> 0.0400000 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> MNSI </td>
   <td style="text-align:left;"> Vibration perception at great toe: Decreased </td>
   <td style="text-align:right;"> 0.0346667 </td>
  </tr>
  <tr>
   <td style="text-align:left;"> Cluster: 3 </td>
   <td style="text-align:left;"> mTCSS </td>
   <td style="text-align:left;"> Tingling?: No </td>
   <td style="text-align:right;"> 0.0315447 </td>
  </tr>
</tbody>
</table></div>

---

## How to make sense of this data?

## How to extract meaning?

Notes for current slide

Notes for next slide

A Data-Driven Approach At Characterizing Heterogeneity In Neuropathy AssessmentsLuke Johnston1 / 16

PURPOSE:

Get feedback, comments on two issues:

Analysis implementation
Extracting key results

2 / 16

BACKGROUND

3 / 16

Diabetic neuropathy: Major complication without strong definition

4 / 16

Diabetic neuropathy: Major complication without strong definition

Many assessments:
- DN4, UENS, TCSS, mTCSS, Monofilament-based, MNSI, Heart rate variability, Sural nerve conduction

4 / 16

Diabetic neuropathy: Major complication without strong definition

Many assessments:
- DN4, UENS, TCSS, mTCSS, Monofilament-based, MNSI, Heart rate variability, Sural nerve conduction

No consensus on assessing neuropathy

4 / 16

Study objectives

Are there specific groups of people who share similar assessment responses?

5 / 16

Study objectives

Are there specific groups of people who share similar assessment responses?
Are some assessment tools better at capturing features of neuropathy?

5 / 16

Study objectives

Are there specific groups of people who share similar assessment responses?
Are some assessment tools better at capturing features of neuropathy?
Based on above, could we simplify what assessment items to give and use the responses?

5 / 16

Study and measurements

Cohort: ~13 year followup of ADDITION-DK (n=526)
Measures: 8 different neuropathy assessment tools (105 total items)

6 / 16

Rationale on statistical analysis

ID	A1	A2	A3	A4	A5	A6
1	absent	present	present	present	present	absent
2	absent	absent	absent	absent	present	present
3	absent	present	absent	absent	present	present
4	present	absent	present	absent	absent	absent
5	absent	present	present	absent	absent	absent
6	absent	absent	absent	absent	absent	present
7	present	present	absent	present	present	present
8	absent	absent	present	present	absent	absent

7 / 16

Groups by row: Hierarchical cluster (HCA)

ID	A1	A2	A3	A4	A5	A6
1	absent	present	present	present	present	absent
2	absent	absent	absent	absent	present	present
3	absent	present	absent	absent	present	present
4	present	absent	present	absent	absent	absent
5	absent	present	present	absent	absent	absent
6	absent	absent	absent	absent	absent	present
7	present	present	absent	present	present	present
8	absent	absent	present	present	absent	absent

8 / 16

"Groups" by variable: Factor analysis

ID	A1	A2	A3	A4	A5	A6
1	absent	present	present	present	present	absent
2	absent	absent	absent	absent	present	present
3	absent	present	absent	absent	present	present
4	present	absent	present	absent	absent	absent
5	absent	present	present	absent	absent	absent
6	absent	absent	absent	absent	absent	present
7	present	present	absent	present	present	present
8	absent	absent	present	present	absent	absent

9 / 16

FIRST ISSUE:

Both methods data-specific, with fixed groups.

What is likelihood individual will be in group?

10 / 16

My idea for implementation:

Run methods on resampled sets (4-fold CV, x 25)

11 / 16

ID	A1	A2	A3	A4	A5	A6
1	absent	present	present	present	present	absent
3	absent	present	absent	absent	present	present
6	absent	absent	absent	absent	absent	present
7	present	present	absent	present	present	present

12 / 16

ID	A1	A2	A3	A4	A5	A6
1	absent	present	present	present	present	absent
3	absent	present	absent	absent	present	present
6	absent	absent	absent	absent	absent	present
7	present	present	absent	present	present	present

ID	A1	A2	A3	A4	A5	A6
2	absent	absent	absent	absent	present	present
5	absent	present	present	absent	absent	absent
7	present	present	absent	present	present	present
8	absent	absent	present	present	absent	absent

12 / 16

HCA results: Likelihood of group membership

Focusing on HCA for time.

13 / 16

SECOND ISSUE:

What are common responses by group?

14 / 16

This is 50 rows of what results look like:

ClusterNumber	Questionnaire	AssessmentResponse	MeanPercent
Cluster: 1	MNSI	Ankle reflex: Present with reinforcement	0.8977778
Cluster: 1	TCSS	Ankle reflex: Decreased(present by reinforcement)	0.8977778
Cluster: 1	HRV	E:i (expiration inspiration): High	0.8107937
Cluster: 1	mTCSS	Tingling?: No	0.7972152
Cluster: 1	UENS	Neurotip section 1: Normal	0.7894309
Cluster: 1	MNSI	Do you ever have any burning pain in your legs and/or feet?: No	0.7872358
Cluster: 1	TCSS	Ataxia?: No	0.7855172
Cluster: 1	MNSI	Do your legs hurt when you walk?: No	0.7803376
Cluster: 1	MNSI	Ulceration foot?: Absent	0.7726740
Cluster: 1	MNSI	Ulceration foot?: Absent	0.7726740
Cluster: 1	mTCSS	Position sensation: Normal	0.7721547
Cluster: 1	UENS	Neurotip section 4: Decreased	0.7600000
Cluster: 1	UENS	Neurotip section 2: Decreased	0.7569231
Cluster: 1	TCSS	Temperature for foot: Abnormal	0.7544304
Cluster: 1	TCSS	Upper limb symptoms?: Yes	0.7446667
Cluster: 1	DPN	Amplitude: Low-mid	0.7406803
Cluster: 1	DN4	Pain in area may reveal hypoesthesia to touch?: No	0.6948315
Cluster: 1	UENS	Vibration on great toe: Decreased	0.6471795
Cluster: 1	MNSI	Have you ever had an open sore on your foot?: Yes	0.4088889
Cluster: 1	DN4	Do you suffer from pain in your feet?: Yes	0.2711111
Cluster: 1	DN4	Pain feels like painful cold?: No	0.2320000
Cluster: 2	mTCSS	Foot pain?: Yes	0.5133333
Cluster: 2	DN4	Pain feels like electric shocks?: Yes	0.5093333
Cluster: 2	TCSS	Knee reflex: Decreased(present by reinforcement)	0.4174359
Cluster: 2	TCSS	Ataxia?: Yes	0.4150000
Cluster: 2	MNSI	Do you ever have any burning pain in your legs and/or feet?: Yes	0.3059259
Cluster: 2	DN4	Pain caused or increased by brushing?: No	0.2794203
Cluster: 2	DPN	Velocity: Low-mid	0.2385185
Cluster: 2	MNSI	Do your legs hurt when you walk?: Yes	0.2350000
Cluster: 2	Monofilament	Light touch under foot, point 4: Abnormal(≤1/3)	0.2112821
Cluster: 2	Monofilament	Light touch under foot, point 1: Normal(≥ 2/3)	0.2088623
Cluster: 2	MNSI	Monofilament great toe: Normal(8-10)	0.2086842
Cluster: 2	UENS	Neurotip section 5: Normal	0.2084291
Cluster: 2	MNSI	Do you ever have any burning pain in your legs and/or feet?: No	0.2000000
Cluster: 2	UENS	Extension great toe: Normal	0.1996101
Cluster: 2	UENS	Neurotip section 3: Decreased	0.1966667
Cluster: 2	UENS	Neurotip section 1: Absent	0.0333333
Cluster: 3	MNSI	Has your doctor ever told you that you have diabetic neuropathy?: Yes	0.2966667
Cluster: 3	Monofilament	Light touch under foot, point 1: Abnormal(≤1/3)	0.2555556
Cluster: 3	DN4	Pain feels like electric shocks?: No	0.1720000
Cluster: 3	Monofilament	Light touch under foot, point 3: Abnormal(≤1/3)	0.1293333
Cluster: 3	HRV	Root mean square of successive differences for hr: Mid-high	0.0720000
Cluster: 3	mTCSS	Upper limb symptoms?: No	0.0525490
Cluster: 3	HRV	High frequency (?): Low	0.0512000
Cluster: 3	TCSS	Ataxia?: No	0.0482270
Cluster: 3	TCSS	Ankle reflex: Normal	0.0477778
Cluster: 3	UENS	Extension great toe: Normal	0.0475789
Cluster: 3	Monofilament	Light touch under foot, point 1: Normal(≥ 2/3)	0.0400000
Cluster: 3	MNSI	Vibration perception at great toe: Decreased	0.0346667
Cluster: 3	mTCSS	Tingling?: No	0.0315447

15 / 16

How to make sense of this data?

How to extract meaning?

16 / 16

PURPOSE:

Get feedback, comments on two issues:

Analysis implementation
Extracting key results

2 / 16

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