Botulinum Toxin Type A Versus Local Anesthetic Injection for Chronic Neuroma Pain After Combat-Related Amputation (NEUROQUIET)

Residual limb pain intensity will be assessed using the 11-point Numeric Rating Scale (NRS). Participants will rate their average residual limb pain during the previous 7 days on a scale from 0 to 10, where 0 indicates "no pain" and 10 indicates "worst imaginable pain." Higher scores indicate greater pain intensity and a worse clinical outcome.

Scale Information:

Numeric Rating Scale (NRS) Minimum Value: 0 Maximum Value: 10 Interpretation: Higher scores indicate worse residual limb pain intensity.

Pain catastrophizing will be assessed using the Pain Catastrophizing Scale (PCS), a validated 13-item self-report questionnaire designed to measure catastrophic thinking related to pain. The PCS evaluates three domains: rumination, magnification, and helplessness. Total scores range from 0 to 52, with higher scores indicating greater levels of pain catastrophizing and a worse psychological pain profile.

Scale Information:

Pain Catastrophizing Scale (PCS) Minimum Value: 0 Maximum Value: 52 Interpretation: Higher scores indicate greater pain catastrophizing and worse pain-related psychological outcomes.

Prosthesis tolerance will be assessed using selected domains of the Prosthesis Evaluation Questionnaire (PEQ), a validated instrument evaluating comfort, utility, satisfaction, and functional use of the prosthesis. Scores range from 0 to 100, with higher scores indicating better prosthesis tolerance and satisfaction.

Scale Information:

Prosthesis Evaluation Questionnaire (PEQ) Minimum Value: 0 Maximum Value: 100 Interpretation: Higher scores indicate better prosthesis tolerance, comfort, and prosthetic adaptation.

Analgesic consumption will be assessed by calculating the total daily analgesic use and converting opioid medications into Oral Morphine Equivalent Daily Dose (OMEDD). Non-opioid analgesics (e.g., acetaminophen, NSAIDs, gabapentinoids) will also be recorded. Higher opioid consumption indicates greater analgesic requirements and potentially more severe pain.

Measurement:

Oral Morphine Equivalent Daily Dose (OMEDD), expressed in milligrams per day (mg/day) Minimum Value: 0 mg/day

Maximum Value:

No predefined maximum value Interpretation: Higher values indicate greater analgesic consumption and higher pain management requirements.

Overall perceived improvement will be assessed using the Patient Global Impression of Change (PGIC) scale. The PGIC is a validated patient-reported outcome measure that evaluates a participant's perception of change in pain, function, and overall health status since the beginning of treatment. Participants rate their overall improvement on a 7-point scale ranging from "Very much worse" to "Very much improved."

Scale Information:

Patient Global Impression of Change (PGIC) Minimum Value: 1 (Very much worse) Maximum Value: 7 (Very much improved) Interpretation: Higher scores indicate greater perceived improvement and better overall clinical outcomes.

Scale Categories:

1. = Very much worse
2. = Much worse
3. = Minimally worse
4. = No change
5. = Minimally improved
6. = Much improved
7. = Very much improved

Adverse events will be assessed by recording the occurrence, type, severity, and relationship to treatment throughout the study period. Events may include medication-related adverse effects, prosthesis-related complications, falls, skin breakdown, residual limb complications, infections, hospitalizations, and other clinically significant events. Severity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0, when applicable.

Measurement:

Number of participants experiencing one or more adverse events. Minimum Value: 0 participants Maximum Value: Number of participants enrolled in the study

Interpretation:

Higher values indicate a greater incidence of adverse events and worse safety outcomes.

Additional Safety Assessment:

Severity of adverse events will be categorized as Grade 1 (Mild) to Grade 5 (Death related to adverse event) according to CTCAE v5.0.

Sleep disturbance will be assessed using the Pittsburgh Sleep Quality Index (PSQI), a validated 19-item questionnaire that evaluates subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction during the previous month. The global PSQI score ranges from 0 to 21, with higher scores indicating poorer sleep quality and greater sleep disturbance.

Scale Information:

Pittsburgh Sleep Quality Index (PSQI) Minimum Value: 0 Maximum Value: 21

Interpretation:

Higher scores indicate worse sleep quality and greater sleep disturbance.

Clinical Interpretation:

A global PSQI score >5 is commonly considered indicative of clinically significant sleep disturbance.

Functional mobility will be assessed using the Amputee Mobility Predictor (AMP), a validated performance-based instrument designed to evaluate ambulatory potential, balance, transfers, gait, and functional mobility in individuals with lower-limb amputation. The scale assesses the patient's ability to perform a series of mobility tasks and predicts prosthetic functional potential.

Scale Information:

Amputee Mobility Predictor (AMP) Minimum Value: 0 Maximum Value: 47 Interpretation: Higher scores indicate better functional mobility, greater ambulatory capacity, and improved rehabilitation outcomes.

Clinical Interpretation: Higher AMP scores are associated with higher functional levels and greater potential for successful prosthetic use.

he need for repeat intervention will be assessed by recording the number of participants who require additional pain-related interventions following the initial treatment. Repeat interventions may include repeat nerve blocks, cryoneurolysis, radiofrequency ablation, neuroma surgery, revision procedures, additional injections, or other clinically indicated pain-management procedures.

Measurement:

Number of participants requiring one or more additional pain-related interventions during follow-up.

Minimum Value: 0 participants Maximum Value: Number of participants enrolled in the study Interpretation: Higher values indicate a greater need for additional interventions and may reflect reduced durability or effectiveness of the initial treatment.

Additional Analysis: Time to first repeat intervention (days) may also be recorded and analyzed as a secondary outcome.

Patient satisfaction will be assessed using the Client Satisfaction Questionnaire (CSQ-8), a validated 8-item patient-reported outcome measure evaluating satisfaction with treatment, services received, and overall care experience. Total scores range from 8 to 32, with higher scores indicating greater satisfaction with treatment outcomes and care.

Scale Information:

Client Satisfaction Questionnaire (CSQ-8) Minimum Value: 8 Maximum Value: 32 Interpretation: Higher scores indicate greater patient satisfaction and better perceived treatment outcomes.

Neuroma size will be assessed using high-resolution ultrasound. The maximum neuroma diameter will be measured in the longitudinal or transverse plane and recorded in millimeters (mm). The largest measured diameter will be used for analysis.

Unit of Measure:

Millimeters (mm)

Minimum Value:

0 mm

Maximum Value:

No predefined maximum value Interpretation: Higher values indicate larger neuroma size and greater structural abnormality.