Doxepin Alone or Combined With Ramelteon Versus Placebo for Improving Sleep Quality After Primary Total Knee Arthroplasty

Insomnia Severity Index (ISI) The Insomnia Severity Index is a 7-item self-reported questionnaire assessing the nature, severity, and impact of insomnia.

• Score range: 0 to 28
• Interpretation: Higher scores indicate worse insomnia severity

Score categories:

• 0-7: No clinically significant insomnia
• 8-14: Subthreshold insomnia
• 15-21: Clinical insomnia (moderate severity)
• 22-28: Clinical insomnia (severe)

Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS):

The KOOS-PS is a 7-item patient-reported outcome measure assessing knee-related physical function, including activities such as rising from bed, putting on socks, rising from sitting, bending to the floor, twisting/pivoting, kneeling, and squatting . Each item is scored on a 5-point Likert scale (None to Extreme). Scores are transformed to a normalized scale ranging from 0 to 100, with higher scores indicating worse physical function (greater disability).

Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR):

The KOOS-JR is a patient-reported outcome measure assessing knee pain, stiffness, and functional limitations during activities of daily living over the past week, including tasks such as twisting/pivoting, stair navigation, standing, rising from sitting, and bending . The instrument consists of 7 items scored on a 5-point Likert scale (None to Extreme). Raw scores (range 0-28) are summed and converted to an interval score ranging from 0 to 100, where 0 represents total knee disability and 100 represents perfect knee health (higher scores indicate better outcomes)

Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10):

The PROMIS-10 is a 10-item patient-reported outcome measure assessing global physical health, mental health, pain, fatigue, and social functioning. Items are scored on 5-point Likert scales (e.g., Excellent to Poor; Not at all to Very much), with one pain item scored from 0 to 10. Raw scores are summed and converted to standardized T-scores for Global Physical Health and Global Mental Health, each ranging approximately from 0 to 100 (mean 50, standard deviation 10), where higher scores indicate better health status

Hospital readmission status within 90 days following primary total knee arthroplasty, defined as any unplanned inpatient admission to a hospital occurring within 90 days after the index procedure. This is a dichotomous outcome (Yes/No), where "Yes" indicates that a readmission occurred and represents a worse outcome.

Medication Compliance:

Medication adherence assessed using patient self-report and pill counts when feasible. Self-reported adherence is measured by patient-reported proportion of prescribed doses taken, and pill counts are used to calculate the percentage of medication consumed relative to the prescribed amount. Adherence is expressed as a percentage from 0 to 100%, where higher values indicate better compliance.

Length of Stay (LOS):

Length of hospital stay following primary total knee arthroplasty, defined as the number of days from hospital admission to discharge (continuous variable, ≥0 days), where higher values indicate longer hospitalization (worse outcome).

Discharge Destination:

Discharge disposition following primary total knee arthroplasty, categorized as home versus skilled nursing facility. This is a categorical outcome where discharge to a skilled nursing facility represents a worse outcome compared to discharge home.

Postoperative Mobility (Step Count):

Postoperative mobility assessed by the number of steps taken during inpatient physical therapy sessions following primary total knee arthroplasty. Step count is recorded as the total number of steps ambulated (continuous variable, ≥0), where higher values indicate better functional recovery.

Level of Assistance Required for Ambulation:

Level of assistance required during inpatient physical therapy following primary total knee arthroplasty, categorized as independent, 1-person assist, 2-person assist, or maximal assist. This is an ordinal outcome where greater assistance requirements indicate worse functional recovery.

Postoperative Falls: Occurrence of patient falls during hospitalization or within the follow-up period after primary total knee arthroplasty, defined as any unintentional descent to the ground or lower level documented in the medical record. This is a dichotomous outcome (Yes/No), where "Yes" indicates a fall occurred and represents a worse outcome.

Occurrence of delirium during hospitalization or follow-up after primary total knee arthroplasty, defined by clinical documentation of acute confusional state or use of delirium-related precautions (e.g., 1:1 sitter, physical restraints). This is a dichotomous outcome (Yes/No), where "Yes" indicates delirium occurred and represents a worse outcome.

Pressure Ulcers (Bed Sores):

Development of pressure ulcers during hospitalization or follow-up after primary total knee arthroplasty, defined as localized injury to the skin or underlying tissue documented in the medical record. This is a dichotomous outcome (Yes/No), where "Yes" indicates a pressure ulcer occurred and represents a worse outcome.

Postoperative Opioid Consumption (Morphine Milligram Equivalents):

Total postoperative opioid use following primary total knee arthroplasty, calculated as cumulative morphine milligram equivalents (MME) administered during hospitalization and follow-up. This is a continuous variable (≥0 mg), where higher values indicate greater opioid consumption (worse outcome).

Postoperative Medical Complications:

Occurrence of medical complications following primary total knee arthroplasty, including myocardial infarction, venous thromboembolism, cerebrovascular accident, acute kidney injury, respiratory failure, urinary tract infection, pneumonia, gastrointestinal obstruction, and need for intensive care unit (ICU) admission during the same hospitalization. This is a composite dichotomous outcome (Yes/No), where "Yes" indicates that one or more complications occurred and represents a worse outcome.

Occurrence of surgical complications following primary total knee arthroplasty, including reoperation, periprosthetic fracture, dislocation, infection, and postoperative stiffness. This is a composite dichotomous outcome (Yes/No), where "Yes" indicates that one or more complications occurred and represents a worse outcome.