Introduction

Methods

Survey 1: Patient Satisfaction

The primary objective of Survey 1 (Table 1) was to evaluate overall patient satisfaction scores on a weekly basis during the trial. Each question was answered using the following ordinal scoring system: “Strongly Disagree” = 1, “Disagree” = 2, “Neutral” = 3, “Agree” = 4, and “Strongly Agree” = 5. Simple descriptive statistics were calculated for individual scores at each timepoint, including median and interquartile ranges (IQR). A composite score of all questions using the pooled median value of patient-specific survey questions was also generated and compared between patient visits. Additionally, for in-text summaries, scores were trichotomized as ≥4 (positive), 3 (neutral), and <2 (negative). For trichotomized scores, counts and percentage of total were calculated. Friedman’s test was used to determine if ordinal response scores significantly changed over time from week 1 to week 4. Box and whisker plots were generated in order to visually show overall and patient-specific results across timepoints.

Table 1. Questions from Survey 1.

Table 1. Questions from Survey 1.

Question	Description
Q1	My Memory is better
Q2	I’m more relaxed
Q3	My thoughts are more positive
Q4	It’s easier to concentrate
Q5	I’m less irritable
Q6	I feel better about myself
Q7	My thinking ability is better
Q8	I’m using less alcohol and/or drugs
Q9	I look forward to and enjoy using the device
Q10	My PTSD Symptoms are reduced
Q11	I would like to keep the device

Survey 2: Severity of PTSD symptoms

The primary objective Survey 2 (Table 2) was to evaluate change from baseline severity of posttraumatic stress symptoms. Survey 2 was based on the National Stressful Events Survey PTSD Short Scale (NSESSS) and was administered at baseline and at week 4 after consistent use of the device. Each question was answered using the following ordinal scoring system: “Not At All” = 0, “A Little Bit” = 1, “Moderately” = 2, “Quite a Bit” = 3, and “Extremely” = 4.

Table 2. Questions from Survey 2.

Table 2. Questions from Survey 2.

Question	Description
Q1	Having "flashbacks", that is, you suddenly acted or felt as if a stressful experience from the past was happening all over again (for example, you re-experienced parts of a stressful experience by seeing, hearing, smelling, or physically feeling parts of the experience)?
Q2	Feeling very emotionally upset when something reminded you of a stressful experience?
Q3	Trying to avoid thoughts, feelings, or physical sensations that reminded you of a stressful experience?
Q4	Thinking that a stressful event happened because you or someone else (who didn't directly harm you) did something wrong or didn't do everything possible to prevent it, or because of something about you?
Q5	Having a very negative emotional state (for example, you were experiencing lots of fear, anger, guilt, shame, or horror) after a stressful experience?
Q6	Losing interest in activities you used to enjoy before having a stressful experience?
Q7	Being "super alert," on guard, or constantly on the lookout for danger?
Q8	Feeling jumpy or easily startled when you hear an unexpected noise?
Q9	Being extremely irritable or angry to the point where you yelled at other people, got into fights, or destroyed things?

We assessed changes in ordinal response scores from patient-specific matched pairs using Wilcoxon’s signed-rank test to determine if there were significant improvements from baseline to week 4. A composite score of all questions using the pooled median value of patient-specific survey questions was also generated and compared between baseline and week 4. Effect sizes from Wilcoxon’s signed rank tests were reported as the median of differences alongside approximates of the 95% confidence interval. Since this nonparametric test works with ranks, it is typically not possible to derive a confidence interval with exactly 95% confidence; instead, the closest approximate was calculated, corresponding to true CIs calculated with 96.88% confidence; for simplicity these are reported as 95% CIs in text.

To formally analyze overall cumulative probability of improved scores across measurement times, we employed a Cumulative Link Mixed Model (CLMM) with a logit link function. The model was specified with the following formula using the clmm() function in the ‘ordinal’ package for R: Score ~ Visit + (1 | Subject), where, ‘Score’ represents individual ordinal-scale responses, ‘Visit’ is the predictor variable of interest (baseline or week 4), and ‘(1 | Subject)’ indicates the inclusion of random intercepts for individual subjects to account for within-subject variability. Laplace approximation was employed to estimate the model parameters due to its suitability for handling ordinal response data. Predicted probabilities and 95% CIs for each score at a given timepoint were extracted from the model. Overall effect sizes from the CLMM model are reported as cumulative odds ratios.

Simple descriptive statistics were also calculated, including median and IQRs. Additionally, for in-text summaries, scores were dichotomized as ≤1 (positive) or >1 (negative). Box and whisker plots were generated in order to visually show overall and patient-specific results across timepoints.

Results

Survey 1

By week 4, all six patients (100%) had positive scores (scores 4 and 5) for feelings of relaxation (Q2), positive thoughts (Q3), enjoying using the device (Q9), and wanting to keep the device (Q11). Regarding feeling better about oneself (Q6) and reduction in PTSD symptoms (Q10), 5 out 6 patients (83%) showed positive scores. Regarding memory (Q1), concentration (Q4), and irritability (Q5), 4 patients (67%) had positive scores. Half of the patients had improved thinking ability (Q7). Patients exhibited the lowest scores regarding using less alcohol and/or drugs (Q8), with 2 out 6 (33%) having positive scores, and the remaining had neutral scores. Of note, no individual patient reported scores of 1 or 2 for any of the questions by week 4, suggesting that no patients disagreed with improved satisfaction scores, and either felt improved or at least neutral.

The pooled median score by week 4 was 4 (IQR: 4-4), and ranged from 3 to 5, suggesting a typically positive outcome and significantly improved overall score over time (p < 0.001). (Table 3). The question that had the largest upward trend from week 1 was regarding improved memory (Q1), showing a statistically significant improvement by week 4 (p < 0.001). Other individual questions did not demonstrate significant time-dependent improvements. Patients had the lowest upward trend regarding thinking ability (Q7) and use of drugs/alcohol (Q8), exhibiting slight, albeit not significant, reductions in score on week 4 compared to week 1.

Table 3. Summary of Survey 1 results across timepoints.

Table 3. Summary of Survey 1 results across timepoints.

Survey Question	Week 1 Median (IQR)	Week 2 Median (IQR)	Week 3 Median (IQR)	Week 4 Median (IQR)	P-value for time-dependent trend of improvement
Q1	3 (2 – 3)	3 (2.75 – 3)	3.5 (3 – 4)	4 (3 – 4)	0.007
Q2	4 (3.5 – 4)	4.5 (3.75 – 5)	4 (4 – 4)	4 (4 – 5)	0.266
Q3	3.5 (3 – 4)	4 (4 – 4)	4 (3 – 4)	4 (4 – 4)	0.125
Q4	3 (3 – 4)	3 (3 – 4)	3 (3 – 4)	4 (3 – 4.25)	0.561
Q5	3.5 (2.75 – 4)	4 (3 – 4)	3.5 (3 – 4)	4 (3 – 4.25)	0.438
Q6	3 (3 – 4)	3 (3 – 4)	4 (3.75 – 4)	4 (3.75 – 4.25)	0.146
Q7	4 (3 – 4)	3 (3 – 4)	3 (3 – 4)	3.5 (3 – 4)	0.719
Q8	3.5 (3 – 4)	3 (3 – 3.25)	3 (3 – 4)	3 (3 – 4)	0.917
Q9	4 (3.5 – 4.25)	5 (3.5 – 5)	4 (3.75 – 4.25)	4 (4 – 5)	0.305
Q10	3 (2.75 – 4)	4 (4 – 4)	4 (3.75 – 4)	4 (3.75 – 4)	0.133
Q11	4 (3.75 – 4)	4 (4 – 5)	4 (4 – 4.25)	4 (4 – 5)	0.333
Overall*	4 (3 – 4)	4 (3 – 4)	4 (3 – 4)	4 (4 – 4)	<0.001

*Overall scores correspond to pooled median value from patient-specific questions.

Survey 2

By week 4, all six patients (100%) had positive scores (0 and 1) for having flashbacks (Q1) and negative emotional state (Q5). Regarding stressful events (Q4), losing interest in activities (Q6), being super alert (Q7), being easily startled (Q8), and being irritable or angry (Q9), 5 out 6 (83%) had positive scores, while 1 patient had moderate severity. No individual patient reported adverse scores of 3 or 4, suggesting no severe symptoms by week 4 (Table 4).

Table 4. Summary of Survey 2 questions at baseline and at week 4.

Table 4. Summary of Survey 2 questions at baseline and at week 4.

Survey Question	Baseline Median (IQR)	Week 4 Median (IQR)	Median of differences [95% CI]	p-value
Q1	2 (0.75 – 2.25)	0 (0 – 1)	-1 [-3; 0]	0.063
Q2	3 (1.75 – 4)	0 (0.75 – 2)	-1.5 [-3; -1]	0.031
Q3	4 (1.75 – 4)	1 (0.75 – 1.5)	-2.5 [-3; 0]	0.063
Q4	2 (0 – 2.5)	0 (0 – 1.25)	-1 [-4; 1]	0.250
Q5	4 (2.5 – 4)	0.25 (0 – 1)	-3.25 [-4; 0]	0.063
Q6	3.5 (0.75 – 4)	0.5 (0 – 1.25)	-2 [-4; 0]	0.063
Q7	4 (3.75 – 4)	1 (0.75 – 1.25)	-3 [-3; -2]	0.031
Q8	4 (2.5 – 4)	1 (0.75 – 1.25)	-2.5 [-3; -1]	0.031
Q9	2.5 (0.75 – 3.25)	0.5 (0 – 1.25)	-2 [-2; 0]	0.063
Overall*	3 (2 – 4)	1 (0 – 1)	-2 [-3; -2]	<0.001

*Overall scores correspond to pooled median value from patient-specific questions.

Of the individual survey questions, patients had statistically significant improvements regarding feelings of being emotionally upset (Q2: MD = -1.5, p = 0.031) and being overly alert (Q7: MD = -3, p = 0.031; Table 5). Although not statistically significant for all individual questions, all patients uniformly had numerically improved scores by week 4. The composite score was substantially improved from baseline, with an overall median score of 3 (IQR: 2 – 4) at baseline to 1 (IQR: 0 – 1) by week 4 (MD = -2 [95% CI: -3; -2], p < 0.001). Overall, the predicted probability of obtaining the best outcome (score=0) was 2% at baseline vs. 43% by week 4. Conversely, the predicted probability of obtaining the worst outcome (score=4) was 39% at baseline vs. 2% at week 4. The overall cumulative odds ratio was 38.2 (p < 0.001), suggesting that on average, the odds of moving from one score to a lower (improved) score at week 4 compared to the baseline are 38.2 times higher. The significant decrease in symptoms based on Survey 2 over time is illustrated in Figure 1.

Table 5. Cumulative link mixed model results of overall improvement in PTSD symptoms.

Table 5. Cumulative link mixed model results of overall improvement in PTSD symptoms.

Survey Score	Baseline Probability [95% CI]	Week 4 probability [95% CI]	Cumulative odds ratio [95% CI]	P-value
Score 0	2% [0 – 5%]	43% [13 – 74%]	38.2 [13.8 – 105.5]	<0.001
Score 1	13% [0 – 27%]	43% [24 – 63%]
Score 2	28% [10 – 47%]	10% [0 – 21%]
Score 3	18% [6 – 29%]	2% [0 – 4%]
Score 4	39% [9 – 68%]	2% [0 – 4%]

Figure 1. Illustration of changes in PTSD symptom severity in 6 patients over the course of the study.

Figure 1. Illustration of changes in PTSD symptom severity in 6 patients over the course of the study.

Discussion

Limitations

Conclusions

References

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