Periodic limb movements of sleep: empirical and theoretical evidence supporting objective at-home monitoring

Figures & data

Table 1 Costs, effectiveness, and probability-based values

Variables	Definition	Value	Comments	References
cHD	Cost of home device	$100 (USD)	Estimated	–
cCT	Cost of clinical tool	$10 (USD)	Estimated	–
cPSG	Cost of polysomnography	$800 (USD)		Pietzsch et al^Citation71
cRx	Cost of treatment	$485 (USD/year)	Based on Rx for RLS	Meyers et al^Citation72
cCL	Cost of clinic visits	$180 (USD/year)	Assumed two visits per year, each $90 (USD)	–
cCV	Cost of a cardiovascular or cerebrovascular event	$17,764.50 (USD)	On average, based on a one-time event	Pietzsch et al^Citation72
eCV	QALY after cardiovascular or cerebrovascular event	0.84	–	Sullivan and Ghushchyan^Citation37; Pietzsch et al^Citation72
Sensitivity HD	–	0.88	–	Plante^Citation39
Specificity HD	–	0.76	–	Plante^Citation39
Sensitivity PSG	–	0.90	–	Plante^Citation39
Specificity PSG	–	0.95	–	Plante^Citation39
Sensitivity CT	–	0.65	Estimate from OR	Current study
Specificity CT	–	0.65	Estimate from OR	Current study
Prev	Prevalence of PLMS	0.039	–	Ohayon and Roth^Citation47
pAcceptRx	Probability of accepting treatment	0.9	Estimate	–
pCV_pos	Risk of a cardiovascular or cerebrovascular event	0.0285	–	Pietzsch et al^Citation72
pDie_Natural	Risk of death other than from a cerebrovascular event	0.0053	–	Pietzsch et al^Citation72
pDie_Cerebrovascular	Risk of dying from a cardiovascular or cerebrovascular event	0.1663	–	Pietzsch et al^Citation72
A	Increasing factor due to having PLMS	1.50	Estimate	–
B	Decreasing factor due to Rx for PLMS	0.50	Estimate	–
g	Increasing factor due to having had a cardiovascular or cerebrovascular event	1.50	Estimate	–

Note: –, Not applicable.

Abbreviations: RLS, restless legs syndrome; QALY, quality-adjusted life-year; OR, odds ratio; PLMS, periodic limb movements of sleep; HD, home device; PSG, polysomnography; CT, clinical tool; eCV, quality of life after a CV event; CHD, cost of home device; cCT, cost of clinical tool; cPSG, cost of PSG; cRx, cost of treatment; cCL, cost of clinic visits; cCV, cost of CV event.

Table 2 Baseline PSG characteristics by OSA status

Variables	AHI <5 and RDI <10 (No-OSA)	AHI ≥5 (Dx-OSA)
TST (min)	371.48 (72.74)	372.41 (58.23)
Eff (%)	88.44 (60.50)	84.36 (11.93)
N1 (min)	43.05 (27.59)	66.13 (39.74)
N1 (%)	14.50 (31.98)	18.64 (12.73)
N2 (min)	195.60 (55.16)	206.55 (57.24)
N2 (%)	52.80 (11.14)	55.02 (11.44)
N3 (min)	69.58 (42.62)	47.51 (36.99)
N3 (%)	18.50 (10.81)	12.64 (9.72)
REM (min)	63.74 (33.06)	52.22 (29.97)
REM (%)	18.60 (30.53)	13.70 (7.15)
AHI (h^−1)	1.42 (1.31)	17.29 (14.05)*
RDI (h^−1)	4.30 (2.70)	30.44 (16.45)*
PLMI (h^−1)	14.16 (28.92)	13.67 (21.80)
LMAI (h^−1)	4.50 (11.93)	2.91 (4.83)

Notes: Values are mean (SD).

* P<0.05, nonparametric rank test.

Abbreviations: PSG, polysomnography; OSA, obstructive sleep apnea; AHI, apnea–hypopnea index; RDI, respiratory disturbance index; TST, total sleep time; Eff, sleep efficiency (%); PLMI, periodic limb movements index; LMAI, limb movements arousal index; min, minute; h, hour; SD, standard deviation; REM, rapid eye movement sleep.

Table 3 Demographic and objective characteristics by OSA status

Variables	AHI <5 and RDI <10 (No-OSA, n=209)	AHI ≥5 (Dx-OSA, n=443)	Test results
			Wilcoxon rank-sum (P-value)	χ^2 test
Age, years	43	55	<0.0001	–
BMI	28	31	<0.0001	–
ESS	7	7	0.36	–
PLMI	4.10	3.90	0.88	–
LMAI	1.10	1.10	0.89	–
Sex, male	36.4%	57.1%	–	24.45*
Leg jerks in sleep	13.4%	12.9%	–	0.04
Smoking	10.5%	8.4%	–	0.82
Psych meds	38.3%	27.8%	–	7.32*
Sleeping pills	37.3%	21.4%	–	18.36*
RLS/PLMS meds	8.6%	5.6%	–	2.03
Stimulants	10.5%	3.2%	–	14.77*
HTNa	31.1%	65.5%	–	67.60*
RLSb	25.8%	25.3%	–	0.02
Caffeinec	64.6%	76.5%	–	10.18*

Notes: Categorical variable data are percentages of affirmative characteristic. Age, BMI, ESS, PLMI, and LMAI are median values. –, Not applicable.

a Either self-reported HTN or listed anti-HTN medication.

b Any RLS symptom.

c Any caffeine intake.

* P-values <0.01. Bold values are statistically significant.

Abbreviations: OSA, obstructive sleep apnea; AHI, apnea–hypopnea index; RDI, respiratory disturbance index; BMI, body mass index; PLMI, periodic limb movement index; LMAI, limb movement arousal index; Psych meds; psychiatric medications; RLS, restless legs symptoms; PLMS, periodic limb movements of sleep; meds, medications; HTN, hypertension; ESS, Epworth Sleepiness Score.

Figure 1 The distribution of PLMI values (x-axis) is given as a cumulative fraction (y-axis) for OSA patients who underwent two PSG nights.

Notes: The vertical gray line indicates PLMI =15 for reference.
Abbreviations: PLMI, periodic limb movement index; OSA, obstructive sleep apnea; PSG, polysomnography; h, hour.

Table 4 Odds ratios values for significant predictors of PLMI ≥15

Variables	No-OSA			Dx-OSA
	OR	Lower 95% CI	Upper 95% CI	OR	Lower 95% CI	Upper 95% CI
Age	1.03	1.01	1.05	1.09	1.06	1.14
Sex	2.35	1.19	4.63	1.86	1.16	2.99
RLS	2.31	1.13	4.72	–	–	–
Psych meds	–	–	–	1.93	1.18	3.17
ESS	–	–	–	1.28	1.04	1.58
Age × ESS	–	–	–	0.996	0.992	0.999

Note: –, Not significant predictors.

Abbreviations: PLMI, periodic limb movement index; OSA, obstructive sleep apnea; OR, odds ratio; CI, confidence interval; RLS, restless legs syndrome; Psych meds; psychiatric medications; ESS, Epworth Sleepiness Score.

Figure 2 Structure of the decision model.

Notes: The schematic shows four strategies to approach occult elevation of PLMI. The first branch strategy is to conduct in-laboratory PSG for everyone (PSG all). Within that approach, those with elevated PLMI will have the chance to receive treatment. The next strategy utilizes a prescreen of a clinical tool, based on clinical history, to risk stratify those who should undergo PSG. Again, those testing positive on PSG will have the chance to receive treatment. The third strategy is to perform home testing using a portable device, and those testing positive in that setting can proceed to treatment (no PSG in this arm). Finally, we included a reference strategy with no testing or treatment for anyone (do-nothing arm). Within each of these arms, a Markov node is placed to allow recurrent annual risk of cardiovascular or cerebrovascular event as well as a low probability of death, to occur. For convenience, these states are shown only for one branch (dotted lines).
Abbreviations: PLMI, periodic limb movement index; PSG, polysomnography; PLMS, periodic limb movements of sleep; CT, clinical tool; HD, home device; M, markov node.

Figure 3 Sensitivity analysis.

Notes: We performed sensitivity analysis on home device accuracy (sensitivity and specificity, on the x and y axes of each plot), across two costs of home device testing per person ($0 and $100) and a range of prevalence of elevated PLMI (rows). Willingness to pay was $50,000 in all cases. Two strategies were never favored in this modeling: clinical tool and PSG for everyone. The red and blue regions indicate parameter space when the preferred choice is the home device arm versus the do-nothing arm, respectively.
Abbreviations: PLMI, periodic limb movement index; PSG, polysomnography; cHD, cost for home device; Sens, sensitivity; Spec, specificity; Prev, prevalence.

Table S1 Assessment of PLMI and LMAI per categorical variable

Variables	No-OSA		Dx-OSA		Rx-OSA
	PLMI	LMAI	PLMI	LMAI	PLMI	LMAI
Sex
Female	3.40	0.90	3.60	1.20	4.55	1.30
Male	5.60*	1.40	4.40	1.00	10.60**	2.30*
Leg jerk
Yes	8.60**	2.80*	7.60	1.50	–	–
No	3.50	1.00	3.70	1.00	–	–
Smoking
Yes	4.75	1.10	4.70	1.10	–	–
No	4.10	1.10	3.90	1.05	–	–
Psych meds
Yes	6.05	1.45	6.00*	1.30	–	–
No	2.80	1.00	3.60	1.00	–	–
Sleeping pills
Yes	5.25	1.20	4.00	0.90	–	–
No	3.50	1.10	3.85	1.25	–	–
RLS/PLMS meds
Yes	6.25	1.30	3.30	0.60	–	–
No	4.00	1.10	3.95	1.10	–	–
Stimulants
Yes	6.60	1.85	3.40	0.75	–	–
No	3.60	1.00	3.90	1.10	–	–
HTNa
Yes	6.50*	0.90	5.00	1.30	–	–
No	3.65	1.20	3.30	1.00	–	–
RLSb
Yes	6.20**	1.90*	5.65	1.10	–	–
No	3.50	1.00	3.70	1.00	–	–
Caffeinec
Yes	3.50	1.00	4.10	1.00	–	–
No	5.40	1.45	3.60	1.35	–	–

Notes: PLMI and LMAI are median values. P-values are via Wilcoxon rank sum test and are not corrected for multiple comparisons. –, Information was derived from questionnaires given at diagnostic PSG nights only.

a Either self-reported HTN or listed anti-HTN medication.

b Any RLS symptom.

c Any caffeine intake.

* P-values between 0.01 and 0.05.

** P-values <0.01.

Abbreviations: PLMI, periodic limb movement index; LMAI, limb movement arousal index; OSA, obstructive sleep apnea; Psych meds; psychiatric medications; RLS, restless legs syndrome; PLMS, periodic limb movements of sleep; meds, medications; HTN, hypertension.

Table S2 Spearman’s correlation analysis for PLMI and LMAI per OSA status

Variables	No-OSA						Dx-OSA
	PLMI			LMAI			PLMI			LMAI
	r	95% CI		r	95% CI		r	95% CI		r	95% CI
Age	0.25**	0.12	0.37	0.16*	0.03	0.29	0.27**	0.19	0.36	0.23**	0.13	0.31
Sex	0.14*	0.01	0.27	0.09	−0.04	0.23	0.06	−0.03	0.16	−0.05	−0.14	0.05
ESS	0.04	−0.09	0.17	0.09	−0.04	0.22	−0.02	−0.11	0.07	−0.002	−0.09	0.09
BMI	−0.02	−0.15	0.12	−0.08	−0.21	0.06	−0.03	−0.12	0.06	−0.02	−0.11	0.07
Leg jerks	0.21**	0.08	0.34	0.17*	0.03	0.29	0.07	−0.03	0.16	0.05	−0.05	0.14
Smoking	−0.008	−0.14	0.13	−0.02	−0.16	0.12	−0.004	−0.09	0.09	−0.02	−0.11	0.07
Psych meds	0.11	−0.02	0.25	0.11	−0.03	0.24	0.09*	0.003	0.19	0.06	−0.03	0.15
Sleeping pills	−0.02	−0.15	0.11	−0.05	−0.18	0.09	0.02	−0.08	0.11	−0.03	−0.13	0.06
RLS/PLMS meds	0.03	−0.10	0.17	−0.002	−0.14	0.13	0.01	−0.08	0.11	−0.02	−0.11	0.08
Stimulant	0.09	−0.04	0.23	0.05	−0.09	0.18	−0.01	−0.09	0.08	0.01	−0.08	0.11
HTNa	0.15*	0.01	0.28	0.05	−0.09	0.18	0.07	−0.02	0.17	0.06	−0.03	0.15
RLSb	0.20**	0.07	0.33	0.14*	0.002	0.27	0.05	−0.04	0.14	0.03	−0.06	0.12
Caffeinec	−0.06	−0.19	0.08	−0.08	−0.21	0.06	0.02	−0.07	0.11	−0.05	−0.14	0.04

Notes:

a Either self-reported HTN or listed anti-HTN medication.

b Any RLS symptom.

c Any caffeine intake.

* P-values between 0.01 and 0.05.

** P-values <0.01.

Abbreviations: PLMI, periodic limb movement index; LMAI, limb movement arousal index; OSA, obstructive sleep apnea; CI, confidence interval; BMI, body mass index; Psych meds; psychiatric medications; RLS, restless legs syndrome; PLMS, periodic limb movements of sleep; meds, medications; HTN, hypertension.

Table S3 Spearman’s correlation analyses for age with multiple covariates

Variables	No-OSA				Dx-OSA
	r	P–value (α=0.05)	Lower 95% CI	Upper 95% CI	r	P-value (α=0.05)	Lower 95% CI	Upper 95% CI
Sex	−0.02	0.79	−0.15	0.12	−0.04	0.40	−0.13	0.05
ESS	−0.05	0.49	−0.19	0.09	−0.14	0.002	−0.23	−0.05
BMI	0.10	0.14	−0.03	0.23	−0.22	<0.0001	−0.31	−0.13
Leg jerks	0.08	0.26	−0.06	0.21	−0.01	0.82	−0.10	0.08
Smoking	0.03	0.64	−0.10	0.17	−0.03	0.55	−0.12	0.07
Psych meds	0.08	0.28	−0.06	0.21	0.03	0.59	−0.07	0.12
Sleeping pills	0.04	0.52	−0.09	0.18	0.02	0.67	−0.07	0.11
RLS/PLMS meds	0.17	0.01	0.04	0.31	0.03	0.54	−0.06	0.12
Stimulant	−0.11	0.12	−0.24	0.03	−0.04	0.36	−0.14	0.05
HTNa	0.32	<0.0001	0.19	0.43	0.18	0.0001	0.09	0.27
RLSb	0.16	0.02	0.02	0.29	−0.02	0.66	−0.11	0.07
Caffeinec	0.12	0.08	−0.01	0.26	0.06	0.25	−0.04	0.15

Notes:

a Either self-reported HTN or listed anti-HTN medication.

b Any RLS symptom.

c Any caffeine intake. Bold values indicate statistical significance, P<0.05.

Abbreviations: OSA, obstructive sleep apnea; CI, confidence interval; BMI, body mass index; Psych meds; psychiatric medications; RLS, restless legs syndrome; PLMS, periodic limb movements of sleep; meds, medications; HTN, hypertension.

Table S4 Spearman’s correlation analyses for sex with multiple covariates (M=1, F=0)

Variables	No-OSA				Dx-OSA
	r	P-value (α=0.05)	Lower 95% CI	Upper 95% CI	r	P-value (α=0.05)	Lower 95% CI	Upper 95% CI
ESS	−0.03	0.65	−0.17	0.10	–0.02	0.67	−0.11	0.07
BMI	−0.14	0.05	−0.27	−0.001	–0.21	<0.0001	−0.29	−0.11
Leg jerks	0.08	0.24	−0.05	0.22	–0.09	0.06	−0.18	0.004
Smoking	0.03	0.64	−0.10	0.17	0.05	0.32	−0.05	0.14
Psych meds	−0.12	0.07	−0.26	0.01	–0.15	0.002	−0.23	−0.05
Sleeping pills	−0.09	0.19	−0.22	0.05	–0.04	0.45	−0.13	0.06
RLS/PLMS meds	−0.13	0.06	−0.26	0.01	0.03	0.48	−0.06	0.13
Stimulant	−0.03	0.64	−0.17	0.10	0.03	0.58	−0.07	0.12
HTNa	−0.01	0.84	−0.15	0.12	–0.04	0.35	−0.14	0.05
RLSb	0.01	0.91	−0.13	0.14	–0.12	0.02	−0.21	0.02
Caffeinec	–0.002	0.98	−0.14	0.13	–0.02	0.72	−0.11	0.08

Notes:

a Either self-reported HTN or listed anti-HTN medication.

b Any RLS symptom.

c Any caffeine intake. Bold data represent significant P values.

Abbreviations: OSA, obstructive sleep apnea; CI, confidence interval; BMI, body mass index; Psych meds; psychiatric medications; RLS, restless legs syndrome; PLMS, periodic limb movements of sleep; meds, medications; M, male; F, female; HTN, hypertension.

Table S5 Spearman’s correlation analyses for BMI with multiple covariates

Variables	No-OSA				Dx-OSA
	r	P-value (α=0.05)	Lower 95% CI	Upper 95% CI	r	P-value (α=0.05)	Lower 95% CI	Upper 95% CI
ESS	−0.02	0.78	−0.15	0.12	0.01	0.77	−0.08	0.11
Leg jerks	−0.11	0.11	−0.24	0.02	0.02	0.62	−0.07	0.12
Smoking	0.08	0.25	−0.06	0.22	−0.02	0.68	−0.11	0.07
Psych meds	0.04	0.53	−0.09	0.18	0.07	0.14	−0.02	0.16
Sleeping pills	0.08	0.25	−0.06	0.21	−0.04	0.43	−0.13	0.06
RLS/PLMS meds	0.03	0.67	−0.11	0.16	0.08	0.09	−0.01	0.17
Stimulant	−0.01	0.92	−0.14	0.13	0.02	0.62	−0.07	0.12
HTNa	0.17	0.02	0.03	0.29	0.04	0.38	−0.052	0.13
RLSb	0.01	0.89	−0.13	0.15	0.13	0.01	0.04	0.22
Caffeinec	0.01	0.83	−0.12	0.15	0.08	0.08	−0.01	0.17

Notes:

a Either self-reported HTN or listed anti-HTN medication.

b Any RLS symptom.

c Any caffeine intake. Bold data represent significant P values.

Abbreviations: BMI, body mass index; OSA, obstructive sleep apnea; CI, confidence interval; Psych meds; psychiatric medications; RLS, restless legs syndrome; PLMS, periodic limb movements of sleep; meds, medications; HTN, hypertension.

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