Impact of obstructive sleep apnoea on cognitive function in multiple sclerosis: A longitudinal study.

Cognitive impairment (CI) and fatigue are common in people with multiple sclerosis (MS), with well-known profound effects on quality of life. Sleep disorders, including obstructive sleep apnoea (OSA), are also common in MS patients. The presence of CI has previously been shown to strongly correlate with OSA diagnosed using polysomnography in MS. Treatment of OSA has not previously been investigated as a potential modality to improve cognition in MS patients. Therefore, we sought to investigate the potential effects of OSA treatment on both cognitive function and fatigue in MS patients. Twenty-three participants with MS reporting significant fatigue were enrolled. CI was assessed by the Brief International Cognitive Assessment in MS and the 3-second Paced Auditory Serial Addition Test. All participants underwent overnight polysomnography to assess for possible OSA. Cognitive and fatigue measures were repeated in those subsequently treated for OSA and in a comparative untreated sample. Seven participants (30%) had a diagnosis of OSA based on an apnoea-hypopnea index greater than 5 per hour, with no correlation between the presence of CI and OSA. Verbal learning at follow-up assessment was seen to improve significantly in those treated for OSA, compared with those who were not treated for a sleep disorder. This small study demonstrates the potential for OSA treatment to improve verbal learning in people with MS, larger studies are indicated to further investigate the potential for cognitive and fatigue improvement in people with MS through treatment of comorbid OSA.

Estimation of respiration rate and sleeping position using a wearable accelerometer.

Wearable inertial sensors offer the possibility to monitor sleeping position and respiration rate during sleep, enabling a comfortable and low-cost method to remotely monitor patients. Novel methods to estimate respiration rate and position during sleep using accelerometer data are presented, with algorithm performance examined for two sensor locations, and accelerometer-derived respiration rate compared across sleeping positions. Eleven participants (9 male; aged: 47.82±14.14 years; BMI 30.9±5.27 kg/m2; AHI 5.77±4.18) undergoing a scheduled clinical polysomnography (PSG) wore a tri-axial accelerometer on their chest and upper abdomen. PSG cannula flow and position data were used as benchmark data for respiration rate (breaths per minute, bpm) and position. Sleeping position was classified using logistic regression, with features derived from filtered acceleration and orientation. Accelerometer-derived respiration rate was estimated for 30 s epochs using an adaptive peak detection algorithm which combined filtered acceleration and orientation data to identify individual breaths. Sensor-derived and PSG respiration rates were then compared. Mean absolute error (MAE) in respiration rate did not vary between sensor locations (abdomen: 1.67±0.37 bpm; chest: 1.89±0.53 bpm; p=0.52), while reduced MAE was observed when participants lay on their side (1.58±0.54 bpm) compared to supine (2.43±0.95 bpm), p<0.01. MAE was less than 2 bpm for 83.6% of all 30 s windows across all subjects. The position classifier distinguished supine and left/right with a ROC AUC of 0.87, and between left and right with a ROC AUC of 0.94. The proposed methods may enable a low-cost solution for in-home, long term sleeping posture and respiration monitoring.

Ambulatory detection of sleep apnea using a non-contact biomotion sensor.

The high prevalence of obstructive sleep apnea has led to increasing interest in ambulatory diagnosis. The SleepMinder™ (SM) is a novel non-contact device that employs radiofrequency wave technology to assess the breathing pattern, and thereby estimate obstructive sleep apnea severity. We assessed the performance of SleepMinder™ in the home diagnosis of obstructive sleep apnea. One-hundred and twenty-two subjects were prospectively recruited in two protocols, one from an unselected sleep clinic cohort (n = 67, mean age 51 years) and a second from a hypertension clinic cohort (n = 55, mean age 58 years). All underwent 7 consecutive nights of home monitoring (SMHOME ) with the SleepMinder™ as well as inpatient-attended polysomnography in the sleep clinic cohort or cardiorespiratory polygraphy in the hypertension clinic cohort with simultaneous SleepMinder™ recordings (SMLAB ). In the sleep clinic cohort, median SMHOME apnea-hypopnea index correlated significantly with polysomnography apnea-hypopnea index (r = .68; p < .001), and in the hypertension clinic cohort with polygraphy apnea-hypopnea index (r = .7; p < .001). The median SMHOME performance against polysomnography in the sleep clinic cohort showed a sensitivity and specificity of 72% and 94% for apnea-hypopnea index ≥ 15. Device performance was inferior in females. In the hypertension clinic cohort, SMHOME showed a 50% sensitivity and 72% specificity for apnea-hypopnea index ≥ 15. SleepMinder™ classified 92% of cases correctly or within one severity class of the polygraphy classification. Night-to-night variability in home testing was relatively high, especially at lower apnea-hypopnea index levels. We conclude that the SleepMinder™ device provides a useful ambulatory screening tool, especially in a population suspected of obstructive sleep apnea, and is most accurate in moderate-severe obstructive sleep apnea.

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 µg daily, or 25 µg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 µg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).

Physician's Prescribing Preference as an Instrumental Variable: Exploring Assumptions Using Survey Data.

BACKGROUND: Physician's prescribing preference is increasingly used as an instrumental variable in studies of therapeutic effects. However, differences in prescribing patterns among physicians may reflect differences in preferences or in case-mix. Furthermore, there is debate regarding the possible assumptions for point estimation using physician's preference as an instrument. METHODS: A survey was sent to general practitioners (GPs) in The Netherlands, the United Kingdom, New Zealand, Ireland, Switzerland, and Germany, asking whether they would prescribe levothyroxine to eight fictitious patients with subclinical hypothyroidism. We investigated (1) whether variation in physician's preference was observable and to what extent it was explained by characteristics of GPs and their patient populations and (2) whether the data were compatible with deterministic and stochastic monotonicity assumptions. RESULTS: Levothyroxine prescriptions varied substantially among the 526 responding GPs. Between-GP variance in levothyroxine prescriptions (logit scale) was 9.9 (95% confidence interval: 8.0, 12) in the initial mixed effects logistic model, 8.3 (6.7, 10) after adding a fixed effect for country and 8.2 (6.6, 10) after adding GP characteristics. The occurring prescription patterns falsified the deterministic monotonicity assumption. All cases in all countries were more likely to receive levothyroxine if a different case of the same GP received levothyroxine, which is compatible with the stochastic monotonicity assumption. The data were incompatible with this assumption for a different definition of the instrument. CONCLUSIONS: Our study supports the existence of physician's preference as a determinant in treatment decisions. Deterministic monotonicity will generally not be plausible for physician's preference as an instrument. Depending on the definition of the instrument, stochastic monotonicity may be plausible.

Isolated nocturnal hypertension and subclinical target organ damage: a systematic review of the literature.

Isolated nocturnal hypertension (INH) is associated with greater mortality and cardiovascular events. Subclinical target organ damage (TOD) is a prognostic marker for cardiovascular events. Our objective is to systematically summarize evidence on the association between INH and subclinical TOD. Observational population studies were considered. INH was defined as nighttime blood pressure (BP) ⩾120 and/or 70 mm Hg with daytime BP <135/85 mm Hg. We systematically searched Pubmed, EMBASE and the Cochrane Library. Abstracts were reviewed by two assessors. Potentially eligible articles were compared with inclusion criteria. The search yielded 954 titles, 13 abstracts were selected for review and four articles fulfilled inclusion criteria. INH was associated with higher ambulatory arterial stiffness index (0.4 unit vs. 0.35 unit, P<0.05), pulse wave velocity (16.2 m s(-1) vs. 14.7 m s(-1), P<0.05), central (140.4% vs. 134.0%, P<0.05) and peripheral (82.6% vs. 76.5%, P<0.01) augmentation index in a Chinese study. In the same population there was no association with left ventricular hypertrophy documented by electrocardiogram. INH was not associated with increased arterial stiffness or left venticular mass index in a Swedish study. An American study demonstrated higher left ventricular mass (152.46 g vs. 136.16 g, P=0.01) and greater odds of left ventricular hypertrophy (odds ratio 3.03, 95% confidence interval 1.02-9.05) in unadjusted analysis. There was no association with proteinuria. Evidence is inconclusive regarding the association between INH and subclinical TOD. Future research should focus on trying to elucidate the mechanisms that generate INH and contribute to the higher mortality associated with this BP pattern.

International variation in GP treatment strategies for subclinical hypothyroidism in older adults: a case-based survey.

BACKGROUND: There is limited evidence about the impact of treatment for subclinical hypothyroidism, especially among older people. AIM: To investigate the variation in GP treatment strategies for older patients with subclinical hypothyroidism depending on country and patient characteristics. DESIGN AND SETTING: Case-based survey of GPs in the Netherlands, Germany, England, Ireland, Switzerland, and New Zealand. METHOD: The treatment strategy of GPs (treatment yes/no, starting-dose thyroxine) was assessed for eight cases presenting a woman with subclinical hypothyroidism. The cases differed in the patient characteristics of age (70 versus 85 years), vitality status (vital versus vulnerable), and thyroid-stimulating hormone (TSH) concentration (6 versus 15 mU/L). RESULTS: A total of 526 GPs participated (the Netherlands n = 129, Germany n = 61, England n = 22, Ireland n = 21, Switzerland n = 262, New Zealand n = 31; overall response 19%). Across countries, differences in treatment strategy were observed. GPs from the Netherlands (mean treatment percentage 34%), England (40%), and New Zealand (39%) were less inclined to start treatment than GPs in Germany (73%), Ireland (62%), and Switzerland (52%) (P = 0.05). Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old females (pooled odds ratio [OR] 0.74 [95% confidence interval [CI] = 0.63 to 0.87]). Females with a TSH of 15 mU/L were more likely to get treated than those with a TSH of 6 mU/L (pooled OR 9.49 [95% CI = 5.81 to 15.5]). CONCLUSION: GP treatment strategies of older people with subclinical hypothyroidism vary largely by country and patient characteristics. This variation underlines the need for a new generation of international guidelines based on the outcomes of randomised clinical trials set within primary care.

Cross-cultural validity of the thyroid-specific quality-of-life patient-reported outcome measure, ThyPRO.

BACKGROUND AND PURPOSE: Thyroid diseases are common and often affect quality of life (QoL). No cross-culturally validated patient-reported outcome measuring thyroid-related QoL is available. The purpose of the present study was to test the cross-cultural validity of the newly developed thyroid-related patient-reported outcome ThyPRO, using tests for differential item functioning (DIF) according to language version. METHODS: The ThyPRO consists of 85 items summarized in 13 multi-item scales and one single item. Scales cover physical and mental symptoms, well-being and function as well as social and daily function and cosmetic concerns. Translation applied standard forward-backward methodology with subsequent cognitive interviews and reviews. Responses (N = 1,810) to the ThyPRO were collected in seven countries: UK (n = 166), The Netherlands (n = 147), Serbia (n = 150), Italy (n = 110), India (n = 148), Denmark (n = 902) and Sweden (n = 187). Translated versions were compared pairwise to the English version by examining uniform and nonuniform DIF, i.e., whether patients from different countries respond differently to a particular item, although they have identical level of the concept measured by the item. Analyses were controlled for thyroid diagnosis. DIF was investigated by ordinal logistic regression, testing for both statistical significance and magnitude (ΔR (2) > 0.02). Scale level was estimated by the sum score, after purification. RESULTS: For twelve of the 84 tested items, DIF was identified in more than one language. Eight of these were small, but four were indicative of possible low translatability. Twenty-one instances of DIF in single languages were identified, indicating potential problems with the particular translation. However, only seven were of a magnitude which could affect scale scores, most of which could be explained by sample differences not controlled for. CONCLUSION: The ThyPRO has good cross-cultural validity with only minor cross-cultural invariance and is recommended for use in international multicenter studies.