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Biomedical subjects

J Stradling

Publications and source records attributed to J Stradling.

17 recordsLinked to original sources
PubMed2003

Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy.

Patients with myotonic dystrophy frequently suffer from excess daytime sleepiness, which can be a significant cause of disability. Previous studies have indicated that this excess daytime sleepiness is only occasionally due to obstructive sleep apnoea and may be principally of central nervous system origin. Modafinil has been successfully used to treat narcolepsy, a central disorder causing excess daytime sleepiness. We have investigated the use of this drug in myotonic dystrophy patients with excess daytime sleepiness. Patients were recruited from a clinic population on the basis of screening with the Epworth Sleepiness Scale. Patients scoring 10 and above were invited to participate in a randomized double-blind crossover trial of modafinil versus placebo, with four weeks in each arm of the study separated by a 2-week washout period. Patients were assessed by polysomnography at baseline. The primary outcome measures were change in both the Epworth Sleepiness Scale and a modified Maintenance of Wakefulness Test, which were measured at the start of each arm of the trial and in week 3 of each intervention period. In agreement with previous smaller studies, sleepiness is not correlated with CTG expansion size. Treatment with modafinil showed a non-significant reduction in median Epworth Sleepiness Scale. However, the median Maintenance of Wakefulness Test score was prolonged by treatment (31.7-40 min, P=0.006). There were no significant adverse cardiac effects of the drug in this group of patients (resting 12 lead and 24 h ECG monitoring). Selected patients with myotonic dystrophy and excess daytime sleepiness may benefit from modafinil. In this patient group the Epworth Sleepiness Scale may not be the most reliable measure of sleepiness. Despite the potential for cardiac disease in these patients, the drug was well tolerated with no adverse effects.

Adult↗
PubMed1998

How should we evaluate health status? A comparison of three methods in patients presenting with obstructive sleep apnoea.

The purpose of this paper is to compare three approaches to the measurement of patient-reported health status which produce summary scales of health status: the Patient-generated Index (PGI) is a measure of individual quality of life (QoL), the EuroQol is a measure of QoL the results of which are weighted by utility values gained from community surveys and the SF-36 which produces two summary scales of health status (the physical component summary (PCS) and the mental component summary (MCS) scores). A follow-up interview survey of patients with obstructive sleep apnoea (OSA) was conducted. The patients received continuous positive airways pressure therapy (CPAP) between the two administrations of the questionnaires. One hundred patients presenting with OSA and who were suitable for CPAP therapy were asked if they would take part in the study. The results on the PGI, EuroQol EQ-5D utility weighted scores and 'thermometer' scores and SF-36 physical and mental summary scores were measured. Eighty-nine respondents provided sufficient data to calculate PGI and EuroQol scores and 86 patients provided sufficient data to calculate SF-36 summary scores. The PGI indicated substantial improvement after CPAP treatment whereas the EuroQol indicated little or no improvement on either utility weighted or thermometer scores. The SF-36 PCS and MCS scores were lower than those of the general population at baseline, but had improved to the normative levels after treatment. The EuroQol provided a substantially different picture of change to either of the ones gained from the SF-36 or PGI. It is suggested that the EuroQol does not contain questions which relate to important aspects of health and well-being and may not accurately reflect the health state of individuals. Consequently, caution must be exercised to assure that an appropriate instrument has been employed when using health outcomes data to assess or prioritize available health care treatments.

Adult↗
PubMed1998

Controlled trial of hypnotherapy for weight loss in patients with obstructive sleep apnoea.

OBJECTIVE: To assess if hypnotherapy assists attempts at weight loss. DESIGN: Randomised, controlled, parallel study of two forms of hypnotherapy (directed at stress reduction or energy intake reduction), vs dietary advice alone in 60 obese patients with obstructive sleep apnoea on nasal continuous positive airway pressure treatment. SETTING: National Health Service hospital in the UK. MEASURES: Weight lost at 1, 3, 6, 9, 12, 15 and 18 months after dietary advice and hypnotherapy, as a percentage of original body weight. RESULTS: All three groups lost 2-3% of their body weight at three months. At 18 months only the hypnotherapy group (with stress reduction) still showed a significant (P < 0.02), but small (3.8 kg), mean weight loss compared to baseline. Analysed over the whole time period the hypnotherapy group with stress reduction achieved significantly more weight loss than the other two treatment arms (P < 0.003), which were not significantly different from each other. CONCLUSIONS: This controlled trial on the use of hypnotherapy, as an adjunct to dietary advice in producing weight loss, has produced a statistically significant result in favour of hypnotherapy. However, the benefits were small and clinically insignificant. More intensive hypnotherapy might of course have been more successful, and perhaps the results of the trial are sufficiently encouraging to pursue this approach further.

Cohort Studies↗
PubMed1997

Comparison of three measures of quality of life outcome in the evaluation of continuous positive airways pressure therapy for sleep apnoea.

Treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (NCPAP) has become a standard treatment since its introduction in 1981. Following such treatment the apnoeas disappear, sleep quality improves as apparently do daytime symptoms of sleepiness. Sleepiness is an unusual symptom and its impact on conventional indices of quality of life has rarely been measured. To allow comparison of NCPAP therapy with treatments for other conditions, measurements of quality of life before and after treatment using standard techniques are required. It is not clear which of the standard measures is most suited to measuring the health gain from nasal NCPAP, and indeed whether the disability of excessive sleepiness is included in all such measures. This study looks at three well recognized quality of life measures in OSA, before and after NCPAP therapy; the Short Form 36 (SF-36), Functional Limitations Profile (FLP), and the EuroQol (EQ-5D). The results were compared with data from normal populations. One hundred and eight patients with OSA undergoing a therapeutic assessment of NCPAP completed the three quality of life questionnaires before and 5 weeks after commencing treatment. Over 90 subjects completed all sections of the three measures on both occasions. The SF-36 revealed substantial adverse effects on subjective health of OSA and that NCPAP treatment produced dramatic positive effects. For example, the effect sizes (difference in score, divided by SD of baseline score) in the Energy/Vitality dimension was 0.98 and for the overall Mental and Physical Component Scores, 0.76 and 0.57, respectively: an effect size over 0.5 is considered moderate and over 0.8 as large. The FLP data showed similar pre treatment decrements in quality of life and substantial improvements following NCPAP. The changes with treatment in the majority of the dimensions from both the SF-36 and FLP were statistically significant (P < 0.01). In contrast the EQ-5D did not show significant improvements with therapy, presumably because of its failure to measure the aspects of quality of life related to severe sleep fragmentation and daytime sleepiness. In conclusion, this study has clearly shown considerable decrements in quality of life in patients with OSA, similar to other chronic disabling conditions. Furthermore, NCPAP therapy returns patients to a quality of life similar to the normal population.

Adult↗
PubMed1997

A shorter form health survey: can the SF-12 replicate results from the SF-36 in longitudinal studies?

BACKGROUND: The SF-36 is a generic health status measure which has gained popularity as a measure of outcome in a wide variety of patient groups and social surveys. However, there is a need for even shorter measures, which reduce respondent burden. The developers of the SF-36 have consequently suggested that a 12-item sub-set of the items may accurately reproduce the two summary component scores which can be derived from the SF-36 [the Physical Component Summary Score (PCS) and Mental Health Component Summary Score (MCS)]. In this paper, we adopt scoring algorithms for the UK SF-36 and SF-12 summary scores to evaluate the picture of change gained in various treatment groups. METHODS: The SF-36 was administered in three treatment groups (ACE inhibitors for congestive heart failure, continuous positive airways therapy for sleep apnoea, and open vs laparoscopic surgery for inguinal hernia). RESULTS: PCS and MCS scores calculated from the SF-36 or a sub-set of 12 items (the 'SF-12') were virtually identical, and indicated the same magnitude of ill-health and degree of change over time. CONCLUSION: The results suggest that where two summary scores of health status are adequate than the SF-12 may be the instrument of choice.

Adult↗
PubMed1997

Sleep apnea and hypertension--what a mess!

It is unarguable that obstructive sleep apnea (OSA) causes pulsatile hypertension during sleep, but whether there is significant carryover of hypertension into waking hours is far from clear. It is perhaps more useful to consider whether OSA is related to the consequences of hypertension (e.g. stroke), since both nocturnal and daytime hypertension could be responsible for these. Furthermore, the effects of nasal continuous positive airway pressure (CPAP) on hypertension (or its consequences) must be assessed by randomized controlled studies, in exactly the same way as trials on hypotensive drugs would be carried out, before treatment is prescribed for OSA in the absence of any daytime symptoms.

Circadian Rhythm↗
PubMed1996

A new approach to the analysis of the human sleep/wakefulness continuum.

The conventional approach to the analysis of human sleep uses a set of pre-defined rules to allocate each 20 or 30-s epoch to one of six main sleep stages. The application of these rules is performed either manually, by visual inspection of the electroencephalogram and related signals, or, more recently, by a software implementation of these rules on a computer. This article evaluates the limitations of rule-based sleep staging and then presents a new method of sleep analysis that makes no such use of pre-defined rules and stages, tracking instead the dynamic development of sleep on a continuous scale. The extraction of meaningful features from the electroencephalogram is first considered, and for this purpose a technique called autoregressive modelling was preferred to the more commonly-used methods of band-pass filtering or the fast Fourier transform. This is followed by a qualitative investigation into the dynamics of the electroencephalogram during sleep using a technique for data visualization known as a self-organizing feature map. The insights gained using this map led to the subsequent development of a new, quantitative method of sleep analysis that utilizes the pattern recognition capabilities of an artificial neural network. The outputs from this network provide a second-by-second quantification of the sleep/wakefulness continuum with a resolution that far exceeds that of rule-based sleep staging. This is demonstrated by the neural network's ability to pinpoint micro-arousals and highlight periods of severely disturbed sleep caused by certain sleep disorders. Both these phenomena are of considerable clinical value, but neither are scored satisfactorily using rule-based sleep staging.

Adult↗
PubMed1994

Changes in pulse transit time and pulse rate as markers of arousal from sleep in normal subjects.

1. Obstructive sleep apnoea and its variants often provoke hundreds of short arousals that lead to the most important symptom, disabling hypersomnolence. The measurement of sleep in these conditions requires the documentation of these short arousals and this is conventionally done by manual inspection of the sleeping EEG, a laborious procedure. 2. Other markers of 'arousal', that are easier to measure and document, include several cardiovascular signals that change as part of the orienting reflex: pulse rate rise, blood pressure rise, skin vasoconstriction, for example. 3. Pulse transit time (measured as the interval from the ECG R-wave until the arrival of the pulse pressure wave at the periphery, about 250 ms) varies inversely with blood pressure and provides a beat-to-beat estimation of blood pressure changes. 4. In eight normal subjects we have assessed the relationship between transient EEG arousals of different length (provoked by external stimuli) and changes in both pulse transit time and heart rate. 5. Significant falls in pulse transit time occurred in response to external stimuli [15.1 (SEM 1.4) ms], indicating a rise in blood pressure, and were significant even when there was no discernible change in the EEG [9.9 (SEM 2.6) ms]. Significant changes in heart rate also occurred [10.3 (SEM 1.2) beats/min], but were slightly less sensitive than changes in pulse transit time. 6. Changes in pulse transit time (and to a lesser extent pulse rate) are sensitive markers of EEG arousal. As such they should be useful to include when monitoring sleep and its disorders, particularly since pulse transit time recorders can easily be made portable for home use.

Adult↗
PubMed1992

Nocturnal hypoxia and arrhythmias in patients with impaired left ventricular function.

OBJECTIVES: To document the incidence of hypoxic episodes in a series of patients with impaired left ventricular function, and to correlate the occurrence of hypoxia with severity of arrhythmia. PATIENTS: 34 patients with breathlessness and clinical evidence of left ventricular dysfunction. MAIN OUTCOME MEASURES: Simultaneous overnight finger oximetry and electrocardiographic monitoring. RESULTS: High grade arrhythmias (Lown grade > III) occurred in 20/34 (59%) of patients, and frequent dips in oxygen saturation were noticed (mean dip frequency 4.8/h, range 0.1-20.0). 20/34 (59%) of patients had episodic hypoxaemia, including 13/34 (38%) with a classical Cheyne Stokes pattern. There was a correlation between dip frequency and the presence of high grade arrhythmias (those with high grade arrhythmia had mean (SD) 6.7 (5.5) dips/h v 2.2 (3.4) in those without, p < 0.01); there was also a correlation between the presence of arrhythmias and episodic hypoxaemia (episodic hypoxaemia in those with high grade arrhythmias occurred in 17/20 (85%) v 3/14 (21%) of those without arrhythmias, p < 0.002). There was no correlation between the presence of high grade arrhythmias or dip frequency and the extent of left ventricular impairment, which was present in all patients (mean (SD) ejection fraction 26% (13%)). CONCLUSION: Noticeable abnormalities of nocturnal oxygen saturation occur in patients with impaired left ventricular function, and these are associated with high grade arrhythmias. Interventions that limit desaturation may have valuable anti-arrhythmic effects.

Adult↗
PubMed1990

Do patients with obstructive sleep apnea have thick necks?

During physical examination of patients with suspected obstructive sleep apnea (OSA), a comment is frequently made that they appear to have a short and fat neck. To confirm this subjective impression by objective measurements, we studied a group of 123 patients referred to us because of snoring and suspected OSA, all of whom had nocturnal polysomnography and measurements of external and internal neck circumference. The external neck circumference was measured at the level of the superior border of the cricothyroid cartilage. Internal neck circumferences were calculated from the measurements of pharyngeal, glottic, and tracheal areas obtained by the acoustic reflection technique. Internal pharyngeal circumference was further subdivided into the proximal, middle, and distal thirds. The acoustic technique also permitted us to measure the distance between the teeth and the glottic minimum, which reflects the length of the upper airway. Stepwise multiple linear regression analysis revealed that the apnea/hypopnea index (AHI) correlated only with the external neck circumference, the body mass index, and the internal circumference of the distal pharynx; these three variables accounted for 39% of the variability in AHI. We conclude that the external and internal neck circumferences and the degree of obesity are important predictors of sleep apnea; it is possible that obesity produces its effect via fat in the neck. We speculate that the static pharyngeal size modulated by the dynamic loading of the airway due to the weight of fatty tissue of the neck may contribute to the pathogenesis of OSA.

Adult↗
PubMed1989

Ventilatory response to an inhaled constant CO2 load and added dead space in healthy men, awake and asleep.

Experiments were conducted in ten adult men to determine if rapid-eye-movement sleep (REMS) reduced the ventilatory response to two 'steady-state' respiratory loads compared to slow wave sleep (SWS). A constant addition of 150 (or 200) ml/min pure CO2 to the inspirate (7 subjects) and 230 ml of added dead space (5 subjects) were the two respiratory loads. Inspiratory ventilation was measured by pneumotachygraph for at least five continuous minutes in wakefulness, SWS and REMS. The increase in ventilation to both stimuli was equal in SWS and REMS with no suggestion of an impaired response during the latter: increases in ventilation during CO2 loading being 49 and 51%, SWS and REMS, respectively, and during additional dead space they were 53 and 59%, SWS and REMS, respectively. Following the addition of extra dead space, end tidal PCO2 levels did not rise significantly more during REMS compared to SWS (P greater than 0.5). These findings show that when ventilatory responses to CO2 are considered across the whole of REMS (including periods with and without actual eye-movements) then they do not appear to be blunted compared to SWS.

Adult↗
PubMedDate not supplied

Chemoreceptor drives and short sleep-wake cycles during hypoxia: a simulation study.

We used a Grodins-type mathematical model of the cardio-pulmonary system to investigate the cycling behaviour of the respiratory system during hypoxia in response to changes of state between waking and sleeping, namely a diminution of respiratory chemosensitivity during sleep. Shifts between waking and sleeping were triggered by various combinations of threshold values for PAO2. Mild or moderate hypoxia was simulated by values of inspired O2 concentration between 13% and 16% (normal 21%). In mild or moderate hypoxia, reductions of overall respiratory gain from about 2 to 0.8 l.min-1 mmHg-1 at sleep onset will produce falls in PAO2 likely to cause sleep-wake cycles with oscillations in PAO2. The higher the arousal threshold (in relation to steady-state PAO2 during sleep), the shorter and more stable the sleep-wake cycles. As the arousal threshold is raised, and as hypoxia is exacerbated from mild (FIO2 = 16%) to moderate (FIO2 = 13%), the sleep-wake cycle length tends to converge to a value around one minute. The level and determinants of the "back-to-sleep" threshold are hard to define from presently available experimental data, but the level is not important in determining the length of the sleep-wake cycle compared to the arousal threshold. Alinearities in chemoreceptor feedback were introduced first by incorporating "drive" thresholds, to simulate central or obstructive apnoea. This produced larger oscillations in respiratory variables, but no change in cycle length. Chemoreceptor thresholds for PCO2 at the level of 38-39 mmHg did produce shorter ventilation cycles, down to about 20 s in length, but these were not related in any simple way to the resulting sleep-wake cycles. The combination of sleep state changes and chemoreceptor feedback alinearities can produce short sleep-wake cycles despite the diminution in chemoreceptor gain occurring in sleep.

Chemoreceptor Cells↗