Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort.

RATIONALE: Obstructive sleep apnea (OSA) has been associated with increased cancer mortality, but whether it is also associated with cancer incidence is unknown. OBJECTIVES: To investigate whether OSA is associated with increased cancer incidence in a large clinical cohort. METHODS: A multicenter, clinical cohort study including consecutive patients investigated for suspected OSA between 2003 and 2007 in seven Spanish teaching hospitals. Apnea-hypopnea index (AHI) and percent nighttime with oxygen saturation less than 90% (TSat(90)) were used as surrogates of OSA severity, both as continuous variables and categorized by tertiles. Cox proportional hazards regression analyses were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for cancer incidence after adjusting for confounding variables. MEASUREMENTS AND MAIN RESULTS: A total of 4,910 patients were analyzed (median follow-up, 4.5 yr; interquartile range, 3.4-5.2). Compared with the lower TSat(90) category (<1.2%), the adjusted hazards (95% CI) of cancer incidence for increasing categories were 1.58 (1.07-2.34) for TSat(90) 1.2-12% and 2.33 (1.57-3.46) for TSat(90) greater than 12%. Continuous TSat(90) was also associated with cancer incidence (adjusted HR, 1.07 [1.02-1.13] per 10-unit increase in TSat(90)). In stratified analyses, TSat(90) was associated with cancer incidence in patients younger than 65 years (adjusted HR, 1.13 [95% CI, 1.06-1.21] per 10-unit increase in TSat(90)) and males (adjusted HR, 1.11 [95% CI, 1.04-1.17] per 10-unit increase in TSat(90)). AHI was not associated with cancer incidence in the adjusted analyses, except for patients younger than 65 years (adjusted HR for AHI >43 vs. <18.7, 1.66; 95% CI, 1.04-2.64). CONCLUSIONS: Increased overnight hypoxia as a surrogate of OSA severity was associated with increased cancer incidence. This association seems to be limited to men and patients younger than 65 years of age.

Effectiveness of sequential automatic-manual home respiratory polygraphy scoring.

Automatic home respiratory polygraphy (HRP) scoring functions can potentially confirm the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS) (obviating technician scoring) in a substantial number of patients. The result would have important management and cost implications. The aim of this study was to determine the diagnostic cost-effectiveness of a sequential HRP scoring protocol (automatic and then manual for residual cases) compared with manual HRP scoring, and with in-hospital polysomnography. We included suspected SAHS patients in a multicentre study and assigned them to home and hospital protocols at random. We constructed receiver operating characteristic (ROC) curves for manual and automatic scoring. Diagnostic agreement for several cut-off points was explored and costs for two equally effective alternatives were calculated. Of 366 randomised patients, 348 completed the protocol. Manual scoring produced better ROC curves than automatic scoring. There was no sensitive automatic or subsequent manual HRP apnoea-hypopnoea index (AHI) cut-off point. The specific cut-off points for automatic and subsequent manual HRP scorings (AHI >25 and >20, respectively) had a specificity of 93% for automatic and 94% for manual scorings. The costs of manual protocol were 9% higher than sequential HRP protocol; these were 69% and 64%, respectively, of the cost of the polysomnography. A sequential HRP scoring protocol is a cost-effective alternative to polysomnography, although with limited cost savings compared to HRP manual scoring.

Therapeutic decision-making for sleep apnea and hypopnea syndrome using home respiratory polygraphy: a large multicentric study.

RATIONALE: Home respiratory polygraphy (HRP) is an alternative to polysomnography (PSG) for sleep apnea-hypopnea syndrome (SAHS) diagnosis. However, therapeutic decision-making is a different process than diagnosis. OBJECTIVES: This study aimed to determine the agreement between HRP and in-hospital PSG for therapeutic decision-making in a large sample. METHODS: Patients with an intermediate or high SAHS suspicion were included in a multicenter study (eight sleep centers) and assigned to home and hospital protocols in a random order. Therapeutic decisions (continuous positive airway pressure, no continuous positive airway pressure, or impossible decision) were made by an investigator in each center, based on using either HRP or PSG and a single set of auxiliary clinical variables. Patients and diagnostic methods (HRP and PSG) were assessed in random order using an electronic database. After a month the same therapeutic decision-making procedure was repeated with the same method. MEASUREMENTS AND MAIN RESULTS: Of 366 randomized patients, 348 completed the protocol. The "impossible decision" case was not observed with either PSG or HRP. Therapeutic decisions using HRP had a sensitivity of 73%, a specificity of 77%, and an agreement level (sum of true positives and negatives) of 76%. Patients with higher HRP apnea-hypopnea index (AHI) scores (≥ 30; 41% of the total sample) had a sensitivity of 94%, a specificity of 44%, and the agreement level was 91%. CONCLUSIONS: The HRP-based therapeutic decision was adequate when AHI was high, but deficient in the large population of patients with mild to moderate AHI. Therefore, both selecting patients with a high suspicion and severity of SAHS and future prospective cost-effectiveness studies are necessary.

Some reflections on intermittent hypoxia. Does it constitute the translational niche for carotid body chemoreceptor researchers?

The views presented in this article are the fruit of reflections and discussion with my colleagues at Valladolid and with the members of the Sleep Apnea Hypopnea Syndrome Group of the CIBERES (Spain). We have assembled the article in three sections. In the first one we provide a mechanistic description of obstructive sleep apnea (OSA) and all of its components, including the repetitive episodes of upper airways (UA) obstruction and accompanying hypoxic hypoxia, the respiratory efforts to fight and overcome the obstruction, and the sleep fragmentation due to the hypoxia-triggered arousal reactions, all events occurring during sleep hours with frequencies that might reach up >40-50 episodes/sleep hour. When OSA is accompanied by some of the elements of a big cohort of associated pathologies (vascular, metabolic, and neuropsychiatric) it conforms the obstructive sleep apnea syndrome (OSAS). The high frequency of OSAS in adults (>35 years old) and the costs in every regard of the treatment makes the syndrome a primary importance socio-sanitary problem. In the second section, we describe the experimental models of OSAS, basically the episodic repetitive hypoxic model described by Fletcher and coworkers in 1992, today named in short intermittent hypoxia (IH). From these lines, we want to call for some kind of consensus among researchers to lessen the dispersion of IH protocols. Finally, in the last section we intend to share our optimism with all ISAC members. The optimism is based on the recognition that carotid body (CB) chemoreceptors are critical elements of one of the main pathophysiologic loops in the genesis of OSAS. Therefore, we believe that all of us, as ISAC members, are well qualified to contribute in multidisciplinary research teams with well defined translational interests.

Effectiveness of home respiratory polygraphy for the diagnosis of sleep apnoea and hypopnoea syndrome.

INTRODUCTION: Home respiratory polygraphy (HRP) may be a cost-effective alternative to polysomnography for the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS), but stronger evidence is needed. Normally, patients transport HRP equipment from the hospital to home and back, which may create difficulties for some patients. OBJECTIVES: To determine both the diagnostic efficacy and cost of HRP (with and without a transportation service moving the device and telematic transmission of data) in a large sample compared with in-hospital polysomnography. METHODS: Patients suspected of having SAHS were included in a multicentre study (eight hospitals). They were assigned to home and hospital protocols in random order. Receiver operating characteristic curves were constructed for manual respiratory polygraphy scoring protocol and different polysomnographic cut-off points. Diagnostic efficacies for several polysomnographic cut-off points were explored and costs for two equally effective alternatives were calculated. RESULTS: Of 366 randomised patients, 348 completed the protocol. The best receiver operating characteristic curve was obtained with a polysomnographic cut-off of the apnoea-hypopnoea index (AHI)≥5. The sensitive HRP AHI cut-off point (<5) had a sensitivity of 96%, a specificity of 57% and a negative likelihood ratio (LR) of 0.07; the specific cut-off (>10) had a sensitivity of 87%, a specificity of 86% and a positive LR of 6.25. The cost of HRP was half that of polysomnography. Telematic transmission costs were similar if the patients' costs were taken in to account. CONCLUSION: HRP is an alternative to polysomnography in patients with suspected SAHS. Telematic procedures may help patients with limited mobility and those who live a long way from the sleep centre.

Long-term effect of continuous positive airway pressure in hypertensive patients with sleep apnea.

RATIONALE: Continuous positive airway pressure (CPAP) is the current treatment for patients with symptomatic obstructive sleep apnea (OSA). Its use for all subjects with sleep-disordered breathing, regardless of daytime symptoms, is unclear. OBJECTIVES: This multicenter controlled trial assesses the effects of 1 year of CPAP treatment on blood pressure (BP) in nonsymptomatic, hypertensive patients with OSA. METHODS: We evaluated 359 patients with OSA. Inclusion criteria consisted of an apnea-hypopnea index (AHI) greater than 19 hour(-1), an Epworth Sleepiness Scale score less than 11, and one of the following: under antihypertensive treatment or systolic blood pressure greater than 140 or diastolic blood pressure greater than 90 mm Hg. Patients were randomized to CPAP (n = 178) or to conservative treatment (n = 181). BP was evaluated at baseline and at 3, 6, and 12 months of follow-up. MEASUREMENTS AND MAIN RESULTS: Mean (SD) values were as follows: age, 56 +/- 10 years; body mass index (BMI), 32 +/- 5 kg x m(-2); AHI, 45 +/- 20 hour(-1); and Epworth Sleepiness Scale score, 7 +/- 3. After adjusting for follow-up time, baseline blood pressure values, AHI, time with arterial oxygen saturation less than 90%, and BMI, together with the change in BMI at follow-up, CPAP treatment decreased systolic blood pressure by 1.89 mm Hg (95% confidence interval: -3.90, 0.11 mm Hg; P = 0.0654), and diastolic blood pressure by 2.19 mm Hg (95% confidence interval: -3.46, -0.93 mm Hg; P = 0.0008). The most significant reduction in BP was in patients who used CPAP for more than 5.6 hours per night. CPAP compliance was related to AHI and the decrease in Epworth Sleepiness Scale score. CONCLUSIONS: In nonsleepy hypertensive patients with OSA, CPAP treatment for 1 year is associated with a small decrease in BP. This effect is evident only in patients who use CPAP for more than 5.6 hours per night. Clinical trial registered with www.clinicaltrials.gov (NCT00127348).

Visual analogical well-being scale for sleep apnea patients: validity and responsiveness : a test for clinical practice.

INTRODUCTION: Health-related quality-of-life (HRQL) tests used in sleep apnea-hypopnea syndrome (SAHS) are time-consuming, complicating their application in clinical practice. The objective was to examine the validity and responsiveness of a simple visual analogical well-being scale (VAWS) for the clinical use. METHOD: The subjects proceed from a cohort of SAHS patients treated with CPAP for 12 weeks. We correlated the VAWS with other HRQL tests, related clinical and polysomnographic measures to concurrent and construct validities. Responsiveness by: (1) comparison of HRQL tests between before and after treatment and effect size. (2) Association of the change with treatment between VAWS with other HRQL tests and between VAWS with clinical parameters. RESULTS: At baseline, VAWS correlated with all HRQL tests but better with functional outcomes in sleep questionnaires (FOSQ) and European quality-of-life questionnaire (EuroQol) thermometer. VAWS and FOSQ correlated better with clinical variables than other HRQL tests. VAWS captures the magnitude change with treatment similarly to FOSQ but better than other HRQL tests. CONCLUSION: VAWS is a very simple test which measures HRQL in SAHS. It could be a useful tool in clinical practice, primarily for the responsiveness of treatment.

Association between habitual naps and sleep apnea.

STUDY OBJECTIVES: Taking an afternoon nap (siesta) is a common habit. A number of studies have shown an increased cardiovascular mortality in habitual nappers. Afternoon nappers have anthropometric characteristics similar to those of patients with sleep apnea. Nappers appear to suffer from more sleep apnea, which could contribute to cardiovascular disorders. Our aim was therefore to determine the association between sleep apnea and napping, as well as to analyze the relationship of sleep apnea and napping with hypertension. DESIGN: Case-control study. SETTING: Residents in the town of Caceres (Spain) with a population of 100,000 inhabitants. PARTICIPANTS: Four hundred five individuals were initially selected (186 nappers and 219 nonnappers). INTERVENTIONS: Telephone interviews were conducted to contact habitual nappers and nonnappers. Out of the total population selected, 90 nappers and 88 nonnappers completed the study protocol (personal interview and polysomnography). MEASUREMENTS AND RESULTS: The nappers had a higher frequency of sleep apnea at the 3 cutoff points studied (apnea and hypopnea index > or = 5, > or = 10, > or = 15). The adjusted odds ratio was between 2.8 (confidence interval, 1.3-5.8) and 5.5 (confidence interval, 2.3-13). Napping was associated with hypertension in the univariate analysis (odds ratio: 2.1; confidence interval, 1.1-4), but this association disappeared once sleep apnea was included as a covariate in the multivariate modeling (odds ratio dropped to 1.1). CONCLUSIONS: Our findings suggest that napping could be regarded as a marker of sleep apnea, which could account for the cardiovascular diseases observed in nappers. Given that napping is common and that sleep apnea is treatable, more attention should be focused on this population.

Efficacy of home single-channel nasal pressure for recommending continuous positive airway pressure treatment in sleep apnea.

INTRODUCTION: Unlike other prevalent diseases, obstructive sleep apnea (OSA) has no simple tool for diagnosis and therapeutic decision-making in primary healthcare. Home single-channel nasal pressure (HNP) may be an alternative to polysomnography for diagnosis but its use in therapeutic decisions has yet to be explored. OBJECTIVES: To ascertain whether an automatically scored HNP apnea-hypopnea index (AHI), used alone to recommend continuous positive airway pressure (CPAP) treatment, agrees with decisions made by a specialist using polysomnography and several clinical variables. METHODS: Patients referred by primary care physicians for OSA suspicion underwent randomized polysomnography and HNP. We analyzed the total sample and both more and less symptomatic subgroups for Bland and Altman plots to explore AHI agreement; receiver operating characteristic curves to establish area under the curve (AUC) measurements for CPAP recommendation; and therapeutic decision efficacy for several HNP AHI cutoff points. RESULTS: Of the 787 randomized patients, 35 (4%) were lost, 378 (48%) formed the more symptomatic and 374 (48%) the less symptomatic subgroups. AHI bias and agreement limits were 5.8 ± 39.6 for the total sample, 5.3 ± 38.7 for the more symptomatic, and 6 ± 40.2 for the less symptomatic subgroups. The AUC were 0.826 for the total sample, 0.903 for the more symptomatic, and 0.772 for the less symptomatic subgroups. In the more symptomatic subgroup, 70% of patients could be correctly treated with CPAP. CONCLUSION: Automatic HNP scoring can correctly recommend CPAP treatment in most of more symptomatic patients with OSA suspicion. Our results suggest that this device may be an interesting tool in initial OSA management for primary care physicians, although future studies in a primary care setting are necessary. CLINICAL TRIALS INFORMATION: Clinicaltrial.gov identifier: NCT01347398.

Should all sleep apnoea patients be treated?

Sleep apnoea is a condition in which people stop breathing during sleep. A number of studies in general and worker populations have shown that the prevalence of an apnoea-hypopnoea index (AHI) >10 is in the range of 20%. Subjects with an AHI >10 that complain of excessive daytime somnolence, tiredness, asphyxic episodes during the night or non-refreshing sleep, among other symptoms, suffer from the sleep apnoea hypopnoea syndrome (SAHS). The prevalence of SAHS is around 4%. Owing to its high prevalence, clinical symptoms, probable secondary cardiovascular consequences and associated social problems, SAHS has a considerable impact on health, management of which is worth considering. Despite the fact that SAHS treatment has been challenged recent studies conclude that nasal continuous positive airway pressure (nCPAP) is undoubtedly effective in clearly symptomatic patients. Its use in clinical practice is adequately supported in the treatment of moderate to severe SAHS. Further studies are needed in order to define the lower range of symptoms to be treated. One of the most important problems encountered in this area results from the combination of two situations. On the one hand, different epidemiological studies have demonstrated that an AHI >10 without symptoms is present in around 15% of the general population. On the other hand, several studies suggest that having a high AHI, even without secondary symptoms, gives rise to some undesirable effects such as traffic accidents and cardiovascular consequences. In this context, comprehensive epidemiological studies are therefore warranted to define the role of nCPAP treatment especially in those subjects with a high AHI but with few or no symptoms.

Obstructive sleep apnea is associated with cancer mortality in younger patients.

OBJECTIVE: The association between obstructive sleep apnea (OSA) and cancer mortality has scarcely been studied. The objective of this study was to investigate whether OSA is associated with increased cancer mortality in a large cohort of patients with OSA suspicion. METHODS: This was a multicenter study in consecutive patients investigated for suspected OSA. OSA severity was measured by the apnea-hypopnea index (AHI) and the hypoxemia index (% night-time spent with oxygen saturation <90%, TSat90). The association between OSA severity and cancer mortality was assessed using Cox's proportional regression analyses after adjusting for relevant confounders. RESULTS: In all, 5427 patients with median follow-up of 4.5 years were included. Of these, 527 (9.7%) were diagnosed with cancer. Log-transformed TSat90 was independently associated with increased cancer mortality in the entire cohort (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.42), as well as in the group of patients with cancer (HR, 1.19; 95% CI, 1.02-1.41). The closest association was shown in patients <65years in both the AHI (continuous log-transformed AHI: HR, 1.87; 95% CI, 1.1-3.2; upper vs lower AHI tertile: HR, 3.98; 95% CI, 1.14-3.64) and the TSat90 (continuous log-transformed TSat90: HR, 1.73; 95% CI, 1.23-2.4; upper vs. lower TSat90 tertile: HR, 14.4; 95% CI, 1.85-111.6). CONCLUSIONS: OSA severity was associated with increased cancer mortality, particularly in patients aged <65 years.

Effectiveness of home single-channel nasal pressure for sleep apnea diagnosis.

INTRODUCTION: Home single-channel nasal pressure (HNP) may be an alternative to polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis, but no cost studies have yet been carried out. Automatic scoring is simpler but generally less effective than manual scoring. OBJECTIVES: To determine the diagnostic efficacy and cost of both scorings (automatic and manual) compared with PSG, taking as a polysomnographic OSA diagnosis several apnea-hypopnea index (AHI) cutoff points. METHODS: We included suspected OSA patients in a multicenter study. They were randomized to home and hospital protocols. We constructed receiver operating characteristic (ROC) curves for both scorings. Diagnostic efficacy was explored for several HNP AHI cutoff points, and costs were calculated for equally effective alternatives. RESULTS: Of 787 randomized patients, 752 underwent HNP. Manual scoring produced better ROC curves than automatic for AHI < 15; similar curves were obtained for AHI ≥ 15. A valid HNP with manual scoring would determine the presence of OSA (or otherwise) in 90% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 74% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 61% of patients with a polysomnographic AHI ≥ 15 cutoff point. In the same way, a valid HNP with automatic scoring would determine the presence of OSA (or otherwise) in 73% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 64% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 57% of patients with a polysomnographic AHI ≥ 15 cutoff point. The costs of either HNP approaches were 40% to 70% lower than those of PSG at the same level of diagnostic efficacy. Manual HNP had the lowest cost for low polysomnographic AHI levels (≥ 5 and ≥ 10), and manual and automatic scorings had similar costs for higher polysomnographic cutoff points (AHI ≥ 15) of diagnosis. CONCLUSION: Home single-channel nasal pressure (HNP) is a cheaper alternative than polysomnography for obstructive sleep apnea diagnosis. HNP with manual scoring seems to have better diagnostic accuracy and a lower cost than automatic scoring for patients with low apnea-hypopnea index (AHI) levels, although automatic scoring has similar diagnostic accuracy and cost as manual scoring for intermediate and high AHI levels. Therefore, automatic scoring can be appropriately used, although diagnostic efficacy could improve if we carried out manual scoring on patients with AHI < 15. CLINICAL TRIALS INFORMATION: Clinicaltrials.gov identifier: NCT01347398.

Significance of including a surrogate arousal for sleep apnea-hypopnea syndrome diagnosis by respiratory polygraphy.

RATIONALE: Respiratory polygraphy is an accepted alternative to polysomnography (PSG) for sleep apnea/hypopnea syndrome (SAHS) diagnosis, although it underestimates the apnea-hypopnea index (AHI) because respiratory polygraphy cannot identify arousals. OBJECTIVES: We performed a multicentric, randomized, blinded crossover study to determine the agreement between home respiratory polygraphy (HRP) and PSG, and between simultaneous respiratory polygraphy (respiratory polygraphy with PSG) (SimultRP) and PSG by means of 2 AHI scoring protocols with or without hyperventilation following flow reduction considered as a surrogate arousal. METHODS: We included suspected SAHS patients from 8 hospitals. They were assigned to home and hospital protocols at random. We determined the agreement between respiratory polygraphy AHI and PSG AHI scorings using Bland and Altman plots and diagnostic agreement using receiver operating characteristic (ROC) curves. The agreement in therapeutic decisions (continuous positive airway pressure treatment or not) between HRP and PSG scorings was done with likelihood ratios and post-test probability calculations. RESULTS: Of 366 randomized patients, 342 completed the protocol. AHI from HRP scorings (with and without surrogate arousal) had similar agreement with PSG. AHI from SimultRP with surrogate arousal scoring had better agreement with PSG than AHI from SimultRP without surrogate arousal. HRP with surrogate arousal scoring had slightly worse ROC curves than HRP without surrogate arousal, and the opposite was true for SimultRP scorings. HRP with surrogate arousal showed slightly better agreement with PSG in therapeutic decisions than for HRP without surrogate arousal. CONCLUSION: Incorporating a surrogate arousal measure into HRP did not substantially increase its agreement with PSG when compared with the usual procedure (HRP without surrogate arousal).

Effectiveness of three sleep apnea management alternatives.

RATIONALE: Home respiratory polygraphy (HRP) may be a cost-effective alternative to polysomnography (PSG) for diagnosis and treatment election in patients with high clinical probability of obstructive sleep apnea (OSA), but there is conflicting evidence on its use for a wider spectrum of patients. OBJECTIVES: To determine the efficacy and cost of OSA management (diagnosis and therapeutic decision making) using (1) PSG for all patients (PSG arm); (2) HRP for all patients (HRP arm); and (3) HRP for a subsample of patients with high clinical probability of being treated with continuous positive airway pressure (CPAP) and PSG for the remainder (elective HRP arm). METHODS: Multicentric study of 366 patients with intermediate-high clinical probability of OSA, randomly subjected to HRP and PSG. We explored the diagnostic and therapeutic decision agreements between the PSG and both HRP arms for several HRP cutoff points and calculated costs for equal diagnostic and/or therapeutic decision efficacy. RESULTS: For equal diagnostic and therapeutic decision efficacy, PSG arm costs were 18% higher than HRP arm costs and 20% higher than elective HRP arm costs. HRP arm costs tended to be lower than elective HRP arm costs, and both tended to be lower than PSG arm costs if patient costs were omitted. CONCLUSION: Home respiratory polygraphy is a less costly alternative than polysomnography for the diagnosis and therapeutic decision making for patients with suspected obstructive sleep apnea. We found no advantage in cost terms, however, in using home respiratory polygraphy for all patients or home respiratory polygraphy for the most symptomatic patients and polysomnography for the rest.

Alternative methods of titrating continuous positive airway pressure: a large multicenter study.

Standard practice for continuous positive airway pressure (CPAP) treatment in sleep apnea and hypopnea syndrome (SAHS) requires pressure titration during attended laboratory polysomnography. However, polysomnographic titration is expensive and time-consuming. The aim of this study was to ascertain, in a large sample of CPAP-naive patients, whether CPAP titration performed by an unattended domiciliary autoadjusted CPAP device or with a predicted formula was as effective as CPAP titration performed by full polysomnography. The main outcomes were the apnea-hypopnea index and the subjective daytime sleepiness. We included 360 patients with SAHS requiring CPAP treatment. Patients were randomly allocated into three groups: standard, autoadjusted, and predicted formula titration with domiciliary adjustment. The follow-up period was 12 weeks. With CPAP treatment, the improvement in subjective sleepiness and apnea-hypopnea index was very similar in the three groups. There were no differences in the objective compliance of CPAP treatment and in the dropout rate of the three groups at the end of the follow-up. Autoadjusted titration at home and predicted formula titration with domiciliary adjustment can replace standard titration. These procedures could lead to considerable savings in cost and to significant reductions in the waiting list.