Continuous positive airway pressure treatment of sleepy patients with milder obstructive sleep apnea: results of the CPAP Apnea Trial North American Program (CATNAP) randomized clinical trial.

RATIONALE: Twenty-eight percent of people with mild to moderate obstructive sleep apnea experience daytime sleepiness, which interferes with daily functioning. It remains unclear whether treatment with continuous positive airway pressure improves daytime function in these patients. OBJECTIVES: To evaluate the efficacy of continuous positive airway pressure treatment to improve functional status in sleepy patients with mild and moderate obstructive sleep apnea. METHODS: Patients with self-reported daytime sleepiness (Epworth Sleepiness Scale score >10) and an apnea-hypopnea index with 3% desaturation and from 5 to 30 events per hour were randomized to 8 weeks of active or sham continuous positive airway pressure treatment. After the 8-week intervention, participants in the sham arm received 8 weeks of active continuous positive airway pressure treatment. MEASUREMENTS AND MAIN RESULTS: The Total score on the Functional Outcomes of Sleep Questionnaire was the primary outcome measure. The adjusted mean change in the Total score after the first 8-week intervention was 0.89 for the active group (n = 113) and -0.06 for the placebo group (n = 110) (P = 0.006). The group difference in mean change corresponded to an effect size of 0.41 (95% confidence interval, 0.14-0.67). The mean (SD) improvement in Functional Outcomes of Sleep Questionnaire Total score from the beginning to the end of the crossover phase (n = 91) was 1.73 ± 2.50 (t[90] = 6.59; P < 0.00001) with an effect size of 0.69. CONCLUSIONS: Continuous positive airway pressure treatment improves the functional outcome of sleepy patients with mild and moderate obstructive sleep apnea.

Evaluation of sham-CPAP as a placebo in CPAP intervention studies.

STUDY OBJECTIVES: To evaluate the use of sham-continuous positive airway pressure (CPAP) treatment as a placebo intervention. DESIGN AND SETTING: Analysis of polysomnograms performed in fixed order without sham-CPAP and on the first night of the sham-CPAP intervention in participants in the CPAP Apnea Trial North American Program (CATNAP), a randomized, placebo controlled trial evaluating the effects of CPAP treatment on daytime function in adults with newly diagnosed mild to moderate obstructive sleep apnea (apnea hypopnea index (AHI) 5-30). PARTICIPANTS: The first 104 CATNAP participants randomized to the sham-CPAP intervention arm. MEASUREMENTS AND RESULTS: Compared to the polysomnographic measures without sham-CPAP, the study on the first night with sham-CPAP had statistically significant differences that suggested a decrease in sleep quality: decreased sleep efficiency, increased arousal index, increased time in stage 1 NREM sleep, and prolonged latency to REM sleep. However, all of these differences had a relatively small effect size. Compared to the polysomnogram without sham-CPAP, the number of hypopneas on the sham-CPAP polysomnogram was significantly increased and the number of apneas significantly decreased. Relatively minor differences in AHI with and without sham-CPAP were present and were dependent on the criteria used to score hypopneas. CONCLUSION: Comparison of polysomnograms with and without sham-CPAP revealed differences that, although statistically significant, were small in magnitude and had relatively low effect sizes suggesting minimal clinical significance. The results support the use of sham-CPAP as a placebo intervention in trials evaluating the effects of CPAP treatment in patients with obstructive sleep apnea. CLINICAL TRIAL INFORMATION: This paper was a secondary analysis of clinical trial data. CATNAP: CPAP Apnea Trial North American Program, the trial from which the data were obtained, is registered with clinicaltrial.gov. Registration #NCT00089752.

Suppression of central sleep apnea by continuous positive airway pressure and transplant-free survival in heart failure: a post hoc analysis of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure Trial (CANPAP).

BACKGROUND: In the main analysis of the Canadian Continuous Positive Airway Pressure (CPAP) for Patients with Central Sleep Apnea (CSA) and Heart Failure Trial (CANPAP), CPAP had no effect on heart transplant-free survival; however, CPAP only reduced the mean apnea-hypopnea index to 19 events per hour of sleep, which remained above the trial inclusion threshold of 15. This stratified analysis of CANPAP tested the hypothesis that suppression of CSA below this threshold by CPAP would improve left ventricular ejection fraction and heart transplant-free survival. METHODS AND RESULTS: Of the 258 heart failure patients with CSA in CANPAP, 110 of the 130 randomized to the control group and 100 of the 128 randomized to CPAP had sleep studies 3 months later. CPAP patients were divided post hoc into those whose apnea-hypopnea index was or was not reduced below 15 at this time (CPAP-CSA suppressed, n=57, and CPAP-CSA unsuppressed, n=43, respectively). Their changes in left ventricular ejection fraction and heart transplant-free survival were compared with those in the control group. Despite similar CPAP pressure and hours of use in the 2 groups, CPAP-CSA-suppressed subjects experienced a greater increase in left ventricular ejection fraction at 3 months (P=0.001) and significantly better transplant-free survival (hazard ratio [95% confidence interval] 0.371 [0.142 to 0.967], P=0.043) than control subjects, whereas the CPAP-CSA-unsuppressed group did not (for left ventricular ejection fraction, P=0.984, and for transplant-free survival, hazard ratio 1.463 [95% confidence interval 0.751 to 2.850], P=0.260). CONCLUSIONS: These results suggest that in heart failure patients, CPAP might improve both left ventricular ejection fraction and heart transplant-free survival if CSA is suppressed soon after its initiation.

Continuous positive airway pressure for central sleep apnea and heart failure.

BACKGROUND: The Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure trial tested the hypothesis that continuous positive airway pressure (CPAP) would improve the survival rate without heart transplantation of patients who have central sleep apnea and heart failure. METHODS: After medical therapy was optimized, 258 patients who had heart failure (mean age [+/-SD], 63+/-10 years; ejection fraction, 24.5+/-7.7 percent) and central sleep apnea (number of episodes of apnea and hypopnea per hour of sleep, 40+/-16) were randomly assigned to receive CPAP (128 patients) or no CPAP (130 patients) and were followed for a mean of two years. During follow-up, sleep studies were conducted and measurements of the ejection fraction, exercise capacity, quality of life, and neurohormones were obtained. RESULTS: Three months after undergoing randomization, the CPAP group, as compared with the control group, had greater reductions in the frequency of episodes of apnea and hypopnea (-21+/-16 vs. -2+/-18 per hour, P<0.001) and in norepinephrine levels (-1.03+/-1.84 vs. 0.02+/-0.99 nmol per liter, P=0.009), and greater increases in the mean nocturnal oxygen saturation (1.6+/-2.8 percent vs. 0.4+/-2.5 percent, P<0.001), ejection fraction (2.2+/-5.4 percent vs. 0.4+/-5.3 percent, P=0.02), and the distance walked in six minutes (20.0+/-55 vs. -0.8+/-64.8 m, P=0.016). There were no differences between the control group and the CPAP group in the number of hospitalizations, quality of life, or atrial natriuretic peptide levels. An early divergence in survival rates without heart transplantation favored the control group, but after 18 months the divergence favored the CPAP group, yet the overall event rates (death and heart transplantation) did not differ (32 vs. 32 events, respectively; P=0.54). CONCLUSIONS: Although CPAP attenuated central sleep apnea, improved nocturnal oxygenation, increased the ejection fraction, lowered norepinephrine levels, and increased the distance walked in six minutes, it did not affect survival. Our data do not support the use of CPAP to extend life in patients who have central sleep apnea and heart failure.

Oral appliances for snoring and obstructive sleep apnea: a review.

We conducted an evidence-based review of literature regarding use of oral appliances (OAs) in the treatment of snoring and obstructive sleep apnea syndrome (OSA) from 1995 until the present. Our structured search revealed 141 articles for systematic scrutiny, of which 87 were suitable for inclusion in the evidence base, including 15 Level I to II randomized controlled trials and 5 of these trials with placebo-controlled treatment. The efficacy of OAs was established for controlling OSA in some but not all patients with success (defined as no more than 10 apneas or hypopneas per hour of sleep) achieved in an average of 52% of treated patients. Effects on sleepiness and quality of life were also demonstrated, but improvements in other neurocognitive outcomes were not consistent. The mechanism of OA therapy is related to opening of the upper airway as demonstrated by imaging and physiologic monitoring. Treatment adherence is variable with patients reporting using the appliance a median of 77% of nights at 1 year. Minor adverse effects were frequent whereas major adverse effects were uncommon. Minor tooth movement and small changes in the occlusion developed in some patients after prolonged use, but the long-term dental significance of this is uncertain. In comparison to continuous positive airway pressure (CPAP), OAs are less efficacious in reducing the apnea hypopnea index (AHI), but OAs appear to be used more (at least by self report), and in many studies were preferred over CPAP when the treatments were compared. OAs have also been compared favorably to surgical modification of the upper airway (uvulopalatopharyngoplasty, UPPP). Comparisons between OAs of different designs have produced variable findings. The literature of OA therapy for OSA now provides better evidence for the efficacy of this treatment modality and considerable guidance regarding the frequency of adverse effects and the indications for use in comparison to CPAP and UPPP.

Case study: providing evidence-based behavioral and nutrition treatment to a toddler with cystic fibrosis and multiple food allergies via telehealth.

Barriers to successful outcome for cystic fibrosis (CF) therapies can include distance from a CF care center, co-morbid conditions that require individualized alterations to the prescribed treatment, and patient-provider interactions, among others. We present the case of a 21-month-old female with CF for whom modifications of an efficacious behavioral and nutrition treatment were made due to food allergies and distance from the CF care center. She was classified as at-risk nutritionally. Following treatment a significant increase in energy intake (calories) was observed in addition to her meeting weight and height growth rates for a child of this age and gender who is growing normally at the 50th percentile.

The role of oral appliance therapy in the treatment of obstructive sleep apnea.

The development of oral appliance treatment for OSA represents an important step in the management of this disease. Randomized, controlled clinical trials have shown them to be an effective treatment option for snoring and OSA in some patients, particularly patients with less severe OSA or simple snoring and patients who have failed other treatment modalities. Although oral appliances are not as effective as CPAP therapy, they work in most patients to relieve symptoms and apnea and are well tolerated by patients. Most patients report improvements in sleep quality and excessive daytime sleepiness. Short-term side effects are generally minor and are related to excessive salivation, jaw and tooth discomfort, and occasional joint discomfort. These symptoms may lead to discontinuation of appliance therapy but usually improve in most patients over time. Serious complications are not common, but occlusal changes are more common than previously believed.

Position paper by Canadian dental sleep medicine professionals on the role of different health care professionals in managing obstructive sleep apnea and snoring with oral appliances.

The present Canadian position paper contains recommendations for the management by dentists of sleep-disordered breathing in adults with the use of oral appliances (OAs) as a treatment option for snoring and obstructive sleep apnea (OSA). The recommendations are based on literature reviews and expert panel consensus. OAs offer an effective, first-line treatment option for patients with mild to moderate OSA who prefer an OA to continuous positive airway pressure (CPAP) therapy, or for severe OSA patients who cannot tolerate CPAP, are inappropriate candidates for CPAP or who have failed CPAP treatment attempts. The purpose of the present position paper is to guide interdisciplinary teamwork (sleep physicians and sleep dentists) and to clarify the role of each professional in the management of OA therapy. The diagnosis of OSA should always be made by a physician, and OAs should be fitted by a qualified dentist who is trained and experienced in dental sleep medicine. Follow-up assessment by the referring physician and polysomnography or sleep studies are required to verify treatment efficacy. The present article emphasizes the need for a team approach to OA therapy and provides treatment guidelines for dentists trained in dental sleep medicine. Many of the dentists and sleep physicians who contributed to the preparation of the present article are members of the Canadian Sleep Society and the authors reached a consensus based on the current literature.

Addressing social determinants of health to improve access to early breast cancer detection: results of the Boston REACH 2010 Breast and Cervical Cancer Coalition Women's Health Demonstration Project.

BACKGROUND: The Boston Racial and Ethnic Approaches to Community Health (REACH) 2010 Breast and Cervical Cancer Coalition developed a case management intervention for women of African descent to identify and reduce medical and social obstacles to breast cancer screening and following up abnormal results. METHODS: We targeted black women at high risk for inadequate cancer screening and follow-up as evidenced by a prior pattern of missed clinic appointments and frequent urgent care use. Case managers provided referrals to address patient-identified social concerns (e.g., transportation, housing, language barriers), as well as navigation to prompt screening and follow-up of abnormal tests. We recruited 437 black women aged 40-75, who received care at participating primary care sites. The study was conducted as a prospective cohort study rather than as a controlled trial and evaluated intervention effects on mammography uptake and longitudinal screening rates via logistic regression and timely follow-up of abnormal tests via Cox proportional hazards models. RESULTS: A significant increase in screening uptake was found (OR 1.53, 95% CI 1.13-2.08). Housing concerns (p < 0.05) and lacking a regular provider (p < 0.01) predicted poor mammography uptake. Years of participation in the intervention increased odds of obtaining recommended screening by 20% (OR 1.20, 95% CI 1.02-1.40), but this effect was attenuated by covariates (p = 0.53). Timely follow-up for abnormal results was achieved by most women (85%) but could not be attributed to the intervention (HR 0.95, 95% CI 0.50-1.80). CONCLUSIONS: Case management was successful at promoting mammography screening uptake, although no change in longitudinal patterns was found. Housing concerns and lacking a regular provider should be addressed to promote mammography uptake. Future research should provide social assessment and address social obstacles in a randomized controlled setting to confirm the efficacy of social determinant approaches to improve mammography use.

Effect of a titration polysomnogram on treatment success with a mandibular repositioning appliance.

STUDY OBJECTIVES: Mandibular repositioning appliance (MRA) therapy is a treatment option for patients with mild to moderate sleep apnea and for patients who do not tolerate continuous positive airway pressure. Titration of MRAs consists of sequential mandibular advancement guided by symptom improvement. The goal of the study was to determine if patients with an elevated apnea hypopnea index (AHI), despite the use of a subjectively optimized MRA, could achieve better results with additional titration during polysomnography (PSG). METHODS: Patients were enrolled if they had an AHI > or = 15/h and were referred for MRA therapy. The MRAwas advanced until symptoms improved. During the PSG, the technologist monitored the patient's sleep and increased mandibular protrusion until the AHI was improved. RESULTS: There was a significant improvement in AHI, minimum oxygen saturation, and total sleep time with the MRA before further advancement. At the final PSG, 65.2% of patients had an AHI < or = 10 associated with at least a 50% reduction in AHI. The incomplete responders had their appliance further titrated, and this improved the results of MRA therapy by 30.4% to a total success rate of 95.6%. CONCLUSIONS: This study shows that it is possible to improve the results of MRA therapy by further advancing the appliance during a titration PSG in patients with an incomplete response. The titration night improved the results of the usual clinical advancement of the MRA with substantially more patients achieving a successful outcome.

Examining clinical trial results with single-subject analysis: an example involving behavioral and nutrition treatment for young children with cystic fibrosis.

OBJECTIVE: To examine the process of change in a clinical trial of behavioral and nutrition treatment for children age 18-48 months with cystic fibrosis (CF) using single-subject analysis. METHODS: The 5-week treatment included nutrition counseling and child behavioral management training for parents and was designed to increase energy intake measured by diet diaries 600-800 calories per day. RESULTS: Energy intake changed at each meal, only when treatment was introduced (week 1: snacks, 420 to 691; week 2: breakfast, 325 to 443; week 4: lunch, 350 to 443; and week 5: dinner, 373 to 460 calories per day). Total daily intake increased in a systematic fashion that exceeded the criterion set each week during treatment. CONCLUSIONS: Toddlers and preschoolers with CF meet energy intake recommendations as a result of behavioral intervention. Single-subject research designs are important methodologies for advancing clinical investigation in pediatric psychology.

Physiologic pacing in patients with obstructive sleep apnea: a prospective, randomized crossover trial.

OBJECTIVES: This study was designed to assess the impact of prevention of bradycardia with physiologic pacing on the severity of obstructive sleep apnea. BACKGROUND: Apneic episodes during sleep are associated with slowing of the heart rate during apnea and tachycardia with subsequent arousal. Patients with permanent pacemakers may have reduced episodes of sleep apnea when their pacemaker rate is set faster than their spontaneous nocturnal heart rate. METHODS: We conducted a prospective, randomized, single-blind crossover trial of temporary atrial pacing in obstructive sleep apnea to reduce the apnea hypopnea index (AHI). Fifteen patients (age 60 +/- 13 years, 12 men) with moderate to severe obstructive sleep apnea (AHI 34 +/- 14) underwent insertion of an externalized atrial permanent pacing system via the left subclavian vein. Patients underwent overnight respiratory sleep studies in hospital, during atrial pacing at 75 beats/min, and with pacing turned off. The order of pacing mode was randomized, with crossover the subsequent night to the other mode. Patients were blinded to pacing mode, and the analysis of sleep recordings was blind to pacing mode. RESULTS: Pacing was tolerated without complications in all patients. Overnight physiologic pacing did not affect the AHI (pacing 39 +/- 21/h vs. control 42 +/- 21/h, p = 0.23, 95% confidence interval -9.3 to 2.5 for difference), desaturation time (pacing 3.8 +/- 6.0% vs. control 3.5 +/- 4.3%, p = 0.70), or the minimum SaO(2) (pacing 75 +/- 10% vs. control 77 +/- 11%, p = 0.38). There was a borderline significant reduction in circulatory time with pacing (pacing 23.4 +/- 3.2 s vs. control 25.5 +/- 4.4 s, p = 0.09). CONCLUSIONS: Temporary atrial pacing does not appear to improve respiratory manifestations of obstructive sleep apnea. Permanent atrial pacing in this patient population does not appear to be justified.

Randomized clinical trial of behavioral and nutrition treatment to improve energy intake and growth in toddlers and preschoolers with cystic fibrosis.

OBJECTIVE: To conduct a randomized clinical trial comparing a behavioral and nutrition intervention (BEH) with a usual care control condition (CTL) for children (ages 18 months to 4 years) with cystic fibrosis (CF) and pancreatic insufficiency. This trial was designed to (1) evaluate a randomized comparison of BEH with CTL over 8 weeks, (2) provide a replication of the impact of BEH by inviting the CTL group to receive BEH after 8 weeks, and (3) examine the maintenance of BEH at 3- and 12-month follow-up. METHODS: Of 14 eligible children, 10 were randomly assigned and initiated treatment (71% recruitment rate). Four participants were randomly assigned to BEH, and 6 were assigned to CTL (5 of whom chose to crossover to BEH). BEH included nutrition counseling to increase energy intake (via types of foods and addables/spreadables) and child behavioral management training to teach parents differential attention and contingency management skills. CTL was consistent with the 2002 CF Foundation Consensus Conference Guidelines for nutritional care. RESULTS: BEH led to greater increases in energy intake pre- to posttreatment than CTL as measured by calories per day (842 kcal/day vs -131 kcal/day change). On receiving BEH, the change in energy intake was replicated with the CTL group (892 kcal/day change). At 3- and 12-month follow-up, energy intake was maintained (672 kcal/day increase from baseline and 750 kcal/day increase from baseline, respectively). Children in this study met or exceeded normal weight and height velocities from pretreatment to the 3-month follow-up (mean weight: 1.4 kg/6 months; mean height: 5.1 cm/6 months) and from posttreatment to the 12-month follow-up (mean weight: 2.5 kg/12 months; mean height: 8.3 cm/12 months). CONCLUSIONS: Toddlers and preschoolers who have CF and received BEH were able to meet the energy intake recommendations for this disease and maintain these gains up to 12 months after treatment. In addition, these children demonstrated weight and height velocities from pretreatment to 12-month follow-up, consistent with the goal of normal growth. BEH is a promising, evidence-based, early nutritional intervention for children with CF. An upcoming multisite clinical trial will test BEH versus an attention control condition using a larger sample (N = 100), providing additional evidence about the efficacy of this treatment for energy intake and growth in young children with CF.

A randomized trial of laser-assisted uvulopalatoplasty in the treatment of mild obstructive sleep apnea.

Laser-assisted uvulopalatoplasty (LAUP) is an outpatient surgical treatment for snoring and obstructive sleep apnea (OSA), but to date, no controlled trials have been published. Forty-five subjects with mild OSA (apnea/hypopnea index [AHI], 10-27 per hour) were randomized to LAUP or to no treatment (control group). The AHI post-LAUP was reduced by 21% overall and to 10 or less per hour in 5 of 21 subjects (24%). Four of 24 subjects in the control group (16.7%) had an AHI of 10 or less per hour at outcome. The AHI decreased with the LAUP compared with no change with the control group at outcome. Ten subjects (48%) reported significantly improved snoring after the LAUP. There was no improvement in excessive daytime sleepiness, but there was a small improvement in quality of life (unless side effects were included in the quality of life score). Side effects were common, but serious complications did not occur. LAUP surgery is effective in some subjects with mild OSA for the treatment of snoring, but the reduction in AHI and the level of symptomatic improvement were minor overall.

A multicomponent behavioral program for oral aversion in children dependent on gastrostomy feedings.

OBJECTIVES: Describe outcomes in nine children with Nissen fundoplication and feeding gastrostomy treated in a multicomponent feeding program. The importance of comprehensive evaluation, appetite regulation, and family-focused intervention within a behavioral feeding program are discussed. METHODS: Prospective clinical intervention with dependent measures evaluated before treatment, after treatment, and at follow-up. RESULTS: Nine children (4 girls; mean age, 3.1 +/- 1.2 years; range, 1.8-5.5 years) and their mothers were admitted for intensive treatment (mean duration, 11.4 +/- 1.7 days; range, 5-16 days). At discharge, 4 of 9 (44%) children were weaned completely from gastrostomy feedings. The mean oral intake of all patients increased 50% from pretreatment to posttreatment assessment. At a mean of 3.1 +/- 0.5 months (range, 2.4-3.6 months) after treatment, six of nine children were weaned completely from gastrostomy feedings. The percent of daily nutritional needs consumed orally increased from a pretreatment mean of 14.6% +/- 21.2% (range, 0%-67%) to a posttreatment mean of 63.4% +/- 18.3% (range, 34%-85%) and a follow-up mean of 88.1% +/- 25.1% (range, 30%-100%). The mean percent ideal body weight for height was not compromised during intensive treatment. CONCLUSIONS: Short-term intensive biobehavioral treatment was successful in improving oral intake and weaning from gastrostomy tube feeding in children with Nissen fundoplication and feeding gastrostomy.

Heart rate variability in obstructive sleep apnea: a prospective study and frequency domain analysis.

BACKGROUND: Cyclic variation of the heart rate is observed during apneic spells in obstructive sleep apnea (OSA). We hypothesized that autonomic changes would affect frequency-domain measures of heart rate variability (HRV). METHODS: We studied 20 patients (15 men, 5 women, mean age 47.2 +/- 12.2 years) with suspected OSA undergoing overnight polysomnography, and five patients (4 men, 1 woman, mean age 49.2 +/- 8.6 years) with recently diagnosed sleep apnea undergoing polysomnography while wearing continuous positive airway pressure (CPAP). Holter monitors were applied during sleep studies and data were analyzed in 5-minute blocks over the course of the night. Using spectral analysis, low frequency (LF) and high frequency (HF) powers were calculated for each interval. Overall mean and standard deviation (SD) for LF power, HF power, and the LF:HF ratio were recorded for each patient. Comparisons were made between patients with severe OSA (apnea hypopnea index (AHI) > 30, n = 8), moderate OSA (AHI 1-30, n = 5), without OSA (AHI < 10, n = 7), and patients wearing CPAP (n = 5). RESULTS: Assessment of overnight LF or HF power revealed no significant difference between the four groups. The LF:HF ratio, which represents sympathovagal balance, was higher among those with moderate disease compared to normals and those with severe OSA (both P = 0.037). The standard deviation of the LF:HF ratio was higher among those with moderate disease compared to normals (P = 0.0064) and those with severe OSA (P = 0.0006). OSA patients receiving CPAP behaved like patients with moderate OSA, with increased SD of the LF:HF ratio. CONCLUSIONS: The observed changes in the LF:HF ratio and its SD suggest an increased sympathetic tone and discordance in sympathovagal activity in moderate OSA, which is blunted in severe OSA. CPAP may restore autonomic defects, characteristic of severe OSA, to moderate levels.