Double vitrification and warming does not compromise the chance of live birth after single unbiopsied blastocyst transfer.

STUDY QUESTION: Does double vitrification and thawing of an embryo compromise the chance of live birth after a single blastocyst transfer? SUMMARY ANSWER: The live birth rate (LBR) obtained after double vitrification was comparable to that obtained after single vitrification. WHAT IS KNOWN ALREADY: Double vitrification-warming (DVW) is commonly practiced to accommodate surplus viable embryos suitable for transfer, to allow retesting of inconclusively diagnosed blastocysts in preimplantation genetic testing (PGT), and to circumvent limitations associated with national policies on embryo culture in certain countries. Despite its popularity, the evidence concerning the impact of DVW practice on ART outcomes is limited and lacking credibility. This is the first thorough investigation of clinical pregnancy and LBR following DVW in the case where the first round of vitrification occurred at the zygote stage and the second round occurred at the blastocyst stage in the absence of biopsy. STUDY DESIGN SIZE DURATION: This is a retrospective observational analysis of n = 407 single blastocyst transfers whereby embryos created by IVF/ICSI were vitrified-warmed once (single vitrification-warming (SVW) n = 310) or twice (DVW, n = 97) between January 2017 and December 2021. PARTICIPANTS/MATERIALS SETTING METHODS: In the SVW group, blastocysts were vitrified on Day 5/6 and warmed on the day of embryo transfer (ET). In the DVW group, two pronuclear (2PN) zygotes were first vitrified-warmed and then re-vitrified on Day 5/6 and warmed on the day of ET. Exclusion criteria were ETs from PGT and vitrified-warmed oocyte cycles. All of the ETs were single blastocyst transfers performed at the University Hospital Zurich in Switzerland following natural or artificial endometrial preparation. MAIN RESULTS AND THE ROLE OF CHANCE: The biochemical pregnancy rate, clinical pregnancy rate (CPR), and LBR were all comparable between the DVW and SVW groups. The CPR for DVW was 44.3% and for SVW it was 42.3% (P = 0.719). The LBR for DVW was 30.9% and for SVW it was 28.7% (P = 0.675). The miscarriage rate was additionally similar between the groups: 27.9% for DVW and 32.1% for SVW groups (P = 0.765). LIMITATIONS REASONS FOR CAUTION: The study is limited by its retrospective nature. Caution should be taken concerning interpretation of these findings in cases where DVW occurs at different stages of embryo development. WIDER IMPLICATIONS OF THE FINDINGS: The result of the present study on DVW procedure provides a framework for counselling couples on their chance of clinical pregnancy per warming cycle. It additionally provides confidence and reassurance to laboratory professionals in certain countries where national policies limit embryo culture strategies making DVW inevitable. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the University Research Priority Program 'Human Reproduction Reloaded' of the University of Zurich. The authors have no conflict of interest related to this study to declare. TRIAL REGISTRATION NUMBER: N/A.

Higher miscarriage rate in subfertile women with endometriosis receiving unbiopsied frozen-warmed single blastocyst transfers.

Background: Assisted reproductive technology treatment is recommended to overcome endometriosis-associated infertility but current evidence is controversial. Endometriosis is associated with lower antral follicle count (AFC) and oocyte yield but similar clinical outcomes compared to controls. Unaffected ovarian stimulation response and embryological outcomes but lower clinical pregnancy and live birth rates and higher miscarriage rates have been reported, implying direct impact on endometrial receptivity. With evidence emerging on the benefit of frozen-warmed and blastocyst stage transfer, we investigated ART outcomes in endometriosis using homogeneous case-control groups. Methods: This is a retrospective observational case-control study including n = 66 frozen-warmed unbiopsied single blastocyst transfers of patients with endometriosis and n = 96 of women exhibiting idiopathic sterility. All frozen-warmed transfers followed artificial endometrial preparation. Results: In control women, the mean number of oocytes recovered at oocyte pick up was higher compared to women with endometriosis (15.3 ± 7.1 vs. 12.7 ± 5.2, p = 0.025) but oocyte maturation index (mature oocytes/total oocytes at oocyte pick up) was significantly higher for endometriosis (48.2% vs. 34.0%, p = 0.005). The same was shown for the subgroup of 44 endometriosis patients after endometrioma surgery when compared with controls (49.1% vs. 34.0%, p = 0.014). Clinical pregnancy rate was not higher in endometriosis but was close to significance (47.0% vs. 32.3%, p = 0.059) while live birth rate was comparable (27.3% vs. 32.3%, p = 0.746). Miscarriage rate was higher in the endometriosis group (19.7% vs. 7.3%, p = 0.018). A significantly higher AFC was observed in the control group in comparison with the endometriosis group (16.3 ± 7.6 vs. 13.4 ± 7.0, p = 0.014). Live birth rate did not differ when comparing all endometriosis cases (p = 0.746), ASRM Stage I/II and Stage III/IV (p = 0.348 and p = 0.888) with the control group but the overall pregnancy rate was higher in ASRM Stage I/II (p = 0.034) and miscarriage rate was higher in ASRM Stage III/IV (p = 0.030) versus control. Conclusion: Blastocyst transfers in women with endometriosis originate from cycles with lower AFC but higher share of mature oocytes than in control women, suggesting that endometriosis might impair ovarian reserve but not stimulation response. A higher miscarriage rate, independent of blastocyst quality may be attributed to an impact of endometriosis on the endometrium beyond the timing of implantation.

Primary atony of the lower uterine segment as a distinct cause of early postpartum haemorrhage: a case series and management recommendations.

Primary atony of the lower uterine segment appears to be a distinct cause of postpartum haemorrhage. We report a case series of women with postpartum haemorrhage where ultrasound and clinical findings revealed a well contracted fundus and upper uterine segment and a ballooned out lower uterine segment, a condition we have called primary atony of the lower uterine segment. We hope that this case series will lead to increased recognition of this condition, stimulate others to report their experience and lead to additional studies to better characterise this entity, and develop more effective therapies.

Imipramine in prepubertal major depressive disorders.

The potential effectiveness of imipramine hydrochloride (up to 5 mg/kg/d) was investigated in 53 prepubertal children suffering from major depressive disorder. Two complementary strategies were used simultaneously: a five-week, double-blind, placebo-controlled design (N = 38), and a plasma level/clinical response study (N = 30). Fifteen of the 16 children randomly assigned to active drug in the first study also participated in the second. Subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children and diagnosed according to unmodified Research Diagnostic Criteria. Response rates in the double-blind study were similar in both groups (imipramine, 56%; placebo, 68%). In the plasma level study, total maintenance plasma level (imipramine plus desipramine) was found to positively and linearly predict clinical response of the depressive syndrome (P less than .003). No evidence of a curvilinear relationship was found. Depressive hallucinations during the episode negatively predicted clinical response (P less than .05). Weight-corrected imipramine dosage did not predict either clinical response or plasma level in the individual subject. No predictors of response were found in the placebo group. These results suggest that the mean imipramine dosage was too low, and that future double-blind, placebo-controlled studies of imipramine in prepubertal major depression should include plasma level titration to above 150 ng/mL and an initial placebo washout period.

Effect of propofol anesthesia on pallidal neuronal discharges in generalized dystonia.

We present the results of continuous microelectrode recordings from individual pallidal neurons in patients with idiopathic torsion dystonia under different levels of propofol anesthesia. Neither the estimated plasma concentration of propofol nor the level of consciousness had a consistent effect on abnormally low neuronal firing rates. Our data support the pathophysiological model of a decreased basal ganglia output in dystonia and argue against a possible pharmacological artifact.

Treatment options and results in cervical myelopathy.

Cervical myelopathy is a clinical entity resulting from external compression of the cervical medulla. The clinical course can be divided into the acute form (secondary to trauma) versus subacute (progression within weeks to months) and chronic cervical myelopathy (months to years). The clinical picture of myelopathy is that of unsteady gait with long-tract signs, such as hyperreflexia, spasticity and extensor plantar responses. Between 1997 and 2000, 359 consecutive patients have been operated on in our department presenting with a variety of symptoms related to compression of the cervical medulla. Beside of standard MRI for all patients we applied SSEPs, gait analysis and dynamic MRI studies as additional helpful tools in evaluating selected patients pre- and postoperatively. We prefer the anterior approach as first-line approach because in the majority of patients the osteophytic spurs are more dominant anteriorly, and after anterior decompression and stabilization the posterior approach appears safer. We also favor the more extended approach of spondylectomy versus multilevel decompression in patients with bisegmental or multisegmental spinal canal stenosis. However it seems to be that radicular decompression is better achieved through multilevel decompression than through spondylectomy.

Oral pemoline kinetics in hyperactive children.

The time course of pemoline in plasma was investigated in seven prepubescent boys with attention-deficit disorders who were hyperactive. Maximum plasma concentrations of 4.3 +/- 1.0 mg/L were reached 2.8 +/- 1.8 hours after a single, 2 mg/kg oral dose of pemoline, followed by a monoexponential decline in plasma concentration over time. Mean t1/2 and total body clearance of pemoline were 8.6 hours and 0.65 ml/min/kg. The 600% interindividual variation in elimination t1/2 and the 300% variation in total body clearance of pemoline may explain the unpredictable nature of its dynamics and associated neurotoxicity in some cases.

Targeting imipramine dose in children with depression.

The response to imipramine (IMI) in children with depression has been shown to correlate with total levels of IMI plus its active metabolite desmethylimipramine (DMI). The pharmacokinetics of IMI + DMI in children with depression are examined, and the single-point prediction of steady-state IMI + DMI levels at minimum therapeutic concentrations for prepubertal depression is proposed. With a single, 25 mg oral dose of IMI, a plasma concentration of IMI + DMI 24 hours after dosing correlates (r = 0.92) with steady-state IMI + DMI levels in children with depression receiving 3 mg/kg/day IMI. The targeting of IMI dose in the child population with depression to rapidly achieve a minimum therapeutic concentration is shown to be feasible and reliable within theoretic limits.

Nasal spray nicotine replacement suppresses cigarette smoking desire and behavior.

The effects of short-term nasal spray nicotine replacement in suppressing desire to smoke and ad libitum cigarette smoking behavior were evaluated in male and female smokers. In study I, 10 male and 10 female smokers received intermittent doses of 0, 7.5, 15, and 30 micrograms/kg nicotine by way of measured-dose nasal spray, with each dose on a separate day. Self-reported desire to smoke was significantly suppressed by each nicotine dose compared with placebo, but there were no significant differences among nicotine doses or between men and women. In study II, eight male and eight female smokers received 0, 15, and 30 micrograms/kg nicotine intermittently and were allowed to smoke their preferred brands of cigarettes ad libitum. Similar to study I, nicotine replacement significantly suppressed number of cigarettes smoked, number of puffs, and carbon monoxide boost and increased latency to smoking, but there were almost no significant differences between the two nicotine doses. Magnitude of smoking suppression attributable to 15 micrograms/kg tended to be greater in men than in women. However, plasma nicotine concentrations were significantly higher after 15 and 30 micrograms/kg versus placebo, suggesting only partial compensation in smoking behavior with short-term nasal nicotine replacement. These findings support the idea that short-term nicotine replacement decreases smoking desire and behavior, but the findings indicate that smoking behavior is partly influenced by factors other than nicotine regulation.

Acute effects of nicotine on resting metabolic rate in cigarette smokers.

The acute effects of nicotine on resting metabolic rate (RMR) were examined to identify a mechanism that may help explain the inverse association between smoking and body weight. Multiple administrations of two nicotine doses (moderate [15 micrograms/kg body wt] and low [7.5 micrograms/kg body wt]) and a placebo (0 micrograms) were presented to 18 male smokers via nasal-spray solution on three separate occasions while RMR was assessed by computerized open-circuit indirect calorimetry. Plasma nicotine levels confirmed the reliability of dosing. RMR increases of 6% above base line after both moderate and low doses were significantly greater than the 3% increase after the placebo. Subsequent examination of the effects of smoking a nonnicotine cigarette suggested that the small placebo effect was due to acute metabolic consequences of inhalation. These results confirm that intake of nicotine, isolated from tobacco smoke, significantly increases RMR in humans. However, the results also indicate that non-pharmacological, behavioral aspects of smoking may also contribute to acutely increasing RMR in smokers.

Metabolic effects of nicotine after consumption of a meal in smokers and nonsmokers.

The thermogenic effect of nicotine intake after calorie consumption was investigated to determine if nicotine influences metabolic response to a calorie challenge. Smokers and nonsmokers (10 males in each group), matched for body weight, age, and physical fitness, each participated in four sessions that involved consuming a liquid calorie load (4.77 kcal/kg body wt) or water, followed by nicotine (15 micrograms/kg body wt) or placebo via nasal spray every 20 min for 2 h. Energy expenditure was significantly increased above baseline resting metabolic rate (RMR) over the 2 h by nicotine alone (6.5% of RMR, p less than 0.01). However, the combined effect of nicotine after calorie load (20.1% of RMR, p less than 0.001) was not significantly greater than the effect of calorie load alone (18.4% of RMR, p less than 0.001). Smokers and nonsmokers did not differ in baseline RMR or in response to nicotine or calorie load. These results confirm the thermogenic effect of nicotine but suggest that the effect of nicotine after calorie consumption is less than additive.

Acute thermogenic effects of nicotine combined with caffeine during light physical activity in male and female smokers.

The thermogenic effects of nicotine and caffeine during physical activity compared with rest were examined in male and female smokers (n = 10 each). During eight sessions, nicotine (15 micrograms/kg) or placebo was given via measured-dose nasal spray intermittently after consumption of decaffeinated coffee with or without added caffeine (5 mg/kg), followed by assessment of energy expenditure by indirect calorimetry while subjects engaged in standardized, low-intensity cycle ergometer riding (activity) or remained at quiet rest. Results indicated significant thermogenic effects of nicotine and caffeine individually, with the combination of nicotine and caffeine producing additive effects. Expenditure attributable to nicotine, caffeine, or their combination was significantly enhanced during activity compared with rest, but only for males and not females. Plasma nicotine concentrations were influenced by activity and caffeine, but these pharmacokinetic changes did not appear to explain the differences in expenditure. These findings suggest a sex difference in thermogenic effects of nicotine and caffeine during casual physical activity and potentially explain some of the apparent individual variability in expenditure due to tobacco smoking.

Event-related potentials and models of performance asymmetries in face and word recognition.

Performance asymmetries in divided visual field studies may be ascribed either to hemispheric differences in processing efficiency or to the costs of interhemispheric transfer towards the superior hemisphere. In order to distinguish between these alternatives, event-related potentials (ERPs) were recorded while subjects had to recognize laterally presented faces or words. As expected, behavioural left- and right-field advantages were observed for faces and words, respectively. Regardless of stimulus type, the ERPs displayed a sustained temporo-parietal negativity over the hemisphere stimulated directly via the contralateral hemifield. Both this hemifield-dependent negativity (HDN) and the performance asymmetries diminished to insignificance when the same stimuli were presented but subjects simply made a left-right decision about stimulus location. We conclude that the HDN is no obligatory, stimulus-bound ERP component but depends on lateralized cognitive processing. The stimulus-unspecific and time-invariant topography of the HDN might indicate that it relates to the allocation of processing resources to the directly stimulated hemisphere. The findings suggest that both faces and words were processed predominantly in the directly stimulated hemisphere, supporting an efficiency explanation of the performance asymmetries.

Neurochemical and physiological effects of cocaine oscillate with sequential drug treatment: possibly a major factor in drug variability.

Variability in response to drug treatment is a poorly understood problem with severe consequences for both the individual and the health care delivery system. Our data suggest that one source of variability may be inherent in the way physiological systems normally respond to repeated drug exposures. We report that for a wide array of endpoints-amphetamine-evoked, in vitro striatal dopamine efflux, amphetamine and K(+)-evoked efflux of heart norepinephrine and nonevoked plasma levels of corticosterone and glucose-repeated, in vivo cocaine (15 mg/kg IP) administration to male rats precipitated successive oscillations in the magnitude or direction of the organism's responsiveness to subsequent cocaine administration. This capacity of cocaine to produce oscillations in response to successive administrations appears to be due to its foreign/stressful aspect rather than its specific pharmacological properties.

Experience with ketoconazole in three major manifestations of progressive coccidioidomycosis.

Forty-seven courses of oral ketoconazole therapy administered to 46 patients with progressive coccidioidomycosis were evaluated. Responses, of varying degrees evaluated by a point system, occurred in 81, 94, and 91 percent of courses evaluated for skeletal, chronic pulmonary, and cutaneous disease, respectively. Presumed side effects occurred in 26 percent of courses and were generally minor and reversible. Relapse occurred in 33, 33, and 11 percent of evaluable responding patients with skeletal, chronic pulmonary and cutaneous disease, respectively. From this experience, ketoconazole appears to be an important advance in the therapy of chronic coccidioidomycosis. Whether cure is possible will require further study and follow-up.

Intraspinal release of immunoreactive calcitonin gene-related peptide during development of inflammation in the joint in vivo--a study with antibody microprobes in cat and rat.

This study addressed the intraspinal release of immunoreactive calcitonin gene-related peptide in vivo during mechanical stimulation of the normal joint and during the development of an acute experimental inflammation in the knee joint in the anaesthetized cat (spinalized) and rat (not spinalized). Release was assessed using microprobes coated with antibody to calcitonin gene-related peptide; inhibition of binding of [125I]calcitonin gene-related peptide to these probes following insertion into the spinal cord is equated with intraspinal release of the endogenous (unlabelled) peptide. Probes inserted prior to inflammation showed marked basal release of immunoreactive calcitonin gene-related peptide in the dorsal horn with a maximum in the superficial dorsal horn in the absence of intentional stimulation. The pattern of binding of [125I]calcitonin gene-related peptide was not or only minimally changed by innocuous mechanical stimuli (flexion of and innocuous pressure to the knee in the cat and innocuous pressure to the knee of the rat) but was significantly altered by electrical stimulation of the tibial nerve in the cat (sufficient to excite unmyelinated afferent fibres), indicating release of the peptide by the latter stimulus. During the first hours of the development of an experimental inflammation in the knee joint induced by intra-articular injections of kaolin and carrageenan, the pattern of binding of [125I]calcitonin gene-related peptide changed. In the cat, the level of immunoreactive calcitonin gene-related peptide showed a persistent increase in the gray matter and up to the surface of the cord and release was slightly increased by innocuous stimuli. In the rat, increased levels of immunoreactive calcitonin gene-related peptide were mainly seen in the superficial and deep dorsal horn during innocuous pressure (this stimulus did not evoke release of the peptide prior to inflammation) and noxious pressure applied to the injected knee, whereas increased basal levels were only observed at later stages. These data show that the development of an acute experimental inflammation in the joint is associated with an enhancement of the intraspinal release of immunoreactive calcitonin gene-related peptide. Since the changes in the release were noted at an early stage, within the first hours, they could contribute to the generation of inflammation-evoked changes of the responsiveness of spinal cord neurons and hence to the mechanisms inducing inflammatory pain.

Split-night studies for the diagnosis and treatment of sleep-disordered breathing.

We examined the effect of split-night polysomnography on compliance with positive pressure via a mask for the treatment of obstructive sleep-disordered breathing. A comparison of objective compliance (hours/day) at the first meter read from the positive-pressure device (4-6 weeks after set-up) in patients who had a successful split-night positive-pressure titration vs. patients who had traditional full-night positive-pressure titration was performed. Patients were matched for age, sex, and severity of the obstructive sleep-disordered breathing. Twelve patients were matched with controls who underwent full-night polysomnography. There were no significant differences between the split-night patients and the full-night patients with regard to age, sex, body mass index, and pretreatment Epworth Sleepiness Score. In addition, there was no significant difference between apnea-hypopnea index and the desaturation-event frequency for both groups pre- and post-treatment. The average daily use of continuous positive airway pressure (CPAP) at the time of the first meter reading in the group that underwent full-night positive-pressure titrations as opposed to split-night titrations was 5.2 hours/day +/- 2.2 vs. 3.8 hours/day +/- 2.9, respectively (p = 0.29). The Epworth Sleepiness Scale on the initial clinic visit (as an index of patient-perceived impairment) did not predict compliance at 4-6 weeks. The time at the final positive pressure did not correlate with compliance. Acceptance of positive pressure in the split-night patients ranged from 62 to 67%.

Resolution of obstructive sleep apnea after microvascular brainstem decompression.

Lesions of the brainstem have been associated with obstructive sleep apnea in previous reports. We now report a case in which retromastoid craniectomy with microvascular decompression of the medulla and ninth and tenth cranial nerves resulted in the complete resolution of severe obstructive sleep apnea. Possible mechanisms for this observation are discussed.

Accuracy of end-tidal and transcutaneous PCO2 monitoring during sleep.

STUDY OBJECTIVE: Although it is intuitively desirable, the measurement of arterial carbon dioxide tension (PaCO2) during diagnostic polysomnography and nocturnal trials of positive pressure therapy is invasive and potentially expensive. The accuracy of end-tidal carbon dioxide tension (PETCO2) and transcutaneous carbon dioxide (tcPCO2) monitoring in these contexts has not been systematically evaluated. This investigation was undertaken to evaluate the accuracy of PETCO2 and tcPCO2 in patients undergoing polysomnography. METHODS AND PROCEDURES: Values of PETCO2 were compared with PaCO2 in 19 patients spontaneously breathing room air (condition 1), in 13 patients receiving supplemental oxygen via nasal cannula (condition 2), and in 22 patients receiving nocturnal positive pressure ventilatory assistance (all but one with continuous positive airway pressure or bilevel positive airway pressure) (condition 3). The accuracy of tcPCO2 monitoring during sleep was also examined by comparing tcPCO2 values with simultaneously recorded PaCO2 values obtained during sleep in patients undergoing nocturnal polysomnography. Data were collected using three commercially available brands of tcPCO2 monitors (capnograph R, n = 17 patients; capnograph S, n = 17; and capnograph N, n = 15). RESULTS: Accuracy of PETCO2--There was significant scatter in the PaCO2 vs PETCO2 relationship such that only 23 percent of the variability in PaCO2 was explained by variation of PETCO2 during condition 1 and only 15 percent and 20 percent of the variability in PaCO2 was explained by variation of PETCO2 during conditions 2 and 3, respectively. 21.3 percent of patients had average PETCO2 values in error by > 10 mm Hg during condition 1, while during conditions 2 and 3, 46.2 and 63.7 percent of patients had average values in error by > 10 mm Hg, respectively. Accuracy of tcPCO2--While capnographs S and N generally overestimated PaCO2 with a wide scatter, capnograph R tended to have offsetting overestimations and underestimations of PaCO2 with a wide scatter. With each capnograph, a relatively small portion of the variability of the PaCO2 was explained by variability of the tcPCO2 (r2 = 0.2, 0.45 and 0.64 for capnographs S, N, and R, respectively). Across the three capnographs, 43.1 to 66.7 percent of measurements were in error by > 10 mm Hg, and 5 to 20 percent of measurements reflected errors > 20 mm Hg. There was no consistent relationship between the tcPCO2 error and the level of PaCO2, nor was the tcPCO2 error consistent in individual patients. There was no relationship between tcPCO2 accuracy and body mass index. CONCLUSION: Neither PETCO2, measured within a face mask, nor tcPCO2 is a consistently accurate reflection of PaCO2. This limits the utility of these variables in monitoring patients during diagnostic and therapeutic sleep studies, and in particular, during trials of nocturnal ventilatory assistance where adequate levels of support are to be established and unacceptable hyperventilation and respiratory alkalosis must be recognized.

CPAP therapy via oronasal mask for obstructive sleep apnea.

STUDY OBJECTIVE: To determine the effectiveness of oronasal masks for positive pressure therapy in alleviating obstructive sleep apnea (OSA). METHODS AND PROCEDURES: Polysomnographic records of all 245 patients with OSA who underwent therapeutic trials of either continuous positive airway pressure (CPAP) or bilevel positive airway pressure between January 1991 and December 1992 were reviewed. Thirty patients who had been prescribed positive pressure therapy employing an oronasal mask were identified. Two patients known to be successfully treated with CPAP via oronasal mask underwent repeat polysomnography. The initial portion of the study was a diagnostic evaluation during which the patients were untreated. During the second portion of the study, both patients used CPAP via an oronasal mask while wearing a mouthpiece designed to maintain oral patency. RESULTS: The 30 patients with OSA who were identified in this study had significant amelioration of OSA while receiving positive pressure therapy via oronasal mask compared with the baseline, diagnostic polysomnogram (apnea index: 55.3 +/- 36.9-->1.6 +/- 3.7, p < 0.001; hypopnea index: 21.2 +/- 20-->2.7 +/- 4.9, p < 0.001; nadir of SaO2: 72.5 +/- 13.9-->87.1 +/- 4.3, p < 0.001, mean +/- SD). Improvement of OSA did not depend on maintenance of a closed mouth, as evidenced by elimination of sleep-disordered breathing in the two patients receiving positive pressure via oronasal mask while wearing a mouthpiece to keep the mouth open. CONCLUSION: Oronasal masks are a viable alternative interface for alleviating OSA with positive pressure therapy in those patients who are unwilling or unable to tolerate conventional nasal interfaces. Although there were no adverse consequences associated with the use of oronasal masks in our patients, appropriate safety precautions should be taken to minimize the possibility of aspiration of gastric contents and avoid untoward sequelae due to positive pressure device failure.