Peri-pharyngeal muscle response to inspiratory loading: comparison of patients with OSA and healthy subjects.

Upper airway patency to airflow and the occurrence of obstructive sleep apnea involve a complex interplay between pharyngeal anatomy and synergic co-activation of peri-pharyngeal muscles. In previous studies we observed large differences in the response to sleep-associated flow limitation between the genioglossus and other (non-GG) peri-pharyngeal muscles. We hypothesized that similar differences are present also during wakefulness. In the present study we compared the response to inspiratory loading of the genioglossus electromyogram and four other peri-pharyngeal muscles. Studies were performed in eight obstructive sleep apnea patients, seven age-matched healthy subjects and five additional younger subjects. Electromyogram activity was evaluated over a range of negative oesophageal pressures and expressed as % of maximal electromyograms. In healthy subjects, the slope response to inspiratory loading (electromyogram/pressures) was similar for the genioglossus and non-GG muscles studied. However, the electromyogram responses were significantly higher in the young subjects compared with older subjects. In contrast, in the obstructive sleep apnea patients, the electromyogram/pressure response of the non-GG muscles was similar to that of the age-matched healthy subjects, whereas the slope response of the genioglossus electromyogram was significantly higher than non-GG muscles. We conclude that both age and the presence of obstructive sleep apnea affect the response of peri-pharyngeal muscles to inspiratory loading. In patients with obstructive sleep apnea the genioglossus seems to compensate for mechanical disadvantages, but non-GG muscles apparently are not included in this neuromuscular compensatory mechanism. Our current and previous findings suggest that attempts to improve obstructive sleep apnea with myofunctional therapy should put added emphasis on the training of non-GG muscles.

Dissociation of electromyogram and mechanical response in sleep apnoea during propofol anaesthesia.

Pharyngeal collapsibility during sleep is believed to increase due to a decline in dilator muscle activity. However, genioglossus electromyogram (EMG) often increases during apnoeas and hypopnoeas, often without mechanical effect. 17 patients with obstructive sleep apnoea were anaesthetised and evaluated from termination of propofol administration to awakening. Genioglossus EMG, flow and pharyngeal area (pharyngoscopy) were monitored. Prolonged hypopnoeas enabled evaluation of the relationships between genioglossus EMG and mechanical events, before and after awakening. Additional dilator muscle EMGs were recorded and compared to the genioglossus. Electrical stimulation of the genioglossus was used to evaluate possible mechanical dysfunction. Prolonged hypopnoeas during inspiration before arousal triggered an increase in genioglossus EMG, reaching mean ± SD 62.2 ± 32.7% of maximum. This augmented activity failed to increase flow and pharyngeal area. Awakening resulted in fast pharyngeal enlargement and restoration of unobstructed flow, with marked reduction in genioglossus EMG. Electrical stimulation of the genioglossus under propofol anaesthesia increased the inspiratory pharyngeal area (from 25.1 ± 28 to 66.3 ± 75.5 mm(2); p<0.01) and flow (from 11.5 ± 6.5 to 18.6 ± 9.2 L · min(-1); p<0.001), indicating adequate mechanical response. All additional dilators increased their inspiratory activity during hypopnoeas. During propofol anaesthesia, pharyngeal occlusion persists despite large increases in genioglossus EMG, in the presence of a preserved mechanical response to electrical stimulation.

[Medical students' views on the use of virtual patients for teaching and assessment of clinical knowledge and reasoning].

BACKGROUND: Computerized cLinical cases ["virtual patient" (VP)] provide a useful teaching and assessment tool for clinicaL knowledge and skiLLs. However, the attitude of medical students toward this new modality needs to be evaluated. We examined students' acceptance of a web-based VP system that was deveLoped in the Technion Faculty of Medicine for teaching and assessment purposes. The VP system enables free conversation (in writing) for history taking and listing of disease symptoms. It aLso depicts images and audio-videos of heart and lung sounds, and enables users to order Laboratory and imaging tests. The system was designed to be learnt without instructors and to provide feedback online. Therefore, the process of Learning and practicing with the VP system was performed by the students at home, during their free time. METHODS: At the end of the clinical introductory course to internal medicine, students (n=91) were asked to complete questionnaires and rate multiple aspects of the VP system. RESULTS: Student acceptance of this web-based modality was high: over 95% fully or partially accepted that the VP practice system facilitates Learning the approach to diseases they were not exposed to during the course, practicing differential diagnosis, and improving their knowledge, clinicaL skills and reasoning. A similar percentage of the students agreed that the VP exam assessed their clinical knowledge and comprehension adequately, correctly and objectively. CONCLUSIONS: These results document high acceptance of web-based instruction and assessment by medical students. However, many students expect that a clinical course should also include bed-side assessment.

Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation.

STUDY OBJECTIVES: The major goal of the study was to determine whether changes in tongue morphology under selective hypoglossal nerve therapy for obstructive sleep apnea were associated with alterations in airway patency during sleep when specific portions of the hypoglossal nerve were stimulated. METHODS: This case series was conducted at the Johns Hopkins Sleep Disorders Center at Johns Hopkins Bayview Medical Center. Twelve patients with apnea implanted with a multichannel targeted hypoglossal nerve-stimulating system underwent midsagittal ultrasound tongue imaging during wakefulness. Changes in tongue shape were characterized by measuring the vertical height and polar dimensions between tongue surface and genioglossi origin in the mandible. Changes in patency were characterized by comparing airflow responses between stimulated and adjacent unstimulated breaths during non-rapid eye movement sleep. RESULTS: Two distinct morphologic responses were observed. Anterior tongue base and hyoid-bone movement (5.4 [0.4] to 4.1 [1.0] cm (median and [interquartile range]) with concomitant increases in tongue height (5.0 [0.9] to 5.6 [0.7] cm) were associated with decreases in airflow during stimulation. In contrast, comparable anterior hyoid movement (tongue protrusion from 5.8 [0.5] to 4.5 [0.9] cm) without significant increases in height (5.2 [1.6] to 4.6 [0.8] cm) were associated with marked increases in airflow during sleep. CONCLUSIONS: Tongue protrusion with preservation of tongue shape predicted increases in patency, whereas anterior movement with concomitant increases in height were associated with decreased pharyngeal patency. These findings suggest that pharyngeal patency can be best stabilized by stimulating lingual muscles that maintain tongue shape while protruding the tongue, thereby preventing it from prolapsing posteriorly during sleep. CITATION: Fleury Curado T, Pham L, Otvos T, et al. Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation. J Clin Sleep Med. 2023;19(5):947-955.

Targeted Hypoglossal Nerve Stimulation for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA). Objective: To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA. Design, Setting, and Participants: This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023. Intervention: Implant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively. Main Outcomes and Measures: Primary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale). Results: Among 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol. Conclusions and Relevance: This randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI. Trial Registration: ClinicalTrials.gov Identifier: NCT02263859.

Treatment of acute exacerbations of chronic obstructive pulmonary disease with acupuncture during hospitalization: a three-arm double-blinded randomized sham-controlled trial.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a healthcare burden. Acupuncture improves dyspnea in patients with chronic obstructive pulmonary disease (COPD) but, to the best of our knowledge, has not been tested in AECOPD. Here, we evaluated the efficacy and safety of true acupuncture added to standard of care (SOC), as compared with both sham procedure plus SOC and SOC only, for the treatment of AECOPD among inpatients. METHODS: This double-blinded randomized sham-controlled trial was set in a tertiary hospital in Israel. Patients with a clinical diagnosis of AECOPD were assigned to true acupuncture with SOC, sham procedure with SOC or SOC only. The primary outcome was dyspnea improvement as measured daily by the validated modified Borg (mBorg) scale. Secondary outcomes included improvement of other patient-reported outcomes and physiologic features, as well as duration of hospitalization and treatment failure. Acupuncture-related side effects were evaluated by the validated Acup-AE questionnaire. RESULTS: Seventy-two patients were randomized: 26 to acupuncture treatment, 24 to sham and 22 to SOC only arms. Baseline characteristics were similar in the three groups. A statistically significant difference in dyspnea intensity was found from the first day of evaluation after treatment (p = 0.014) until day 3 after treatment. Similar results were found for sputum production, but no statistical significance was found when comparing physiologic features between the three arms. Acupuncture was not associated with adverse events. CONCLUSION: Acupuncture seems to be efficacious in the treatment of AECOPD among inpatients hospitalized in internal medicine departments. TRIAL REGISTRATION NUMBER: NCT03398213 (ClinicalTrials.gov).

Treating obstructive sleep apnea with hypoglossal nerve stimulation.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent pharyngeal collapse secondary to sleep-induced hypotonia of peri-pharyngeal structures. Therapy for OSA is sometimes poorly tolerated and not always effective. The current study reviews a new treatment modality, hypoglossus stimulation, recently evaluated by multiple physiological studies and currently assessed by several clinical studies. RECENT FINDINGS: A phase-I, implantable hypoglossus nerve stimulation multicenter study was published in 2001. Significant reduction in apnea-hypopnea index (AHI) was reported in seven of the eight implanted OSA patients, but technical faults precluded prolonged follow-up. Over the past 2 years, three new hypoglossus nerve stimulation systems have been evaluated in more than 60 OSA patients. In adequately selected patients, a more than 50% reduction in AHI was observed. Usually, a decrease in OSA severity from moderate-severe to mild-minimal can be achieved. SUMMARY: Ongoing research, including recent initiation of a large multicenter phase-III study, suggests that hypoglossus nerve stimulators are likely to be available as a new treatment modality within a few years. Additional data are needed to define which OSA patients are most likely to benefit from hypoglossus nerve stimulation. Continuous refinement of electrodes design is likely to improve stimulation efficacy in coming years.

Long experience with a web-based, interactive, conversational virtual patient case simulation for medical students' evaluation: comparison with oral examination.

Virtual patients (VP) have been advocated as reliable tools for teaching and evaluating clinical skills and competence. We have developed an internet-based, OSCE-like, conversational VP system designed both for training and assessment of medical students. The system, that encompasses complete patient management from H&P to diagnostic procedures and treatment, has now been used regularly during the clerkship of internal medicine. The present article describes the system and compares assessments undertaken with the VP-system over the last five years, to traditional bed-side oral exams. All students practiced on their own exercise VP cases, while preparing for the final exam. A total of 586 students were evaluated simultaneously with both assessment modalities. The αCronbach of the VP exam averaged 0.86. No correlation was found between the grades obtained in the two exams, indicating that the VP exam evaluated different parameters than those assessed by the examiners in the oral examinations. We conclude that a VP system can be utilized as a valid and reliable examination tool. It is also most useful for independent training by students during their ward-based learning, as well as when not studying in classes, wards or clinics, when social distancing is required.

Relationship between the activity of the genioglossus, other peri-pharyngeal muscles and flow mechanics during wakefulness and sleep in patients with OSA and healthy subjects.

INTRODUCTION: In patients with OSA, substantial increases in genioglossus (GG) activity during hypopneas/apneas usually fail to restore normal airflow. The present study was undertaken to evaluate if this phenomenon can be explained by reduced activation of other peri-pharyngeal muscles. METHODS: We recorded EMGs of the GG and four other peri-pharyngeal muscles (accessory dilators, AD), in 8 patients with OSA and 12 healthy subjects, during wakefulness and sleep. Repetitive events of flow limitation were induced during sleep. The events with the highest increases in AD activity were evaluated, to assess if combined activation of both the GG and AD to levels higher than while awake ameliorate airflow reduction during sleep. RESULTS: Flow limitation triggered large increases in GG-EMG, but only modest augmentation in AD activity. Nevertheless, phasic EMG activity was present in 40 % of the ADs during sleep. In multiple events, increases of both GG and AD activity to levels substantially higher than while awake were not associated with improvement in airflow. CONCLUSIONS: We conclude that sleep-induced reduction in AD response to airway obstruction cannot completely explain the failure of upper airway dilators to maintain pharyngeal patency. We speculate that reduction in dilator muscle efficacy may be due to the alterations in motor units recruitment patterns during sleep.

Interacting effects of genioglossus stimulation and mandibular advancement in sleep apnea.

Both mandibular advancement (MA) and stimulation of the genioglossus (GG) have been shown to improve upper airway patency, but neither one achieves the effect of continuous positive airway pressure (CPAP) treatment. In the present study we assessed the combined effect of MA and GG stimulation on the relaxed pharynx in patients with obstructive sleep apnea (OSA). We evaluated responses of upper airway pressure-flow relationships and endoscopically determined pharyngeal cross-sectional area to MA and electrical stimulation of the GG in 14 propofol-anesthetized OSA patients. Measurements were undertaken at multiple levels of CPAP, enabling calculation of the critical closing pressure (Pcrit), upstream resistance (Rus), and pharyngeal compliance. GG stimulation, MA, and the combination of both shifted the pressure:flow relationships toward higher flow levels, resulting in progressively lower Pcrit (from baseline of 2.9 +/- 2.2 to 0.9 +/- 2.5, -1.4 +/- 2.9, and -4.2 +/- 3.3 cmH(2)O, respectively), without significant change in Rus. DeltaPcrit during GG stimulation was significantly larger during MA than under baseline conditions (-2.8 +/- 1.4 vs. -2.0 +/- 1.4 cmH(2)O, P = 0.011). Combining the effect of GG stimulation with MA lowered Pcrit below 0 in all patients and restored pharyngeal patency to a level that enabled flow above the hypopnea level in 10/14 of the patients. Velopharyngeal compliance was not affected by either manipulation. We conclude that the combined effect of MA and GG stimulation is additive and may act in synergy, preventing substantial flow limitation of the relaxed pharynx in most OSA patients.

[Electrical stimulation of the genioglossus to improve pharyngeal patency in obstructive sleep apnea: comparison of results obtained during sleep and anesthesia].

Contraction of the geniogtossus (GG) has been shown to improve upper airway patency in patients with sleep apnea during sleep and anesthesia. However, a large variability in response exists, requiring selection of adequate patients if GG stimulation should be used as a treatment modality. In the present study, we compared responses in upper airway pressure-flow relationships to electrical stimulation of the GG in patients with obstructive sleep apnea during sleep and mild anesthesia. Nine patients studied during sleep were matched with 9 patients evaluated during propofol anesthesia. Stimulation was performed with fine wire electrodes inserted near the mandibular insertion of the GG. Airflow was measured at muLtiple levels of CPAP, and upper airway collapsibility was defined by the pressure below which airflow ceased (the "critical" pressure, Pcrit). ELectrical stimulation shifted the pressure-flow reLationships toward higher flow Levels in all patients over the entire range of CPAP applied. Pcrit decreased significantly during stimulation-induced contraction of the GG, and similarly in the patients evaluated during sleep and during anesthesia (from 1.6 +/- 2.0 to -1.6 +/- 2.5, and from 1.8 +/- 1.8 to -0.2 +/- 1.8 cmH2O, during steep and anesthesia, respectively, p < 0.01, without a significant change in upstream resistance. Our findings imply that responses in Pcrit to electrical stimulation of the main tongue protrusor during propofoL anesthesia may reflect those observed during sleep, and evaluation of the response of sleep apnea patients to GG stimulation can be evaluated during short anesthesia.

Spectral analysis of peri-pharyngeal muscles' EMG in patients with OSA and healthy subjects.

INTRODUCTION: In addition to dyscoordination of upper airway dilator muscles activity, sleep may also alter the pattern of intra-muscular activation of single motor units (SMUs). Such changes should be identifiable by a state dependent change in EMG power spectrum, i.e., a shift in centroid frequency (ƒc) during sleep. METHODS: EMGs of the genioglossus and four other peri-pharyngeal muscles were recorded in OSA patients (n = 8), age-matched healthy subjects (n = 7), and 5 young healthy subjects, and ƒc was calculated for wakefulness and sleep periods. RESULTS: ƒc decreased with the onset of sleep and returned to baseline levels after arousal. ƒc of all muscles decreased similarly and significantly during sleep in the OSA and the age-matched healthy subjects, but not in the young subjects. CONCLUSIONS: The pattern of decrease in ƒc is compatible with altered synchronization of SMUs during sleep. We speculate that these changes may contribute to the failure of dilator muscles to improve flow limitation during sleep in older subjects.

A simplified fall-risk assessment tool for patients hospitalized in medical wards.

BACKGROUND: Falls are a common problem among hospitalized patients, having a significant impact on quality of life and resource utilization. OBJECTIVES: To develop and validate a fall-risk assessment tool for patients hospitalized in the department of medicine that will combine simplicity with adequate accuracy for routine use. METHODS: This observational cohort study was conducted on the medical wards of an urban tertiary teaching hospital, and included all patients who fell in the medical wards during a 1 year period (n = 140) compared to other hospitalized patients. RESULTS: Significant correlates of falls were previous falls, impairing medical conditions, impaired mobility, and altered mental state. In multivariate logistic regression analyses, only previous falls (odds ratio 3.8 with 95% confidence interval 2.65-5.45, P < 0.0001) and acute impairing medical conditions (OR 1.56, CI 1.06-2.29, P < 0.05) correlated independently with a higher risk for falls. Impaired mobility retained an OR of 1.46 (CI 0.95-2.24, P = 0.084). Accordingly, defining patients with either a history of previous falls or both acute impairing medical state and impaired mobility as fall-prone patients provided a sensitivity and specificity of 67% and 63%, respectively. In a subsequent prospective validation trial on 88 patients who fell during hospitalization and 436 controls, the sensitivity and specificity of this fall-risk grouping were 64% and 68% respectively. CONCLUSIONS: Our new simple and easy-to-use fall-risk assessment tool identified most of the fall-prone patients. These findings suggest that this tool may enable us to prevent two-thirds of falls on the medical ward by providing effective fall-prevention facilities to only one-third of the patients.

Alteration in upper airway dilator muscle coactivation during sleep: comparison of patients with obstructive sleep apnea and healthy subjects.

In patients with obstructive sleep apnea (OSA), substantial increases in genioglossus (GG) activity during hypopneas/apneas usually fail to restore normal airflow. We have previously suggested that sleep-induced alteration in tongue muscle coordination may explain this finding, as retractor muscle coactivation was reduced during sleep compared with wakefulness. The present study was undertaken to evaluate whether these alterations in dilator muscle activation during sleep play a role in the pathogenesis of OSA and whether coactivation of additional peripharyngeal muscles (non-GG muscles: styloglossus, geniohyoid, sternohyoid, and sternocleidomastoid) is also impaired during sleep. We compared GG and non-GG muscle electromyographic (EMG) activity in 8 patients with OSA and 12 healthy subjects during wakefulness while breathing through inspiratory resistors with the activity observed during sleep toward the end of flow limitation, before arousal, at equivalent esophageal pressures. During wakefulness, resistive breathing triggered increases in both GG and non-GG muscle activity. During sleep, flow limitation was associated with increases in GG-EMG that reached, on average, >2-fold the level observed while awake. In contrast, EMGs of the non-GG muscles, recorded simultaneously, reached, on average, only ~2/3 the wakefulness level. We conclude that during sleep GG activity may increase to levels that substantially exceed those sufficient to prevent pharyngeal collapse during wakefulness, whereas other peripharyngeal muscles do not coactivate during sleep in both patients with OSA and healthy subjects. We speculate that upper airway muscle dyssynchrony during sleep may explain why GG-EMG activation fails to alleviate flow limitation and stabilize airway patency during sleep. NEW & NOTEWORTHY Pharyngeal obstruction during sleep may trigger genioglossus activity to levels substantially exceeding those observed during wakefulness, without ameliorating flow limitation. In contrast, other peripharyngeal muscles exhibit a much lower activity during sleep in both patients with obstructive sleep apnea and healthy subjects. Coordinated muscular synergy stabilizes the pharynx despite relatively low activity while awake, yet even higher genioglossal activity allows the pharynx to obstruct when simultaneous activity of other dilator muscles is inadequate during sleep.

Neurostimulation Treatment of OSA.

Over the past 30 years, hypoglossal nerve stimulation has moved through a development pathway to become a viable treatment modality for patients with OSA. Initial pilot studies in animals and humans laid the conceptual foundation for this approach, leading to the development of fully implantable stimulating systems for therapeutic purposes. These devices were then shown to be both safe and efficacious in feasibility studies. One such closed-loop stimulating device was found to be effective in treating a limited spectrum of apneic patients and is currently approved by the US Food and Drug Administration for this purpose. Another open-loop stimulating system is currently being rigorously tested in a pivotal trial. Collectively, clinical trials of hypoglossal nerve stimulating systems have yielded important insights that can help optimize therapeutic responses to hypoglossal nerve stimulation. These insights include specific patient selection criteria and methods for delivering stimulation to specific portions of the hypoglossal nerve and/or genioglossus muscle. New approaches for activating efferent and afferent motor pathways are currently in early-stage laboratory development and hold some long-term promise as a novel therapy.

Effect of coactivation of tongue protrusor and retractor muscles on pharyngeal lumen and airflow in sleep apnea patients.

The present study evaluated the effect of coactivation of tongue protrusors and retractors on pharyngeal patency in patients with obstructive sleep apnea. The effect of genioglossus (GG), hyoglossus (HG), and coactivation of both on nasal pressure (Pn):flow relationships was evaluated in a sleep study (SlS, n = 7) and during a propofol anesthesia study (AnS, n = 7). GG was stimulated with sublingual surface electrodes in SlS and with intramuscular electrodes in AnS, while HG was stimulated with surface electrodes in both groups. In the AnS, the cross-sectional area (CSA):Pn relationships was measured with a pharyngoscope to estimate velopharyngeal compliance . In the SlS, surface stimulation of GG had no effect on the critical pressure (Pcrit), HG increased Pcrit from 2.8 +/- 1.7 to 3.7 +/- 1.6 cmH(2)O, but coactivation lowered Pcrit to 0.2 +/- 1.9 cmH(2)O (P < 0.01 for both). In the AnS, intramuscular stimulation of GG lowered Pcrit from 2.6 +/- 1.3 to 1.0 +/- 2.8 cmH(2)O, HG increased Pcrit to 6.2 +/- 2.5 cmH(2)O (P < 0.01), and coactivation had a similar effect to that of GG (Pcrit = 1.2 +/- 2.4 cmH(2)O, P < 0.05). None of the interventions affected significantly velopharyngeal compliance. We conclude that the beneficial effect of coactivation depends on the pattern of GG fiber recruitment: although surface stimulation of GG failed to protrude the tongue, it prevented the occlusive effect of the retractor, thereby improving pharyngeal patency during coactivation. Stimulation of deeper GG fibers with intramuscular electrodes enlarged the pharynx, and coactivation had no additive effect.

Circulating levels of tumor necrosis factor-alpha correlate positively with severity of peripheral oedema in patients with right heart failure.

BACKGROUND: Several previous studies have shown that circulating levels of tumor necrosis factor-alpha (TNF) are elevated in patients with advanced congestive heart failure. However, the relationship between circulating levels of TNF and severity of peripheral oedema in these patients has not been previously evaluated. AIMS: To investigate the relationship between circulating levels of TNF, and severity of peripheral oedema in patients with right-sided heart failure (RHF). METHODS AND RESULTS: Circulating levels of TNF were measured in 15 healthy volunteers, and in 83 patients with RHF with various levels of peripheral oedema. At presentation, 13 patients had no peripheral oedema (grade 0), 22 patients had mild peripheral oedema (grade 1), 23 patients had moderate peripheral oedema (grade 2), and 25 patients had severe peripheral oedema (grade 3). The values of circulating TNF levels (mean +/- S.E.M.) at presentation in the control group and in the RHF patients (oedema grades 0-3) were 2.98+/-0.21, 4.22+/-0.55, 4.67+/-0.29, 7.66+/-0.44, and 10.94+/-0.67 pg/mL respectively. There was a significant difference between the groups (p < 0.0001, ANOVA), and a significant positive correlation was found between circulating TNF levels and severity of peripheral oedema (r = 0.77, p<0.0001). CONCLUSION: A significant relationship is present between circulating levels of TNF and severity of peripheral oedema in patients with RHF.

Prevention of prescription errors by computerized, on-line surveillance of drug order entry.

AIMS: The present study was undertaken to quantify the impact of computerized drug order entry system (CDOE) connected to the patients' database, on the incidence and type of prescription errors (PEs) in the medical service, and to delineate the causes for remaining errors. METHODS: Drug orders were reviewed daily by a physician-reviewer, in a department of internal medicine that used for more than 3 years a CDOE (CDOEdept), and in a similar department in which drug orders were handwritten (HWdept). PEs were divided into those not related to the individual patient (type 1 PEs), and PEs resulting from drug-laboratory, drug-disease, and drug-allergy interactions (type 2 PEs). RESULTS: Ten thousand and two hospitalization days were evaluated. The incidence of type 1 PEs was 5.21 and 1.36 per 100 hospitalization days in the HWdept and CDOEdept, respectively (p<0.0001). Type 2 PEs were more common, 7.20 and 3.02 per 100 hospitalization days in the HWdept and CDOEdept, respectively (p<0.0001), and about 75% of them were due to few drug-laboratory interactions. Most of the remaining errors in the CDOEdept were due to inadequate adjustment of drugs and doses to renal function, or failure to perform adequate changes when new laboratory results became available. CONCLUSIONS: We conclude that linking the CDOE with few, specific, laboratory results has a large impact on the prevention of PEs. Combining the CDOE with a drug-laboratory alert system is expected to further reduce the incidence of PEs.

Asynchrony of lingual muscle recruitment during sleep in obstructive sleep apnea.

Pharyngeal collapsibility during sleep increases primarily due to decline in dilator muscle activity. However, genioglossus EMG is known to increase during apneas and hypopneas, usually without reversing upper airway obstruction or inspiratory flow limitation. The present study was undertaken to test the hypothesis that intense activation of the genioglossus fails to prevent pharyngeal obstruction during sleep, and to evaluate if sleep-induced changes in tongue muscle coordination may be responsible for this phenomenon. We compared genioglossus and tongue retractors EMG activity in 13 obstructive sleep apnea (OSA) patients during wakefulness, while breathing through inspiratory resistors, to the activity observed at the end of apneas and hypopneas after 25 mg of brotizolam, before arousal, at equal esophageal pressure. During wakefulness, resistive breathing triggered increases in both genioglossus and retractor EMG. Activation of agonist tongue muscles differed considerably from that of the arm, as both genioglossus and retractors were activated similarly during all tongue movements. During sleep, flow limitation triggered increases in genioglossal EMG that could reach more than twofold the level observed while awake. In contrast, EMGs of the retractors reached less than half the wakefulness level. In sleeping OSA patients, genioglossal activity may increase during obstructed breathing to levels that exceed substantially those required to prevent pharyngeal collapse during wakefulness. In contrast, coactivation of retractors is deficient during sleep. These findings suggest that sleep-induced alteration in tongue muscle coordination may be responsible for the failure of high genioglossal EMG activity to alleviate flow limitation.