Somatic arousal and sleepiness/fatigue among patients with sleep-disordered breathing.

OBJECTIVES: In a large clinical sample, we tested the hypothesis that levels of sleepiness and fatigue among upper airway resistance syndrome (UARS) patients are correlated with levels of somatic arousal (SA; reflecting the sympathetic nervous system component of the stress response). We also tested the correlations of post-treatment change in these three parameters, and we extended the investigation to obstructive sleep apnea/hypopnea (OSA/H) patients. METHODS: From 5 years of patient data, we obtained scores on the body sensation questionnaire (BSQ), measuring the level of SA, the fatigue severity scale (FSS), and Epworth sleepiness scale (ESS) for 152 consecutive UARS patients and 150 consecutive OSA/H patients. For each group, we correlated the FSS and ESS scores with the BSQ scores. Among the 45 UARS patients and 49 OSA/H patients treated with nasal CPAP who provided post-treatment data, we correlated change in FSS and ESS scores with change in BSQ scores. RESULTS: Scores on the BSQ, FSS, and ESS for UARS patients and OSA/H patients were comparable. In both UARS and OSA/H patients, both the FSS and ESS scores were positively correlated with the BSQ score. Nasal CPAP use decreased all three questionnaire scores in both patient groups. In the pooled data, changes in FSS were significantly correlated with changes in BSQ. CONCLUSIONS: Our findings confirm our preliminary observations that sleepiness and fatigue among UARS patients are correlated with their level of SA and suggest that the same is true for OSA/H patients. The decrease of SA following treatment suggests that SDB is a cause of SA among patients with UARS and OSA/H.

Somatic syndromes, insomnia, anxiety, and stress among sleep disordered breathing patients.

OBJECTIVES: We tested the hypothesis that the prevalence of somatic syndromes, anxiety, and insomnia among sleep disordered breathing (SDB) patients is correlated with their levels of somatic arousal, the symptoms of increased sympathetic nervous system tone under conditions of stress. METHODS: We administered the Body Sensation Questionnaire (BSQ; a 17-item questionnaire with increasing levels of somatic arousal scored 17-85) to 152 consecutive upper airway resistance syndrome (UARS) patients and 150 consecutive obstructive sleep apnea/hypopnea (OSA/H) patients. From medical records, we characterized each patient in terms of the presence of syndromes and symptoms into three categories: somatic syndromes (six syndromes), anxiety (anxiety disorders, nightmares, use of benzodiazepines), and insomnia (sleep onset, sleep maintenance, and use of hypnotics). For the pooled sample of SDB patients, we modeled the correlation of the BSQ score with the presence of each syndrome/symptom parameter within each of the three categories, with adjustment for male vs. female. RESULTS: Mean BSQ scores in females were significantly higher than those in males (32.5 ± 11.1 vs. 26.9 ± 8.2; mean ± SD). Increasing BSQ scores significantly correlated with increasing prevalence rates of somatic syndromes (p < 0.0001), of anxiety (p < 0.0001), and of insomnia (p ≤ 0.0001). In general, females had higher prevalence rates of somatic syndromes and symptoms of anxiety than males at any BSQ score while rates of insomnia were similar. CONCLUSIONS: In patients with SDB, there is a strong association between the level of somatic arousal and the presence of stress-related disorders like somatic syndromes, anxiety, and insomnia.

A comparison of inspiratory airflow dynamics during sleep between upper airway resistance syndrome patients and healthy controls.

OBJECTIVES: A test of the hypothesis that upper airway resistance syndrome (UARS) patients have an increased prevalence of inspiratory airflow limitation (IFL) during sleep compared to healthy controls. METHODS: We compared inspiratory airflow dynamics during sleep between 12 UARS patients (nine females and three males) and 12 healthy controls matched for age, gender and obesity with maximal age limited at 45 years. A standard clinical polysomnogram (airflow measured with a nasal/oral pressure catheter) was performed to assess the impact of SDB on the participants' natural sleep. A second full-night polysomnogram with a pneumotachograph and a supraglottic pressure catheter to measure airflow and effort was performed to compare the maximal inspiratory airflow and effort and the percentage of flow-limited breaths during supine, continuous stage 2 sleep between groups. RESULTS: During clinical polysomnography, UARS participants did not differ significantly from controls in sleep architecture or fragmentation. We observed a small difference in apnea hypopnea index between UARS participants and controls (1.6 ± 1.9 vs. 0.4 ± 0.3, respectively; p = 0.035). During supine, continuous stage 2 sleep, 64.2 % (35.8; mean (SD)) of UARS participants' breaths were flow-limited compared with 34.0 % (39.3) of controls' breaths (p = 0.06). The groups did not differ in maximal inspiratory airflow or inspiratory effort. CONCLUSIONS: Our findings indicate a less-than-robust difference in respiratory parameters during sleep between UARS patients and healthy controls and no difference in standard sleep parameters or sleep fragmentation. We consider a pathophysiology of UARS that incorporates these findings.

Symptoms of sleep disordered breathing: Association with the apnea-hypopnea index and somatic arousal.

We investigated the association of typical symptoms of obstructive sleep apnea with a measure of daytime somatic arousal and with the apnea-hypopnea index. We extended the finding of an association between sleepiness, fatigue and somatic arousal previously reported in a US sleep apnea population to a German sleep apnea population (n = 374) and to other typical sleep apnea symptoms, insomnia, anxiety, daytime alertness and non-restorative sleep. Somatic arousal was measured using the body sensation questionnaire (BSQ). Correlations of apnea-hypopnea index and BSQ were computed with values of polysomnographic variables derived from overnight sleep studies and with severity of OSA symptoms. Apnea-hypopnea index and BSQ scores showed only a small negative correlation with each other; each correlated independently with the Epworth Sleepiness Scale score. Controlling for BSQ score, the apnea-hypopnea index was found to affect sleepiness only when it exceeded 50/h. Severity of all other sleep apnea symptoms did not increase with increasing apnea-hypopnea index. In contrast, severity of all symptoms of sleep apnea increased consistently with increasing BSQ scores. Thus, autonomic stress associated with obstructive sleep apnea may be the driving force behind sleep apnea symptoms rather than the sleep fragmentation associated with obstructive sleep apnea severity (apnea-hypopnea index). These findings support previously reported correlations by Gold and associates between the levels of somatic arousal, sleepiness and fatigue. Using the apnea-hypopnea index and BSQ together renders a more comprehensive assessment of sleep apnea than apnea-hypopnea index alone, which appears to impact only on sleepiness and only when it exceeds 50/h. More work is needed to elucidate the source of the chronic stress, which appears to arise endogenously in affected individuals, likely as a function of sleep disordered breathing, such as snoring/inspiratory flow limitation.

The effect of nasal continuous positive airway pressure on the symptoms of Gulf War illness.

PURPOSE: We performed a pilot study to determine whether nasal continuous positive airway pressure (CPAP) alleviates the symptoms of veterans with Gulf War illness (GWI) and sleep disordered breathing (SDB). METHODS: Eighteen male veterans with GWI and SDB recruited by advertisement, participated in a randomized, single-masked, sham-controlled treatment trial. Participants received 3 weeks of treatment during sleep with either therapeutic nasal CPAP or sham nasal CPAP. Using validated questionnaires, pain, fatigue, cognitive function, sleep disturbance, and general health were assessed by self-report before and after treatment. One of the participants assigned to therapeutic CPAP was excluded from the trial before starting treatment, leaving 17 participants. RESULTS: Compared to the nine sham nasal CPAP recipients, the eight participants receiving therapeutic nasal CPAP experienced improvements in pain (34%; p = 0.0008), fatigue (38%; p = 0.0002), cognitive function (33%; p = 0.004), sleep quality (41%; p = 0.0003), physical health (34%; p = 0.0003), and mental health (16%; p = 0.03). CONCLUSIONS: Our findings in this pilot study suggest that nasal CPAP may greatly improve symptoms in veterans with GWI and SDB.

Inspiratory airflow dynamics during sleep in veterans with Gulf War illness: a controlled study.

PURPOSE: To determine whether veterans with Gulf War Illness (GWI) are distinguished by sleep-disordered breathing, we compared inspiratory airflow dynamics during sleep between veterans with GWI and asymptomatic veterans of the first Gulf War. METHODS: We recruited 18 male veterans with GWI and 11 asymptomatic male veterans of the first Gulf War by advertisement. The two samples were matched for age and body mass index. Each participant underwent a first full-night polysomnogram (PSG) while sleeping supine using standard clinical monitoring of sleep and breathing. A second PSG was performed measuring airflow with a pneumotachograph in series with a nasal mask and respiratory effort with a supraglottic pressure (Psg) catheter to assess the presence of inspiratory airflow limitation during supine N2 sleep. We determined the prevalence of flow-limited breaths by sampling continuous N2 sleep and plotting inspiratory flow against Psg for each breath in the sample. We expressed the prevalence of flow-limited breaths as their percentage in the sample. RESULTS: Compared to controls, veterans with GWI had an increased frequency of arousals related to apneas, hypopneas, and mild inspiratory airflow limitation. During supine N2 sleep, veterans with GWI had 96 ± 5% (mean ± SD) of their breaths flow-limited while controls had 36 ± 25% of their breaths flow limited (p < 0.0001). CONCLUSIONS: Veterans with GWI experience sleep-disordered breathing that may distinguish them from asymptomatic veterans of the first Gulf War.

An open-label, long-term safety and tolerability trial of diclofenac sodium 1% gel in patients with knee osteoarthritis.

OBJECTIVE: To evaluate the long-term safety and tolerability of topical diclofenac sodium 1% gel (DSG) in the treatment of knee osteoarthritis (OA) for up to 12 months. METHODS: This was a multicenter open-label, extension of two 3-month, randomized, double-blind studies of DSG in patients with knee OA (NCT ID: NCT00171691, "Safety of Diclofenac Sodium Gel in Knee Osteoarthritis"). To ensure adequate enrollment, some DSG-naïve patients with OA who had not participated in the double-blind studies were also enrolled. Patients applied 4 g DSG to 1 or both knees 4 times daily for 9 to 12 months. Safety was evaluated through adverse event (AE) reporting, physical examination, and laboratory investigations. Patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and physical function scales every 3 months to assess long-term effectiveness. RESULTS: The extension study enrolled 583 patients; 294 patients completed the study. Use of DSG was documented for 578 patients (safety population). The mean age was 62.3 years, and 63.7% of patients were women. Overall, 112 (19.4%) patients reported ≥ 1 treatment-related AE, and the only treatment-related AE occurring in ≥ 1% of patients was application-site dermatitis. Treatment-related gastrointestinal, renal-function, hepatic-function, and cardiovascular AEs were reported by 3, 1, 2, and 0 patients, respectively. There were no serious AEs or deaths. At 1 year, improvements from baseline for WOMAC pain, stiffness, and physical function scale scores were 39.8%, 33.4%, and 36.9%, respectively. CONCLUSION: The long-term safety profile of DSG was consistent with previous 12-week studies, and DSG remained effective for a 1-year period.

War-related illness symptoms among Operation Iraqi Freedom/ Operation Enduring Freedom returnees.

OBJECTIVE: Our objective was to determine the pattern of war-related illness (WRI) symptoms among returnees of Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) living on Long Island, NY. METHODS: We conducted an anonymous mail survey of WRI symptoms of a random cohort of 786 returnees (718 male, 68 female) living on Long Island from among 5,500 who registered with the OIF/OEF Registry. RESULTS: From among the 786 returnees whom we surveyed, we subsequently excluded 111 whose surveys were either returned unopened or who changed address. Two hundred seventy-four of the remaining 675 returnees responded to the survey (a 41% response rate). Disabling WRI symptoms were documented in approximately 2/3 of the responders and 75% of these responders had two or more symptoms. CONCLUSION: War-related illness symptoms are very common among OIF/OEF returnees suggesting the need for management strategies targeting their symptoms. BACKGROUND: Military conflicts have produced war-related illness (WRI) among our troops and veterans since the Civil War. Common to all these WRIs are a group of symptoms including body pain, fatigue, headache, sleep disturbance, diarrhea, forgetfulness, and impaired concentration. Also common to them is the absence of a discernable pathophysiology. Because WRI is poorly understood, we cannot prevent new occurrences with each new engagement of our armed forces.

Inspiratory airflow dynamics during sleep in irritable bowel syndrome: a pilot study.

PURPOSE: This study is a preliminary test of the hypothesis that the pathophysiology of irritable bowel syndrome (IBS) derives from pharyngeal collapse during sleep. MATERIALS AND METHODS: We studied inspiratory airflow dynamics during sleep in 12 lean females with IBS and 12 healthy female controls matched for age and obesity. A standard clinical polysomnogram (airflow measured with a nasal/oral pressure catheter) was performed to assess the impact of pharyngeal collapse on the participants' natural sleep. A second polysomnogram with a pneumotachograph and a supraglottic pressure catheter to measure airflow and effort was performed to compare the maximal inspiratory airflow and effort and the prevalence of inspiratory airflow limitation (IFL) during supine stage 2 sleep between groups. RESULTS: During clinical polysomnography, IBS participants did not differ significantly from controls in sleep architecture or respiration. The difference in apnea-hypopnea index between IBS participants and controls, however, approached statistical significance (2.8 +/- 2.7 vs 1.1 +/- 1.5, respectively; p = 0.079). Although nine of the 12 IBS participants had a prevalence of IFL of at least 33% during supine stage 2 sleep, they did not differ from controls in maximal inspiratory airflow, inspiratory effort, or the prevalence of IFL. Controls, however, differed from IBS participants in having their prevalence of IFL during stage 2 sleep positively correlated with age (r = 0.86; p = 0.0003) while IBS participants demonstrated no relationship between the prevalence of IFL and age. CONCLUSIONS: Our findings, while less than definitive, suggest a prevalence pattern of pharyngeal collapse during sleep among females with IBS that differs from that of healthy females, providing necessary background to inform further work on the relationship of pharyngeal collapse during sleep to IBS.

Lower extremity edema and pulmonary hypertension in morbidly obese patients with obstructive sleep apnea.

INTRODUCTION: In 70 consecutive male patients with obstructive sleep apnea (OSA) diagnosed at the Northport VA Medical Center Sleep Disorders Center, we have characterized the association between obesity, OSA, and pulmonary hypertension (PH). MATERIALS AND METHODS: By including anthropometric, pulmonary function, and sleep study parameters in a multivariate logistic regression model, we found that a BMI of >40 kg/m(2) and the minimum oxygen saturation in non-rapid eye movement (NREM) sleep predicted the presence of pretibial edema in this sleep apnea population. We then characterized the hemodynamics of those OSA patients that had lower extremity edema. Twenty-nine of the 70 consecutive patients with sleep apnea (41%) had pretibial edema, and right heart catheterization data was obtained for 28 (97%) of these patients. RESULTS AND DISCUSSION: Ninety-three percent (26/28) of the patients had right heart failure (mean RAP > 5 mm Hg; RAP range = 0-32 mmHg) and PH (PA mean >or= 20 mm Hg) was present in 86% (24/28.) The OSA patients with lower extremity edema had an increased cardiac output (7.0 + 1.4 l/min) with a normal cardiac index (2.9 + 0.5 l/min/m(2)) in the setting of an elevated pulmonary capillary wedge pressure (PCWP 17 +/- 7 mmHg) and a normal pulmonary vascular resistance (122 + 70 dynes s cm(-5)). While PCWP, FEV(1)% predicted, and the minimum oxygen saturation in NREM sleep all independently predicted PH, PCWP was the most important predictor of PH. CONCLUSION: We conclude that pulmonary hypertension is commonly seen in patients with OSA with pretibial edema and that pretibial edema is a highly specific sign of PH in OSA patients. Pulmonary hypertension appears to result from an elevated back pressure and diastolic dysfunction with contributions from lung function and nocturnal oxygen saturation.

Hypersomnolence, insomnia and the pathophysiology of upper airway resistance syndrome.

OBJECTIVE: In order to test the hypothesis that upper airway resistance syndrome (UARS) is merely an extension of the pathophysiology of obstructive sleep apnea/hypopnea (OSA/H) to less severe pharyngeal collapse during sleep, we compared the severity of hypersomnolence and the prevalence of insomnia in UARS patients to the patterns observed for OSA/H patients. Our goal was to determine whether the severity of hypersomnolence and the prevalence of insomnia observed in UARS patients could have been predicted from the patterns observed among OSA/H patients. METHODS: We performed a retrospective study of a large consecutive patient series evaluated at an academic sleep disorders center, including 220 OSA/H patients and 137 UARS patients. Patients had no other sleep-related diagnosis and underwent an initial evaluation that included a measure of hypersomnolence [a multiple sleep latency test (MSLT); 95%] or insomnia questionnaire (87%). Patients were characterized by anthropometric data, polysomnographic descriptive measures of sleep, MSLT data and insomnia questionnaire data. RESULTS: Severity of hypersomnolence decreased over the continuum from severe to mild OSA/H. A model fit to the OSA/H patients to predict severity of hypersomnolence significantly underestimated hypersomnolence in UARS patients, which was comparable in severity to that of patients with mild OSA/H. The frequency of sleep-onset insomnia increased over the continuum from severe to mild OSA/H and increased further in UARS. CONCLUSIONS: UARS is, in some respects, an extension of OSA/H to less severe pharyngeal collapse, but this does not adequately account for the symptom profile of patients with UARS. A physical model is proposed to account for the excess somnolence in UARS relative to expectations and the increasing frequency of sleep-onset insomnia along the continuum from severe OSA/H to UARS.

Inspiratory airflow dynamics during sleep in women with fibromyalgia.

STUDY OBJECTIVES: To determine whether women with fibromyalgia have inspiratory airflow dynamics during sleep similar to those of women with upper-airway resistance syndrome (UARS). DESIGN: A descriptive study of consecutive female patients with fibromyalgia. SETTING: An academic sleep disorders center. PATIENTS OR PARTICIPANTS: Twenty-eight women with fibromyalgia diagnosed by rheumatologists using established criteria. Fourteen of the women gave a history of snoring, while 4 claimed to snore 'occasionally' and 10 denied snoring. The comparison group comprised 11 women with UARS matched for age and obesity. INTERVENTIONS: Eighteen of the 28 women with fibromyalgia and all of the women with UARS had a full-night polysomnogram. All participants had a nasal continuous positive airway pressure (CPAP) study with quantitative monitoring of inspiratory airflow and effort between atmospheric pressure and therapeutic CPAP. Fourteen patients with fibromyalgia and all patients with UARS had a successful determination of pharyngeal critical pressure. MEASUREMENTS AND RESULTS: Twenty-seven of 28 women with fibromyalgia had sleep-disordered breathing. One of the 27 had obstructive sleep apnea hypopnea while 26 had milder inspiratory airflow limitation with arousals. One patient had no apnea or hypopnea or inspiratory airflow limitation during sleep. While the patients were sleeping at atmospheric pressure, apnea-hypopnea index, arousal index, the prevalence of flow-limited breaths, and maximal inspiratory flow were similar between groups. The pharyngeal critical pressure of the patients with fibromyalgia was -6.5 +/- 3.5 cmH2O (mean +/- SD) compared to -5.8 +/- 3.5 cmH2O for patients with UARS (P = .62). Treatment of 14 consecutive patients with nasal CPAP resulted in an improvement in functional symptoms ranging from 23% to 47%, assessed by a validated questionnaire. CONCLUSION: Inspiratory airflow limitation is a common inspiratory airflow pattern during sleep in women with fibromyalgia. Our findings are compatible with the hypothesis that inspiratory flow limitation during sleep plays a role in the development of the functional somatic syndromes.

The symptoms and signs of upper airway resistance syndrome: a link to the functional somatic syndromes.

STUDY OBJECTIVES: The functional somatic syndromes are associated with a variety of symptoms/signs of uncertain etiology. We determined the prevalence of several of those symptoms/signs in patients with sleep-disordered breathing and examined the relationship between the prevalence of the symptoms/signs and the severity of sleep-disordered breathing. DESIGN: A descriptive study without intervention. SETTING: A university sleep-disorders center located in a suburban setting. PATIENTS OR PARTICIPANTS: Three groups of 25 consecutively collected patients with sleep-disordered breathing. Groups varied in their apnea hypopnea indexes (AHIs) as follows: upper airway resistance syndrome (UARS) [AHI < 10/h), mild-to-moderate obstructive sleep apnea/hypopnea (OSA/H) [AHI >or= 10 to < 40/h), and moderate-to-severe OSA/H (AHI >or= 40/h). MEASUREMENTS AND RESULTS: Patients underwent comprehensive medical histories, physical examinations, and full-night polysomnography. The diagnosis of UARS included quantitative measurement of inspiratory airflow and inspiratory effort with demonstration of inspiratory flow limitation. The percentage of women among the patients with sleep-disordered breathing (p = 0.001) and the prevalence of sleep-onset insomnia (p = 0.04), headaches (p = 0.01), irritable bowel syndrome (p = 0.01), and alpha-delta sleep (p = 0.01) was correlated with decreasing severity of AHI group. CONCLUSIONS: We conclude that patients with UARS, mild-to-moderate OSA/H and moderate-to-severe OSA/H differ in their presenting symptoms/signs. The symptoms/signs of UARS closely resemble those of the functional somatic syndromes.

Upper airway collapsibility during sleep in upper airway resistance syndrome.

STUDY OBJECTIVES: To compare upper airway collapsibility during sleep between patients with upper airway resistance syndrome (UARS), normal subjects, and patients with obstructive sleep apnea/hypopnea syndrome (OSA/H). DESIGN: A descriptive study of a series of clinical patients and a cohort of normal control subjects. SETTING: Two academic sleep-disorders centers. PATIENTS OR PARTICIPANTS: One hundred six adult patients with sleep-disordered breathing evaluated at the SUNY Sleep Disorders Center-Medicine and 12 adult subjects without habitual snoring or daytime sleepiness and with an apnea/hypopnea index (AHI) < 5/h evaluated at the Johns Hopkins Pediatric Sleep Disorders Center. INTERVENTIONS: All subjects underwent full-night polysomnography and a determination of pharyngeal critical pressure (Pcrit). All patients had a determination of therapeutic level of nasal continuous positive airway pressure (Ptherapeutic). MEASUREMENTS AND RESULTS: The mean +/- SD Pcrit of the 12 normal subjects was - 15.4 +/- 6.1 cm H(2)O; the mean Pcrit of the 22 UARS patients was - 4.0 +/- 2.1 cm H(2)O; the mean Pcrit of the 37 patients with mild-to-moderate OSA/H (AHI > or = 10/h and < 40/h) was - 1.6 +/- 2.6 cm H(2)O; and the mean Pcrit of the 47 patients with moderate-to-severe OSA/H (AHI > or = 40/h) was 2.4 +/- 2.8 cm H(2)O. The Pcrit of each group differed from that of all other groups (p < 0.01). The mean Ptherapeutic of patients with UARS was 6.9 +/- 1.7 cm H(2)O; the mean Ptherapeutic of patients with mild-to moderate OSA/H was 7.9 +/- 1.9 cm H(2)O (p = 0.08 compared with the Ptherapeutic of UARS patients); and the mean Ptherapeutic of patients with moderate-to severe OSA/H was 10.5 +/- 2.4 cm H(2)O (p < 0.0001 compared to each of the other patient groups). CONCLUSION: UARS is a syndrome of increased upper airway collapsibility during sleep. The upper airway collapsibility during sleep of patients with UARS is intermediate between that of normal subjects and that of patients with mild-to moderate OSA/H.

A multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled, parallel-group comparison of diclofenac-K and ibuprofen for the treatment of adults with influenza-like symptoms.

BACKGROUND: The alleviation of influenza-like symptoms, such as fever, headache, and muscle/joint aches and pains, is important so that sufferers can return to their normal daily activities. A flexible dosing regimen is proposed, starting with an initial dose of 2 tablets (2 x 12.5 mg), followed by 1 to 2 tablets every 4 to 6 hours as needed, to a maximum daily dose of 75 mg for up to 3 days for fever and 5 days for pain. This flexible dosing regimen matches the existing over-the-counter dosing regimen of ibuprofen, which allows the patient to adjust the treatment according to the type, duration, and severity of symptoms. OBJECTIVE: This study assessed the efficacy and tolerability of diclofenac-K 12.5 mg versus ibuprofen 200 mg and placebo against influenza-like symptoms (oral temperature > or = 38.1 degrees C, and at least moderate headache and muscle/joint aches and pains). METHODS: This was a 3-day, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial conducted in Germany. The flexible dosing regimens comprised 2 tablets of diclofenac-K (12.5 mg), ibuprofen (200 mg), or placebo, then 1 to 2 tablets every 4 to 6 hours as needed, to a maximum of 6 tablets/d. Primary efficacy outcomes were fever reduction after the initial dose and an end-of-study global assessment of overall symptom relief. Secondary efficacy outcomes included reduction of feverishness; relief of headache; and relief of muscle/joint aches and pains, after the first dose and at the end of days 1, 2, and 3. Use of rescue medication (paracetamol 500-mg tablets) and usage patterns of study medication were also studied. Tolerability was monitored by recording of patients' adverse events. RESULTS: A total of 356 patients were enrolled (n = 121, 120, and 115 patients in the diclofenac-K, ibuprofen, and placebo groups, respectively). All patients were white except 1 Asian patient in the diclofenac-K group; 55% to 60% of patients in all 3 groups were male; the mean age in each treatment group was approximately 40 years. At baseline, mean oral temperature ranged from 38.65 degrees C in the placebo group to 38.74 degrees C in the diclofenac-K group. Mean oral temperatures in both active groups were significantly lower than that of the placebo group from 30 minutes through 6 hours (P < 0.001), dropping 0.85 degrees C after 4 hours in the diclofenac-K group and 0.76 degrees C in the ibuprofen group versus 0.32 degrees C for placebo. In the end-of-study global treatment assessment, 89.0% of diclofenac-K and 89.1% of ibuprofen patients rated global efficacy as "good" to "excellent" versus only 32.1% for placebo. Diclofenac-K was superior to placebo (P < 0.001) and similar to ibuprofen on all direct assessments of fever and aches and pains. Both active treatments were as well tolerated as was placebo. CONCLUSIONS: In this 3-day study, diclofenac-K 12.5 mg taken in a flexible dosing regimen was more effective than placebo in relieving influenza-like symptoms, with comparable tolerability Efficacy and tolerability of diclofenac-K were similar to those of ibuprofen 200 mg.

Low-dose diclofenac potassium in the treatment of episodic tension-type headache.

BACKGROUND: Several clinical trials have demonstrated that low doses of non-steroidal anti-inflammatory drugs relieve episodic tension-type headache (ETH). AIMS: The aims of this placebo-controlled study were to determine whether single doses of diclofenac-K 12.5 and 25mg effectively relieve ETH in adults and to compare it to ibuprofen 400mg. METHODS: A single-dose multicentre, randomised, double-blind, double-dummy, clinical trial was conducted at 22 primary care centres in Germany. All subjects had a history of ETH according to the classification of the International Headache Society. Of 684 subjects randomised, 620 used the study drugs for an episode of tension headache occurring within one month after enrolment: diclofenac-K 12.5mg (n=160), diclofenac-K 25mg (n=156), ibuprofen 400mg (n=151) and placebo (n=153). The primary efficacy variable was total pain relief, calculated as the time-weighted sum of the pain relief assessments from baseline to the 3h evaluation time (TOTPAR-3). RESULTS: For TOTPAR-3, all active treatments were superior to placebo; no statistically significant difference between the three active treatments could be detected. A similar pattern was also observed with regard to TOTPAR-6 (6h evaluation time), > or =50%maxTOTPAR at 3 and 6h, weighted pain intensity difference at 3 and 6h (SPID-3; SPID-6), percentage of patients with complete headache relief at 2h, end of study global evaluation and time to rescue medication. The number-needed-to-treat (NNT) at 6h was 4.5 (2.9-9.2) in the ibuprofen 400mg group, 4.0 (2.8-7.3) in the diclofenac-K 12.5mg group and 3.9 (2.7-7.1) in the diclofenac-K 25mg group. These differences were not statistically significant. CONCLUSION: Diclofenac-K, administered as single doses of 12.5 and 25mg effectively relieves ETH and is comparable to ibuprofen 400mg.

Analgesic efficacy of low-dose diclofenac versus paracetamol and placebo in postoperative dental pain.

AIMS: To compare the efficacy and safety of diclofenac-K (12.5 mg) vs paracetamol (500 mg) and placebo given in a flexible dosage regimen to treat pain resulting from extraction of impacted third molar teeth. METHODS: This was a 2-day, double-blind, double-dummy, randomized, parallel-group, placebo-controlled study of diclofenac-K (12.5 mg) tablets vs paracetamol (500 mg) tablets and placebo in patients with moderate or severe pain within 8 hours of extraction of impacted third molars. RESULTS: After the first 2-tablet dose, patients took on average 2.5 additional tablets of diclofenac-K or 2.4 tablets of paracetamol, almost all as 1-tablet doses. Most placebo patients discontinued by taking rescue medication (ibuprofen 200 mg) on the first day. Pain relief after the initial dose of diclofenac-K (2 x 12.5 mg) was superior to placebo (P < .01 for all efficacy outcomes) and comparable to paracetamol (2 x 500 mg). About 30% of patients in each active treatment group took rescue medication during the study, compared to 78% on placebo. About 70% in each active treatment group considered the overall pain relief to be "some," "a lot," or "complete" compared to only 15% on placebo. The incidence of adverse events in each active treatment group was low and comparable between the treatments. CONCLUSION: An initial double-dose of diclofenac-K (2 x 12.5 mg) or paracetamol (2 x 500 mg) adequately relieved the most intense postoperative pain, and the flexible multiple dose regimen (1 or 2 tablets) maintained adequate pain relief thereafter. Most patients needed only 1-tablet doses following the initial 2-tablet dose.

The association of somatic arousal with the symptoms of upper airway resistance syndrome.

OBJECTIVES: We tested the hypothesis that the symptoms of upper airway resistance syndrome (UARS) are manifestations of chronic stress. To accomplish this, we utilized the score on a self-report questionnaire for somatic arousal (a component of stress) to compare somatic arousal between UARS patients and healthy controls and, among all participants, to correlate the level of somatic arousal with the severity of UARS symptoms. METHODS: We administered the Mood and Anxiety Symptom Questionnaire anxious arousal subscale (MASQaas; a 17-item questionnaire with increasing levels of arousal scored 17-85) to 12 UARS patients and 12 healthy controls and compared scores between groups. For all participants, we correlated the MASQaas scores with scores for the Epworth Sleepiness Scale (ESS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, Pittsburgh Sleep Quality Index (PSQI), SF-36 Health Survey, and Perceived Deficits Questionnaire (PDQ; assessing cognitive function). RESULTS: Compared to healthy controls, UARS patients demonstrated increased somatic arousal (MASQaas scores of 18±2 and 28±7, respectively; p<0.0001). For all participants, the MASQaas scores correlated significantly with scores of the ESS (r=0.64; p=0.0008), the FACIT-Fatigue scale (r=-0.89; p<0.0001), the PSQI (r=0.70; p=0.0002), SF-36 Physical component (r=-0.78; p<0.0001), SF-36 Mental component (r=-0.74; p<0.0001), and the PDQ (r=0.89; p<0.0001). CONCLUSIONS: Our findings suggest that UARS patients have increased levels of the stress component, somatic arousal, proportionate to the severity of their symptoms.