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.

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.

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.

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.

Tolerability of diclofenac sodium 1% gel with concomitant medications known to interact with diclofenac.

BACKGROUND: Topical diclofenac sodium 1% gel (DSG) has demonstrated efficacy and tolerability in patients with osteoarthritis (OA) of the knees or hands, including elderly patients and those with an increased risk of gastrointestinal, cardiovascular, and renal adverse events (AEs). Medications known to interact with diclofenac were disallowed in a clinical trial of DSG for knee OA; however, patients were not to be discontinued for intake of disallowed treatment, unless there was a safety issue. This post hoc analysis examined the frequency and type of AEs in patients who received DSG concomitantly with drugs known to have potential interactions with diclofenac. MATERIALS AND METHODS: This was a post hoc analysis of a randomized controlled trial of DSG for knee OA pain. Patients (n = 254) aged ≥ 35 years with OA in one or both knees, but with clinical OA symptoms in only one knee, administered DSG topically to the target knee four times daily (total dose, 16 g/d) for 12 weeks. Drugs with the potential for major or moderate drug-drug interactions (DDIs) were identified via Drugs.com. AE rates were compared in patients with versus those without ≥1 potential DDI. RESULTS: At least one AE was experienced by 62.6% (107/171) of patients with ≥1 DDI and by 55.4% (46/83) of patients with no DDIs. Gastrointestinal AEs (upper and lower) were reported in 5.3% (9/171) and 7.2% (6/83), cardiovascular AEs in 4.7% (8/171) and 1.2% (1/83), renal AEs in 1.2% (2/171) and 0%, and hepatic AEs in 0% and 1.2% (1/83) of patients with ≥1 DDI compared with patients with no DDIs, respectively. CONCLUSION: Concurrent use of DSG with medications that had potential for major to moderate DDIs had little impact on the frequency of AEs in this population. Further research is needed to consider how factors such as dose, duration, and timing of concomitant drug administration may affect the likelihood of clinically evident AEs resulting from a potential DDI.

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.

Long-term tolerability of topical diclofenac sodium 1% gel for osteoarthritis in seniors and patients with comorbidities.

BACKGROUND: Adverse events associated with nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat knee and hand osteoarthritis may be more frequent in certain patient populations. Topical NSAIDs, such as diclofenac sodium 1% gel (DSG), have equivalent efficacy and fewer adverse events compared with oral NSAIDs. This post hoc analysis assessed the long-term tolerability of DSG in elderly patients and patients with an elevated risk of gastrointestinal, cardiovascular, and renal adverse events. METHODS: Patients ≥ 35 years of age with knee osteoarthritis applied DSG (4 g) to one or both knees for 12 weeks during either of two primary studies and for 9 months during a long-term extension study. Other patients entered the long-term extension study directly and applied DSG for 12 months. Safety was assessed by reported adverse events. Subpopulations were defined based on age, or the comorbidities of hypertension, type 2 diabetes mellitus, and cerebrovascular or cardiovascular disease. RESULTS: The safety population consisted of 947 patients who received at least one dose of DSG during the primary or extension study. Patients aged < 65 years (68.2%) and ≥65 years (67.2%) experienced any adverse event at similar rates. The percentage of patients who experienced any adverse event was similar between patients with and without hypertension (65.5% versus 69.7%, respectively), type 2 diabetes mellitus (64.0% versus 68.2%), or cerebrovascular or cardiovascular disease (61.9% versus 68.5%). Among the 15 patients with all three comorbidities, the percentage of patients with any adverse event (53.3%) was less than that of patients who did not have all three comorbidities (68.0%). CONCLUSION: These results suggest that long-term DSG treatment is safe in patient subpopulations with an elevated risk of NSAID-related adverse events, such as the elderly and those with the comorbidities of hypertension, type 2 diabetes mellitus, and cerebrovascular or cardiovascular disease.

The effects of a mid-day nap on the neurocognitive performance of first-year medical residents: a controlled interventional pilot study.

PURPOSE: Despite shorter duty hours, fatigue remains a problem among medical residents. The authors tested the effect of a short, mid-day nap on the cognitive functioning and alertness of first-year internal medicine (IM) residents during normal duty hours. METHOD: This was a controlled, interventional study performed between July 2008 and April 2010. The authors recruited a nap group of 18 residents and a rest (control) group of 11 residents. Investigators connected all participants to an ambulatory sleep monitor before the beginning of their shifts in order to monitor rolling eye movements, a proxy for attention failures. At mid-day, both groups took Conner's Continuous Performance Test (CPT II) to evaluate their cognitive functioning and then were placed in a reclining chair designed for napping. The authors instructed nap group residents to nap for up to 20 minutes and chatted with control group residents to prevent them from napping. All residents took the CPT II again immediately after the intervention. Residents' attention failures were recorded until the end of the workday. The authors compared the mean outcome parameters of the two groups through analysis of variance, using effect-of-treatment and baseline covariates. RESULTS: Nap group participants slept a mean of 8.4±3.0 minutes. Compared with controls whose cognitive functioning and number of attention failures did not change from morning to afternoon, the nap group's cognitive functioning improved and their number of attention failures decreased. CONCLUSIONS: A short, mid-day nap can improve cognitive functioning and alertness among first-year IM residents.

Tolerability of topical diclofenac sodium 1% gel for osteoarthritis in seniors and patients with comorbidities.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a dose-related risk of cardiovascular, renal, and gastrointestinal adverse events (AEs). Topical NSAIDs produce lower systemic NSAID exposure compared with oral NSAIDs, offering potential benefits. OBJECTIVE: To evaluate the safety of topical diclofenac sodium 1% gel (DSG) for knee and hand osteoarthritis (OA) in older and younger patients and in patients with versus without comorbid hypertension, type 2 diabetes, or cerebrovascular or cardiovascular disease. METHODS: Post hoc analysis of pooled data from 5 randomized, double-blind, placebo-controlled trials involving 1426 patients (aged ≥35 years) with mild to moderate OA of the knee and 783 patients (aged ≥40 years) with mild to moderate OA of the hand. Patients applied 4 g of DSG or vehicle to affected knees QID for 12 weeks or 2 g of DSG or vehicle to affected hands QID for 8 weeks. RESULTS: In patients with knee OA, the percentage with ≥1 adverse event was similar in patients aged <65 years (56.6%) versus ≥65 years (55.8%) and was similar in patients with versus without comorbid hypertension (53.4% vs 59.0%, respectively), type 2 diabetes mellitus (50.0% vs 57.2%), or cerebrovascular or cardiovascular disease (53.8% vs 56.5%). In patients with hand OA, the percentage with ≥1 AE was similar in patients aged ≥65 years (42.7%) versus <65 years (39.1%) and was similar in patients with versus without hypertension (39.6% vs 41.7%, respectively), lower in patients with versus without type 2 diabetes mellitus (28.0% vs 41.6%), and higher in patients with versus without cerebrovascular or cardiovascular disease (48.5% vs 39.2%). Gastrointestinal, cardiovascular, and renal AEs were rare and did not differ according to age or comorbidity. Application site reactions were the primary cause for the greater frequency of AEs with DSG versus vehicle. CONCLUSION: The similar and low rates of AEs in DSG-treated patients aged ≥65 years and <65 years and in those with and without comorbid hypertension, type 2 diabetes, or cerebrovascular or cardiovascular disease suggest that DSG treatment is generally well tolerated.

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.

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.

Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients: pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials.

BACKGROUND: NSAIDs used for the treatment of osteoarthritis (OA) have dose-related risks for gastrointestinal, cardiovascular and renal adverse events (AEs), particularly in elderly patients. Topical NSAIDs reduce systemic NSAID exposure and may mitigate these risks. OBJECTIVE: To evaluate the safety and efficacy of topical diclofenac sodium 1% gel (DSG) versus vehicle in patients aged 25-64 or ≥65 years who have been diagnosed with knee OA. STUDY DESIGN: Pooled data from three 12-week, randomized, double-blind, parallel-group, multicentre trials. SETTING: US primary care, internal medicine, orthopaedic and rheumatology practices. PATIENTS: Aged ≥25 years with mild to moderate (Kellgren-Lawrence grade 1-3) knee OA. INTERVENTION: After a 1-week analgesic washout, patients applied 4 g of DSG or vehicle four times daily to one knee. Rescue paracetamol (acetaminophen) up to 4 g/day was allowed. MAIN OUTCOME MEASURE: Key efficacy outcomes common to the three trials were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (0-20) and physical function (0-68) subscales, global rating of disease (GRD; 100-mm visual analogue scale [VAS]) and pain on movement (POM; 100-mm VAS). ANOVA was used to compare efficacy outcome differences (DSG vs vehicle) by age (25-64 or ≥65 years). A flare design was used that defined a subset of patients who experienced increased pain during the washout period (modified efficacy subpopulation [MES]). RESULTS: The MES included both patients aged 25-64 (n = 602) and ≥65 (n = 374) years. Patients in each age group applied >90% of scheduled doses. Among patients aged 25-64 years, the improvement from baseline to week 12 (least squares mean [standard error]) was greater for DSG versus vehicle for WOMAC pain (-5.8 [0.3] vs -4.7 [0.3], p = 0.007), WOMAC physical function (-17.9 [0.9] vs -14.2 [0.9], p = 0.002), GRD (-29.5 [1.6] vs -23.8 [1.6], p = 0.01) and POM (-37.3 [1.8] vs -29.0 [1.8], p < 0.001). Among patients aged ≥65 years, the improvements from baseline for most efficacy outcome scores were significantly greater with DSG versus vehicle: WOMAC pain (-5.3 [0.3] vs -4.1 [0.4], p = 0.02), WOMAC physical function (-15.5 [1.1] vs -11.0 [1.1], p = 0.004) and POM (-33.7 [2.2] vs -26.4 [2.2], p = 0.02). The efficacy of DSG did not differ significantly between patients aged 25-64 years and ≥65 years: WOMAC pain (p = 0.85), WOMAC physical function (p = 0.70), GRD (p = 0.86) and POM (p = 0.81). The incidence of any AE was greater with DSG than with vehicle among patients aged 25-64 years (56.6% vs 50.8%) and ≥65 years (55.8% vs 43.9%). Treatment-related application site dermatitis was more common with DSG compared with vehicle in both younger (4.0% vs 0.7%, respectively) and older (5.8% vs 0.4%, respectively) patients and was the main reason for the difference in treatment-related AEs between the DSG and vehicle groups. Gastrointestinal AEs were infrequent among patients treated with DSG and similar to incidence rates with vehicle in both age groups. CONCLUSIONS: DSG was effective and generally well tolerated in adults regardless of age. These data support the topical application of DSG for relief of OA knee pain in elderly and younger patients. Clinicaltrials.gov registration numbers NCT00171626, NCT00171678, NCT00426621.

Safety and efficacy of topical diclofenac sodium 1% gel in knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may provide an alternative to oral NSAIDs to relieve pain from osteoarthritis (OA), reducing systemic exposure. This 12-week, randomized, double-blind, parallel-group, multicenter trial examined the efficacy and safety of topical diclofenac sodium 1% gel (DSG) for symptomatic knee OA. METHODS: Eligible patients were aged >/= 35 years with symptomatic Kellgren-Lawrence grade (KLG) 1 to 3 OA in 1 or both knees for >/= 6 months. Patients meeting entry criteria applied DSG 4 g or vehicle 4 times daily to the symptomatic knee(s). Primary endpoints were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales and global rating of benefit at week 12. Pain on movement at week 4 was an additional primary endpoint for European regulatory purposes. Secondary endpoints included primary outcomes at weeks 1, 4, and 8; WOMAC stiffness subscale; spontaneous pain; global rating of disease; and global evaluation of treatment. Subanalyses were performed according to KLG, the number of knees treated, and age. RESULTS: Four hundred twenty patients were randomly assigned to DSG (n = 208) or vehicle (n = 212). At week 12, DSG provided significantly greater reductions in WOMAC pain (52.6% vs 43.1%; P = 0.008) and physical function (49.7% vs 39.4%; P = 0.004) versus vehicle and provided significant improvements in most secondary endpoints. Treatment-related adverse events (AEs) were infrequent (DSG, 7.7%; vehicle, 4.2%), with application site dermatitis being the most common AE (DSG, 4.8%; vehicle, 0%). No treatment-related gastrointestinal or serious AEs occurred with DSG. CONCLUSION: Topical DSG treatment provided effective pain relief and functional improvement of OA in 1 or both knees and was well tolerated, irrespective of disease severity or patient age.

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.

Correlation of pain relief with physical function in hand osteoarthritis: randomized controlled trial post hoc analysis.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs are recommended for the relief of pain associated with hand osteoarthritis (OA) but do not alter the underlying structural changes that contribute to impaired physical function. The current analysis examined the relationship of pain relief with measures of function and global rating of disease in patients with hand OA. METHODS: This was a combined analysis of 2 prospective, randomized, double-blind, 8-week, multicenter, parallel-group studies comparing diclofenac sodium 1% gel with placebo gel (vehicle) in patients with radiographically confirmed mild to moderate hand OA. Patients (n = 783) aged > or = 40 years applied diclofenac sodium 1% gel (2 g) or vehicle to each hand 4 times daily for 8 weeks. Outcome measures included pain intensity assessed on a 100-mm Visual Analog Scale (VAS); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscales for pain, stiffness, and physical function (100-mm VAS); and a global rating of disease (100-mm VAS). Change in VAS pain intensity from baseline to week 8 was categorized (<0%, 0%-<15%, 15%-<30%, 30%-<50%, 50%-<70%, and > or = 70%) without regard to treatment and compared in each category with the mean change from baseline in each AUSCAN subindex and the global rating of disease. Pearson correlations between changes in outcome measures from baseline to week 8 were calculated. RESULTS: Changes in VAS pain intensity were accompanied by similar changes in AUSCAN scores and global rating of disease. Pearson correlations confirmed significant associations (P < 0.001) between change in VAS pain intensity and changes in AUSCAN pain (correlation coefficient [r] = 0.81), AUSCAN function (r = 0.75), AUSCAN stiffness (r = 0.66), and global rating of disease (r = 0.76). CONCLUSIONS: Pain relief correlated with improvements in physical function, stiffness, and global rating of disease in patients with hand OA, irrespective of treatment. This suggests that pain or anticipation of pain inhibits physical function and influences patient perception of disease severity in hand OA. These results also suggest that any intervention to relieve the pain of hand OA may improve function and patient perception of disease severity, despite the absence of a disease-modifying mechanism of action. TRIAL REGISTRATION: Clinicaltrials.gov NCT00171652, NCT00171665.

Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis.

OBJECTIVES: Nonsteroidal anti-inflammatory drugs have dose-related adverse effects. Topical nonsteroidal anti-inflammatory drugs may offer local efficacy with low systemic drug levels. This study assessed the efficacy and safety of topical diclofenac sodium 1% gel (DSG) in mild to moderate symptomatic knee osteoarthritis. METHODS: In a randomized, double-blind, vehicle-controlled trial, 492 adults aged >or=35 years with symptomatic knee osteoarthritis of >or=6 months' duration were randomized to DSG 4 g (n = 254) or vehicle (n = 238) 4 times daily for 12 weeks. Primary efficacy outcomes at week 12 were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, WOMAC physical function subscale, and global rating of disease. Secondary outcomes included these outcomes assessed after 1, 4, and 8 weeks, and pain on movement assessed using a 100-mm visual analog scale. All adverse events were recorded. RESULTS: At week 12, the DSG group had significant decreases versus the vehicle group in mean WOMAC pain (P = 0.01), mean WOMAC physical function (P = 0.001), and mean global rating of disease (P < 0.001). Efficacy outcomes significantly favored DSG versus vehicle beginning at week 1. Application site reactions occurred in 5.1% and 2.5% of patients in the DSG and vehicle groups, respectively. The incidence of gastrointestinal disorders was 5.9% with DSG and 5.0% with vehicle. CONCLUSIONS: Over a 3-month treatment period, topical treatment with DSG achieved statistically and clinically significant improvements of pain and measures of physical function in patients with knee osteoarthritis.

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.