Assessment of intralesional injection of botulinum toxin type A in hypertrophic scars and keloids: Clinical and pathological study.

Keloids and hypertrophic scars are cosmetic problems with significant morbidity. Many clinical modalities were tried in order to modulate the disfigurement related to these pathologic scars. To evaluate the clinical and histopathological effects of Botulinum toxin type A (BTX-A) injection on keloids and hypertrophic scars. Twelve patients with keloids and 8 with hypertrophic scars were enrolled in this study. Botulinum toxin type A was injected intralesional (1 session/month) for three sessions. Clinical outcome was assessed via Vancouver Scar Scale (VSS), Observer Scar Assessment Scale (OSAS), and the Patient Scar Assessment Scale (PSAS). Histologic grading scores were used to assess the changes in the quality of collagen and elastic tissues and image analysis was used to detect their quantitative morphometric changes. This study showed a high statistically significant difference between baseline and the result after each of the three sessions of injection and 3, 6 months after the last session regarding VSS, OSAS, and PSAS with p value ≤0.001 for each. The study also showed that there was a statistically significant difference between the histopathologic findings before injection of BTX and 1 month after the third session regarding all parameters used. Botulinum toxin type A can be a good therapeutic maneuver for management of keloid and hypertrophic scars with significant clinical and histologic improvement.

Assessment of the effect of the dual orexin receptor antagonist daridorexant on various indices of disease severity in patients with mild to moderate obstructive sleep apnea.

BACKGROUND: The dual orexin receptor antagonist daridorexant did not impact nighttime respiratory function as assessed by the apnea/hypopnea index (AHI) and nocturnal oxygen saturation (SpO2) and improved sleep in patients with mild to moderate obstructive sleep apnea (OSA). These analyses were supplemented with further evaluations of various indices of OSA severity and sleep variables. METHODS: In this randomized, double-blind, placebo-controlled, two-period, crossover study, 50 mg daridorexant or placebo was administered every evening for 5 days to 28 patients with mild to moderate OSA. Treatment differences (daridorexant - placebo) were explored for indices of OSA severity including the number and duration of apneas and hypopneas, mean and lowest nocturnal SpO2, sleep duration during each hour of polysomnography recording, and the number and mean and longest duration of awakenings. RESULTS: After repeated-dose daridorexant, more respiratory events were observed compared to placebo, ie., treatment difference of 16.4 events (90% confidence interval: -0.4, 33.2) which is explained by a longer total sleep time. However, no treatment difference was detected for the longest duration of apneas and hypopneas (1.5 s [-8.3, 11.2] and 8.2 s [-6.6, 23.0], respectively), and lowest SpO2 (0.9% [-0.3, 2.1]). The number of awakenings was similar between daridorexant and placebo while daridorexant shortened the longest duration by 16.2 min (8.5, 23.8). Overall, results were similar after single and repeated dosing for both respiratory and sleep aspects. CONCLUSION: These results suggest safe use of daridorexant in patients with mild to moderate OSA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03765294. A study to investigate the effects of ACT-541468 on nighttime respiratory function in patients with mild to moderate obstructive sleep apnea. https://clinicaltrials.gov/ct2/show/NCT03765294.

Association of Opioid and Benzodiazepine Use with Adverse Respiratory Events in Older Adults with Chronic Obstructive Pulmonary Disease.

Rationale: Older adults with chronic obstructive pulmonary disease (COPD) are at substantially increased risk for medication-related adverse events. Two frequently prescribed classes of drugs that pose a particular risk to this patient group are opioids and benzodiazepines. Research on this topic has yielded conflicting findings.Objectives: The purpose of this study was to examine, among older adults with COPD, whether: 1) independent or concurrent use of opioid and benzodiazepine medications was associated with hospitalizations for respiratory events, and 2) this association was exacerbated by the presence of obstructive sleep apnea (OSA).Methods: We conducted a case-control study of Medicare beneficiaries aged ≥66 years, who were diagnosed with COPD in 2013, using the 5% national Medicare database. Cases (n = 3,232) were defined as patients hospitalized for a primary COPD-related respiratory diagnosis in 2014 and were matched with up to two control subjects (n = 6,247) on index date, age, sex, socioeconomic status, comorbidity, presence of OSA, COPD medication, and COPD complexity.Results: In comparison to the referent (no opioid or benzodiazepine use), opioid use alone (adjusted odds ratio [aOR], 1.73; 95% confidence interval [CI], 1.52-1.97), benzodiazepine use alone (aOR, 1.42; 95% CI, 1.21-1.66), and concurrent opioid/ benzodiazepine use (aOR, 2.32; 95% CI, 1.94-2.77) in the 30 days before the event/index date were all associated with an increased risk of hospitalization for a respiratory condition. Risk of hospitalization was higher with concurrent opioid and benzodiazepine use when compared with use of either medication alone. There was no statistically significant interaction between OSA and either of the drugs, alone or in combination. However, the adverse respiratory effects of concurrent opioid and benzodiazepine use were increased in patients with a high degree of COPD complexity. All of the above findings persisted using exposure windows that extended to 60 and 90 days before the event/index date.Conclusions: Among older adults with COPD, use of opioid and benzodiazepine medications alone or in combination were associated with increased adverse respiratory events. The adverse effects of these medications were not exacerbated in patients with COPD-OSA overlap syndrome. However, the adverse impact of dual opioid and benzodiazepine was greater in patients with high-complexity COPD.

Comparison of the Efficacy, Side Effects, and Cost of Modafinil and Intranasal Mometasone Furoate in Obstructive Sleep Apnea-Hypopnea Syndrome: A Preliminary Clinical Study.

BACKGROUND Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repeated episodes of reduction in airflow due to the collapse of the upper airway during sleep. The aim of this study was to compare clinical outcome, side effects, and cost of treatment between modafinil and intranasal mometasone furoate in patients with OSAHS. MATERIAL AND METHODS Patients with OSAHS (N=250) were divided into two groups: the modafinil group (MG) (N=125) were treated with 100 mg modafinil twice a day; the intranasal mometasone furoate group (IMFG) (N=125) were treated with 100 µg of intranasal mometasone furoate in the evening. Quality of life, grading of OSAHS, plain-film radiography, the adenoidal-nasopharyngeal ratio (AN ratio), side effects, cost of treatment, and beneficial effects after discontinuation of treatment were evaluated for all patients. RESULTS Duration of sleep apnea was significantly reduced in the IMFG compared with the MG (p=0.0145, q=9.262). Modafinil and intranasal mometasone furoate both had moderate effects on improvement of the OSAHS score. The IMFG showed a significantly greater beneficial effect on the AN ratio when compared with the MG (p=0.0001, q=6.584). No adverse events of treatment with modafinil and intranasal mometasone furoate were reported. Cost of treatment and beneficial effect after discontinuation were both significantly greater for the IMFG compared with the MG. CONCLUSIONS The findings of this preliminary clinical study were that for patients diagnosed with OSAHS, night-time treatment with intranasal mometasone furoate was more effective than modafinil.

What Is the Prevalence of Symptomatic Obstructive Sleep Apnea Syndrome in Chronic Spinal Pain Patients? An Assessment of the Correlation of OSAS with Chronic Opioid Therapy, Obesity, and Smoking.

BACKGROUND: In modern medicine, obstructive sleep apnea syndrome (OSAS) is a commonly described sleep disorder with airway obstruction, disrupted sleep, and excessive daytime sleepiness. Since its description in 1976 by Guilleminault et al, numerous epidemiologic studies and systematic reviews, with multiple comorbidities related to cardiovascular sequelae, altered cognitive function, and multiple other potential complications have been described. Multiple risk factors have been identified included obesity, smoking, alcohol consumption, and other factors. Chronic pain and chronic opioid therapy also have been described to contribute to a large proportion of patients with OSAS. Chronic pain, obesity, smoking, and chronic opioid therapy are often found together, yet there is a paucity of literature describing OSAS in chronic pain patients. OBJECTIVES: To assess the prevalence of symptomatic OSAS in chronic spinal pain patients receiving chronic opioid therapy and determine the association of OSAS with multiple risk factors and comorbidities. STUDY DESIGN: A retrospective assessment of patients who attend a single interventional pain management practice from January 1, 2010to December 31, 2014. SETTING: A private interventional pain management practice in the United States. METHODS: The data were collected from 4,036 consecutive patients presenting for assessment to a pain management center from January 1, 2010 to December 31, 2014. All assessments were comprehensive and performed by 2 physicians. The comprehensive assessment included a complete history, a physical examination, and a review of records. RESULTS: The prevalence of OSAS in patients with chronic spinal pain was 13.8%. The results showed a higher prevalence in males compared to females (15.1% versus 12.8%), a higher prevalence in those aged 45 or older compared to those 25-45 years and those 18-25 years (16.3% versus 10.7% or 2.5%), higher prevalence in Hispanics and Asians compared to African Americans and whites (23.7% versus 16.2% versus 13.4%), higher prevalence in patients with combined back and neck pain compared to patients with thoracic pain only or back pain only (16.3% versus 8.2% to 11%). Prevalence also varied by body mass index (BMI): 32.4% in morbidly obese patients, 20.3% in severely obese patients, 15.7% in obese patients, 9.2% in those who were overweight, and only 5.7% in those with normal weight. A significant correlation with OSAS was also observed in patients smoking more than 40 pack years and multiple respiratory symptoms except for chronic bronchitis and multiple cardiovascular ailments. LIMITATIONS: The retrospective nature of the assessment. CONCLUSION: This retrospective assessment of over 4,000 patients suffering from chronic pain and receiving chronic opioid therapy indicated a prevalence of sleep apnea syndrome as 13.8%. Multiple risk factors including obesity, chronic obstructive pulmonary disease (COPD), chronic sinus and nasal discharge, and multiple comorbidities including cardiovascular and related ailments have been identified. KEY WORDS: Obstructive sleep apnea syndrome, chronic pain, chronic spinal pain, chronic opioid therapy, obesity, smoking, cardiovascular risk factors, pulmonary risk factors.

Assessment of oxidative stress markers and hearing thresholds in patients with obstructive sleep apnea-hypopnoea treated with cysteine and superoxide dismutase therapy.

BACKGROUND AND AIM OF THE WORK: In OSAHS, the hypoxia and reoxygenation cicles, maintain a state of oxidative stress, which seems to cause a change in the oxidative balance. Our aim is to compare the markers of oxidative stress with audiological findings and OSAHS severity, in OSAHS patients untreated and also treated ones, with cysteine and superoxide dismutase. METHODS: 65 patients (42 Men, 23 Women) with 30-65 years age range have been enrolled, with a mean age of 52.6 ± 13.3 years with moderate OSAHS. We have analyzed plasma and lymphocyte markers of oxidative stress (glutathione, thioredoxin and heat shock protein) and they were underwent tonal audiometry. Patients were divided in two groups: Group A (32 patients) included patients treated for 8 weeks with cysteine and superoxide dismutase; Group B (33 patients) included patients untreated. RESULTS: The research showed a significant increase in reduced glutathione levels (p<0.05) in OSAHS patients treated; conversely, it showed a decrease of oxidized glutathione level (p<0.05) in treated patients than OSAHS untreated ones. The thioredoxin values, in untreated OSAHS patients, appear to be reduced than in OSAHS patients treated (p<0.05), and that the heat shock protein values were more elevated in untreated OSAHS patients (p<0.05). Finally, it was found that a correlation exists between the severity of OSAHS and auditory dysfunction. CONCLUSIONS: The study of the oxidative stress markers has produced results which lead to support the idea that, in a personalized therapy context, the use of antioxidant therapy can cooperate effectively the first choice treatment.

Assessment of CHADS2 and CHA 2DS 2-VASc scores in obstructive sleep apnea patients with atrial fibrillation.

PURPOSE: Assessment of stroke risk and implementation of appropriate antithrombotic therapy is an important issue in atrial fibrillation patients. Current risk scores do not take into consideration the comorbidities associated with elevated thromboembolic like obstructive sleep apnea (OSA). The aim of the study was to establish whether atrial fibrillation patients with coexisting OSA have higher stroke risk according to CHADS2 and CHA2DS2-VASc scores. METHODS: Two hundred fifty-four consecutive patients hospitalized with a primary diagnosis of atrial fibrillation participated in the study. All patients underwent whole night polygraphy and were scored in both CHADS2 and CHA2DS2-VASc according to their medical records or de novo diagnosis. RESULTS: The study population was predominantly male (65.4%; mean age, 57.5 ± 10.0 years) with a high prevalence of hypertension (73.6%), dyslipidemia (63.4%), and obesity (42.9%). OSA was present in 47.6% of patients, who more often had history of stroke (p = 0.0007). Stroke risk profile assessed by both CHADS2 and CHA2DS2-VASc scores was higher in patients with OSA (1.2 ± 0.9 vs. 0.8 ± 0.6; p < 0.0001 and 2.2 ± 1.7 vs. 1.5 ± 1.1; p = 0.001) than without it. Differences in the stroke risk remained significant across different age strata, and the trend for point values in CHADS2 and CHA2DS2-VASc scores rose along with OSA severity according to the apnea-hypopnea index (AHI; p for trend <0.001). CONCLUSIONS: OSA was highly prevalent in atrial fibrillation patients. Patients with OSA have higher CHADS2 and CHA2DS2-VASc scores. Mean CHADS2 and CHA2DS2-VASc scores rise with OSA severity. Future studies should prospectively research on potential inclusion of OSA to stroke prediction models.

Eszopiclone: an update on its use in insomnia.

Eszopiclone is the single (S)-enantiomer of the cyclopyrrolone hypnotic zopiclone. It was marketed in the U.S. in December 2004. Its kinetics and possible mode of action, pivotal regulatory trials and its use in insomnia comorbid with other conditions are reviewed, together with trials in patients with obstructive sleep apnea syndromes. Safety and tolerability aspects are discussed, including its dysgeusic profile and effects on memory, cognitive and psychomotor function. U.S.-based pharmacoeconomic data are included together with the design features of key regulatory studies submitted for regulatory approval in Japan.

Reimbursed drugs in patients with sleep-disordered breathing: A static-charge-sensitive bed study.

BACKGROUND: Co-morbidities in men and women with sleep-disordered breathing (SDB) were compared retrospectively to an age-standardized, general Finnish population. The prevalence of diseases was based on the reimbursement refunds of medications. METHODS: Two hundred thirty-three age- and BMI-matched male-female pairs and 368 consecutive women identified from our sleep recording database were included. Data on medication were gathered from the National Agency for Medicines and Social Insurance Institution database. RESULTS: Men with SDB had three-fold prevalence of reimbursed medication for diabetes and two-fold prevalence of reimbursed medication for chronic arrhythmia. Women with SDB had three-fold prevalence of reimbursed medication for thyroid insufficiency, and postmenopausal women had two-fold prevalence of reimbursed medication for psychosis. BMI and age did not explain prevalence of reimbursed medications for chronic arrhythmia or psychosis. In both genders with SDB, prevalence of reimbursed medications compared to the general population was two-fold for hypertension and seven-fold for asthma and/or chronic obstructive pulmonary disease (COPD). Partial upper airway obstruction was associated with three-fold prevalence of reimbursed medication for asthma and/or COPD in both genders and 60% reduced prevalence of reimbursed medication for hypertension in females matched for age and BMI. CONCLUSIONS: Co-morbidity profile differed between genders. Our results emphasize the importance of diagnosis and treatment of co-morbidities and partial upper airway obstruction.

Assessment of the test-retest reliability of laboratory polysomnography.

STATEMENT OF THE PROBLEM: When conducting a treatment intervention study, it is assumed that a level of reliability can be obtained from the measurement tool such that the outcome can be reasonably assessed. PURPOSE OF STUDY: Investigate the reliability of laboratory polysomnography, the gold standard for assessment of treatment outcomes for obstructive sleep apnea, at a 1-month interval. MATERIALS AND METHODS: In a clinical trial of 118 patients recruited to assess the effects of a pharmaceutical treatment intervention, a subset of 20 patients designated as placebo controls completed two polysomnography studies, one at baseline and one at least one month later. RESULTS: The correlation between the overall Apnea/Hypopnea indices from the two polysomnography (PSG) studies was poor (r = 0.44) and the results were biased, with a mean increase of seven events per hour on night 2. Twenty-five percent of the subjects had an increase greater than 20 events/hour on night 2 and only 45% of participants had a night-to-night difference of < or =5 events/hour. The correlation between overall apnea indexes for nights 1 and 2 (r = 0.61) was improved, compared to the overall apnea/hypopnea indexes. The correlation in sleep efficiency across the two nights was relatively week (r = 0.52) but significant. The correlations between nights 1 and 2 for the percentage of time supine (r = 0.70) and the supine apnea-hypopnea index (AHI) (r = 0.69) were similar and highly significant. The correlation for the non-supine AHI was only 0.25 CONCLUSIONS: In this study, the reliability of a single-night PSG in measuring treatment outcome was compromised as a result of the large night-to-night variability of subjects' obstructive sleep apnea (OSA). Studies employing the AHI as an outcome need to be adequately powered with respect to the inherent night-to-night variability in the measurement. When assessing treatment intervention outcomes, there may be benefit from the acquisition and averaging of multiple nights of data in order to mitigate the inherent night-to-night variability of OSA and improve the accuracy of the outcome assessment.

Armodafinil: a new treatment for excessive sleepiness.

BACKGROUND: Armodafinil is a wake-promoting agent developed by Cephalon that was approved in mid-2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder. It is the R-enantiomer of the compound modafinil. Like modafinil, the mechanism of action for armodafinil is not fully characterized. OBJECTIVE: To determine what data are available to support the potential use of armodafinil in clinical settings. METHODS: There are limited data on armodafinil available in the public domain, particularly in regard to chemistry and pharmacokinetics/dynamics. Data were reviewed from refereed journals, scientific presentations, and published labeling. RESULTS/CONCLUSION: Clinical trials demonstrated efficacy and safety profiles that were similar to those of the parent compound with wake promotion sustained throughout the day. The longer duration of effect has the potential for improved patient response and compliance but this will require further study. The primary commercial challenge may be the future availability of generic modafinil.

Sedating medications and undiagnosed obstructive sleep apnea: physician determinants and patient consequences.

BACKGROUND: Sedative medications may be inadvertently prescribed to patients with undiagnosed obstructive sleep apnea (OSA) and may worsen daytime sleepiness. STUDY OBJECTIVES: To determine whether patients with undiagnosed OSA were prescribed sedative medications and whether such prescriptions increased the risk for traffic accidents. A secondary objective was to determine physician characteristics associated with such prescription practices. DESIGN: Retrospective chart review. Telephone interviews of patients and physicians. INTERVENTION: None. PATIENTS: One hundred fifty-one consecutive patients at a sleep laboratory. RESULTS: Forty-one of 137 (30%) patients with undiagnosed OSA had received prescriptions for sedating medications. Regression analysis identified self-report of sleepiness while driving (p = .05) and prescription for risperidone as independent risk factors for motor vehicle accidents (p = .005), while prescription of any sedative (excluding risperidone) tended to be associated with accidents (p =.10). In patients with severe OSA, prescription of sedating medications was associated with a greater risk for motor vehicle accidents than those without such prescriptions (relative risk = 2.6; p = .04). In patients with prescription for sedating medications (n = 41), the apnea-hypopnea index was directly proportional to the risk for motor vehicle accidents (r2 = 0.26; p = .001) suggesting a 'dose effect' of severity of sleep-disordered breathing on risk for accidents. Physicians who did not usually treat patients with sleep disorders were more likely to prescribe sedatives to patients with undiagnosed OSA than were physicians with such expertise: neurologist, pulmonologist, or psychiatrist (52% vs 10%; relative risk = 5.2; p = .02) CONCLUSION: Prescription of sedating medications may increase the risk of road accidents in patients with undiagnosed severe OSA, and such prescription practices are less likely to occur in physicians with expertise in sleep medicine.