Insomnia and risk of mortality in older adults.

Existing evidence linking insomnia to all-cause mortality in older individuals remains inconclusive. We conducted a retrospective study of a large cohort of veterans aged 65-80 years old identified from the Corporate Data Warehouse, a large data repository derived from the Veterans Health Administration integrated medical records. Veterans' enrollees with and without International Classification of Diseases, Ninth and Tenth Revision, codes corresponding to insomnia diagnosis between 1 January 2010 and 30 March 2019 were assessed for eligibility. The primary outcome was all-cause mortality. A total of 36,269 veterans, 9584 with insomnia and 26,685 without insomnia, were included in the analysis. Baseline mean (SD) age was 72.6 (4.2) years. During a mean follow-up of 6.0 (2.9) years of the propensity score matched sample, the mortality rate was 34.8 [95% confidence interval: 33.2-36.6] deaths per 1000 person-years among patients with insomnia compared with 27.8 [95% confidence interval: 26.6-29.1] among patients without insomnia. In a Cox proportional hazards model, insomnia was significantly associated with higher mortality (hazard ratio: 1.39; [95% confidence interval: 1.27-1.52]). Patients with insomnia also had a higher risk of non-fatal cardiovascular events (hazard ratio: 1.21; [95% confidence interval: 1.06-1.37]). Secondary stratified analyses by sex, race, ethnicity and hypertension showed no evidence of effect modification. A higher risk of mortality (hazard ratio: 1.51; [95% confidence interval: 1.33-1.71]) was observed when depression was present compared with absent (hazard ratio: 1.26; [95% confidence interval: 1.12-1.44]; p = 0.02). In this cohort study, insomnia was associated with increased risk-adjusted mortality and non-fatal cardiovascular events in older individuals.

Association Between Hypnotic Use and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease and Insomnia.

Purpose: Hypnotics are commonly prescribed in patients with COPD to manage insomnia. Given the considerable risks associated with these drugs, the aim of the study was to evaluate the risk of all-cause mortality associated with hypnotics in a cohort of veterans with COPD presenting with insomnia. Methods: We conducted a retrospective cohort study that used Veterans Health Administration Corporate Data Warehouse with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2010 through 2019. The primary outcome was all-cause mortality. Analyses were conducted using propensity score 1:1 matching to balance baseline characteristics. Results: Of the 5759 veterans with COPD (mean [SD] age, 71.7 [11.2]; 92% men), 3585 newly initiated hypnotic agents during the study period. During a mean follow-up of 7.4 (SD, 2.7) years, a total of 2301 deaths occurred, with 65.2 and 48.7 total deaths per 1000 person-years among hypnotic users and nonusers, respectively. After propensity matching, hypnotic use was associated with a 22% increased risk of mortality compared with hypnotic nonusers (hazard ratio [HR] 1.22; 95% confidence interval [CI],1.11-1.35). The benzodiazepine receptor agonists (BZRAs) group experienced a higher incidence rate of all-cause mortality compared to hypnotic nonusers (Incidence rate ratio [IRR] 1.27; 95% CI, 1.14-1.43). Conversely, the mortality rate of non-BZRA hypnotics decreased after the first 2 years and was not significantly different for hypnotic nonusers (IRR 1.04; 95% CI, 0.82-1.11). Conclusion: Among patients with COPD and insomnia, treatment with hypnotics was associated with a higher risk of all-cause mortality. The association was observed in patients prescribed BZRAs. The risk of mortality for non-BZRAs moderated after the first 2 years, indicating a class effect.

The risk of major adverse cardiovascular events associated with the use of hypnotics in patients with insomnia.

OBJECTIVES: To examine whether hypnotic use in patients with insomnia reduces major adverse cardiovascular events, including all-cause mortality and nonfatal major adverse cardiovascular events. METHODS: Using the Veterans Affairs Corporate Data Warehouse, we conducted a retrospective cohort study of 16,064 patients who were newly diagnosed with insomnia between January 1, 2010, and December 31, 2019. A pair of 3912 hypnotic users and nonusers were selected based on a 1:1 propensity score methodology. The primary outcome was extended major adverse cardiovascular events, a composite of the first occurrence of all-cause mortality or nonfatal major adverse cardiovascular events. RESULTS: During the median follow-up of 4.8 years, a total of 2791 composite events occurred, including 2033 deaths and 762 nonfatal major adverse cardiovascular events. Although the incidence rates of major adverse cardiovascular events were comparable between hypnotic users and nonusers in the propensity-matched cohort, users of benzodiazepines and Z-drugs had a higher risk of all-cause mortality (hazard ratio 1.47 [95% CI, 1.17-1.88] and 1.20 [95% CI, 1.03-1.39], respectively), while serotonin antagonist and reuptake inhibitors users had a survival advantage (hazard ratio 0.79 [95% CI, 0.69-0.91]) compared with nonusers. There were no differences in the risk of nonfatal major adverse cardiovascular events between all classes of hypnotics. Male patients and those aged 60 years or younger who were using benzodiazepines or Z-drugs experienced higher major adverse cardiovascular events than their counterparts. CONCLUSIONS: In patients with newly diagnosed insomnia, treatment with hypnotics resulted in higher extended major adverse cardiovascular events but not nonfatal major adverse cardiovascular events with benzodiazepine and Z-drug users compared with nonusers. The use of serotonin antagonist and reuptake inhibitors agents had a protective effect against major adverse cardiovascular events warranting further investigation.

Residual sleepiness in veterans with post-traumatic stress disorder and obstructive sleep apnea.

PURPOSE: The causes of residual excessive sleepiness (RES) in patients with post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are multifactorial and modulated by comorbid conditions. The aim of the present study was to elucidate clinical and polysomnographic determinants of RES in continuous positive airway pressure (CPAP)-adherent OSA veterans with PTSD. METHODS: The study protocol consisted of a retrospective analysis of consecutive cases of patients with PTSD who presented to the Veterans Affairs sleep clinics with adequately treated OSA between June 1, 2017 and October 15, 2021. Based on the Epworth Sleepiness Scale (ESS), patients were categorized into RES (ESS ≥ 11) and no RES (ESS < 11) groups. Demographic and PSG data were subjected to univariate and multivariate analyses to ascertain predictive factors of RES. RESULTS: Out of 171 veterans with PTSD who were adherent to CPAP, 59 (35%) continued to experience RES. The RES group had a decrease in mean ESS score of 1.2 ± 4.5 after CPAP treatment compared with 4.6 ± 4.9 for the no RES group (< 0.001). A dose-response was observed between CPAP use and RES (p = 0.003). Multivariate regression analysis identified higher baseline ESS (OR 1.30; 95% CI 1.16-1.44), greater percentage of time spent in REM sleep (OR 0.91; 95% CI 0.85-0.96), CPAP use less than 6 h (OR 2.82; 95% CI 1.13-7.01), and a positive screen for depression (OR 1.69; 95% CI 1.03-4.72) as independent predictors of RES in patients with PTSD and OSA. CONCLUSION: RES is highly prevalent in patients with PTSD and OSA despite adherence to CPAP and is independently associated with percentage time spent in REM, duration of CPAP utilization, and symptoms of depression.

Cardiovascular events in insomnia patients with post-traumatic stress disorder.

BACKGROUND: Both post-traumatic stress disorder (PTSD) and insomnia are independently associated with a greater risk of cardiovascular mortality. The objective of this study is to determine whether PTSD plus insomnia is associated with a higher risk of major adverse cardiovascular events (MACEs) than either condition alone in a large cohort of veterans. METHODS: We conducted a retrospective analysis of the national Veterans Health Administration (VHA) electronic medical records covering veterans 18 years or older with the diagnosis of PTSD, insomnia, or both from January 1, 2015, to December 31, 2020. MACE was defined as new-onset myocardial infarction (MI), transient ischemic attack (TIA) or stroke, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient encounters. RESULTS: A total of 19,080 veterans, 1840 with PTSD plus insomnia and 17,240 with either PTSD or insomnia, were included in the analysis. Baseline mean (SD) age was 46.3 (11.5) years. During median follow-up of 3.9 (interquartile range, 2.4-5.1) years, 206 (1%) veterans developed incident MACE. Cumulative incidence for MI, TIA and/or stroke was larger in veterans with PTSD plus insomnia compared to PTSD and insomnia alone (p=0.008). In a Cox proportional hazards model, PTSD plus insomnia was significantly associated with greater risk of developing MACEs (hazard ratio [HR], 1.44; 95% CI, 1.38-1.50, p=0.01) than either condition after adjusting for multiple covariates including age, gender, smoking, hypertension, depression, and burden of comorbidities. CONCLUSIONS: This cohort study found that PTSD plus insomnia is a risk factor for MACEs of greater magnitude than PTSD- or insomnia-alone.

Outcomes of multiple sclerosis patients admitted with COVID-19 in a large veteran cohort.

BACKGROUND: Given concerns over immune function, the decision whether to continue disease modifying therapy (DMT) in multiple sclerosis (MS) patients during the COVID-19 pandemic has been challenging, complicated by the risk of MS disease progression in the absence of treatment. METHODS: This retrospective analysis of patients treated for COVID-19 infection at veteran affairs healthcare systems across the United States, investigated 30-day all-cause mortality after first positive COVID-19 in patients with and without MS. We examined mortality risk impact of disease modifying therapy for MS, accounting for other relevant factors known to be associated with COVID-19 mortality. Patients were propensity score matched in a 1:20 fashion based on MS diagnosis. RESULTS: 49,737 COVID-19 inpatient cases were identified, of which 258 were diagnosed with MS. In the propensity score matched cohort, MS patients taking DMT (excluding those receiving anti-CD20 antibodies) had a lower odds of 30 day mortality (OR: 0.18 [95%CI: 0.00988-0.94] p=0.041). Similarly, in the unmatched cohort, patients on DMT had a lower risk of death (OR: 0.16 [95%CI: 0.01-0.82] p=0.023). There was no statistically significant difference in mortality between those with and without MS. In the propensity matched cohort, age over 65, heart failure, chronic kidney disease (CKD), and diabetes increased the risk of mortality while vaccination reduced the risk of mortality. CONCLUSION: Veteran patients with MS hospitalized for COVID-19 were less likely to die when taking DMTs (excluding those receiving anti-CD20 antibodies), accounting for other relevant factors. Results suggest that, in relation to the COVID-19 pandemic, not only is it safe to continue most DMTs in people with MS, but it may be beneficial given the decreased risk of COVID-19 mortality and decreased risk of MS disease progression.

Pharmacotherapy of residual excessive sleepiness among continuous positive airway pressure (CPAP) treated patients with sleep apnea.

INTRODUCTION: Patients with persistent sleepiness after adequate treatment of obstructive sleep apnea (OSA) with nasal continuous positive airway pressure (nCPAP) experience impaired cognition, reduced productivity, and worse quality of life. Although the mechanisms responsible for this phenomenon are not completely understood, neuroimaging studies have identified reduced gray matter in the frontal cortex and alterations in white matter integrity suggestive of axonal and myelin damage. The intermittent hypoxia with resulting oxidative injury is considered a prime culprit behind the loss of wake-promoting catecholaminergic neurons. AREAS COVERED: This narrative review gives an overview of the pathophysiology and approaches to managing patients with residual sleepiness. The authors explore different targeted strategies aimed at improving selection of appropriate pharmacotherapy. EXPERT OPINION: Wake-stimulant medications (modafinil and armodafinil) have demonstrated efficacy in reducing sleepiness in adequately treated OSA. The recent FDA approval of pitolisant and solriamfetol complements the use of modafinil by substituting for direct sympathomimetic agents. The distinctive pharmacologic profile and mode of action of each of these agents offer the opportunity of a personalized approach to the management of this disorder. Further studies should be conducted on the long-term effect of these agents alone or in combination on brain structural and functional changes.

All-cause mortality in COVID-19 patients receiving statin therapy: analysis of veterans affairs database cohort study.

Statins have been advocated as a potential treatment for coronavirus disease-2019 (COVID-19) due to its pleotropic properties. The aim of the study was to elucidate the association between antecedent statin exposure and 30-day all-cause mortality, intensive care unit (ICU) admission and hypoxic respiratory failure requiring mechanical ventilation in patients diagnosed with COVID-19. Observational cohort study derived from the VA Corporate Data Warehouse of all veterans tested positive for COVID-19 between January 1st and May 31st, 2020. Antecedent use of statins was defined as a redeemed drug prescription in the 6 months prior to COVID-19 diagnosis. Propensity-matched mixed-effects logistic regression was performed, stratified by statin use. The study population comprised 14,268 patients with COVID-19 (median age 66 years (25th-75th percentile, 53-74), 90.7% men), of whom 7,168 were receiving a prescription for statins. Patients with statin exposure had a greater prevalence of comorbidities and a higher risk of mortality (Odd ratio [OR] 1.52; 95% confidence interval [CI] 1.37-1.68). After adjusting for covariates, statin exposure was not associated with a decreased mortality in the overall cohort by either Cox proportional hazards stratified model (HR 0.99; 95% CI 0.88-1.12) or propensity matching (HR .86; 95% CI 0.74-1.01). Similarly, there was no demonstrated advantage of statins in reducing the risk of ICU admission (HR 0.92; 95% CI 0.74-1.31) or hypoxic respiratory failure requiring mechanical ventilation (HR 1.02; 95% CI 0.81-1.29). Antecedent statin exposure in patients with COVID-19 was not associated with a decreased risk of 30-day all-cause mortality or need for mechanical ventilation.

The Nightmare Quality of Life Questionnaire.

RATIONALE: Patient-centered outcomes are increasingly sought to evaluate social interactions and healthcare interventions in patients with sleep disorders. Yet, measures to assess quality of life (QoL) are lacking for those who experience nightmares. OBJECTIVE: The aim of the study is to describe the development and validation of a new health-related quality of life (HRQoL) instrument for patients with nightmares. METHODS: Attributes obtained from a focus group of patients (n = 113) with established nightmares were analyzed using exploratory factor analysis to elicit salient QoL themes for the new instrument. A validation cohort (n = 34) was used to determine the psychometric performance of the 16-item questionnaire including item-scaling, concurrent validity, and test-retest reliability tested four weeks apart. RESULTS: Four factors (sleep health, emotional and psychological well-being, social interaction, and motivation) explained 53.9% of the total variance. The Nightmare Quality of Life (NQoL) showed good internal consistency (Cronbach's alpha 0.85) and test-retest reliability (ICC = 0.89). Concurrent validity was evidenced by a strong correlation with the Nightmare Distress Questionnaire (r = 0.87; p < .001) and more modest associations with the Nightmare Frequency Questionnaire (r = , 0.69; p < .001), SF-36 (r = -0.68; p < .001), and PSQI (r = 0.45; p = .007). CONCLUSIONS: The NQoL has demonstrable construct validity and reliability and represents a promising multi-dimensional instrument to assess outcome measures for quality of life in patients with nightmares.

Smoking status related to Covid-19 mortality and disease severity in a veteran population.

INTRODUCTION: Cigarette smoking is associated with development of significant comorbidities. Patients with underlying comorbidities have been found to have worse outcomes associated with Coronavirus Disease 2019 (Covid-19). This study evaluated 30-day mortality in Covid-19 positive patients based on smoking status. METHODS: This retrospective study of veterans nationwide examined Covid-19 positive inpatients between March 2020 and January 2021. Bivariate analysis compared patients based on smoking history. Propensity score matching adjusted for age, gender, race, ethnicity, Charlson comorbidity index (0-5 and 6-19) and dexamethasone use was performed. A multivariable logistic regression with backwards elimination and Cox Proportional Hazards Ratio was utilized to determine odds of 30-day mortality. RESULTS: The study cohort consisted of 25,958 unique Covid-19 positive inpatients. There was a total of 2,995 current smokers, 12,169 former smokers, and 8,392 non-smokers. Death was experienced by 13.5% (n = 3503) of the cohort within 30 days. Former smokers (OR 1.15; 95% CI, 1.05-1.27) (HR 1.13; 95% CI, 1.03-1.23) had higher risk of 30-day mortality compared with non-smokers. Former smokers had a higher risk of death compared to current smokers (HR 1.16 95% CI 1.02-1.33). The odds of death for current vs. non-smokers did not significantly differ. CONCLUSION: Compared to veteran non-smokers with Covid-19, former, but not current smokers with Covid-19 had a significantly higher risk of 30-day mortality.

Clinical Course and Outcome of COVID-19 Acute Respiratory Distress Syndrome: Data From a National Repository.

BACKGROUND: Mortality attributable to coronavirus disease-19 (COVID-19) 2 infection occurs mainly through the development of viral pneumonia-induced acute respiratory distress syndrome (ARDS). RESEARCH QUESTION: The objective of the study is to delineate the clinical profile, predictors of disease progression, and 30-day mortality from ARDS using the Veterans Affairs Corporate Data Warehouse. STUDY DESIGN AND METHODS: Analysis of a historical cohort of 7,816 hospitalized patients with confirmed COVID-19 infection between January 1, 2020, and August 1, 2020. Main outcomes were progression to ARDS and 30-day mortality from ARDS, respectively. RESULTS: The cohort was comprised predominantly of men (94.5%) with a median age of 69 years (interquartile range [IQR] 60-74 years). 2,184 (28%) were admitted to the intensive care unit and 643 (29.4%) were diagnosed with ARDS. The median Charlson Index was 3 (IQR 1-5). Independent predictors of progression to ARDS were body mass index (BMI) ≥40 kg/m2, diabetes, lymphocyte counts <700 × 109/L, LDH >450 U/L, ferritin >862 ng/ml, C-reactive protein >11 mg/dL, and D-dimer >1.5 ug/ml. In contrast, the use of an anticoagulant lowered the risk of developing ARDS (OR 0.66 [95% CI 0.49-0.89]. Crude 30-day mortality rate from ARDS was 41% (95% CI 38%-45%). Risk of death from ARDS was significantly higher in those who developed acute renal failure and septic shock. Use of an anticoagulant was associated with 2-fold reduction in mortality. Survival benefit was observed in patients who received corticosteroids and/or remdesivir but there was no advantage of combination therapy over either agent alone. CONCLUSIONS: Among those hospitalized for COVID-19, nearly 1 in 10 progressed to ARDS. Septic shock, and acute renal failure are the leading causes of death in these patients. Treatment with either remdesivir and corticosteroids reduced the risk of mortality from ARDS. All hospitalized patients with COVID-19 should be placed at a minimum on prophylactic doses of anticoagulation.

Impact of low arousal threshold on treatment of obstructive sleep apnea in patients with post-traumatic stress disorder.

PURPOSE: We sought to determine the prevalence of low arousal threshold (LAT) in veterans with post-traumatic stress disorder (PTSD) and whether or not LAT is associated with decreased use of continuous positive airway pressure (CPAP). METHODS: We conducted a retrospective study of all veterans with documented PTSD who had an apnea hypopnea index > 5/h over a 27-month period. Demographic, clinical characteristics, and CPAP usage were extracted from the medical records. A multivariate analysis was conducted to assess predictors of CPAP use at 3 months in patients with LAT after adjusting for severity of PTSD. RESULTS: LAT was identified in 55% of 119 patients with PTSD and newly diagnosed OSA. LAT was associated with younger age (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.86-0.95), lower BMI (OR 0.82; 95% CI 0.73-0.91), presence of insomnia (OR 1.34; 95% CI 1.19-1.81), and use of antidepressant (OR 1.14; 95% CI 1.09-2.01). PTSD severity, REM rebound, and the presence of baseline comorbid insomnia were each associated with CPAP use at 3 months. Neither daytime sleepiness, body mass index (BMI), nor LAT endotype was correlated with CPAP utilization. Insomnia was the only factor associated with decreased CPAP use in patients with PTSD and LAT (P = 0.04). CONCLUSION: The LAT endotype is common among veterans with PTSD. An improved understanding of how insomnia in this population affects CPAP utilization would be instrumental in designing targeted therapy to improve sleep quality.

Comparison of in-hospital mortality risk prediction models from COVID-19.

OBJECTIVE: Our objective is to compare the predictive accuracy of four recently established outcome models of patients hospitalized with coronavirus disease 2019 (COVID-19) published between January 1st and May 1st 2020. METHODS: We used data obtained from the Veterans Affairs Corporate Data Warehouse (CDW) between January 1st, 2020, and May 1st 2020 as an external validation cohort. The outcome measure was hospital mortality. Areas under the ROC (AUC) curves were used to evaluate discrimination of the four predictive models. The Hosmer-Lemeshow (HL) goodness-of-fit test and calibration curves assessed applicability of the models to individual cases. RESULTS: During the study period, 1634 unique patients were identified. The mean age of the study cohort was 68.8±13.4 years. Hypertension, hyperlipidemia, and heart disease were the most common comorbidities. The crude hospital mortality was 29% (95% confidence interval [CI] 0.27-0.31). Evaluation of the predictive models showed an AUC range from 0.63 (95% CI 0.60-0.66) to 0.72 (95% CI 0.69-0.74) indicating fair to poor discrimination across all models. There were no significant differences among the AUC values of the four prognostic systems. All models calibrated poorly by either overestimated or underestimated hospital mortality. CONCLUSIONS: All the four prognostic models examined in this study portend high-risk bias. The performance of these scores needs to be interpreted with caution in hospitalized patients with COVID-19.

Selecting a pharmacotherapy regimen for patients with chronic insomnia.

INTRODUCTION: Chronic insomnia, whether it is primary or in combination with another medical or psychiatric disorder, is a prevalent condition associated with significant morbidity, reduced productivity, increased risk of accidents, and poor quality of life. Pharmacologic and behavioral treatments have equivalent efficacy with each having its own advantages and limitations. AREAS COVERED: The purpose of this perspective is to delineate the limitations encountered in implementing cognitive behavioral therapy (CBT) and to review the pharmacological treatments designed to target the different phenotypes of insomnia. The discussions address how to choose the optimal medication or combination thereof based on patients' characteristics, available medications, and the presence of comorbid conditions. Selective nonbenzodiazepine sedative 'Z-drug' hypnotics, melatonin receptor agonist-ramelteon, and low-dose doxepin are the agents of choice for treatment of primary and comorbid insomnia. EXPERT OPINION: A pharmacological intervention should be offered if cognitive behavioral therapy for insomnia is not available or has failed to achieve its goals. Increasing evidence of the significant adverse consequences of long-term benzodiazepines should limit the prescription of these agents to specific conditions. Testing novel dosing regimens with a combination of hypnotic classes augmented with CBT deserve further investigation.

Predictive factors for COPD exacerbations and mortality in patients with overlap syndrome.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA)-overlap syndrome-have a substantially greater risk of morbidity and mortality, compared to those with either COPD or OSA alone. OBJECTIVES: The aim of this retrospective study was to identify clinical modifiable factors associated with COPD exacerbations and all-cause mortality in patients with overlap syndrome. METHODS: The electronic records of patients with simultaneous COPD and OSA who had a documented acute exacerbation of COPD during a 42-month period were evaluated for reviewed. A control group of overlap syndrome patients without exacerbations was matched 1:1 for age and body mass index. Vital status and cause of death were assessed through the population death registry. RESULTS: Out of 225 eligible cases, 92 patients had at least one episode of COPD exacerbation. There was no significant association between severity of airflow limitation and apnoea hypopnea index (P = .31). After adjusting for confounding variables, patients who had at least one COPD exacerbation were more likely to be active smokers (P = .01), have poorer lung function (P = .001) and less likely to adhere to continuous positive airway pressure (CPAP) use (P = .03). All-cause mortality was also correlated with low forced expiratory volume in 1 second (P = .006), CPAP use (P = .007), and burden of comorbidities (P < .001). CONCLUSION: Lung function and CPAP use were independent predictors of COPD exacerbations and all-cause mortality in a cohort of patients with overlap syndrome. These factors should be taken into account when considering the management and prognosis of these patients.

Predictors of cognitive behavioral therapy outcomes for insomnia in veterans with post-traumatic stress disorder.

BACKGROUND: Insomnia is a well-recognized co-morbid condition in veterans with post-traumatic stress disorder (PTSD) with negative personal and social consequences. Cognitive behavioral therapy (CBT) is considered an efficacious treatment, yet little attention has been devoted to treatment response in this population. The aim of this study was to identify factors that may predict clinical response to CBT for insomnia (CBT-I) in veterans with PTSD. METHODS: A retrospective chart review of 136 veterans with PTSD-related insomnia was conducted. Epworth Sleepiness Score (ESS), PTSD Checklist (PCL), and Insomnia Severity Index (ISI) were assessed at baseline. We converted prescribed antidepressant and hypnotic dosages before and after CBT-I to dose equivalent of fluoxetine diazepam, respectively. A 6-point reduction or greater in ISI scores at 6-month follow-up visit was defined as CBT-I responsiveness. RESULTS: CBT-I responsiveness was observed in 47% of veterans with PTSD. Seventy-seven percent completed treatment. Lack of perceived benefit was the most given reason for failure to return for follow-up. In contrast to hypnotics, antidepressants usage decreased in those who had experienced benefit from CBT-I (p = 0.001). Younger age, non-white race, and use of hypnotics prior to behavioral therapy were independently associated with lack of response to CBT-I. CONCLUSIONS: While CBT-I ameliorates insomnia in veterans with PTSD, the use of hypnotics prior to instituting behavioral therapy may negatively affect the response rate to CBT-I. Future studies should examine whether racial and cultural influences on the generation of insomnia in veterans with PTSD affects the response to CBT-I.

Drug treatment strategies for insomnia in patients with post-traumatic stress disorder.

INTRODUCTION: Insomnia is among the most reported sleep disturbances in patients with post-traumatic stress disorder (PTSD). The pervasiveness of this disorder among trauma-inflicted civilians and military personnel has been associated with reduced quality of life, impaired psychosocial functioning including cognitive impairments, negative mood swings, cardiovascular complications, and increased utilization of medical services. AREAS COVERED: This review describes the current state of science with respect to the impact of the most dispensed pharmacological interventions for posttraumatic insomnia. At the present, there are no established treatment algorithms for PTSD-related insomnia. Pharmacotherapy offers an alternative treatment modality for patients with PTSD who fail or decline cognitive behavioral therapy (CBT). Selection of a hypnotic/sedative agent should be based on the patient's history, precipitating and perpetuating factors of insomnia, side effect profile, and potential medication-related interactions. Antipsychotics and benzodiazepines appear ineffective or are associated with significant harm in treating PTSD-related insomnia. EXPERT OPINION: In the absence of randomized controlled trials, prescription patterns have been guided by anecdotal reports and expert opinion. Due to the complexity and multifactorial etiology of insomnia in PTSD, clinical investigations should examine available pharmacologic agents in comparative trials or in combination with CBT or complementary therapies to assess both short-term and long-term sleep outcomes in this population.

Adult Outpatients With Acute Cough Due to Suspected Pneumonia or Influenza: CHEST Guideline and Expert Panel Report.

BACKGROUND: Patients commonly present to primary care services with upper and lower respiratory tract infections, and guidelines to help physicians investigate and treat acute cough due to suspected pneumonia and influenza are needed. METHODS: A systematic search was carried out with eight patient, intervention, comparison, outcome questions related to acute cough due to suspected pneumonia or influenza. RESULTS: There was a lack of randomized controlled trials in the setting of outpatients presenting with acute cough due to suspected pneumonia or influenza who were not hospitalized. Both clinical suggestions and research recommendations were made on the evidence available and CHEST Expert Cough Panel advice. CONCLUSIONS: For outpatient adults with acute cough due to suspected pneumonia, we suggest the following clinical symptoms and signs are suggestive of pneumonia: cough; dyspnea; pleural pain; sweating, fevers, or shivers; aches and pains; temperature ≥ 38°C; tachypnea; and new and localizing chest examination signs. Those suspected of having pneumonia should undergo chest radiography to improve diagnostic accuracy. Although the measurement of C-reactive protein levels strengthens both the diagnosis and exclusion of pneumonia, there was no added benefit of measuring procalcitonin levels in this setting. We suggest that there is no need for routine microbiological testing. We suggest the use of empiric antibiotics according to local and national guidelines when pneumonia is suspected in settings in which imaging cannot be performed. Where there is no clinical or radiographic evidence of pneumonia, we do not suggest the routine use of antibiotics. There is insufficient evidence to make recommendations for or against specific nonantibiotic, symptomatic therapies. Finally, for outpatient adults with acute cough and suspected influenza, we suggest that initiating antiviral treatment (according to Centers for Disease Control and Prevention advice) within 48 hours of symptoms could be associated with decreased antibiotic use and hospitalization and improved outcomes.