Impact of PTSD and Obstructive Sleep Apnea on Cognition in Older Adult Veterans.

Background: Posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are highly prevalent and comorbid among older adult male veterans. Both PTSD and OSA are independently associated with cognitive deficits in older adults, but little research regarding the impact of comorbid PTSD and OSA among older adults exists. Purpose: The current study aimed to examine the independent and interactive effects of PTSD and OSA on cognitive functioning in older adult veterans. Study Sample: Older adult male veterans with (n = 106) and without PTSD (n = 69), ranging in age from 55 to 89 (M = 63.35). Data Collection: Participants underwent polysomnography evaluation to assess severity of OSA symptoms and comprehensive neuropsychological evaluation to assess cognitive functioning in 3 domains: attention and processing speed, learning and memory, and executive functioning. Results: Multiple regression analyses showed that the interaction between PTSD and OSA did not predict cognitive performance. However, PTSD significantly predicted poorer attention and processing speed, and increased OSA severity predicted poorer learning and memory. Conclusions: While PTSD and OSA did not have a synergistic detrimental impact on cognition, each independently predicted poorer cognitive functioning within certain domains, suggesting that older adults with these comorbid conditions may experience a wider array of cognitive difficulties.

Fatigue and sleepiness determine respiratory quality of life among veterans evaluated for sleep apnea.

BACKGROUND: In those with symptoms indicative of obstructive sleep apnea (OSA), respiratory-specific health-related quality of life (HRQL) may be an important patient-centered outcome. The aim of this study was to assess the associations between sleepiness, fatigue, and impaired general and respiratory-specific HRQL among persons with suspected OSA. METHODS: We evaluated military veterans consecutively referred for suspected OSA with sleep studies yielding apnea-hypopnea index (AHI) values. They also completed the sleepiness (Epworth Sleepiness Scale [ESS]), and fatigue (Fatigue Severity Scale [FSS]) questionnaires, as well as two HRQL instruments (the generic Short-Form SF-12v2 yielding the Physical Component Scale [PCS] and the respiratory-specific Airways Questionnaire [AQ]-20R). Multiple linear regression tested the associations between ESS and FSS (standardized as Z scores for scaling comparability) with AQ-20R, accounting for AHI, SF-12v2-PCS and comorbid respiratory conditions other than OSA. RESULTS: We studied 1578 veterans (median age 61.1 [IQR 16.8] years; 93.9% males). Of these, 823 (52%) met AHI criteria for moderate to severe OSA (AHI ≥15/h). The majority reported excessive daytime sleepiness (53%; median ESS 11 [IQR 9]) or fatigue (61%; median FSS 42 [IQR 23]). The median AQ-20R was 4 [IQR 1-8]. Controlling for AHI, SF-12v2-PCS, respiratory co-morbid conditions, body mass index, and demographics, both ESS and FSS were significantly associated with poorer AQ-20R: for each; ESS, 1.6 points (95% CI 1.4-1.9), and for FSS, 2.5 points (95% CI, 2.3-2.7). CONCLUSIONS: Greater daytime sleepiness and fatigue are associated with poorer respiratory-specific HRQL, over and above the effects of OSA, respiratory comorbidity, and generic physical HRQL.

Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from theAmerican College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the diagnosis of obstructive sleep apnea in adults. METHODS: This guideline is based on published literature on this topic that was identified by using MEDLINE (1966 through May 2013), the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular mortality, nonfatal cardiovascular disease, stroke, hypertension, type 2 diabetes, postsurgical outcomes, and quality of life. Sensitivities, specificities, and likelihood ratios were also assessed as outcomes of diagnostic tests. This guideline grades the evidence and recommendations by using ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends a sleep study for patients with unexplained daytime sleepiness. (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 2: ACP recommends polysomnography for diagnostic testing in patients suspected of obstructive sleep apnea. ACP recommends portable sleep monitors in patients without serious comorbidities as an alternative to polysomnography when polysomnography is not available for diagnostic testing. (Grade: weak recommendation, moderate-quality evidence).

Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults.

The Centers for Disease Control and Prevention convened panels of anthrax experts to review and update guidelines for anthrax postexposure prophylaxis and treatment. The panels included civilian and military anthrax experts and clinicians with experience treating anthrax patients. Specialties represented included internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. Panelists discussed recent patients with systemic anthrax; reviews of published, unpublished, and proprietary data regarding antimicrobial drugs and anthrax antitoxins; and critical care measures of potential benefit to patients with anthrax. This article updates antimicrobial postexposure prophylaxis and antimicrobial and antitoxin treatment options and describes potentially beneficial critical care measures for persons with anthrax, including clinical procedures for infected nonpregnant adults. Changes from previous guidelines include an expanded discussion of critical care and clinical procedures and additional antimicrobial choices, including preferred antimicrobial drug treatment for possible anthrax meningitis.

Management of obstructive sleep apnea in adults: A clinical practice guideline from the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of obstructive sleep apnea (OSA) in adults. METHODS: This guideline is based on published literature from 1966 to September 2010 that was identified by using MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A supplemental MEDLINE search identified additional articles through October 2012. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included cardiovascular disease (such as heart failure, hypertension, stroke, and myocardial infarction), type 2 diabetes, death, sleep study measures (such as the Apnea-Hypopnea Index), measures of cardiovascular status (such as blood pressure), measures of diabetes status (such as hemoglobin A1c levels), and quality of life. This guideline grades the evidence and recommendations using ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends that all overweight and obese patients diagnosed with OSA should be encouraged to lose weight. (Grade: strong recommendation; low-quality evidence) RECOMMENDATION 2: ACP recommends continuous positive airway pressure treatment as initial therapy for patients diagnosed with OSA. (Grade: strong recommendation; moderate-quality evidence) RECOMMENDATION 3: ACP recommends mandibular advancement devices as an alternative therapy to continuous positive airway pressure treatment for patients diagnosed with OSA who prefer mandibular advancement devices or for those with adverse effects associated with continuous positive airway pressure treatment. (Grade: weak recommendation; low-quality evidence).

Modeling the effects of obstructive sleep apnea and hypertension in Vietnam veterans with PTSD.

PURPOSE: The present work aimed to extend models suggesting that obstructive sleep apnea (OSA) is associated with worse cognitive performance in community-dwelling older adults. We hypothesized that in addition to indices of OSA severity, hypertension is associated with worse cognitive performance in such adults. METHODS: The PTSD Apnea Clinical Study recruited 120 community-dwelling, male veterans diagnosed with PTSD, ages 55 and older. The Rey Auditory Verbal Learning Test (RAVLT) and Color-Word Interference Test (CWIT) were measures of auditory verbal memory and executive function, respectively. Apnea-hypopnea index (AHI), minimum and mean pulse oximeter oxygen saturation (min SpO(2), mean SpO(2)) indicators were determined during standard overnight polysomnography. Multivariate linear regression and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: In regression models, AHI (ß = -4.099; p < 0.01) and hypertension (ß = -4.500; p < 0.05) predicted RAVLT; hypertension alone (ß = 9.146; p < 0.01) predicted CWIT. ROC analyses selected min SpO(2) cut-points of 85% for RAVLT (κ = 0.27; χ² = 8.23, p < 0.01) and 80% for CWIT (κ = 0.25; χ² = 12.65, p < 0.01). Min SpO(2) cut-points and hypertension were significant when added simultaneously in a regression model for RAVLT (min SpO(2), ß = 4.452; p < 0.05; hypertension, ß = -4.332; p < 0.05), and in separate models for CWIT (min SpO(2), ß = -8.286; p < 0.05; hypertension, ß = -8.993; p < 0.01). CONCLUSIONS: OSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.

Systematic review: safety and efficacy of extended-duration antiviral chemoprophylaxis against pandemic and seasonal influenza.

BACKGROUND: Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic. PURPOSE: To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza. DATA SOURCES: Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries. STUDY SELECTION: Randomized, placebo-controlled, double-blind human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events. DATA EXTRACTION: 2 reviewers independently assessed study quality and abstracted information from eligible studies. DATA SYNTHESIS: Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. Chemoprophylaxis with NAIs decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], -3.9 percentage points [CI, -5.8 to -1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, -0.4 percentage point [CI, -1.6 to 0.9 percentage point]). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, -0.2 to 0.4 percentage point]), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir. LIMITATIONS: All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine. CONCLUSION: Extended-duration zanamivir and oseltamivir chemoprophylaxis seems to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.

Tuberculosis in liver transplant recipients: a systematic review and meta-analysis of individual patient data.

Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid-related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short-term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18-fold increase in the prevalence of active MTB infection and a 4-fold increase in the case-fatality rate. For high-risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894-906, 2009. (c) 2009 AASLD.

Mycobacterium tuberculosis infection in transplant recipients: early diagnosis and treatment of resistant tuberculosis.

PURPOSE OF REVIEW: To provide a better understanding and summarize recent advances in the diagnosis and treatment of Mycobacterium tuberculosis (MTB) infection in solid organ transplant (SOT) candidates and recipients. RECENT FINDINGS: Despite advances in SOT medicine, MTB causes substantial morbidity and mortality in SOT recipients, with reported prevalence rates of 0.4-6%. The primary source of posttransplant MTB is reactivation of pretransplant latent MTB infection. The short-term mortality rate in SOT recipients with drug-susceptible active MTB is 30%. In immunocompromised persons with extensively drug-resistant MTB, the mortality rate approaches 100%. Clinical presentation is often atypical with more than half of SOT recipients presenting with extrapulmonary or disseminated disease. Pretransplant latent MTB infection screening and treatment is the cornerstone for preventing reactivation and dissemination of active MTB posttransplant. Treatment of active MTB in SOT recipients is problematic, given significant drug toxicity and interaction with immunosuppressive agents. SUMMARY: A high degree of suspicion for latent and active MTB infection in SOT candidates and recipients is warranted to establish a timely diagnosis and initiate life-saving appropriate therapy.

Use of blood biomarkers to screen for obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased risk for cardiovascular disease, diabetes, and other chronic conditions. Unfortunately, up to 90% of individuals with OSA remain without a diagnosis or therapy. We assess the relationship between OSA and blood biomarkers, and test the hypothesis that combinations of markers provide a characteristic OSA signature with diagnostic screening value. This validation study was conducted in an independent cohort in order to replicate findings from a prior feasibility study. PATIENTS AND METHODS: This multicenter prospective study consecutively enrolled adult male subjects with clinically suspected OSA. All subjects underwent overnight sleep studies. An asymptomatic control group was also obtained. Five biomarkers were tested: glycated hemoglobin (HbA1c), C-reactive protein (CRP), uric acid, erythropoietin (EPO), and interleukin-6 (IL-6). RESULTS: The study enrolled 264 subjects. The combination of HbA1c+CRP+EPO (area under the curve 0.78) was superior to the Epworth Sleepiness Scale (ESS; 0.53) and STOP-Bang (0.70) questionnaires. In non-obese subjects, the combination of biomarkers (0.75) was superior to body mass index (BMI; 0.61). Sensitivity and specificity results, respectively, were: HbA1c+CRP+EPO (81% and 60%), ESS (78% and 19%), STOP-Bang (75% and 52%), BMI (81% and 56%), and BMI in non-obese patients (81% and 38%). CONCLUSION: We verify our hypothesis and replicate our prior feasibility findings that OSA is associated with a characteristic signature cluster of biomarker changes in men. Concurrent elevations of HbA1c, CRP, and EPO levels should generate a high suspicion of OSA and may have utility as an OSA screening tool. Biomarker combinations correlate with OSA severity and, therefore, may assist sleep centers in identifying and triaging higher risk patients for sleep study diagnosis and treatment.

Inhalational, gastrointestinal, and cutaneous anthrax in children: a systematic review of cases: 1900 to 2005.

OBJECTIVE: To systematically review all published case reports of children with anthrax to evaluate the predictors of disease progression and mortality. DATA SOURCES: Fourteen selected journal indexes (1900-1966), MEDLINE (1966-2005), and the bibliographies of all retrieved articles. STUDY SELECTION: Case reports (any language) of anthrax in persons younger than 18 years published between January 1, 1900, and December 31, 2005. Main Exposures Cases with symptoms and culture or Gram stain or autopsy evidence of anthrax infection. MAIN OUTCOME MEASURES: Disease progression, treatment responses, and mortality. RESULTS: Of 2499 potentially relevant articles, 73 case reports of pediatric anthrax (5 inhalational cases, 22 gastrointestinal cases, 37 cutaneous cases, 6 cases of primary meningoencephalitis, and 3 atypical cases) met the inclusion criteria. Only 10% of the patients were younger than 2 years, and 24% were girls. Of the few children with inhalational anthrax, none had nonheadache neurologic symptoms, a key finding that distinguishes adult inhalational anthrax from more common illnesses, such as influenza. Overall, observed mortality was 60% (3 of 5) for inhalational anthrax, 65% (13 of 20) for gastrointestinal anthrax, 14% (5 of 37) for cutaneous anthrax, and 100% (6 of 6) for primary meningoencephalitis. Nineteen of the 30 children (63%) who received penicillin-based antibiotics survived, and 9 of the 11 children (82%) who received anthrax antiserum survived. CONCLUSIONS: The clinical presentation of children with anthrax is varied. The mortality rate is high in children with inhalational anthrax, gastrointestinal anthrax, and anthrax meningoencephalitis. Rapid diagnosis and effective treatment of anthrax in children requires recognition of the broad spectrum of clinical presentations of pediatric anthrax.

Systematic review: a century of inhalational anthrax cases from 1900 to 2005.

BACKGROUND: Mortality from inhalational anthrax during the 2001 U.S. attack was substantially lower than that reported historically. PURPOSE: To systematically review all published inhalational anthrax case reports to evaluate the predictors of disease progression and mortality. DATA SOURCES: MEDLINE (1966-2005), 14 selected journal indexes (1900-1966), and bibliographies of all retrieved articles. STUDY SELECTION: Case reports (in any language) between 1900 and 2005 that met predefined criteria. DATA EXTRACTION: Two authors (1 author for non-English-language reports) independently abstracted patient data. DATA SYNTHESIS: The authors found 106 reports of 82 cases of inhalational anthrax. Mortality was statistically significantly lower for patients receiving antibiotics or anthrax antiserum during the prodromal phase of disease, multidrug antibiotic regimens, or pleural fluid drainage. Patients in the 2001 U.S. attack were less likely to die than historical anthrax case-patients (45% vs. 92%; P < 0.001) and were more likely to receive antibiotics during the prodromal phase (64% vs. 13%; P < 0.001), multidrug regimens (91% vs. 50%; P = 0.027), or pleural fluid drainage (73% vs. 11%; P < 0.001). Patients who progressed to the fulminant phase had a mortality rate of 97% (regardless of the treatment they received), and all patients with anthrax meningoencephalitis died. LIMITATIONS: This was a retrospective case review of previously published heterogeneous reports. CONCLUSIONS: Despite advances in supportive care, fulminant-phase inhalational anthrax is usually fatal. Initiation of antibiotic or anthrax antiserum therapy during the prodromal phase is associated with markedly improved survival, although other aspects of care, differences in clinical circumstances, or unreported factors may contribute to this observed reduction in mortality. Efforts to improve early diagnosis and timely initiation of appropriate antibiotics are critical to reducing mortality.

Does untreated obstructive sleep apnea cause secondary erythrocytosis?

BACKGROUND: The current literature suggests a relationship between obstructive sleep apnea (OSA) severity and hematocrit. However, the degree that OSA contributes to clinically significant erythrocytosis is uncertain. The aim of this study is to evaluate this association in a large study sample controlling for multiple confounders. METHODS: We evaluated consecutive subjects with suspected untreated OSA using multivariate analysis to test the associations between apnea-hypopnea index (AHI) and hematocrit. Subjects were evaluated with sleep studies, comprehensive sleep questionnaires, and detailed electronic medical record reviews to document their medical comorbidities, and demographic and laboratory information. RESULTS: 1604 consecutive veterans (age 57.6 ± 13.4 years, 92% male) were included in the analysis with 77.4% diagnosed with OSA. However, few included subjects (1.6%) had clinical erythrocytosis. OSA severity defined by AHI was not associated with hematocrit or clinically significant erythrocytosis. Rather, awake oxygen saturation (-0.17 points, p < 0.001) and mean nocturnal oxygen saturation (-0.08 points, p = 0.04) were inversely proportional to hematocrit (per standardized Z-score). Other factors including active tobacco, increased alcohol ingestion and exogenous testosterone therapy were associated with higher hematocrit. Although AHI was not predictive of erythrocytosis, having severe OSA was predictive of nocturnal hypoxemia (adjusted OR 7.4, p < 0.001). CONCLUSIONS: Hematocrit levels and presence of erythrocytosis appear not associated with OSA severity, but rather with hypoxemia as measured by awake and to a lesser extent mean nocturnal oxygen saturation. Nocturnal oximetry may provide diagnostic utility in the evaluation of unexplained secondary polycythemia and polysomongraphy may be warranted in those with unexplained nocturnal hypoxemia and erythrocytosis.

Anthrax: a systematic review of atypical presentations.

During the 2001 US anthrax attacks, mortality from inhalational anthrax was significantly lower than had been reported historically, which was attributed in part to early identification and timely treatment. During future attacks, clinicians will rely on published descriptions of the clinical features of inhalational anthrax to rapidly diagnose patients and institute appropriate treatment. Published descriptions of typical inhalation anthrax usually include patients presenting with cough, dyspnea, or chest pain and found to have abnormal lung examination results with pleural effusions or enlarged mediastinum. The purpose of this article is to evaluate whether atypical presentations of inhalational anthrax occur and to describe the features of these presentations. We define atypical presentations as those in patients with confirmed anthrax infection who do not have known cutaneous, gastrointestinal, or inhalational ports of entry. We reviewed the case reports of 42 patients with atypical anthrax (published between 1900 and 2004) that may have had an inhalational source of infection to evaluate whether their clinical presentations differed from the typical findings of inhalational anthrax. Patients with atypical anthrax were less likely to have cough, chest pain, or abnormal lung examination results than patients with typical inhalational anthrax (P<.05 for all comparisons). A previously published screening protocol for patients with suspected anthrax correctly identified 91% of patients with atypical presentations. We conclude that although uncommon, atypical presentations of inhalational anthrax likely occur. Timely diagnosis and treatment of patients with inhalational anthrax require clinical awareness of the full spectrum of signs and symptoms associated with inhalational anthrax.

Reducing mortality from anthrax bioterrorism: strategies for stockpiling and dispensing medical and pharmaceutical supplies.

A critical question in planning a response to bioterrorism is how antibiotics and medical supplies should be stockpiled and dispensed. The objective of this work was to evaluate the costs and benefits of alternative strategies for maintaining and dispensing local and regional inventories of antibiotics and medical supplies for responses to anthrax bioterrorism. We modeled the regional and local supply chain for antibiotics and medical supplies as well as local dispensing capacity. We found that mortality was highly dependent on the local dispensing capacity, the number of individuals requiring prophylaxis, adherence to prophylactic antibiotics, and delays in attack detection. For an attack exposing 250,000 people and requiring the prophylaxis of 5 million people, expected mortality fell from 243,000 to 145,000 as the dispensing capacity increased from 14,000 to 420,000 individuals per day. At low dispensing capacities (<14,000 individuals per day), nearly all exposed individuals died, regardless of the rate of adherence to prophylaxis, delays in attack detection, or availability of local inventories. No benefit was achieved by doubling local inventories at low dispensing capacities; however, at higher dispensing capacities, the cost-effectiveness of doubling local inventories fell from 100,000 US dollars to 20,000 US dollars/life year gained as the annual probability of an attack increased from 0.0002 to 0.001. We conclude that because of the reportedly rapid availability of regional inventories, the critical determinant of mortality following anthrax bioterrorism is local dispensing capacity. Bioterrorism preparedness efforts directed at improving local dispensing capacity are required before benefits can be reaped from enhancing local inventories.

Maxillomandibular Advancement for Treatment of Obstructive Sleep Apnea: A Meta-analysis.

IMPORTANCE: Maxillomandibular advancement (MMA) is an invasive yet effective surgical option for obstructive sleep apnea (OSA) that achieves enlargement of the upper airway by physically expanding the facial skeletal framework. OBJECTIVE: To identify criteria associated with surgical outcomes of MMA using aggregated individual patient data from multiple studies. DATA SOURCES: The Cochrane Library, Scopus, Web of Science, and MEDLINE from June 1, 2014, to March 16, 2015, using the Medical Subject Heading keywords maxillomandibular advancement, orthognathic surgery, maxillary osteotomy, mandibular advancement, sleep apnea, surgical, surgery, sleep apnea syndrome, and obstructive sleep apnea. STUDY SELECTION: Inclusion criteria consisted of studies in all languages of (1) adult patients who underwent MMA as treatment for OSA; (2) report of preoperative and postoperative quantitative outcomes for the apnea-hypopnea index (AHI) and/or respiratory disturbance index (RDI); and (3) report of individual patient data. Studies of patients who underwent adjunctive procedures at the time of MMA (including tonsillectomy, uvulopalatopharyngoplasty, and partial glossectomy) were excluded. DATA EXTRACTION: Three coauthors systematically reviewed the articles and updated the review through March 16, 2015. The PRISMA statement was followed. Data were pooled using a random-effects model and analyzed from July 1, 2014, to September 23, 2015. MAIN OUTCOMES AND MEASURES: The primary outcomes were changes in the AHI and RDI after MMA for each patient. Secondary outcomes included surgical success, defined as the percentage of patients with more than 50% reduction of the AHI to fewer than 20 events/h, and OSA cure, defined as a post-MMA AHI of fewer than 5 events/h. RESULTS: Forty-five studies with individual data from 518 unique patients/interventions were included. Among patients for whom data were available, 197 of 268 (73.5%) had undergone prior surgery for OSA. Mean (SD) postoperative changes in the AHI and RDI after MMA were -47.8 (25.0) and -44.4 (33.0), respectively; mean (SE) reductions of AHI and RDI outcomes were 80.1% (1.8%) and 64.6% (4.0%), respectively; and 512 of 518 patients (98.8%) showed improvement. Significant improvements were also seen in the mean (SD) postoperative oxygen saturation nadir (70.1% [15.6%] to 87.0% [5.2%]; P < .001) and Epworth Sleepiness Scale score (13.5 [5.2] to 3.2 [3.2]; P < .001). Rates of surgical success and cure were 389 (85.5%) and 175 (38.5%), respectively, among 455 patients with AHI data and 44 (64.7%) and 13 (19.1%), respectively, among 68 patients with RDI data. Preoperative AHI of fewer than 60 events/h was the factor most strongly associated with the highest incidence of surgical cure. Nevertheless, patients with a preoperative AHI of more than 60 events/h experienced large and substantial net improvements despite modest surgical cure rates. CONCLUSIONS AND RELEVANCE: Maxillomandibular advancement is an effective treatment for OSA. Most patients with high residual AHI and RDI after other unsuccessful surgical procedures for OSA are likely to benefit from MMA.

A Cost-Effectiveness Analysis of Surgery for Middle-Aged Men with Severe Obstructive Sleep Apnea Intolerant of CPAP.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Conventional OSA therapy necessitates indefinite continuous positive airway pressure (CPAP). Although CPAP is an effective treatment modality, up to 50% of OSA patients are intolerant of CPAP. We explore whether surgical modalities developed for those intolerant of CPAP are cost-effective. METHODS: We construct a lifetime semi-Markov model of OSA that accounts for observed increased risks of stroke, cardiovascular disease, and motor vehicle collisions for a 50-year-old male with untreated severe OSA. Using this model, we compare the cost-effectiveness of (1) no treatment, (2) CPAP only, and (3) CPAP followed by surgery (either palatopharyngeal reconstructive surgery [PPRS] or multilevel surgery [MLS]) for those intolerant to CPAP. RESULTS: Compared with the CPAP only strategy, CPAP followed by PPRS (CPAP-PPRS) adds 0.265 quality adjusted life years (QALYs) for an increase of $2,767 (discounted 2010 dollars) and is highly cost effective with an incremental cost-effectiveness ratio (ICER) of $10,421/QALY for a 50-year-old male with severe OSA. Compared to a CPAP-PPRS strategy, the CPAP-MLS strategy adds 0.07 QALYs at an increase of $6,213 for an ICER of $84,199/QALY. The CPAP-PPRS strategy appears cost-effective over a wide range of parameter estimates. CONCLUSIONS: Palatopharyngeal reconstructive surgery appears cost-effective in middle-aged men with severe OSA intolerant of CPAP. Further research is warranted to better define surgical candidacy as well as short-term and long-term surgical outcomes. COMMENTARY: A commentary on this article appears in this issue on page 509.