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.

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.

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.

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.

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.

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).

Tracheostomy as treatment for adult obstructive sleep apnea: a systematic review and meta-analysis.

OBJECTIVES/HYPOTHESIS: To systematically review outcomes for polysomnography, sleepiness, and mortality in patients who undergo tracheostomy for the treatment of adult obstructive sleep apnea (OSA). DATA SOURCES: MEDLINE, Scopus, and the Cochrane Library were searched from inception to March 2013, followed by extensive hand searching for the identification of relevant English language studies that met predefined criteria. REVIEW METHODS: Adult studies of tracheostomies or tracheotomies as treatment for OSA with outcomes for apnea index (AI), apnea-hypopnea index (AHI), oxygen desaturation index (ODI), effect on daytime sleepiness or mortality were identified, abstracted and pooled (as appropriate). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: The systematic search identified 18 relevant studies that were primarily case series, using retrospective review. Posttracheostomy AI improved from 73.0 ± 27.1 to 0.2 ± 1.2/h and an AI mean difference of -83.47 (95% CI, -106.07 to -60.87; P < 0.0001). Mean AHI decreased from 92.0 ± 34.8 to 17.3 ± 20.5/h and an AHI mean difference -79.82 (95% CI, -63.74 to -95.90; P < 0.0001) compared with preoperative status was observed. Postsurgically, there was a development of central apneas; however, the central AI demonstrated near normalization to a mean of 2.1 ± 3.5/h after 14 weeks. ODI decreased from 78.2 ± 25.8/h to 20.8 ± 25.5/h. Four studies demonstrated a statistically significant improvement in subjective sleepiness posttracheostomy. Postoperative statistically significant reductions in overall and in cardiovascular mortality compared with untreated historical cohorts was reported. CONCLUSION: Tracheostomies significantly decrease apnea index, oxygen desaturation index, sleepiness, and mortality in OSA subjects.

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.

Opioids, sleep, and sleep-disordered breathing.

Opioid medications are increasingly used to treat chronic pain. Opioid-associated respiratory depression, and their potential to cause nocturnal apneas, is increasingly recognized as a major contributor to nocturnal hypoxemia and sleep-disordered breathing. Given the widespread use of opioids, understanding their mechanism of action and their potential to cause adverse effects particularly during sleep is critical. This article reviews the salient features of the physiologic control of respiration and sleep, and the role opioids play in altering that regulation. Additionally, we summarize the evidence regarding the association between opioid use and sleep-disordered breathing and explore treatment modalities for opioid-associated nocturnal respiratory depression and apneas.

REM-related bradyarrhythmia syndrome.

Cardiac arrhythmias during sleep are relatively common and include a diverse etiology, from benign sinus bradycardia to potentially fatal ventricular arrhythmias. Predisposing factors include obstructive sleep apnea and cardiac disease. Rapid eye movement (REM)-related bradyarrhythmia syndrome (including sinus arrest and complete atrioventricular block with ventricular asystole) in the absence of an underlying cardiac or physiologic sleep disorder was first described in the early 1980s. Although uncertain, the underlying pathophysiology likely reflects abnormal autonomic neural-cardiac inputs during REM sleep. The autonomic nervous system (ANS) is a known key modulator of heart rate fluctuations and rhythm during sleep and nocturnal heart rate reflects a balance between the sympathetic-parasympathetic systems. Whether the primary trigger for REM-related bradyarrhythmias reflects abnormal centrally mediated control of the ANS during REM sleep or anomalous baroreflex parasympathetic influences is unknown. This review focuses on the salient features of the REM-related bradyarrhythmia syndrome and explores potential mechanisms with a particular assessment of the relationship between the ANS and nocturnal heart rate fluctuations.

Surgical options for the treatment of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a prevalent condition characterized by repetitive airway obstruction during sleep with associated increased morbidity and mortality. Although CPAP is the preferred treatment, poor compliance is common. Patients intolerant of conventional OSA medical treatment may benefit from surgical therapy to alleviate pharyngeal obstruction. Case series suggest that maxillomandibular advancement has the highest surgical efficacy (86%) and cure rate (43%). Soft palate surgical techniques are less successful, with uvulopalatopharyngoplasty having an OSA surgical success rate of 50% and cure rate of 16%. Further research is needed to more thoroughly assess clinical outcomes (eg, quality of life, morbidity), better identify key preoperative patient and clinical characteristics that predict success, and confirm long-term effectiveness of surgical modalities to treat OSA.

Maxillomandibular advancement for the treatment of obstructive sleep apnea: a systematic review and meta-analysis.

The reported efficacy of maxillomandibular advancement (MMA) for the treatment of obstructive sleep apnea (OSA) is uncertain. We performed a meta-analysis and systematic review to estimate the clinical efficacy and safety of MMA in treating OSA. We searched Medline and bibliographies of retrieved articles, with no language restriction. We used meta-analytic methods to pool surgical outcomes. Fifty-three reports describing 22 unique patient populations (627 adults with OSA) met inclusion criteria. Additionally, 27 reports provided individual data on 320 OSA subjects. The mean apnea-hypopnea index (AHI) decreased from 63.9/h to 9.5/h (p<0.001) following surgery. Using a random-effects model, the pooled surgical success and cure (AHI <5) rates were 86.0% and 43.2%, respectively. Younger age, lower preoperative weight and AHI, and greater degree of maxillary advancement were predictive of increased surgical success. The major and minor complication rates were 1.0% and 3.1%, respectively. No postoperative deaths were reported. Most subjects reported satisfaction after MMA with improvements in quality of life measures and most OSA symptomatology. We conclude that MMA is a safe and highly effective treatment for OSA.

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.

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.