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IMPORTANCE: Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE: To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS: A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROM EVIDENCE SYNTHESIS: Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS: Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE: These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

OBJECTIVE: To determine the incidence, cost, and outcome of severe sepsis in the United States. DESIGN: Observational cohort study. SETTING: All nonfederal hospitals (n = 847) in seven U.S. states. PATIENTS: All patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification of Diseases, Ninth Revision, Clinical Modification. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We linked all 1995 state hospital discharge records (n = 6,621,559) from seven large states with population and hospital data from the U.S. Census, the Centers for Disease Control, the Health Care Financing Administration, and the American Hospital Association. We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We validated these criteria against prospective clinical and physiologic criteria in a subset of five hospitals. We generated national age- and gender-adjusted estimates of incidence, cost, and outcome. We identified 192,980 cases, yielding national estimates of 751,000 cases (3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges), of whom 383,000 (51.1%) received intensive care and an additional 130,000 (17.3%) were ventilated in an intermediate care unit or cared for in a coronary care unit. Incidence increased >100-fold with age (0.2/1,000 in children to 26.2/1,000 in those >85 yrs old). Mortality was 28.6%, or 215,000 deaths nationally, and also increased with age, from 10% in children to 38.4% in those >85 yrs old. Women had lower age-specific incidence and mortality, but the difference in mortality was explained by differences in underlying disease and the site of infection. The average costs per case were $22,100, with annual total costs of $16.7 billion nationally. Costs were higher in infants, nonsurvivors, intensive care unit patients, surgical patients, and patients with more organ failure. The incidence was projected to increase by 1.5% per annum. CONCLUSIONS: Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction. It is especially common in the elderly and is likely to increase substantially as the U.S. population ages.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is known about TAVR in low-risk patients. METHODS: We performed a randomized noninferiority trial in which TAVR with a self-expanding supraannular bioprosthesis was compared with surgical aortic-valve replacement in patients who had severe aortic stenosis and were at low surgical risk. When 850 patients had reached 12-month follow-up, we analyzed data regarding the primary end point, a composite of death or disabling stroke at 24 months, using Bayesian methods. RESULTS: ). CONCLUSIONS: In patients with severe aortic stenosis who were at low surgical risk, TAVR with a self-expanding supraannular bioprosthesis was noninferior to surgery with respect to the composite end point of death or disabling stroke at 24 months. (Funded by Medtronic; ClinicalTrials.gov number, NCT02701283.).

Abstract. We present and discuss a new dataset of gridded emissions covering the historical period (1850–2000) in decadal increments at a horizontal resolution of 0.5° in latitude and longitude. The primary purpose of this inventory is to provide consistent gridded emissions of reactive gases and aerosols for use in chemistry model simulations needed by climate models for the Climate Model Intercomparison Program #5 (CMIP5) in support of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment report (AR5). Our best estimate for the year 2000 inventory represents a combination of existing regional and global inventories to capture the best information available at this point; 40 regions and 12 sectors are used to combine the various sources. The historical reconstruction of each emitted compound, for each region and sector, is then forced to agree with our 2000 estimate, ensuring continuity between past and 2000 emissions. Simulations from two chemistry-climate models are used to test the ability of the emission dataset described here to capture long-term changes in atmospheric ozone, carbon monoxide and aerosol distributions. The simulated long-term change in the Northern mid-latitudes surface and mid-troposphere ozone is not quite as rapid as observed. However, stations outside this latitude band show much better agreement in both present-day and long-term trend. The model simulations indicate that the concentration of carbon monoxide is underestimated at the Mace Head station; however, the long-term trend over the limited observational period seems to be reasonably well captured. The simulated sulfate and black carbon deposition over Greenland is in very good agreement with the ice-core observations spanning the simulation period. Finally, aerosol optical depth and additional aerosol diagnostics are shown to be in good agreement with previously published estimates and observations.

) is then derived that uniquely defines intermolecular interaction regions. An attractive feature of the IGM methodology is to provide a workflow that automatically generates data composed solely of intermolecular interactions for drawing the corresponding 3D isosurface representations.

Colloidal synthesis offers a route to nanoparticles (NPs) with controlled composition and structural features. This Perspective describes the use of polyvinylpyrrolidone (PVP) to obtain such nanostructures. PVP can serve as a surface stabilizer, growth modifier, nanoparticle dispersant, and reducing agent. As shown with examples, its role depends on the synthetic conditions. This dependence arises from the amphiphilic nature of PVP along with the molecular weight of the selected PVP. These characteristics can affect nanoparticle growth and morphology by providing solubility in diverse solvents, selective surface stabilization, and even access to kinetically controlled growth conditions. This Perspective includes discussions of the properties of PVP-capped NPs for surface enhanced Raman spectroscopy (SERS), assembly, catalysis, and more. The contribution of PVP to these properties as well as its removal is considered. Ultimately, the NPs accessed through the use of PVP in colloidal syntheses are opening new applications, and the concluding guidelines provided herein should enable new nanostructures to be accessed facilely.

OBJECTIVES/HYPOTHESIS: The objective was to develop an abbreviated voice handicap assessment instrument and compare it with the Voice Handicap Index (VHI). STUDY DESIGN: Item analysis of the VHI in individuals without voice disorders and patients with voice disorders and creation and validation of the abbreviated VHI. METHODS: Clinical consensus review of the VHI items was held to prioritize the clinical value of each of the VHI items (30 items in all). Item analysis of the VHI was performed using the VHI responses of 100 patients with voice problems and 159 control subjects. The 10 most robust VHI items were selected using the item analysis and clinical consensus results to form the Voice Handicap Index-10 (VHI-10). Statistical analysis comparing the validity of the VHI-10 with the VHI was performed with 819 patients representing a wide spectrum of voice disorders. RESULTS: Statistical analysis of the VHI and VHI-10 scores from the study group showed no statistically significant differences between the VHI and the VHI-10. Irrespective of diagnosis, the correlation between the VHI and the VHI-10 was greater than .90 (P = .01). The ratios of the VHI-10 to VHI scores for a variety of voice disorder categories were analyzed and found to be consistently greater than the expected value (33%). This suggests that the VHI-10 may be a more robust instrument than the VHI. CONCLUSION: The VHI-10 is a powerful representation of the VHI that takes less time for the patient to complete without loss of validity. Thus, the VHI-10 can replace the VHI as an instrument to quantify patients' perception of their voice handicap.

BACKGROUND: Infection control programs were created three decades ago to control antibiotic-resistant healthcare-associated infections, but there has been little evidence of control in most facilities. After long, steady increases of MRSA and VRE infections in NNIS System hospitals, the Society for Healthcare Epidemiology of America (SHEA) Board of Directors made reducing antibiotic-resistant infections a strategic SHEA goal in January 2000. After 2 more years without improvement, a SHEA task force was appointed to draft this evidence-based guideline on preventing nosocomial transmission of such pathogens, focusing on the two considered most out of control: MRSA and VRE. METHODS: Medline searches were conducted spanning 1966 to 2002. Pertinent abstracts of unpublished studies providing sufficient data were included. RESULTS: Frequent antibiotic therapy in healthcare settings provides a selective advantage for resistant flora, but patients with MRSA or VRE usually acquire it via spread. The CDC has long-recommended contact precautions for patients colonized or infected with such pathogens. Most facilities have required this as policy, but have not actively identified colonized patients with surveillance cultures, leaving most colonized patients undetected and unisolated. Many studies have shown control of endemic and/or epidemic MRSA and VRE infections using surveillance cultures and contact precautions, demonstrating consistency of evidence, high strength of association, reversibility, a dose gradient, and specificity for control with this approach. Adjunctive control measures are also discussed. CONCLUSION: Active surveillance cultures are essential to identify the reservoir for spread of MRSA and VRE infections and make control possible using the CDC's long-recommended contact precautions.

This article reports on the development of short forms from the Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) item banks. Results from post-hoc computerized adaptive testing (CAT) simulations, item discrimination parameters, item means, and clinical judgments were used to select the best-performing 8 items for SD and SRI. The final 8-item short forms provided less test information than the corresponding full banks, but correlated strongly with the longer forms. The short forms had greater measurement precision than the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), as indicated by larger test information values across the continuum of severity, despite having fewer total items--a major advantage for both research and clinical settings.

Abstract. The Model of Emissions of Gases and Aerosols from Nature (MEGANv2.1) together with the Modern-Era Retrospective Analysis for Research and Applications (MERRA) meteorological fields were used to create a global emission data set of biogenic volatile organic compounds (BVOC) available on a monthly basis for the time period of 1980–2010. This data set, developed under the Monitoring Atmospheric Composition and Climate project (MACC), is called MEGAN–MACC. The model estimated mean annual total BVOC emission of 760 Tg (C) yr−1 consisting of isoprene (70%), monoterpenes (11%), methanol (6%), acetone (3%), sesquiterpenes (2.5%) and other BVOC species each contributing less than 2%. Several sensitivity model runs were performed to study the impact of different model input and model settings on isoprene estimates and resulted in differences of up to ±17% of the reference isoprene total. A greater impact was observed for a sensitivity run applying parameterization of soil moisture deficit that led to a 50% reduction of isoprene emissions on a global scale, most significantly in specific regions of Africa, South America and Australia. MEGAN–MACC estimates are comparable to results of previous studies. More detailed comparison with other isoprene inventories indicated significant spatial and temporal differences between the data sets especially for Australia, Southeast Asia and South America. MEGAN–MACC estimates of isoprene, α-pinene and group of monoterpenes showed a reasonable agreement with surface flux measurements at sites located in tropical forests in the Amazon and Malaysia. The model was able to capture the seasonal variation of isoprene emissions in the Amazon forest.

Abstract. Atmospheric remote sounding from satellites is an essential component of the observational strategy deployed to monitor atmospheric pollution and changing composition. The IASI nadir looking thermal infrared sounder onboard MetOp will provide 15 years of global scale observations for a series of key atmospheric species, with unprecedented spatial sampling and coverage. This paper gives an overview of the instrument's capability for measuring atmospheric composition in the perspective of chemistry and air quality. The assessment is made in terms of species, accuracy and vertical information. Global distributions are presented for CO, CH4, O3 (total and tropospheric), HNO3, NH3, and volcanic SO2. Local distributions of organic species measured during fire events, such as C2H4, CH3OH, HCOOH, and PAN are also shown. For each species or process, the link is made to specialized papers in this issue.

AIMS: Several decades of research have shown that lesbian, gay and bisexual (LGB) adults are at high risk for substance use and substance use disorders (SUDs). These problems may often start prior to young adulthood; however, relatively little is known about risk for substance use in LGB adolescents. The primary aims of this paper were to conduct a meta-analysis of the relationship between sexual orientation and adolescent substance use and a systematic review and critique of the methodological characteristics of this literature. METHODS: Medical and social science journals were searched using Medline and PsychInfo. Studies were included if they tested the relationship between sexual orientation and adolescent substance use. Eighteen published studies were identified. Data analysis procedures followed expert guidelines, and used National Institutes of Health (NIH)-sponsored meta-analysis software. RESULTS: LGB adolescents reported higher rates of substance use compared to heterosexual youth (overall odds ratio = 2.89, Cohen's d = 0.59). Effect sizes varied by gender, bisexuality status, sexual orientation definition and recruitment source. None of the studies tested mediation and only one tested moderation. One employed a matched comparison group design, one used a longitudinal design, and very few controlled for possible confounding variables. CONCLUSIONS: The odds of substance use for LGB youth were, on average, 190% higher than for heterosexual youth and substantially higher within some subpopulations of LGB youth (340% higher for bisexual youth, 400% higher for females). Causal mechanisms, protective factors and alternative explanations for this effect, as well as long-term substance use outcomes in LGB youth, remain largely unknown.

Myocarditis is defined clinically as inflammation of the heart muscle. First introduced into the medical literature at the beginning of the 19th century, the term “myocarditis” was initially used to describe diseases of the heart muscle not associated with valvular abnormalities.1 With the recognition of the importance of coronary-artery occlusion as a cause of heart-muscle disease at the beginning of the 20th century, the term was largely discarded. In the second half of the 20th century, a constellation of clinical observations renewed interest in inflammation of the heart muscle: myocarditis was recognized in a surprisingly large number of postmortem studies . . .

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

Epithelial-mesenchymal transition (EMT), a process by which differentiated epithelial cells undergo a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury. However, the degree to which this process contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent. EMT is often preceded by and closely associated with chronic interstitial inflammation and could be an adaptive response of epithelial cells to a hostile or changing microenvironment. In addition to tubular epithelial cells, recent studies indicate that endothelial cells and glomerular podocytes may also undergo transition after injury. Phenotypic alteration of podocytes sets them in motion to functional impairment, resulting in proteinuria and glomerulosclerosis. Several intracellular signal transduction pathways such as TGFbeta/Smad, integrin-linked kinase (ILK) and Wnt/beta-catenin signaling are essential in controlling the process of EMT and presently are potential targets of antifibrotic therapy. This review highlights the current understanding of EMT and its underlying mechanisms to stimulate further discussion on its role, not only in the pathogenesis of renal interstitial fibrosis but also in the onset of podocyte dysfunction, proteinuria, and glomerulosclerosis.

Chronic sleep deficiency, defined as a state of inadequate or mistimed sleep, is a growing and underappreciated determinant of health status. Sleep deprivation contributes to a number of molecular, immune, and neural changes that play a role in disease development, independent of primary sleep disorders. These changes in biological processes in response to chronic sleep deficiency may serve as etiological factors for the development and exacerbation of cardiovascular and metabolic diseases and, ultimately, a shortened lifespan. Sleep deprivation also results in significant impairments in cognitive and motor performance which increase the risk of motor vehicle crashes and work-related injuries and fatal accidents. The American Academy of Sleep Medicine and the Sleep Research Society have developed this statement to communicate to national health stakeholders the current knowledge which ties sufficient sleep and circadian alignment in adults to health.

BACKGROUND: Endobronchial valves that allow air to escape from a pulmonary lobe but not enter it can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with pulmonary hyperinflation related to advanced emphysema. METHODS: We compared the safety and efficacy of endobronchial-valve therapy in patients with heterogeneous emphysema versus standard medical care. Efficacy end points were percent changes in the forced expiratory volume in 1 second (FEV1) and the 6-minute walk test on intention-to-treat analysis. We assessed safety on the basis of the rate of a composite of six major complications. RESULTS: Of 321 enrolled patients, 220 were randomly assigned to receive endobronchial valves (EBV group) and 101 to receive standard medical care (control group). At 6 months, there was an increase of 4.3% in the FEV1 in the EBV group (an increase of 1.0 percentage point in the percent of the predicted value), as compared with a decrease of 2.5% in the control group (a decrease of 0.9 percentage point in the percent of the predicted value). Thus, there was a mean between-group difference of 6.8% in the FEV1 (P=0.005). Roughly similar between-group differences were observed for the 6-minute walk test. At 12 months, the rate of the complications composite was 10.3% in the EBV group versus 4.6% in the control group (P=0.17). At 90 days, in the EBV group, as compared with the control group, there were increased rates of exacerbation of chronic obstructive pulmonary disease (COPD) requiring hospitalization (7.9% vs. 1.1%, P=0.03) and hemoptysis (6.1% vs. 0%, P=0.01). The rate of pneumonia in the target lobe in the EBV group was 4.2% at 12 months. Greater radiographic evidence of emphysema heterogeneity and fissure completeness was associated with an enhanced response to treatment. CONCLUSIONS: Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation. (Funded by Pulmonx; ClinicalTrials.gov number, NCT00129584.)

In this review, a developmental traumatology model of child maltreatment and the risk for the intergenerational cycle of abuse and neglect using a mental health or posttraumatic stress model was described. Published data were reviewed that support the hypothesis that the psychobiological sequelae of child maltreatment may be regarded as an environmentally induced complex developmental disorder. Data to support this view, including the descriptions of both psychobiological and brain maturation studies in maltreatment research, emphasizing the similarities and differences between children, adolescents, and adults, were reviewed. Many suggestions for important future psychobiological and brain maturation research investigations as well as public policy ideas were offered.

Antibodies to alpha-synuclein (AS) now provide a sensitive and specific method for the detection of Lewy bodies (LBs) and their use will allow a more accurate determination of the prevalence of LBs in Alzheimer's Disease (AD). Studies using AS immunohistochemistry (IHC) have found LBs in the amygdala of over 60% early onset familial AD and in 50% of Down's syndrome patients with AD, however, no studies have reported the use of AS IHC to detect LBs in a large cohort of sporadic AD. This study examined 145 sporadic AD cases diagnosed using CERAD criteria from 1995-1999 for the presence of LBs using AS IHC. AS IHC detected LBs in 88/145 (60.7%) of sporadic AD cases. Similarly, LBs were found in 56.8% of the 95 cases fulfilling the more stringent NIA-RI criteria for the diagnosis of AD (Braak stage 5-6). In all cases with LBs, the amygdala was involved and LBs were always most numerous in this area, however, in some cases LBs in the substantia nigra were rare or not present. In conclusion, this study found that AS IHC detects LBs in the majority of sporadic AD cases and that the amygdala is the most commonly affected region.

Human papillomavirus (HPV) has been associated with head and neck squamous cell carcinomas (HNSCC), especially of the oropharynx, with highest distribution in the tonsils. HPV infection has been associated with improved outcome, although not all the studies show consistent results. The reason for this is not clear. We reviewed all published articles and conducted a meta-analysis on the overall relationship between HPV infection and overall survival (OS) and disease-free survival (DFS) in HNSCC. Patients with HPV-positive HNSCC had a lower risk of dying (meta HR: 0.85, 95% CI: 0.7-1.0), and a lower risk of recurrence (meta HR: 0.62, 95%CI: 0.5-0.8) than HPV-negative HNSCC patients. Site-specific analyses show that patients with HPV-positive oropharyngeal tumours had a 28% reduced risk of death (meta HR: 0.72, 95%CI: 0.5-1.0) in comparison to patients with HPV-negative oropharyngeal tumours. Similar observations were made for DFS (meta HR: 0.51, 95% CI: 0.4-0.7). There was no difference in OS between HPV-positive and negative non-oropharyngeal patients. The observed improved OS and DFS for HPV-positive HNSCC patients is specific to the oropharynx; these tumours may have a distinct etiology from those tumours in non-oropharyngeal sites.