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PURPOSE: For those who stutter, verbal communication is typically compromised in social situations. This may attract negative responses from listeners and stigmatization by society. These have the potential to impair health-related quality of life across a range of domains, including qualitative and quantitative impacts on speech output, mental health issues, and failure to attain educational and occupational potential. These systematic reviews were designed to explore this matter using traditional health economics perspectives of utility measures and cost of illness. METHOD: Studies were included if they involved children, adolescents, or adults with stuttering as a primary diagnosis. The quality of life search strategy identified 2,607 reports, of which three were included in the quality of life analysis. The cost of illness search strategy identified 3,778 reports, of which 39 were included in the cost of illness analysis. RESULTS: Two of the three studies included in the quality of life analysis had a high risk of bias. When measured using utility scores, quality of life for people who stutter was in the range of those reported for chronic health conditions such as diabetes mellitus, cardiovascular disease, and cancer. However, there is little such evidence of quality of life impairment during the preschool years. Studies included in the cost of illness analysis carried considerable risk of bias overall. CONCLUSIONS: For people who stutter, there are substantive direct and indirect costs of illness. These include impairment, challenges, and distress across many domains throughout life, including income, education, employment, and social functioning. Evidence of quality of life impairment using utility measures is extremely limited. If this situation is not remedied, the lifetime impairment, challenges, and distress experienced by those who stutter cannot be documented in a form that can be used to influence health policy and health care spending. SUPPLEMENTAL MA

PURPOSE: Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown. METHODS: We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality. RESULTS: The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10-year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status. CONCLUSION: We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established.

Introduction For individuals presenting to the emergency department (ED) for a suicide attempt, the period after discharge from hospital is marked by heightened vulnerability for further suicide attempts. Effective care following a suicidal crisis has the potential to significantly decrease this risk. The current study aims to examine the impact of the LifeSpan multilevel suicide prevention model on experiences of care following a suicidal crisis. Perspectives from healthcare consumers (individuals who have presented to the ED following a suicidal crisis), carers, and health professionals will be explored. The LifeSpan model is currently being evaluated as a high-fidelity trial in four geographically defined regions in New South Wales, Australia. Methods and analysis This study will use a mixed methods prospective cohort design. Quantitative data collection includes a structured survey, administered to healthcare consumers from LifeSpan sites and control sites. Two cohorts of healthcare consumers will be recruited 12 months apart with baseline assessment occurring within 18 months of the ED presentation, and follow-up 12 months after the initial assessment. Survey participants will be recruited online and through participating EDs, mental health organisations and aftercare services. Qualitative interview data from healthcare consumers, carers who have accompanied a loved one to the ED following a suicidal crisis and health professionals who provide care to people at risk of suicide will be collected concurrently with the recruitment of the first cohort of survey participants. Purposive and convenience sampling techniques will be used for recruitment of interview participants. The primary outcome for this study will be healthcare consumers' experiences of service provided at the ED. Analysis will be undertaken of the change over time within LifeSpan sites, as well as between LifeSpan sites and control sites, using mixed effects repeated measures models as principal m

Background: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and Methods: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Result(s): HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. Conclusion(s): The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.Copyright © 2019 THE AUTHORS

Background: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and Methods: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Result(s): HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. Conclusion(s): The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.Copyright © 2019 The Author(s). Published by Oxford Univers