Associations of HPV-16 Gene Methylation With Oral HPV-16 Persistence Among a Multinational Sample of Men.

ABSTRACT: Using data from the Human Papillomavirus (HPV) Infection in Men cohort study, we demonstrate HPV-16 methylation associations with persistent oral HPV infection, the obligate precursor to oropharyngeal cancer. Human papillomavirus type 16 persistence was significantly associated with methylation of HPV-16 L2 CpG-4268 (Wilcoxon P = 0.04), and methylation of HPV-16 E2 CpG Pos 4 (Wilcoxon P = 0.04).

Recurrence Patterns for Regionally Metastatic Melanoma Treated in the Era of Adjuvant Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: The purpose of this systematic review was to examine the timing and patterns of recurrence for patients with regionally metastatic melanoma on the basis of nodal management and receipt of adjuvant therapy. METHODS: We identified randomized controlled trials and non-randomized studies published between 2010 and 2020 that reported timing and/or patterns of recurrence. We evaluated recurrence-free survival (RFS), location of recurrence, and surveillance strategy on the basis of receipt of adjuvant systemic therapy and nodal management with observation versus completion dissection. We compared differences in patterns of recurrence across studies using RevMan. RFS was evaluated graphically using point estimates and confidence intervals. RESULTS: Among the 19 publications, there was wide variation in study populations, imaging surveillance regimens, and format of recurrence reporting. Patterns of disease recurrence did not differ between adjuvant and placebo/observation groups. A total of 11 studies reported RFS at variable time intervals, which ranged in adjuvant therapy groups (38-88% at 1 year, 29-67% at 2 years, 33-58% at 3 years, and 34-53% at 5 years) and placebo/observation groups (47-63% at 1 year, 39-47% at 2 years, 33-68% at 3 years, and 57% at 5 years). Anti-PD-1 immune therapy and BRAF/MEK inhibitor therapy were superior to placebo at year 1. DISCUSSION: We found that adjuvant treatment improved RFS but did not alter the patterns of disease recurrence compared with patients managed without adjuvant systemic treatment. Future studies should separately report sites of disease recurrence on the basis of specific adjuvant systemic treatment and surveillance practices to better advise patients about their patterns and risk of recurrence.

Effects of Urtica dioica on Metabolic Profiles in Type 2 Diabetes: A Systematic Review and Meta-analysis of Clinical Trials.

BACKGROUND: Several studies have investigated the effect of Urtica dioica (UD) consumption on metabolic profiles in patients with type 2 diabetes mellitus (T2DM); however, the findings are inconsistent. This systematic review and meta-analysis of clinical trials were performed to summarize the evidence of the effects of UD consumption on metabolic profiles in patients with T2DM. METHODS: Eligible studies were retrieved from searches of PubMed, Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar databases until December 2019. Cochran (Q) and I-square statistics were used to examine heterogeneity across included clinical trials. Data were pooled using a fixed-effect or random-effects model and expressed as weighted mean difference (WMD) and 95% confidence interval (CI). RESULTS: Among 1485 citations, thirteen clinical trials were found to be eligible for the current metaanalysis. UD consumption significantly decreased levels of fasting blood glucose (FBG) (WMD = - 17.17 mg/dl, 95% CI: -26.60, -7.73, I2 = 93.2%), hemoglobin A1c (HbA1c) (WMD = -0.93, 95% CI: - 1.66, -0.17, I2 = 75.0%), C-reactive protein (CRP) (WMD = -1.09 mg/dl, 95% CI: -1.64, -0.53, I2 = 0.0%), triglycerides (WMD = -26.94 mg/dl, 95 % CI = [-52.07, -1.82], P = 0.03, I2 = 90.0%), systolic blood pressure (SBP) (WMD = -5.03 mmHg, 95% CI = -8.15, -1.91, I2 = 0.0%) in comparison to the control groups. UD consumption did not significantly change serum levels of insulin (WMD = 1.07 µU/ml, 95% CI: -1.59, 3.73, I2 = 63.5%), total-cholesterol (WMD = -6.39 mg/dl, 95% CI: -13.84, 1.05, I2 = 0.0%), LDL-cholesterol (LDL-C) (WMD = -1.30 mg/dl, 95% CI: -9.95, 7.35, I2 = 66.1%), HDL-cholesterol (HDL-C) (WMD = 6.95 mg/dl, 95% CI: -0.14, 14.03, I2 = 95.4%), body max index (BMI) (WMD = -0.16 kg/m2, 95% CI: -1.77, 1.44, I2 = 0.0%), and diastolic blood pressure (DBP) (WMD = -1.35 mmHg, 95% CI: -2.86, 0.17, I2= 0.0%) among patients with T2DM. CONCLUSION: UD consumption may result in an improvement in levels of FBS, HbA1c, CRP, triglycerides, and SBP, but did not affect levels of insulin, total-, LDL-, and HDL-cholesterol, BMI, and DBP in patients with T2DM.

Surveillance of Sentinel Node-Positive Melanoma Patients Who Receive Adjuvant Therapy Without Undergoing Completion Lymph Node Dissection.

INTRODUCTION: Adjuvant therapy trials required completion lymph node dissection (CLND) for sentinel lymph node (SLN)-positive melanoma prior to systemic treatment, but nodal surveillance without CLND is now common. For patients receiving adjuvant therapy without CLND, patterns of recurrence are unknown and the value of regional nodal ultrasound alongside cross-sectional imaging is not well-defined. METHODS: In a retrospective cohort of SLN-positive melanoma patients managed with nodal surveillance from June 2014 to June 2019, we evaluated the association between adjuvant treatment and location of first recurrence (locoregional, nodal, distant, or multisite) using Chi-square tests. We compared methods of recurrence detection and cost by surveillance intensity using Chi-square and Dunn's tests. RESULTS: Among 177 nodal surveillance patients, 66 (37%) received adjuvant therapy. Median follow-up was 24 months, during which 48 patients (27%) recurred. Adjuvant treatment did not alter patterns of initial recurrence (p = 0.76). Adjuvant therapy recipients more often had both nodal ultrasound and cross-sectional imaging surveillance (p < 0.01). Among 13 isolated nodal recurrences, 85% were within the first year and 85% were detected by examination and/or ultrasound. Increasing surveillance intensity was not associated with recurrence detection rates but increased overall cost and cost per detected recurrence. CONCLUSION: Regardless of adjuvant treatment, most nodal recurrences occurred in the first year and were initially detected clinically or by ultrasound. Findings support continued use of examination and nodal basin ultrasound in addition to any planned cross-sectional imaging surveillance.

Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males.

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7-3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7-3.1) and 3.5 (95% CI: 1.9-6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.

Burden of Tracheal, Bronchus, and Lung Cancer and Its Attributable Risk Factors in 204 Countries and Territories, 1990 to 2019.

INTRODUCTION: Understanding trends in the annual incidence, mortality, and disability-adjusted life-years (DALYs) for tracheal, bronchus, and lung (TBL) cancer globally is important to enable appropriate targeting of resources for prevention, clinical practice improvement, and research. The aim of this study was to determine the global, regional, and national burdens of TBL cancer in 204 countries and territories from 1990 to 2019 by age, sex, and sociodemographic index. METHODS: Estimates were produced through various data inputs including the following: cancer registries (nsite-years = 5318), vital registration (nsite-years = 22,553), vital registration-sample (nsite-years = 825), and verbal autopsies (nsite-years = 516). Annual incidence, mortality, and DALYs were estimated and presented as counts and age-standardized rates per 100,000 population. RESULTS: There were 2.3 million (95% uncertainty interval [UI]: 2.1-2.5) incident cases of TBL cancer, with an age-standardized annual incidence rate of 27.7 (95% UI: 25.3-30), which decreased by 2.6% (95% UI: -12.4 to 6.5) between 1990 and 2019. TBL cancer was responsible for 2 million (95% UI: 1.9-2.2) deaths globally with an age-standardized death rate of 25.2 (95% UI: 23.2-27), a decrease of 7.8% (95% UI: -15.9 to 0.2) between 1990 and 2019. Moreover, TBL accounted for 45.9 million (95% UI: 42.3-49.3) DALYs at the global level, with an age-standardized rate of 551.6 (95% UI: 509-593.1) DALYs per 100,000 population. The standardized DALY rate declined by 16.2% (95% UI: -24 to -8.2) from 1990 to 2019. Greenland (77.7 [95% UI: 64.4-90.6]), Monaco (75.6 [95% UI: 61.4-90.8]), and Montenegro (56.7 [95% UI: 46.5-68.9]) had the three highest age-standardized annual incidence rates. The aforementioned three countries also had the three highest age-standardized death and DALY rates of TBL cancer. Honduras (68% [95% UI: 14.5-137.7]), Cabo Verde (62.2% [95% UI: 24.1-101.3]), and Monaco (58.2% [95% UI: 19.2-109.7]) had the largest increase in age-standardized annual incidence rates for TBL cancer during 1990 to 2019. The largest increases were found in age-standardized death rates of TBL cancer in Honduras (67.1% [95% UI: 14.7-133.1]), Cabo Verde (64.4% [95% UI: 25-103.4]), and Mozambique (49.9% [95% UI: 7.9 -101.3]). Age-standardized annual incidence and death rates were higher in male than female individuals and increased with population aging. There were nonlinear but generally positive associations between age-standardized DALY rates with corresponding sociodemographic index of countries. Globally, smoking (62.4%), ambient particulate matter (15.3%), and high fasting plasma glucose (9.9%) had the top three highest percent of attributable DALYs owing to TBL cancer in 2019 for both sexes. CONCLUSIONS: This study found a decline in burden globally but with some countries having an increase. These results are crucial to set priorities for prevention and treatment of TBL cancer and would be beneficial for policymakers, government officials, clinicians, and researchers.

Factors Associated With Persistence and Clearance of High-Risk Oral Human Papillomavirus (HPV) Among Participants in the HPV Infection in Men (HIM) Study.

BACKGROUND: Human papillomavirus (HPV)-attributable oropharyngeal cancer (HPV-OPC) incidence is increasing in many high-income countries among men. Factors associated with oral HPV persistence, the precursor of HPV-OPC, are unknown. Data from the HPV Infection in Men (HIM) Study, which followed participants >7 years, were utilized to examine rates of persistence and associated factors. METHODS: Oral gargle samples from 3095 HIM study participants were HPV genotyped using the SPF10 PCR-DEIA-LiPA25 assay (DDL Diagnostic Laboratory). Oral HPV persistence for individual and grouped high-risk HPV types among 184 men positive for any high-risk HPV at their oral baseline visit was assessed at 6-month intervals. Factors associated with grouped high-risk HPV/HPV16 persistence were examined using logistic regression. Kaplan-Meier curves were constructed to examine median time to HPV clearance overall, and by selected risk factors. RESULTS: Among the 7 HPV vaccine types, HPV33 had the longest median duration (7.6 months) followed by HPV16 and HPV45 (6.4 months). 10-30% of oral high-risk HPV infections persisted ≥24 months. Six months' persistence of oral high-risk HPV infections was positively associated with age and gingivitis and negatively with lifetime number of sexual partners, while 12 months' persistence was only inversely associated with lifetime number of sexual partners. Oral HPV16 persistence was positively associated with baseline HPV16 L1 antibody status. CONCLUSIONS: Eighteen percent of HPV16 infections persisted beyond 24 months, potentially conferring higher risk of HPV-OPC among these men. Older age appears to be an important factor associated with oral high-risk HPV persistence. More studies among healthy men are required to understand the progression of oral HPV infection to HPV-OPC.

Vaccination Inequality in India, 2002-2013.

INTRODUCTION: India's childhood vaccination coverage has increased amid the implementation of national health policies intended to improve immunization levels. However, there is a dearth of contemporary studies comparing state-level childhood vaccination rates across India's highly diverse states and territories. This study assesses SES-based inequalities in childhood vaccination by state for 2002-2013. METHODS: National surveys from 2002 to 2004, 2007 to 2008, and 2012 to 2013 were used for analyses. Household SES was assessed using an asset index created through principal component analysis. Full vaccination comprised 1 dose bacille Calmette-Guerin, 3 doses diphtheria-pertussis-tetanus vaccine, 3 doses oral polio vaccine, and 1 dose measles-containing vaccine at age 12-60 months. Inequality analyses were stratified by 3 time periods and by government-designated high focus group versus non-high focus group states. RESULTS: Childhood vaccination steadily increased between 2002 and 2013 in high focus group states but fell in some non-high focus group states, whereas SES-based vaccination inequalities generally decreased in both. In 2012-2013, rural areas had lower vaccination rates than urban areas in high focus group states but similar vaccination rates as urban areas in non-high focus group states. Increases in vaccination rates were not consistently accompanied by improvements in SES-based inequalities in vaccination. CONCLUSIONS: Childhood vaccination in India has improved overall, although increases are more pronounced in high focus group states than in non-high focus group states over the study period. The gap in coverage between these states decreased over time owing in part to the latter experiencing reductions in full vaccination rates during 2007-2013. SES-based vaccination disparities persist in India, highlighting the need to improve vaccination rates for all children, especially those from disadvantaged and underserved groups. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Global Vaccination Equity, which is sponsored by the Global Institute for Vaccine Equity at the University of Michigan School of Public Health.

Differences in Factors Associated With High- and Low-Risk Oral Human Papillomavirus Genotypes in Men.

BACKGROUND: Human papillomavirus (HPV) causes oral warts and oropharyngeal cancer (OPC). Human papillomavirus-attributable OPC incidence among men is significantly increasing worldwide, yet few studies have reported oral HPV across multiple countries or examined factors associated with low- and high-risk HPV separately. METHODS: Oral gargles from 3095 men in the multinational HPV Infection in Men (HIM) Study were HPV genotyped. Multivariable models assessed factors independently associated with high-risk and low-risk HPV prevalence. RESULTS: The prevalence of high-risk and low-risk HPV was 6.0% and 2.8%, respectively. Greater number of sexual partners was only associated with high-risk HPV (1.88; 95% confidence interval [CI], 1.22-2.90) prevalence. In multivariable models, residing in Mexico (1.66; 95% CI, 1.15-2.40) and smoking (1.66; 95% CI, 1.13-2.44) were significantly associated with high-risk HPV, and history of consistent gum bleeding (2.16; 95% CI, 1.35-3.45) was significantly associated with low-risk HPV. Gender of the sexual partner did not alter the results for either high- or low-risk HPV endpoints. CONCLUSIONS: Different factors were independently associated with high- and low-risk oral HPV. Oral sexual behaviors were associated with high-risk HPV, and oral health was associated with low-risk HPV. High-risk HPV prevalence differed by country of residence, highlighting the need for additional studies in multiple countries.

Impact of Multiple Risk Factors on Vaccination Inequities: Analysis in Indian Infants Over 2 Decades.

INTRODUCTION: Several authors have explored the effect of individual risk factors on vaccination inequity in Indian infants. This study explores the combined impact of >1 risk factor on the probability of full vaccination. METHODS: The proportion of fully vaccinated infants (aged 1-2 years) was calculated from the National Family Health Survey conducted during 1997-1998 (National Family Health Survey-2, n=10,211), 2005-2006 (National Family Health Survey-3, n=9,582), and 2015-2016 (National Family Health Survey-4, n=48,715). Full vaccination was defined as receiving Bacille Calmette‒Guerin (1 dose); diphtheria, pertussis, tetanus (3 doses); oral polio (3 doses); and measles (1 dose) vaccines. The association between full vaccination status and 6 factors (infant sex, birth order, family wealth status, maternal education level, residence type, and religion) was analyzed individually, followed by the combined impact of ≥1 of the first 4, using logistic regression models. RESULTS: The AORs for full vaccination in the 3 surveys, respectively, were 1.09, 1.13, and 1.00 for male versus female infants; 0.68, 0.71, and 0.88 for birth order >1 versus birth order 1; 1.54, 1.96, and 1.20 for greater wealth versus lowest wealth stratum; 2.21, 2.27, and 1.27 for any maternal education versus none; 1.08, 1.10, and 1.08 for Hindu versus other religion; and 1.51, 1.10, and 0.88 for urban versus rural residence. The respective ORs of full vaccination in the 3 surveys by the number of risk factors were as follows: 1.26, 1.54, and 1.27 for 3 risk factors; 2.41, 3.23, and 1.68 for 2 risk factors; 4.42, 6.45, and 2.18 for 1 risk factor; and 7.32, 9.84, and 2.61 for no risk factor. CONCLUSIONS: The presence of multiple risk factors had a cumulative negative impact on infant vaccination in India. Despite an improvement over 2 decades, significant inequities persist. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Global Vaccination Equity, which is sponsored by the Global Institute for Vaccine Equity at the University of Michigan School of Public Health.

The burden of kidney cancer and its attributable risk factors in 195 countries and territories, 1990-2017.

Kidney cancer globally accounts for more than 131,000 deaths each year and has been found to place a large economic burden on society. However, there are no recent articles on the burden of kidney cancer across the world. The aim of this study was to present a status report on the incidence, mortality and disability-adjusted life years (DALYs) associated with kidney cancer in 195 countries, from 1990 to 2017. Vital registration and cancer registry data (total of 23,660 site-years) were used to generate the estimates. Mortality was estimated first and the incidence and DALYs were calculated based on the estimated mortality values. All estimates were presented as counts and age-standardised rates per 100,000 population. The estimated rates were calculated by age, sex and according to the Socio-Demographic Index (SDI). In 2017, kidney cancer accounted for 393.0 thousand (95% UI: 371.0-404.6) incident cases, 138.5 thousand (95% UI: 128.7-142.5) deaths and 3.3 million (95% UI: 3.1-3.4) DALYs globally. The global age-standardised rates for the incidence, deaths and DALY were 4.9 (95% UI: 4.7-5.1), 1.7 (95% UI: 1.6-1.8) and 41.1 (95% UI: 38.7-42.5), respectively. Uruguay [15.8 (95% UI: 13.6-19.0)] and Bangladesh [1.5 (95% UI: 1.0-1.8)] had highest and lowest age-standardised incidence rates, respectively. The age-standardised death rates varied substantially from 0.47 (95% UI: 0.34-0.58) in Bangladesh to 5.6 (95% UI: 4.6-6.1) in the Czech Republic. Incidence and mortality rates were higher among males, than females, across all age groups, with the highest rates for both sexes being observed in the 95+ age group. Generally, positive associations were found between each country's age-standardised DALY rate and their corresponding SDI. The considerable burden of kidney cancer was attributable to high body mass index (18.5%) and smoking (16.6%) in both sexes. There are large inter-country differences in the burden of kidney cancer and it is generally higher in countries with a high SDI. The findings from this study provide much needed information for those in each country that are making health-related decisions about priority areas, resource allocation, and the effectiveness of prevention programmes. The results of our study also highlight the need for renewed efforts to reduce exposure to the kidney cancer risk factors and to improve the prevention and the early detection of this disease.

A comparison of nasogastric tube insertion by SORT maneuver (sniffing position, NGT orientation, contralateral rotation, and twisting movement) versus neck flexion lateral pressure in critically ill patients admitted to ICU: a prospective randomized clinical trial.

BACKGROUND: Although many techniques have been introduced to facilitate nasogastric tube (NGT) insertion using anatomic landmarks and a group of devices, there is a lack of general consensus regarding a standard method. The current study purposed to investigate if SORT maneuver (sniffing position, NGT orientation, contralateral rotation, and twisting movement) increases the success rate of NGT correct placement versus neck flexion lateral pressure (NFLP) method. METHODS: A randomized controlled trial study was conducted in two university affiliated intensive care units (tertiary referral center). Three hundred and ninety-six critically ill patients older than 18 years of age were randomly divided into SORT (n = 200) and NFLP (n = 196) groups. The technique was classified as "failed" after the third unsuccessful attempt. Patient characteristics, success rate for the first attempt, time required for the successful first attempt and overall successful insertion time, various complications including kinking, coiling and bleeding and ease of insertion were noted as main outcomes measured. RESULTS: Ease of insertion was significantly better in the SORT group compared to the NFLP group (P < 0.001). The number of failed attempts was significantly higher in the NFLP group (7.5%) vs the SORT group (3.0%) (P = 0.046). The pattern of complications was not different between two study groups (P = 0.242). The odds of stage II (odds ratio (OR) = 49.9; 95% confidence interval (CI) 25.2 to 98.6), stage III (OR = 67.1; 95% CI 14.9 to 302.8)) and stage IV (OR = 11.8; 95% CI 3.4 to 41.2) ease of insertion were much higher in NFLP compared to SORT group, after adjusting for age and body mass index (BMI). The odds of failure was not significantly different in NFLP group compared to SORT group (OR = 2.3; 95% CI 0.85 to 6.3), after adjusting for age and BMI. CONCLUSIONS: SORT technique may be considered as a promising method for successful NGT insertions in critically ill patients. However, more trials are needed to confirm the results of this study. The decision must account for individual patient and clinical factors and the operator's experience and preference. TRIAL REGISTRATION: The study was registered at government registry of clinical trials in Iran (http://www.IRCT.ir) (number: IRCT20091012002582N18, 13 March 2018).

Oral HPV prevalence assessment by Linear Array vs. SPF10 PCR-DEIA-LiPA25 system in the HPV Infection in Men (HIM) study.

INTRODUCTION: Oral human papillomavirus (HPV) attributable oropharyngeal cancers are on the rise in many countries. Oral HPV infections among healthy individuals are commonly detected using oral gargle samples. However, the optimal method for HPV genotyping oral gargle specimens in research studies has not been previously evaluated. MATERIALS AND METHODS: Oral gargle samples from 1455 HPV Infection in Men (HIM) study participants were HPV genotyped using two different methods: Linear Array and the SPF10 PCR-DEIA-LiPA25. The sensitivity of the two tests for detecting individual HPV types and grouped HPV types, high-risk HPV, low-risk HPV, grouped 4-HPV-vaccine types, and grouped 9-HPV-vaccine-types, and the degree of concordance between the two tests was assessed. We also examined whether socio-demographic-behavioral factors were associated with concordance between the two assays. RESULTS: The sensitivity of SPF10 PCR-DEIA-LiPA25 was higher than Linear Array, with the exception of HPV 70, for the detection of oral HPV. The prevalence ratio of SPF10 PCR-DEIA-LiPA25 to Linear Array varied between 1.0 and 9.0 for individual HPV genotypes, excluding HPV 70, and between 3.8 and 4.4 for grouped 4-valent and 9-valent HPV vaccine types, respectively. There was no association between socio-demographic-behavioral factors and discordance in results between the two tests for oral HPV 16 detection. DISCUSSION: SPF10 PCR-DEIA-LiPA25 was more sensitive than Linear Array for detecting HPV in oral gargle samples. Given the growing importance of detecting oral HPV infection for research studies of oral HPV natural history and vaccine effectiveness evaluation, we recommend using methods with higher sensitivity such as SPF10 PCR-DEIA-LiPA25 for detecting HPV in oral gargle samples.

Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017.

OBJECTIVES: To report the level and trends of prevalence, incidence and years lived with disability (YLDs) for osteoarthritis (OA) in 195 countries and territories from 1990 to 2017 by age, sex and Socio-demographic index (SDI; a composite of sociodemographic factors). METHODS: Publicly available modelled data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 were used. The burden of OA was estimated for 195 countries and territories from 1990 to 2017, through a systematic analysis of prevalence and incidence modelled data using the methods reported in the GBD 2017 Study. All estimates were presented as counts and age-standardised rates per 100 000 population, with uncertainty intervals (UIs). RESULTS: Globally, the age-standardised point prevalence and annual incidence rate of OA in 2017 were 3754.2 (95% UI 3389.4 to 4187.6) and 181.2 (95% UI 162.6 to 202.4) per 100 000, an increase of 9.3% (95% UI 8% to 10.7%) and 8.2% (95% UI 7.1% to 9.4%) from 1990, respectively. In addition, global age-standardised YLD rate in 2017 was 118.8 (95% UI 59.5 to 236.2), an increase of 9.6% (95% UI 8.3% to 11.1%) from 1990. The global prevalence was higher in women and increased with age, peaking at the >95 age group among women and men in 2017. Generally, a positive association was found between the age-standardised YLD rate and SDI at the regional and national levels. Age-standardised prevalence of OA in 2017 ranged from 2090.3 to 6128.1 cases per 100 000 population. United States (6128.1 (95% UI 5729.3 to 6582.9)), American Samoa (5281 (95% UI 4688 to 5965.9)) and Kuwait (5234.6 (95% UI 4643.2 to 5953.6)) had the three highest levels of age-standardised prevalence. Oman (29.6% (95% UI 24.8% to 34.9%)), Equatorial Guinea (28.6% (95% UI 24.4% to 33.7%)) and the United States 23.2% (95% UI 16.4% to 30.5%)) showed the highest increase in the age-standardised prevalence during 1990-2017. CONCLUSIONS: OA is a major public health challenge. While there is remarkable international variation in the prevalence, incidence and YLDs due to OA, the burden is increasing in most countries. It is expected to continue with increased life expectancy and ageing of the global population. Improving population and policy maker awareness of risk factors, including overweight and injury, and the importance and benefits of management of OA, together with providing health services for an increasing number of people living with OA, are recommended for management of the future burden of this condition.

Global, regional, and national burden of neck pain in the general population, 1990-2017: systematic analysis of the Global Burden of Disease Study 2017.

OBJECTIVE: To use data from the Global Burden of Disease Study between 1990 and 2017 to report the rates and trends of point prevalence, annual incidence, and years lived with disability for neck pain in the general population of 195 countries. DESIGN: Systematic analysis. DATA SOURCE: Global Burden of Diseases, Injuries, and Risk Factors Study 2017. MAIN OUTCOME MEASURES: Numbers and age standardised rates per 100 000 population of neck pain point prevalence, annual incidence, and years lived with disability were compared across regions and countries by age, sex, and sociodemographic index. Estimates were reported with uncertainty intervals. RESULTS: Globally in 2017 the age standardised rates for point prevalence of neck pain per 100 000 population was 3551.1 (95% uncertainty interval 3139.5 to 3977.9), for incidence of neck pain per 100 000 population was 806.6 (713.7 to 912.5), and for years lived with disability from neck pain per 100 000 population was 352.0 (245.6 to 493.3). These estimates did not change significantly between 1990 and 2017. The global point prevalence of neck pain in 2017 was higher in females compared with males, although this was not significant at the 0.05 level. Prevalence increased with age up to 70-74 years and then decreased. Norway (6151.2 (95% uncertainty interval 5382.3 to 6959.8)), Finland (5750.3 (5058.4 to 6518.3)), and Denmark (5316 (4674 to 6030.1)) had the three highest age standardised point prevalence estimates in 2017. The largest increases in age standardised point prevalence estimates from 1990 to 2017 were in the United Kingdom (14.6% (10.6% to 18.8%)), Sweden (10.4% (6.0% to 15.4%)), and Kuwait (2.6% (2.0% to 3.2%)). In general, positive associations, but with fluctuations, were found between age standardised years lived with disability for neck pain and sociodemographic index at the global level and for all Global Burden of Disease regions, suggesting the burden is higher at higher sociodemographic indices. CONCLUSIONS: Neck pain is a serious public health problem in the general population, with the highest burden in Norway, Finland, and Denmark. Increasing population awareness about risk factors and preventive strategies for neck pain is warranted to reduce the future burden of this condition.

Oral human papillomavirus prevalence and type distribution by country (Brazil, Mexico and the United States) and age among HPV infection in men study participants.

Incidence of human papillomavirus (HPV) attributable oropharyngeal cancers (OPCs) has been increasing globally, especially among men in high-income countries. There is a lack of studies comparing oral HPV prevalence by age and country among healthy men. The purpose of our study was to assess oral HPV prevalence by country and age. Participants of the HPV Infection in Men Study (HIM), a cohort of 3,098 healthy men from São Paulo, Brazil, Cuernavaca, Mexico and Tampa, USA, were studied. Oral HPV prevalence and type distribution were assessed using the SPF10 PCR-DEIA-LiPA25 system. The prevalence of any HPV in Brazil, Mexico and the US was 8.7% (95% CI: 7.1%, 10.4%), 10.0% (95% CI: 8.3%, 12.1%) and 7.6% (95% CI: 5.9%, 9.5%), respectively, while the prevalence of high-risk HPV was 5.3% (95% CI: 4.1%, 6.7%), 7.3% (95% CI: 5.7%, 9.0%) and 5.4% (95% CI: 4.0%, 7.0%), respectively. No significant differences in prevalence of grouped HPV types were observed by country despite significant differences in sexual behaviors. However, the age-specific prevalence of oral HPV differed by country. Brazilian (6.0% [95% CI: 3.4%, 9.7%]) and Mexican (9.2% [95% CI: 5.6%, 14.0%]) participants had peak high-risk HPV prevalence among men aged 41-50 years whereas the US participants had peak prevalence at ages 31-40 years (11.0% [95% CI: 6.4%, 17.3%]). In conclusion, oral HPV prevalence was low with no difference in overall prevalence observed by country. Factors associated with the differences in oral HPV age-patterning by country and sexual orientation require further study.

Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017.

OBJECTIVES: To provide the level and trends of prevalence, incidence and disability adjusted life years (DALYs) for rheumatoid arthritis (RA) in 195 countries from 1990 to 2017 by age, sex, Socio-demographic Index (SDI; a composite of sociodemographic factors) and Healthcare Access and Quality (an indicator of health system performance) Index. METHODS: Data from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2017 were used. GBD 2017 modelled the burden of RA for 195 countries from 1990 to 2017, through a systematic analysis of mortality and morbidity data to estimate prevalence, incidence and DALYs. All estimates were presented as counts and age-standardised rates per 100 000 population, with uncertainty intervals (UIs). RESULTS: Globally, the age-standardised point prevalence and annual incidence rates of RA were 246.6 (95% UI 222.4 to 270.8) and 14.9 (95% UI 13.3 to 16.4) in 2017, which increased by 7.4% (95% UI 5.3 to 9.4) and 8.2% (95% UI 5.9 to 10.5) from 1990, respectively. However, the age-standardised rate of RA DALYs per 100 000 population was 43.3 (95% UI 33.0 to 54.5) in 2017, which was a 3.6% (95% UI -9.7 to 0.3) decrease from the 1990 rate. The age-standardised prevalence and DALY rates increased with age and were higher in females; the rates peaked at 70-74 and 75-79 age groups for females and males, respectively. A non-linear association was found between age-standardised DALY rate and SDI. The global age-standardised DALY rate decreased from 1990 to 2012 but then increased and reached higher than expected levels in the following 5 years to 2017. The UK had the highest age-standardised prevalence rate (471.8 (95% UI 428.9 to 514.9)) and age-standardised incidence rate (27.5 (95% UI 24.7 to 30.0)) in 2017. Canada, Paraguay and Guatemala showed the largest increases in age-standardised prevalence rates (54.7% (95% UI 49.2 to 59.7), 41.8% (95% UI 35.0 to 48.6) and 37.0% (95% UI 30.9 to 43.9), respectively) and age-standardised incidence rates (48.2% (95% UI 41.5 to 55.1), 43.6% (95% UI 36.6 to 50.7) and 36.8% (95% UI 30.4 to 44.3), respectively) between 1990 and 2017. CONCLUSIONS: RA is a major global public health challenge. The age-standardised prevalence and incidence rates are increasing, especially in countries such as Canada, Paraguay and Guatemala. Early identification and treatment of RA is vital especially among females, in order to reduce the ongoing burden of this condition. The quality of health data needs to be improved for better monitoring of disease burden.

Are community health workers cost-effective for childhood vaccination in India?

INTRODUCTION: Accredited Social Health Activists (ASHAs) are female community health workers whose primary role is to promote utilization of primary healthcare services and improve sanitation in rural areas and are financially incentivized for services provided. Prior studies evaluating ASHAs have been largely qualitative, and assess their knowledge, skills, and practice. Globally, there have been very few studies that have quantitatively assessed community health workers. We analyzed the cost effectiveness of ASHAs in facilitating measles vaccination among children under 5 years during 2012-2013. METHODS: We utilized Markov modeling simulating a cohort of children in villages with and without ASHAs. We extrapolated the health states to a lifetime of 68 years to estimate the effects of ASHA intervention. Measles vaccination rates were obtained from 2013 District Level Household and Facilities Survey 4. Other parameter estimates were obtained from a review of relevant literature. RESULTS: ASHA intervention was highly cost effective at $162 per DALY averted compared to no ASHA and remained cost effective with the ASHA incentive increased from $2 to $15, across the range of probabilities and cost parameters. Analyses were sensitive to probability of death due to childhood pneumonia, susceptibility to measles after one dose measles vaccine, and probability of pneumonia after measles infection. CONCLUSION: ASHAs were cost-effective under a wide range of scenarios even when a single health outcome such as measles vaccination was considered. The Government of India and individual state governments of India should consider increasing the incentives provided to ASHAs.

Factors Associated with Vaccination Status of Children Aged 12-48 Months in India, 2012-2013.

Objectives India has more unvaccinated children than any other country despite provision of free vaccines through the government's Universal Immunization Program. In this study, we calculated the proportion of children aged 12-48 months who were fully vaccinated, under-vaccinated, or who had not received any vaccines. Childhood, household, and sociocultural factors associated with under-vaccination and non-vaccination were evaluated. Methods Using data from India's 4th District-level Health and Facility Survey, 2012-2013 (DLHS-4) and the 2012-2013 Annual Health Survey (AHS), we calculated the proportion of children who were non-vaccinated, under-vaccinated, or fully vaccinated with 1 dose of Bacillus Calmette-Guérin, 3 doses of oral polio vaccine, 3 doses of diphtheria-pertussis-tetanus, and 1 dose of measles-containing vaccine. The odds of full vaccination compared to non-vaccination and under-vaccination relative to various factors was assessed using a multivariable, multinomial logistic regression which accounted for survey design. Results Of 1,929,580 children aged 12-48 months, 59% were fully vaccinated, 34% were under-vaccinated, and 7% were non-vaccinated. Compared to children born in government institutions, children delivered in non-institutional settings with a skilled birth attendant present had higher odds of non-vaccination (OR 1.66) and those without a skilled attendant present had still greater odds of non-vaccination (OR 2.39) and under-vaccination (OR 1.11). Conclusions for Practice India's vaccination rates among children aged 12-48 months remains unacceptably low. The Indian government should encourage institutional delivery or birthing with a skilled attendant to ensure women receive adequate health education through antenatal care that includes the importance of childhood vaccination.