BACKGROUND: Performing catheter-care observations in outpatient hemodialysis facilities are one of the CDC's core interventions, which have been proven to reduce bloodstream infections. However, staff have many competing responsibilities. Efforts to increase and streamline the process of performing observations are needed. We developed an electronic catheter checklist, formatted for easy access with a mobile device, and conducted a pilot project to determine the feasibility of implementing it in outpatient dialysis facilities. METHODS: The tool contained the following content: (1) patient education videos; (2) catheter-care checklists (connection, disconnection, and exit-site care); (3) prepilot and postpilot surveys; and (4) a pilot implementation guide. Participating hemodialysis facilities performed catheter-care observations on either a weekly or monthly schedule and provided feedback on implementation of the tool. RESULTS: The pilot data were collected from January 6 through March 12, 2020, at seven participating facilities. A total of 954 individual observations were performed. The catheter-connection, disconnection, and exit-site steps were performed correctly for most individual steps; however, areas for improvement were (1) allowing for appropriate antiseptic dry time, (2) avoiding contact after antisepsis, and (3) applying antibiotic ointment to the exit site. Postpilot feedback from staff was mostly favorable. Use of the electronic checklists facilitated patient engagement with staff and was preferred over paper checklists, because data are easily downloaded and available for use in facility Quality Assurance and Performance Improvement (QAPI) meetings. The educational video content was a unique learning opportunity for both patients and staff. CONCLUSIONS: Converting the CDC's existing catheter checklists to electronic forms reduced paperwork and improved the ease of collating data for use during QAPI meetings. An additional benefit was the educational content provided on the tablet, which was readily available for viewing by patients and staff while in the hemodialysis facility.

RATIONALE & OBJECTIVE: Infection prevention efforts in dialysis centers can avert patient morbidity and mortality but are challenging to implement. The objective of this study was to better understand how the design of the work system might contribute to infection prevention in outpatient dialysis centers. STUDY DESIGN: Mixed methods, observational study. SETTING & PARTICIPANTS: Six dialysis facilities across the United States were visited by a multidisciplinary team over 8 months. ANALYTICAL APPROACH: At each facility, structured macroergonomic observations were undertaken by a multidisciplinary team using the SEIPS 1.0 model. Ethnographic observations were collected about staff encounters with dialysis patients including the content of staff conversations. Selective and axial coding were used for qualitative analysis and quantitative data were reported using descriptive statistics. RESULTS: Organizational and sociotechnical barriers and facilitators to infection prevention in the outpatient dialysis setting were identified. Features related to human performance, (e.g., alarms, interruptions, and task stacking), work system design (e.g., physical space, scheduling, leadership, and culture), and extrinsic factors (e.g., patient-related characteristics) were identified. LIMITATIONS: This was an exploratory evaluation. A small sample size. CONCLUSION: This study used a systematic macroergonomic approach in multiple outpatient dialysis facilities to identify infection prevention barriers and facilitators related to human performance. Several features common across facilities were identified that may influence infection prevention in outpatient care and warrant further exploration.

Introduction: During March-December 2020, Zambia recorded 20,725 confirmed COVID-19 cases, with the first wave peaking between July and August. Of the 388 COVID-19-related deaths occurring nationwide, most occurred in the community. We report findings from COVID-19 mortality surveillance among community deaths brought to the University Teaching Hospital (UTH) mortuary in Lusaka. Method(s): In Zambia, when a person dies in the community, and is brought into a health facility mortuary, they are recorded as 'brought in dead' (BID). The UTH mortuary accepts persons BID for Lusaka District, the most populated district in Zambia. We analyzed data for persons BID at UTH during 2020. We analyzed two data sources: weekly SARS-CoV-2 test results for persons BID and monthly all-cause mortality numbers among persons BID. For all-cause mortality among persons BID, monthly deaths during 2020 that were above the upper bound of the 95% confidence interval for the historic mean (2017-2019) were considered significant. Spearman's rank test was used to correlate the overall percent positivity in Zambia with all-cause mortality and SARS-CoV-2 testing among persons BID at UTH mortuary. Result(s): During 2020, 7,756 persons were BID at UTH (monthly range 556-810). SARS-CoV-2 testing began in April 2020, and through December 3,131 (51.9%) of 6,022 persons BID were tested. Of these, 212 (6.8%) were SARS-CoV-2 positive with weekly percent test positivity ranging from 0-32%, with the highest positivity occurring during July 2020. There were 1,139 excess persons BID from all causes at UTH mortuary in 2020 compared to the 2017-2019 mean. The monthly number of persons BID from all causes was above the upper bound of the 95% confidence interval during June-September and December. Conclusion(s): Increases in all-cause mortality and SARS-CoV-2 test positivity among persons BID at UTH mortuary corresponded with the first peak of the COVID-19 epidemic in June and August 2020, indicating possible increased mortality related to the COVID-19 epidemic in Zambia. Combining all-cause mortality and SARS-CoV-2 testing for persons BID provides useful information about the severity of the epidemic in Lusaka and should be implemented throughout Zambia. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Challenges in measuring early childhood development (ECD) at scale have been docu-mented, yet little is known about the specific difficulties related to questionnaire design and question interpretation. The purpose of this paper is to discuss the challenges of measuring ECD at scale in the context of household surveys and to show how to overcome them. The paper uses examples from the cognitive interviewing exercises that were conducted as part of the methodological work to develop a measure of ECD outcomes, the ECDI2030. It describes the methodological work carried out to inform the selection and improvement of question items and survey implementation tools as a fun-damental step to reduce and mitigate systematic measurement error and improve data quality. The project consisted of a total of five rounds of testing, comprising 191 one-on-one, in-depth cognitive interviews across six countries (Bulgaria, India, Jamaica, Mexico, Uganda, and the USA). Qualitative data analysis methods were used to determine matches and mismatches between intention of items and false positives or false negative answers among subgroups of respondents. Key themes emerged that could potentially lead to systematic measurement error in population-based surveys on ECD: (1) willingness of child to perform task versus ability of child to perform task; (2) performing task versus performing task correctly; (3) identifying letters or numbers versus recognizing letters or numbers; (4) consistently performing task versus correctly performing task; (5) applicability of skills being asked versus observability of skills being asked; and (6) language production versus language comprehension. Through an iterative process of testing and subsequent revision, improvements were made to item wording, response options, and interviewer training instructions. Given the difficulties inherent in population-level data collection in the context of global monitoring, this study’s findings confirm the importance of cognitive testing as a crucial step in careful, culturally relevant, and sensitive questionnaire design and as a means to reduce response bias in cross-cultural contexts. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

IMPORTANCE: Information on underlying conditions and severe COVID-19 illness among children is limited. OBJECTIVE: To examine the risk of severe COVID-19 illness among children associated with underlying medical conditions and medical complexity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients aged 18 years and younger with International Statistical Classification of Diseases, Tenth Revision, Clinical Modification code U07.1 (COVID-19) or B97.29 (other coronavirus) during an emergency department or inpatient encounter from March 2020 through January 2021. Data were collected from the Premier Healthcare Database Special COVID-19 Release, which included data from more than 800 US hospitals. Multivariable generalized linear models, controlling for patient and hospital characteristics, were used to estimate adjusted risk of severe COVID-19 illness associated with underlying medical conditions and medical complexity. EXPOSURES: Underlying medical conditions and medical complexity (ie, presence of complex or noncomplex chronic disease). MAIN OUTCOMES AND MEASURES: Hospitalization and severe illness when hospitalized (ie, combined outcome of intensive care unit admission, invasive mechanical ventilation, or death). RESULTS: Among 43 465 patients with COVID-19 aged 18 years or younger, the median (interquartile range) age was 12 (4-16) years, 22 943 (52.8%) were female patients, and 12 491 (28.7%) had underlying medical conditions. The most common diagnosed conditions were asthma (4416 [10.2%]), neurodevelopmental disorders (1690 [3.9%]), anxiety and fear-related disorders (1374 [3.2%]), depressive disorders (1209 [2.8%]), and obesity (1071 [2.5%]). The strongest risk factors for hospitalization were type 1 diabetes (adjusted risk ratio [aRR], 4.60; 95% CI, 3.91-5.42) and obesity (aRR, 3.07; 95% CI, 2.66-3.54), and the strongest risk factors for severe COVID-19 illness were type 1 diabetes (aRR, 2.38; 95% CI, 2.06-2.76) and cardiac and circulatory congenital anomalies (aRR, 1.72; 95% CI, 1.48-1.99). Prematurity was a risk factor for severe COVID-19 illness among children younger than 2 years (aRR, 1.83; 95% CI, 1.47-2.29). Chronic and complex chronic disease were risk factors for hospitalization, with aRRs of 2.91 (95% CI, 2.63-3.23) and 7.86 (95% CI, 6.91-8.95), respectively, as well as for severe COVID-19 illness, with aRRs of 1.95 (95% CI, 1.69-2.26) and 2.86 (95% CI, 2.47-3.32), respectively. CONCLUSIONS AND RELEVANCE: This cross-sectional study found a higher risk of severe COVID-19 illness among children with medical complexity and certain underlying conditions, such as type 1 diabetes, cardiac and circulatory congenital anomalies, and obesity. Health care practitioners could consider the potential need for close observation and cautious clinical management of children with these conditions and COVID-19.

This cohort study uses data from the Premier Healthcare Database Special COVID-19 Release to assess the association of demographic and clinical characteristics with severe COVID-19 illness among hospitalized US pediatric patients with COVID-19.

BACKGROUND: Older adults and people from certain racial and ethnic groups are disproportionately represented in coronavirus disease 2019 (COVID-19) hospitalizations and deaths. METHODS: Using data from the Premier Healthcare Database on 181( )813 hospitalized adults diagnosed with COVID-19 during March-September 2020, we applied multivariable log-binomial regression to assess the associations between age and race/ethnicity and COVID-19 clinical severity (intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], and death) and to determine whether the impact of age on clinical severity differs by race/ethnicity. RESULTS: Overall, 84( )497 (47%) patients were admitted to the ICU, 29( )078 (16%) received IMV, and 27( )864 (15%) died in the hospital. Increased age was strongly associated with clinical severity when controlling for underlying medical conditions and other covariates; the strength of this association differed by race/ethnicity. Compared with non-Hispanic White patients, risk of death was lower among non-Hispanic Black patients (adjusted risk ratio, 0.96; 95% CI, 0.92-0.99) and higher among Hispanic/Latino patients (risk ratio [RR], 1.15; 95% CI, 1.09-1.20), non-Hispanic Asian patients (RR, 1.16; 95% CI, 1.09-1.23), and patients of other racial and ethnic groups (RR, 1.13; 95% CI, 1.06-1.21). Risk of ICU admission and risk of IMV were elevated among some racial and ethnic groups. CONCLUSIONS: These results indicate that age is a driver of poor outcomes among hospitalized persons with COVID-19. Additionally, clinical severity may be elevated among patients of some racial and ethnic minority groups. Public health strategies to reduce severe acute respiratory syndrome coronavirus 2 infection rates among older adults and racial and ethnic minorities are essential to reduce poor outcomes.

In light of the disproportionate risk of hospitalization and death attributable to coronavirus disease 2019 (COVID-19) among racial and ethnic minority groups, parental attitudes and concerns regarding school reopening were assessed by race and ethnicity using data from three online CARAVAN omnibus surveys conducted during July 8-12, 2020, by ENGINE Insights.* Survey participants included 858 parents who had children and adolescents in kindergarten through grade 12 (school-aged children) living in their household. Overall, 56.5% of parents strongly or somewhat agreed that school should reopen this fall, with some differences by race/ethnicity: compared with 62.3% of non-Hispanic White (White) parents, 46.0% of non-Hispanic Black or African American (Black) parents (p = 0.007) and 50.2% of Hispanic parents (p = 0.014) agreed that school should reopen this fall. Fewer White parents (62.5%) than Hispanic (79.5%, p = 0.026) and non-Hispanic parents of other racial/ethnic groups (66.9%, p = 0.041) were supportive of a mask mandate for students and staff members. Understanding parental attitudes and concerns is critical to informing communication and messaging around COVID-19 mitigation. Families' concerns also highlight the need for flexible education plans and equitable resource provision so that youth education is not compromised.

Coronavirus disease 2019 (COVID-19) is a complex clinical illness with potential complications that might require ongoing clinical care (1-3). Few studies have investigated discharge patterns and hospital readmissions among large groups of patients after an initial COVID-19 hospitalization (4-7). Using electronic health record and administrative data from the Premier Healthcare Database,* CDC assessed patterns of hospital discharge, readmission, and demographic and clinical characteristics associated with hospital readmission after a patient's initial COVID-19 hospitalization (index hospitalization). Among 126,137 unique patients with an index COVID-19 admission during March-July 2020, 15% died during the index hospitalization. Among the 106,543 (85%) surviving patients, 9% (9,504) were readmitted to the same hospital within 2 months of discharge through August 2020. More than a single readmission occurred among 1.6% of patients discharged after the index hospitalization. Readmissions occurred more often among patients discharged to a skilled nursing facility (SNF) (15%) or those needing home health care (12%) than among patients discharged to home or self-care (7%). The odds of hospital readmission increased with age among persons aged ≥65 years, presence of certain chronic conditions, hospitalization within the 3 months preceding the index hospitalization, and if discharge from the index hospitalization was to a SNF or to home with health care assistance. These results support recent analyses that found chronic conditions to be significantly associated with hospital readmission (6,7) and could be explained by the complications of underlying conditions in the presence of COVID-19 (8), COVID-19 sequelae (3), or indirect effects of the COVID-19 pandemic (9). Understanding the frequency of, and risk factors for, readmission can inform clinical practice, discharge disposition decisions, and public health priorities such as health care planning to ensure availability of resources needed for acute and follow-up care of COVID-19 patients. With the recent increases in cases nationwide, hospital planning can account for these increasing numbers along with the potential for at least 9% of patients to be readmitted, requiring additional beds and resources.

Approximately 56 million school-aged children (aged 5-17 years) resumed education in the United States in fall 2020.* Analysis of demographic characteristics, underlying conditions, clinical outcomes, and trends in weekly coronavirus disease 2019 (COVID-19) incidence during March 1-September 19, 2020 among 277,285 laboratory-confirmed cases in school-aged children in the United States might inform decisions about in-person learning and the timing and scaling of community mitigation measures. During May-September 2020, average weekly incidence (cases per 100,000 children) among adolescents aged 12-17 years (37.4) was approximately twice that of children aged 5-11 years (19.0). In addition, among school-aged children, COVID-19 indicators peaked during July 2020: weekly percentage of positive SARS-CoV-2 test results increased from 10% on May 31 to 14% on July 5; SARS-CoV-2 test volume increased from 100,081 tests on May 31 to 322,227 on July 12, and COVID-19 incidence increased from 13.8 per 100,000 on May 31 to 37.9 on July 19. During July and August, test volume and incidence decreased then plateaued; incidence decreased further during early September and might be increasing. Percentage of positive test results decreased during August and plateaued during September. Underlying conditions were more common among school-aged children with severe outcomes related to COVID-19: among school-aged children who were hospitalized, admitted to an intensive care unit (ICU), or who died, 16%, 27%, and 28%, respectively, had at least one underlying medical condition. Schools and communities can implement multiple, concurrent mitigation strategies and tailor communications to promote mitigation strategies to prevent COVID-19 spread. These results can provide a baseline for monitoring trends and evaluating mitigation strategies.

Undetected infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) contributes to transmission in nursing homes, settings where large outbreaks with high resident mortality have occurred (1,2). Facility-wide testing of residents and health care personnel (HCP) can identify asymptomatic and presymptomatic infections and facilitate infection prevention and control interventions (3-5). Seven state or local health departments conducted initial facility-wide testing of residents and staff members in 288 nursing homes during March 24-June 14, 2020. Two of the seven health departments conducted testing in 195 nursing homes as part of facility-wide testing all nursing homes in their state, which were in low-incidence areas (i.e., the median preceding 14-day cumulative incidence in the surrounding county for each jurisdiction was 19 and 38 cases per 100,000 persons); 125 of the 195 nursing homes had not reported any COVID-19 cases before the testing. Ninety-five of 22,977 (0.4%) persons tested in 29 (23%) of these 125 facilities had positive SARS-CoV-2 test results. The other five health departments targeted facility-wide testing to 93 nursing homes, where 13,443 persons were tested, and 1,619 (12%) had positive SARS-CoV-2 test results. In regression analyses among 88 of these nursing homes with a documented case before facility-wide testing occurred, each additional day between identification of the first case and completion of facility-wide testing was associated with identification of 1.3 additional cases. Among 62 facilities that could differentiate results by resident and HCP status, an estimated 1.3 HCP cases were identified for every three resident cases. Performing facility-wide testing immediately after identification of a case commonly identifies additional unrecognized cases and, therefore, might maximize the benefits of infection prevention and control interventions. In contrast, facility-wide testing in low-incidence areas without a case has a lower proportion of test positivity; strategies are needed to further optimize testing in these settings.

INTRODUCTION: Caring for an Ebola patient is a known risk factor for disease transmission. In Sierra Leone during the outbreak in 2014/2015, isolation of patients in specialised facilities was not always immediately available and caring for a relative at home was sometimes the only alternative. This study sought to assess population-level protective caregiving intentions, to understand how families cared for their sick and to explore perceived barriers and facilitators influencing caregiving behaviours. METHODS: Data from a nationwide household survey conducted in December 2014 were used to assess intended protective behaviours if caring for a family member with suspected Ebola. Their association with socio-demographic variables, Ebola-specific knowledge and risk perception was analysed using multilevel logistic regression. To put the results into context, semi-structured interviews with caregivers were conducted in Freetown. RESULTS: Ebola-specific knowledge was positively associated with the intention to avoid touching a sick person and their bodily fluids (adjusted OR (AOR) 1.29; 95% CI 1.01 to 1.54) and the intention to take multiple protective measures (AOR 1.38; 95% CI 1.16 to 1.63). Compared with residing in the mostly urban Western Area, respondents from the initial epicentre of the outbreak (Eastern Province) had increased odds to avoid touching a sick person or their body fluids (AOR 4.74; 95% CI 2.55 to 8.81) and to take more than one protective measure (AOR 2.94; 95% CI 1.37 to 6.34). However, interviews revealed that caregivers, who were mostly aware of the risk of transmission and general protective measures, felt constrained by different contextual factors. Withholding care was not seen as an option and there was a perceived lack of practical advice. CONCLUSIONS: Ebola outbreak responses need to take the sociocultural reality of caregiving and the availability of resources into account, offering adapted and acceptable practical advice. The necessity to care for a loved one when no alternatives exist should not be underestimated.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Importance: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. Objective: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. Evidence Review: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. Findings: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. Conclusion and Relevance: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

BACKGROUND: Few autism spectrum disorder (ASD) studies have estimated non-medical costs for treatment or addressed possible differences in provision of services across gender, race-ethnic, age or demographic or expenditure categories, especially among adults. METHODS: The California Department of Developmental Services (CDDS) provides services to residents with developmental disabilities. CDDS provided aggregate data on primarily non-medical spending for fiscal year 2012-2013 for persons with ASD with or without intellectual disability (ID) (main sample, n = 42,274), and two sub-samples: ASD only (n = 30,164), and ASD+ID (n = 12,110). Demographic variables included sex, age and race-ethnicity. Spending categories included Employment Support, Community Care Facilities, Day Care, Transportation, and in-home and out-of-home Respite. RESULTS: Per-person spending for males and females were approximately the same: $10,488 and $10,791 for males and females for ages 3-17 and $26,491 and $26,627 for ages 18+. Among race/ethnicity categories, the ranking from highest to lowest among ages 3-17 was white non-Hispanics ($11,480), Asian non-Hispanics ($11,036), "Others" ($11,031), Hispanics ($9,571), and African-American non-Hispanics ($9,482). For ages 18+, the ranking was whites ($31,008), African-Americans ($26,831), "Others" ($25,395), Asians ($22,993), and Hispanics ($18,083). The ASD+ID sub-sample exerted disproportionate influence on findings from the main sample for persons 18+. Combining all ages, the top two expenditure categories for per-person spending were Community Care Facilities ($43,867) and Day Care ($11,244). For most adult age groups, the percentage of recipients participating were highest for Day Care (44.9% - 62.4%) and Transportation (38.6% - 50.9%). Per-person spending for Day Care, Transportation, and Employment Support was relatively low for children but relatively high for adults. CONCLUSION: White non-Hispanics received the highest per-person spending and Hispanics among the least. Amounts within spending categories varied considerably across age groups. Our estimates may be useful as baseline measures for stakeholders preparing for increasing ASD prevalence, especially among adults.

BACKGROUND: For the years 1992-2010 musculoskeletal disorders (MSDs) accounted for 29-35% of all occupational injuries and illnesses involving days away from work in the United States (US) (AFL-CIO, 2012). According to the American Federation of Labor and Congress of Industrial Organizations (AFL-CIO) 2012 report 'Death on the Job', for the years 1992 through 2010 the percent of cases involving MSDs in private industry were highest in 2000 (35%) and lowest in 2007 (29%). In 2010, the median number of days away from work for MSDs was 11 compared to 8 for all occupational injury cases involving days away from work; the median number of days away from work for Carpal Tunnel Syndrome (CTS) was 25, more than three times as high as for all other BLS injuries involving days away from work (BLS, 2011). This study estimated the costs of work related MSDs, and given that the number of days lost due to CTS is very high, it also estimated the costs of CTS separately in the United States (US) for the years 2003 through 2007. METHODS: The costs of work related MSDs and CTS in the US were estimated using the cost-of-illness, human capital method (Leigh etal., 2000), using some of the costs from the literature. This method decomposes costs into direct and indirect categories. Estimates of total cost of MSDs and CTS were obtained from the product of average costs of MSDs and CTS and the number of MSDs and CTS. The number of MSDs and CTS were obtained from BLS data. RESULTS: The number of reported work-related MSDs declined from 435,180 in 2003 to 335,390 in 2007 and the reported number of CTS also declined from 22,110 in 2003 to 11,920 in 2007. The direct costs of MSDs and CTS were respectively $1.5 billion and $0.1 billion for the year 2007. The indirect costs were $1.1 billion and $0.1 billion for MSDs and CTS respectively for the year 2007. DISCUSSION: This study found that the total costs of work-related MSDs and CTS declined during the period 2003 through 2007 but the average costs per case went up signifying that medical costs and other associated costs increased during this period. RELEVANCE TO INDUSTRY: The costs of MSDs are important to the industries too as a significant part of these costs are borne by the employers. Industries with higher prevalence of MSDs are affected more in terms of lost productivities due to the employees' days away from work because of MSDs. In cases of MSDs causing permanent disabilities, new hiring and training costs are also a part of the losses experienced by the employers.

The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health (NIH), has developed a Standard Reference Material (SRM) to support technology development in metabolomics research. SRM 1950 Metabolites in Human Plasma is intended to have metabolite concentrations that are representative of those found in adult human plasma. The plasma used in the preparation of SRM 1950 was collected from both male and female donors, and donor ethnicity targets were selected based upon the ethnic makeup of the U.S. population. Metabolomics research is diverse in terms of both instrumentation and scientific goals. This SRM was designed to apply broadly to the field, not toward specific applications. Therefore, concentrations of approximately 100 analytes, including amino acids, fatty acids, trace elements, vitamins, hormones, selenoproteins, clinical markers, and perfluorinated compounds (PFCs), were determined. Value assignment measurements were performed by NIST and the Centers for Disease Control and Prevention (CDC). SRM 1950 is the first reference material developed specifically for metabolomics research.

BACKGROUND: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS: Global DALYs remained stable from 1990 (2.503 billion) to 2010 (2.490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). METHODS: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. FINDINGS: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0.37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. INTERPRETATION: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS: In 2010, the three leading risk factors for global disease burden were high blood pressure (7.0% [95% uncertainty interval 6.2-7.7] of global DALYs), tobacco smoking including second-hand smoke (6.3% [5.5-7.0]), and alcohol use (5.5% [5.0-5.9]). In 1990, the leading risks were childhood underweight (7.9% [6.8-9.4]), household air pollution from solid fuels (HAP; 7.0% [5.6-8.3]), and tobacco smoking including second-hand smoke (6.1% [5.4-6.8]). Dietary risk factors and physical inactivity collectively accounted for 10.0% (95% UI 9.2-10.8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0.9% (0.4-1.6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. FUNDING: Bill & Melinda Gates Foundation.

Modified vaccinia virus Ankara (MVA) is a safe, attenuated orthopoxvirus that is being developed as a vaccine vector but has demonstrated limited immunogenicity in several early-phase clinical trials. Our objective was to rationally improve the immunogenicity of MVA-based HIV/AIDS vaccines via the targeted deletion of specific poxvirus immune-modulatory genes. Vaccines expressing codon-optimized HIV subtype C consensus Env and Gag antigens were generated from MVA vector backbones that (i) harbor simultaneous deletions of four viral immune-modulatory genes, encoding an interleukin-18 (IL-18) binding protein, an IL-1beta receptor, a dominant negative Toll/IL-1 signaling adapter, and CC-chemokine binding protein (MVADelta4-HIV); (ii) harbor a deletion of an additional (fifth) viral gene, encoding uracil-DNA glycosylase (MVADelta5-HIV); or (iii) represent the parental MVA backbone as a control (MVA-HIV). We performed head-to-head comparisons of the cellular and humoral immune responses that were elicited by these vectors during homologous prime-boost immunization regimens utilizing either high-dose (2 x 10(8) PFU) or low-dose (1 x 10(7) PFU) intramuscular immunization of rhesus macaques. At all time points, a majority of the HIV-specific T cell responses, elicited by all vectors, were directed against Env, rather than Gag, determinants, as previously observed with other vector systems. Both modified vectors elicited up to 6-fold-higher frequencies of HIV-specific CD8 and CD4 T cell responses and up to 25-fold-higher titers of Env (gp120)-specific binding (nonneutralizing) antibody responses that were relatively transient in nature. While the correlates of protection against HIV infection remain incompletely defined, our results indicate that the rational deletion of specific genes from MVA vectors can positively alter their cellular and humoral immunogenicity profiles in nonhuman primates.

The average costs of Musculoskeletal Disorder (MSD) and odds ratios for filing medical claims related to MSD were examined. The medical claims were identified by ICD 9 codes for four US Census regions within retail trade. Large private firms' medical claims data from Thomson Reuters Inc. MarketScan databases for the years 2003 through 2006 were used. Average costs were highest for claims related to lumbar region (ICD 9 Code: 724.02) and number of claims were largest for low back syndrome (ICD 9 Code: 724.2). Whereas the odds of filing an MSD claim did not vary greatly over time, average costs declined over time. The odds of filing claims rose with age and were higher for females and southerners than men and non-southerners. Total estimated national medical costs for MSDs within retail trade were $389 million (2007 USD).