Christina Fitzmaurice

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013

BACKGROUND With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS We estimated mortality using natural history models for acute hepatitis infections and GBDs cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING Bill & Melinda Gates Foundation.

Trends and Patterns of Disparities in Cancer Mortality Among US Counties, 1980-2014.

Introduction Cancer is a leading cause of morbidity and mortality in the United States and results in a high economic burden. Objective To estimate age-standardized mortality rates by US county from 29 cancers. Design and Setting Deidentified death records from the National Center for Health Statistics (NCHS) and population counts from the Census Bureau, the NCHS, and the Human Mortality Database from 1980 to 2014 were used. Validated small area estimation models were used to estimate county-level mortality rates from 29 cancers: lip and oral cavity; nasopharynx; other pharynx; esophageal; stomach; colon and rectum; liver; gallbladder and biliary; pancreatic; larynx; tracheal, bronchus, and lung; malignant skin melanoma; nonmelanoma skin cancer; breast; cervical; uterine; ovarian; prostate; testicular; kidney; bladder; brain and nervous system; thyroid; mesothelioma; Hodgkin lymphoma; non-Hodgkin lymphoma; multiple myeloma; leukemia; and all other cancers combined. Exposure County of residence. Main Outcomes and Measures Age-standardized cancer mortality rates by county, year, sex, and cancer type. Results A total of 19 511 910 cancer deaths were recorded in the United States between 1980 and 2014, including 5 656 423 due to tracheal, bronchus, and lung cancer; 2 484 476 due to colon and rectum cancer; 1 573 593 due to breast cancer; 1 077 030 due to prostate cancer; 1 157 878 due to pancreatic cancer; 209 314 due to uterine cancer; 421 628 due to kidney cancer; 487 518 due to liver cancer; 13 927 due to testicular cancer; and 829 396 due to non-Hodgkin lymphoma. Cancer mortality decreased by 20.1% (95% uncertainty interval [UI], 18.2%-21.4%) between 1980 and 2014, from 240.2 (95% UI, 235.8-244.1) to 192.0 (95% UI, 188.6-197.7) deaths per 100 000 population. There were large differences in the mortality rate among counties throughout the period: in 1980, cancer mortality ranged from 130.6 (95% UI, 114.7-146.0) per 100 000 population in Summit County, Colorado, to 386.9 (95% UI, 330.5-450.7) in North Slope Borough, Alaska, and in 2014 from 70.7 (95% UI, 63.2-79.0) in Summit County, Colorado, to 503.1 (95% UI, 464.9-545.4) in Union County, Florida. For many cancers, there were distinct clusters of counties with especially high mortality. The location of these clusters varied by type of cancer and were spread in different regions of the United States. Clusters of breast cancer were present in the southern belt and along the Mississippi River, while liver cancer was high along the Texas-Mexico border, and clusters of kidney cancer were observed in North and South Dakota and counties in West Virginia, Ohio, Indiana, Louisiana, Oklahoma, Texas, Alaska, and Illinois. Conclusions and Relevance Cancer mortality declined overall in the United States between 1980 and 2014. Over this same period, there were important changes in trends, patterns, and differences in cancer mortality among US counties. These patterns may inform further research into improving prevention and treatment.

Global Burden of Urologic Cancers, 1990–2013

CONTEXT Kidney, prostate, and bladder cancers increase with age and are influenced partly by modifiable risk factors. Urological cancer rates may increase substantially amid a growing, aging population. OBJECTIVE To describe kidney, bladder, and prostate cancer incidence, mortality, and risk factor-attributable bladder and kidney cancer deaths between 1990 and 2013, by age, sex, and development status. EVIDENCE ACQUISITION Cancer mortality data were derived from global vital registries. Incidence data from cancer registries were transformed to mortality estimates using separately estimated mortality incidence ratios. These sources served as input data for an ensemble modeling approach to estimate bladder, prostate, and kidney cancer mortality. Cause-specific mortality estimates were transformed into incidence estimates using mortality incidence ratios. EVIDENCE SYNTHESIS In 2013, 2.1 million kidney, bladder, and prostate cancers cases occurred worldwide, increasing 2.5-fold since 1990. Mortality increased 1.6-fold between 1990 and 2013. Eight-two percent of new cases in 2013 occurred in individuals aged 60 yr and older. Men from developed countries had the highest age-standardized death rates among all three cancers. Smoking-attributable kidney cancer deaths decreased while obesity-related deaths rose, most prominently in women from developing countries. Smoking-related bladder cancer deaths increased among women from developed countries and decreased among men. CONCLUSIONS Urologic cancer burden has increased globally amid population growth and aging. High income countries face the highest incidence and death rates; however, obesity-attributed kidney cancer deaths are increasing in developing countries. Efforts to expand the global oncologic workforce and reduce preventable factors may lessen cancer disparities in developing countries. PATIENT SUMMARY We describe the impact of population growth, aging, and lifestyle factors such as smoking and obesity, on kidney, bladder, and prostate cancer rates worldwide. More new cancer cases and deaths occur in developed countries compared with developing countries. In addition to preventive efforts, healthcare systems must emphasize training of a urologic oncology workforce.

The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015

Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.

The global burden of melanoma: Results from the Global Burden of Disease Study 2015

Despite recent improvements in prevention, diagnosis and treatment, vast differences in melanoma burden still exist between populations. Comparative data can highlight these differences and lead to focused efforts to reduce the burden of melanoma.

Estimation of the global burden of mesothelioma deaths from incomplete national mortality data

Background Mesothelioma is increasingly recognised as a global health issue and the assessment of its global burden is warranted. Objectives To descriptively analyse national mortality data and to use reported and estimated data to calculate the global burden of mesothelioma deaths. Methods For the study period of 1994 to 2014, we grouped 230 countries into 59 countries with quality mesothelioma mortality data suitable to be used for reference rates, 45 countries with poor quality data and 126 countries with no data, based on the availability of data in the WHO Mortality Database. To estimate global deaths, we extrapolated the gender-specific and age-specific mortality rates of the countries with quality data to all other countries. Results The global numbers and rates of mesothelioma deaths have increased over time. The 59 countries with quality data recorded 15 011 mesothelioma deaths per year over the 3 most recent years with available data (equivalent to 9.9 deaths per million per year). From these reference data, we extrapolated the global mesothelioma deaths to be 38 400 per year, based on extrapolations for asbestos use. Conclusions Although the validity of our extrapolation method depends on the adequate identification of quality mesothelioma data and appropriate adjustment for other variables, our estimates can be updated, refined and verified because they are based on commonly accessible data and are derived using a straightforward algorithm. Our estimates are within the range of previously reported values but higher than the most recently reported values.

Population health and regional variations of disease burden in Japan, 1990–2015: a systematic subnational analysis for the Global Burden of Disease Study 2015

Summary Background Japan has entered the era of super-ageing and advanced health transition, which is increasingly putting pressure on the sustainability of its health system. The level and pace of this health transition might vary across regions within Japan and concern is growing about increasing regional variations in disease burden. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides a comprehensive, comparable framework. We used data from GBD 2015 with the aim to quantify the burden of disease and injuries, and to attribute risk factors in Japan at a subnational, prefecture-level. Methods We used data from GBD 2015 for 315 causes and 79 risk factors of death, disease, and injury incidence and prevalence to measure the burden of diseases and injuries in Japan and in the 47 Japanese prefectures from 1990 to 2015. We extracted data from GBD 2015 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy, and healthy life expectancy (HALE) in Japan and its 47 prefectures. We split extracted data by prefecture and applied GBD methods to generate estimates of burden, and attributable burden due to known risk factors. We examined the prefecture-level relationships of common health system inputs (eg, health expenditure and workforces) to the GBD outputs in 2015 to address underlying determinants of regional health variations. Findings Life expectancy at birth in Japan increased by 4·2 years from 79·0 years (95% uncertainty interval [UI] 79·0 to 79·0) to 83·2 years (83·1 to 83·2) between 1990 and 2015. However, the gaps between prefectures with the lowest and highest life expectancies and HALE have widened, from 2·5 to 3·1 years and from 2·3 to 2·7 years, respectively, from 1990 to 2015. Although overall age-standardised death rates decreased by 29·0% (28·7 to 29·3) from 1990 to 2015, the rates of mortality decline in this period substantially varied across the prefectures, ranging from −32·4% (−34·8 to −30·0) to −22·0% (−20·4 to −20·1). During the same time period, the rate of age-standardised DALYs was reduced overall by 19·8% (17·9 to 22·0). The reduction in rates of age-standardised YLDs was very small by 3·5% (2·6 to 4·3). The pace of reduction in mortality and DALYs in many leading causes has largely levelled off since 2005. Known risk factors accounted for 34·5% (32·4 to 36·9) of DALYs; the two leading behavioural risk factors were unhealthy diets and tobacco smoking in 2015. The common health system inputs were not associated with age-standardised death and DALY rates in 2015. Interpretation Japan has been successful overall in reducing mortality and disability from most major diseases. However, progress has slowed down and health variations between prefectures is growing. In view of the limited association between the prefecture-level health system inputs and health outcomes, the potential sources of regional variations, including subnational health system performance, urgently need assessment. Funding Bill & Melinda Gates Foundation, Japan Ministry of Education, Science, Sports and Culture, Japan Ministry of Health, Labour and Welfare, AXA CR Fixed Income Fund and AXA Research Fund.

Metastatic Pancreatic Small-Cell Carcinoma Presenting As Acute Pancreatitis

A 77-year-old woman presented with nausea and acute onset of severe epigastric pain with radiation to her back. Physical examination revealed epigastric tenderness without rebound or guarding. Laboratory analysis showed lipase at 1,970 U/L (reference range, 23 to 300 U/L) and amylase at 220 U/L (reference range, 30 to 110 U/L) with normal liver chemistries, including bilirubin at 0.3 mg/dL (reference range, 0.2 to 1.3 mg/dL), alkaline phosphatase at 100 U/L (reference range, 38 to 136 U/L), ALT at 22 U/L (reference range, 9 to 72 U/L), and AST at 35 U/L (reference range, 14 to 59 U/L). She was diagnosed with acute pancreatitis, and gastroenterology consultation was obtained for further evaluation and management. A right upper quadrant ultrasound demonstrated a 2.3 cm 1.9 cm area of hypoechogenicity in the pancreatic head suggestive of a primary pancreatic neoplasm. An abdominal computed tomography (CT) scan confirmed an ill-defined 2.2-cm low-attenuation mass in the pancreatic head. Also seen were bilateral adrenal masses measuring up to 5 cm in size. Her cancer antigen 19-9 (CA 19-9) was 26 U/L (reference range, 37 U/L). The liver appeared normal without evidence of metastatic disease. An endoscopic ultrasound with fine-needle aspiration of the pancreatic head (Fig 1) and adrenal (Fig 2) masses revealed small-cell carcinoma (Fig 3). Immunohistochemistry was performed, and thyroid transcription factor 1, synaptophysin, and chromogranin were positive, confirming the diagnosis. The patient did not have any respiratory complaints but was a long-time smoker with a 55-pack-year history. A chest CT demonstrated enlarged axillary, mediastinal, and hilar lymph nodes as well as a solitary 8-mm sclerotic lesion in the midthoracic spine but was notably negative for pulmonary nodules or masses. Further staging work-up included a brain CT scan that showed several small enhancing masses consistent with diffuse brain metastasis. Given the extent of her disease she elected not to undergo chemotherapy or radiation treatment and succumbed to her disease within 2 months of her initial diagnosis. Small-cell carcinoma of the pancreas (SCCP) is a rare and aggressive tumor with a high metastasis rate. Only 1% of all primary pancreatic neoplasms are small-cell carcinomas and 4% of all small-cell carcinomas have an extrapulmonary origin. In a review of all published cases of SCCP, 91% were metastatic at the time of initial diagnosis. The most common sites for metastases are peripancreatic lymph nodes, liver, lungs, bone marrow, bone, colon, and adrenal gland. Bilateral adrenal metastases from a primary small-cell carcinoma of the pancreas, as described in our patient, is exceedingly rare

Incidence, prevalence, mortality, disability-adjusted life years and risk factors of cancer in Australia and comparison with OECD countries, 1990–2015: findings from the Global Burden of Disease Study 2015

BACKGROUND Comparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden - incidence, prevalence, mortality, disability-adjusted life years (DALYs) - and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD). METHODS The general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors. RESULTS In 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908-217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061-49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2-29.8) of total deaths and 17.0% (95% UI: 15.0-19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1-37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24th based on ASIR and ASDR, respectively. CONCLUSION The incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge.

Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016

Introduction Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of MM is needed to help direct health policy, resource allocation, research, and patient care. Objective To describe the burden of MM and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016. Design and Setting We report incidence, mortality, and disability-adjusted life-year (DALY) estimates from the Global Burden of Disease 2016 study. Data sources include vital registration system, cancer registry, drug availability, and survey data for stem cell transplant rates. We analyzed the contribution of aging, population growth, and changes in incidence rates to the overall change in incident cases from 1990 to 2016 globally, by sociodemographic index (SDI) and by region. We collected data on approval of lenalidomide and bortezomib worldwide. Main Outcomes and Measures Multiple myeloma mortality; incidence; years lived with disabilities; years of life lost; and DALYs by age, sex, country, and year. Results Worldwide in 2016 there were 138 509 (95% uncertainty interval [UI], 121 000-155 480) incident cases of MM with an age-standardized incidence rate (ASIR) of 2.1 per 100 000 persons (95% UI, 1.8-2.3). Incident cases from 1990 to 2016 increased by 126% globally and by 106% to 192% for all SDI quintiles. The 3 world regions with the highest ASIR of MM were Australasia, North America, and Western Europe. Multiple myeloma caused 2.1 million (95% UI, 1.9-2.3 million) DALYs globally in 2016. Stem cell transplantation is routinely available in higher-income countries but is lacking in sub-Saharan Africa and parts of the Middle East. In 2016, lenalidomide and bortezomib had been approved in 73 and 103 countries, respectively. Conclusions and Relevance Incidence of MM is highly variable among countries but has increased uniformly since 1990, with the largest increase in middle and low-middle SDI countries. Access to effective care is very limited in many countries of low socioeconomic development, particularly in sub-Saharan Africa. Global health policy priorities for MM are to improve diagnostic and treatment capacity in low and middle income countries and to ensure affordability of effective medications for every patient. Research priorities are to elucidate underlying etiological factors explaining the heterogeneity in myeloma incidence.