Background Worldwide, both the incidence and death rates of pancreatic cancer are increasing. Evaluation of pancreatic cancer burden and its global, regional, and national patterns is crucial to policy making and better resource allocation for controlling pancreatic cancer risk factors, developing early detection methods, and providing faster and more effective treatments. Methods Vital registration, vital registration sample, and cancer registry data were used to generate mortality, incidence, and disability-adjusted life-years (DALYs) estimates. We used the comparative risk assessment framework to estimate the proportion of deaths attributable to risk factors for pancreatic cancer: smoking, high fasting plasma glucose, and high body-mass index. All of the estimates were reported as counts and age-standardised rates per 100 000 person-years. 95% uncertainty intervals (UIs) were reported for all estimates. Findings In 2017, there were 448 000 (95% UI 439 000-456 000) incident cases of pancreatic cancer globally, of which 232 000 (210 000-221 000; 51•9%) were in males. The age-standardised incidence rate was 5•0 (4•9-5•1) per 100 000 person-years in 1990 and increased to 5•7 (5•6-5•8) per 100 000 person-years in 2017. There was a 2•3 times increase in number of deaths for both sexes from 196 000 (193 000-200 000) in 1990 to 441 000 (433 000-449 000) in 2017. There was a 2•1 times increase in DALYs due to pancreatic cancer, increasing from 4•4 million (4•3-4•5) in 1990 to 9•1 million (8•9-9•3) in 2017. The age-standardised death rate of pancreatic cancer was highest in the highincome super-region across all years from 1990 to 2017. In 2017, the highest age-standardised death rates were observed in Greenland (17•4 [15•8-19•0] per 100 000 person-years) and Uruguay (12•1 [10•9-13•5] per 100 000 personyears). These countries also had the highest age-standardised death rates in 1990. Bangladesh (1•9 [1•5-2•3] per 100 000 person-years) had the lowest rate in 2017, and São Tomé and Príncipe (1•3 [1•1-1•5] per 100 000 personyears) had the lowest rate in 1990. The numbers of incident cases and deaths peaked at the ages of 65-69 years for males and at 75-79 years for females. Age-standardised pancreatic cancer deaths worldwide were primarily attributable to smoking (21•1% [18•8-23•7]), high fasting plasma glucose (8•9% [2•1-19•4]), and high body-mass index (6•2% [2•5-11•4]) in 2017. Interpretation Globally, the number of deaths, incident cases, and DALYs caused by pancreatic cancer has more than doubled from 1990 to 2017. The increase in incidence of pancreatic cancer is likely to continue as the population ages. Prevention strategies should focus on modifiable risk factors. Development of screening programmes for early detection and more effective treatment strategies for pancreatic cancer are needed. Funding Bill & Melinda Gates Foundation.

Background Data about the global, regional, and country-specific variations in the levels and trends of colorectal cancer are required to understand the impact of this disease and the trends in its burden to help policy makers allocate resources. Here we provide a status report on the incidence, mortality, and disability caused by colorectal cancer in 195 countries and territories between 1990 and 2017. Methods Vital registration, sample vital registration, verbal autopsy, and cancer registry data were used to generate incidence, death, and disability-adjusted life-year (DALY) estimates of colorectal cancer at the global, regional, and national levels. We also determined the association between development levels and colorectal cancer age-standardised DALY rates, and calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. All of the estimates are reported as counts and age-standardised rates per 100 000 person-years, with some estimates also presented by sex and 5-year age groups. Findings In 2017, there were 1•8 million (95% UI 1•8-1•9) incident cases of colorectal cancer globally, with an agestandardised incidence rate of 23•2 (22•7-23•7) per 100 000 person-years that increased by 9•5% (4•5-13•5) between 1990 and 2017. Globally, colorectal cancer accounted for 896 000 (876 300-915 700) deaths in 2017, with an agestandardised death rate of 11•5 (11•3-11•8) per 100 000 person-years, which decreased between 1990 and 2017 (-13•5% [-18•4 to-10•0]). Colorectal cancer was also responsible for 19•0 million (18•5-19•5) DALYs globally in 2017, with an age-standardised rate of 235•7 (229•7-242•0) DALYs per 100 000 person-years, which decreased between 1990 and 2017 (-14•5% [-20•4 to-10•3]). Slovakia, the Netherlands, and New Zealand had the highest age-standardised incidence rates in 2017. Greenland, Hungary, and Slovakia had the highest age-standardised death rates in 2017. Numbers of incident cases and deaths were higher among males than females up to the ages of 80-84 years, with the highest rates observed in the oldest age group (≥95 years) for both sexes in 2017. There was a non-linear association between the Socio-demographic Index and the Healthcare Access and Quality Index and age-standardised DALY rates. In 2017, the three largest contributors to DALYs at the global level, for both sexes, were diet low in calcium (20•5% [12•9-28•9]), alcohol use (15•2% [12•1-18•3]), and diet low in milk (14•3% [5•1-24•8]). Interpretation There is substantial global variation in the burden of colorectal cancer. Although the overall colorectal cancer age-standardised death rate has been decreasing at the global level, the increasing age-standardised incidence rate in most countries poses a major public health challenge across the world. The results of this study could be useful for policy makers to carry out cost-effective interventions and to reduce exposure to modifiable risk factors, particularly in countries with high incidence or increasing burden. Funding Bill & Melinda Gates Found...

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Background: The purpose of the present study is to investigate the association of nonal-coholic fatty liver disease (NAFLD) with the doppler waveform pattern of hepatic veins and portal vein doppler indices. Objectives: This assay may be useful in evaluating the natural course of NAFLD and monitor treatment efficacy on follow-up. Patients and Methods: This case control study was performed in 31 patients with NAFLD and 31 normal healthy adults who served as the control group. The patients presented with elevated liver enzymes levels (ALT/AST) and hyperechogenic livers in the B-mode ultrasonography examination. Eleven patients had a liver biopsy. After an 8-hour fast, B-mode and duplex doppler ultrasonography were performed, and the waveform patterns of the right hepatic vein, portal vein diameter, grade of fatty liver, portal vein pulsatility index (VPI), and mean flow velocity (MFV) were measured. Results: VPI and MFV values were 0.42 ± 0.92 and 17.27 ± 5.34 cm/second, respectively, in the control group and 0.25 ± 0.50 and 12.82 ± 4.32 cm/second in patients with NAFLD (P < 0.01). The frequency of abnormal hepatic vein doppler waveform patterns (biphasic or monophasic) was significantly higher in patients with NAFLD (55.2%) versus control subjects (3.2%) (P < 0.001). There was no correlation between the degree of fat infiltration and VPI (P = 0.714), MFV (P = 0.911), or hepatic vein waveform pattern (P = 0.197). We found no correlation between liver enzyme levels and MFV or VPI. However, the rate of abnormal hepatic vein was higher in patients with enzyme levels that exceeded twice the normal value (P = 0.05). Conclusions: Patients with NAFLD have a high rate of abnormal hepatic vein doppler waveform patterns, and decreased VPI and MFV are suggestive of reduced vascular compliance in the liver. Elevated liver enzymes levels do not influence VPI or MFV, but patients with abnormal enzymes have higher rates of abnormal hepatic vein doppler waveform patterns.

Background and Aim Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir‐containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir‐based treatment in patients with severe renal impairment, including those on hemodialysis. Method We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m2 from 13 centers in Iran. Patients were treated for 12 weeks with a single daily pill containing 400‐mg sofosbuvir and 60‐mg daclatasvir. Patients with cirrhosis were treated for 24 weeks. Response to treatment was evaluated 12 weeks after end of treatment (sustained viral response [SVR]). http://ClinicalTrials.gov identifier: NCT03063879. Results A total of 103 patients were enrolled from 13 centers. Seventy‐five patients were on hemodialysis. Thirty‐nine had cirrhosis and eight were decompensated. Fifty‐three were Genotype 1, and 27 Genotype 3. Twenty‐seven patients had history of previous failed interferon‐based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow‐up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed. Conclusions The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.

Background The combination of sofosbuvir and daclatasvir is a potent, pangenotypic regimen suitable for mass-scale hepatitis C treatment, especially in resource-limited countries where newer, expensive combinations are not available. This combination has been widely tested on genotype 4. However, Phase III trials of this combination in other genotypes have been cost prohibitive. With the introduction of generic, low-cost sofosbuvir and daclatasvir, large-scale studies in resource-limited countries are now possible. Methods Sofosbuvir at 400 mg and daclatasvir at 60 mg were coformulated into a fixed-dose combination (FDC) tablet (Sovodak, Rojan Pharma, Tehran, Iran). Patients from 46 centers were dosed for 12 or 24 weeks with or without ribavirin, in line with existing guidelines. Responses to treatment were evaluated 12 weeks after the end of treatment (for a sustained virological response at Week 12; SVR12). Results There were 1361 patients recruited. Overall, the patients were 21% female, with a mean age of 50 years; 39% were cirrhotic; 22% were treatment-experienced; 47% were genotype 1, 41% were genotype 3, and 2% were other genotypes. The genotype was not known in 10% of the patients. The intention-to-treat and per-protocol SVR12 rates were 94.7% and 98.8%, respectively. The safety profile was unremarkable, treatment was well tolerated, and compliance with the single-tablet regimen was excellent. Conclusions The treatment with FDC of sofosbuvir and daclatasvir achieved high SVR12 rates, equivalent to those seen in Phase III trials of other pangenotypic options, and has been conducted at a similar scale in a representative, real-world population at a cost of under $100 per patient, which makes this combination suitable for elimination protocols in resource-limited countries. Clinical Trials Registration NCT03200184.