SummaryDespite the advent of safe and highly effective COVID-19 vaccines1–4, pervasive inequities in global distribution persist5. In response, multinational partners have proposed programs to allocate vaccines to low- and middle-income countries (LMICs)6. Yet, there remains a substantial funding gap for such programs7. Further, the optimal vaccine supply is unknown and the cost-effectiveness of investments into global vaccination programs has not been described. We used a validated COVID-19 simulation model8 to project the health benefits and costs of reaching 20%-70% vaccine coverage in 91 LMICs. We show that funding 20% vaccine coverage over one year among 91 LMICs would prevent 294 million infections and 2 million deaths, with 26 million years of life saved at a cost of US$6.4 billion, for an incremental cost effectiveness ratio (ICER) of US$250/year of life saved (YLS). Increasing vaccine coverage up to 50% would prevent millions more infections and save hundreds of thousands of additional lives, with ICERs below US$8,000/YLS. Results were robust to variations in vaccine efficacy and hesitancy, but were more sensitive to assumptions about epidemic pace and vaccination costs. These results support efforts to fund vaccination programs in LMICs and complement arguments about health equity9, economic benefits10, and pandemic control11.

Objective: To determine whether statin exposure is associated with decreased cancer and mortality risk among persons with HIV (PWH) and uninfected persons. Statins appear to have immunomodulatory and anti-inflammatory effects and may reduce cancer risk, particularly among PWH as they experience chronic inflammation and immune activation. Design: Propensity score-matched cohort of statin-exposed and unexposed patients from 2002 to 2017 in the Veterans Aging Cohort Study (VACS), a large cohort with cancer registry linkage and detailed pharmacy data. Methods: We calculated Cox regression hazard ratios (HRs) and 95% confidence intervals (CI) associated with statin use for all cancers, microbial cancers (associated with bacterial or oncovirus coinfection), nonmicrobial cancers, and mortality. Results: :The propensity score-matched sample ( N = 47 940) included 23 970 statin initiators (31% PWH). Incident cancers were diagnosed in 1160 PWH and 2116 uninfected patients. Death was reported in 1667 (7.0%) statin-exposed, and 2215 (9.2%) unexposed patients. Statin use was associated with 24% decreased risk of microbial-associated cancers (hazard ratio 0.76; 95% CI 0.69–0.85), but was not associated with nonmicrobial cancer risk (hazard ratio 1.00; 95% CI 0.92–1.09). Statin use was associated with 33% lower risk of death overall (hazard ratio 0.67; 95% CI 0.63–0.72). Results were similar in analyses stratified by HIV status, except for non-Hodgkin lymphoma where statin use was associated with reduced risk (hazard ratio 0.56; 95% CI 0.38–0.83) for PWH, but not for uninfected ( P interaction = 0.012). Conclusion: In both PWH and uninfected, statin exposure was associated with lower risk of microbial, but not nonmicrobial cancer incidence, and with decreased mortality.

Many problems that appear in biomedical decision making, such as diagnosing disease and predicting response to treatment, can be expressed as binary classification problems. The costs of false positives and false negatives vary across application domains and receiver operating characteristic (ROC) curves provide a visual representation of this trade-off. Nonparametric estimators for the ROC curve, such as a weighted support vector machine (SVM), are desirable because they are robust to model misspecification. While weighted SVMs have great potential for estimating ROC curves, their theoretical properties were heretofore underdeveloped. We propose a method for constructing confidence bands for the SVM ROC curve and provide the theoretical justification for the SVM ROC curve by showing that the risk function of the estimated decision rule is uniformly consistent across the weight parameter. We demonstrate the proposed confidence band method and the superior sensitivity and specificity of the weighted SVM compared to commonly used methods in diagnostic medicine using simulation studies. We present two illustrative examples: diagnosis of hepatitis C and a predictive model for treatment response in breast cancer.

Objective: Chronic diseases are among the major causes of disability, and are associated with substantial individual and societal economic losses. The objective of this study was to assess the association of the different levels of disability, functioning, and work limitation, with chronic diseases. Methods: A total of 516 workers were classified according to chronic disease status, and evaluated for disability, functioning and work Limitation. Quantile regression was performed to assess the associations across the quantiles of the disability, functioning, and work limitation. Results: Overall disability was significantly associated with chronic diseases across all quantiles, while work limitation was only significant at the median and higher quantiles. Functioning domains showed a variable pattern of associations across their quantiles. Conclusions: Chronic diseases showed a variable magnitude and significance of associations across the levels of disability, functioning, and work limitation.

Objective: The aim of this study was to evaluate the effect of chronic disease(s) on work productivity. Methods: Using the Health & Work Performance Questionnaire, information was collected from 516 workers on chronic disease status and work productivity. Propensity-score matching was performed to identify matched-pairs of workers. Results: In the propensity-score matched sample, workers with chronic diseases were more likely to have increased absenteeism and presenteeism rates, 6.34 and 2.36 times the rates if no chronic diseases, respectively. In addition, they had greater odds for getting negative critical work incidents and less odds for positive incidents than none or balanced status. Multimorbidity showed more significant increase in absenteeism and presenteeism rates, as well as increased odds for excess negative critical work incidents. Conclusion: Chronic disease(s) can significantly reduce work productivity by increasing absenteeism, presenteeism, and net negative critical incidents.

Abstract Background: Pancreatic cancer is uncommon, however, it is a fatal cancer that ranks the fourth in mortality in United States. Risk factors of pancreatic cancer include infections, smoking, hormonal, alcoholism, genetic, and environmental factors. Pancreatitis is one of the risk factors of pancreatic cancer which is also, one of the observed extrahepatic manifestations of hepatitis C virus (HCV) infection. HCV infection mortality and morbidity are increasing; therefore it is important to understand the relationship between HCV infection and pancreatic cancer and the role of HCV-related pancreatitis. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Medicare linked (SEER-Medicare) database to employ a population-based nested case control study among United States elder. The study included 29,892 pancreatic cancer cases and 100,000 controls. In this study, we calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) using unconditional logistic regression. Models were adjusted for the matching variables including age, sex, and calendar year. To examine the hypothesis that pancreatitis is in the causal pathway between HCV and pancreatic cancer; and therefore, is a mediator (intermediate endpoint), we used mediation modeling to calculate the percentage of the total effect of HCV that is mediated by pancreatitis. Results: HCV infection was reported in 0.42% pancreatic cancer cases and 0.32% controls. Pancreatitis was observed in 6.2% of HCV infected, and 1.4% non-HCV infected. Pancreatitis was reported in 2.6%, and 1.4% of cancer and controls respectively. Adjusting for matching variables, HCV infection was associated with higher odds of pancreatic cancer [OR (95% CI); 1.36(1.10-1.68)]. In the mediation modeling, pancreatitis significantly mediated the HCV effect, such that 11.4% of HCV effect was mediated by pancreatitis. Conclusion: HCV is a risk factor of pancreatic cancer. HCV effect is mediated in part by pancreatitis. Further studies are warranted to understand the various mechanisms that might explain the excess risk of pancreatic cancer among HCV infected individuals, and to determine the effect of HCV treatment on pancreatic cancer risk. Citation Format: Fatma M. Shebl. HCV infected elderly are at excess risk of pancreatic cancer: a population based SEER-Medicare study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4812. doi:10.1158/1538-7445.AM2013-4812

Although most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear. We examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55–74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified. After adjusting for potential confounders, the hazard ratios (HRs) of prostate cancer associated with <1 and ⩾1 pill of aspirin daily were 0.98 (95% confidence interval (CI), 0.90–1.07) and 0.92 (95% CI: 0.85–0.99), respectively, compared with never use (P for trend 0.04). The effect of taking at least one aspirin daily was more pronounced when restricting the analyses to men older than age 65 or men who had a history of cardiovascular-related diseases or arthritis (HR (95% CI); 0.87 (0.78–0.97), 0.89 (0.80–0.99), and 0.88 (0.78–1.00), respectively). The data did not support an association between ibuprofen use and prostate cancer risk. Daily aspirin use, but not ibuprofen use, was associated with lower risk of prostate cancer risk.

Serum lipids, diabetes, and obesity, individual components of metabolic syndrome, are associated with biliary tract cancer and stone risk, but the associations of metabolic syndrome or insulin resistance with biliary tract cancers and stones are not well studied. In this population-based case-control study in Shanghai, China (627 biliary tract cancers, 1037 biliary stones, and 959 controls), metabolic syndrome was defined as the presence of any three of the five components, including high waist circumference, high triglycerides, low high-density lipoprotein cholesterol (HDL), high blood pressure, and diabetes. Insulin resistance and β-cell function were assessed, using homeostasis assessment models. Metabolic syndrome was significantly associated with gallbladder cancer (odds ratio (OR)=2.75, 95% confidence interval (95% CI)=1.82–4.15) and biliary stones (OR=1.64, 95% CI=1.24–2.16), with a significant dose effect with increasing number of metabolic syndrome components (P trend <0.0001). The observed association persisted among subjects without a history of diabetes. The association between insulin resistance and gallbladder cancer was borderline (P trend=0.06). There was a significant inverse association between β-cell function and gallbladder cancer risk (P trend <0.001). Our findings suggest that metabolic syndrome and insulin resistance have a role in the aetiology of biliary tract cancers and biliary stones, and if confirmed, they imply that lifestyle control of these factors may lower the risk of biliary stones and biliary tract cancer.

Background: Biliary tract cancers are rare but fatal malignancies. Diabetes has been related to biliary stones, but its association with biliary tract cancers is less conclusive. Methods: In a population-based case–control study of 627 cancers, 1037 stones, and 959 controls in Shanghai, China, we examined the association between diabetes and the risks of biliary tract cancer and stones, as well as the effect of potential mediating factors, including serum lipids and biliary stones (for cancer), contributing to the causal pathway from diabetes to biliary diseases. Results: Independent of body mass index (BMI), diabetes was significantly associated with gallbladder cancer and biliary stones ((odds ratio (OR) (95% confidence interval)=2.6 (1.5–4.7) and 2.0 (1.2–3.3), respectively). Biliary stones and low serum levels of high-density lipoprotein (HDL) were significant mediators of the diabetes effect on gallbladder cancer risk, accounting for 60 and 17% of the diabetes effect, respectively. High-density lipoprotein was also a significant mediator of the diabetes effect on biliary stones, accounting for 18% of the diabetes effect. Conclusions: Independent of BMI, diabetes is a risk factor for gallbladder cancer, but its effect is mediated in part by biliary stones and serum HDL levels, suggesting that gallbladder cancer risk may be reduced by controlling diabetes, stones, and HDL levels.

OBJECTIVES:Population-based landline telephone surveys are potentially biased due to inclusion of only people with landline telephones. This article examined the degree of telephone coverage bias in a low-income population.METHODS:The Charles County Cancer Survey (CCCS) was conducted to evaluate cancer screening practices and risk behaviors among low-income, rural residents of Charles County, Maryland. We conducted face-to-face interviews with 502 residents aged 18 years and older. We compared the prevalence of health behaviors and cancer screening tests for those with and without landline telephones. We calculated the difference between whole sample estimates and estimates for only those respondents with landline telephones to quantify the magnitude of telephone coverage bias.RESULTS:Of 499 respondents who gave information on telephone use, 80 (16%) did not have landline telephones. We found differences between those with and without landline telephones for race/ethnicity, health-care access, insurance coverage, and several types of cancer screening. The absolute coverage bias ranged up to 6.5 percentage points. Simulation scenarios showed the magnitude of telephone coverage bias decreases as the percent of the population with landline telephone coverage increases, and as landline telephone coverage increases, the estimates from a landline telephone survey would approximate the estimates from a face-to-face survey.CONCLUSIONS:Our findings highlighted the need for targeted face-to-face surveys to supplement telephone surveys to more fully characterize hard-to-reach subpopulations. Our findings also indicated that landline telephone-based surveys continue to offer a cost-effective method for conducting large-scale population studies in support of policy and public health decision-making.

Summary. Kinetics of hepatitis C virus (HCV) during pegylated interferon (PEG‐IFN) and early monitoring of viral decline were recently described to predict treatment outcomes and in turn reduce the course of treatment, adverse effects and cost. However, there is limited (if any) information on the viral dynamics of HCV‐4. Our aim is to follow the HCV‐RNA kinetics during PEG‐IFN alpha 2a and ribavirin therapy and the best time for predicting sustained viral response (SVR) in genotype‐4 patients. Serum HCV‐RNA levels before initial dosing (baseline level) and at 24 h, week 1, week 4, week 12, week 24, week 48 and week 72 were assessed in 84 HCV genotype‐4 patients treated weekly by PEG‐IFN alpha 2a and daily ribavirin. At the end of treatment, out of the 84 treated patients, 19 (22.6%) were non‐responders while 65 (77%) showed end‐of‐treatment response (ETR). However, 8 patients relapsed (9.5%), thus the SVR was observed in 57 patients (67.9%). Younger patients were more likely to attain SVR, where the odds of SVR increased by a factor of 0.94 for each year increase in age (95% CI: 0.90–0.99, P = 0.019). Although a significant negative correlation between stage of fibrosis and rate of viral decline at weeks 1 and 4 (P < 0.005 and 0.001, respectively) was seen, neither fibrosis stage (χ2 = 3.4882, P > 0.1) nor grade of inflammation (χ2 = 0.0057, P > 0.1) significantly predicted response to treatment. Non‐responders had no or only a limited decline at week 1 and week 4, whereas sustained virological responders had a significant decline at both week 1 and week 4. Area under the (receiver operating characteristic) curve (AUC) revealed that week 12 is better than any other time point in predicting the SVR (AUC = 0.97; 95% CI: 0.94–1.01), (sensitivity 98.3%; 95% CI: 90.7–99.9), (specificity 88.5%; 95% CI: 71.0–96.0), positive predictive value of 94.9% and negative predictive value of 95.8%. A drop of more than 1.17 log viral load at week 1 and viral clearance or decline >3 log were considered as the earliest predictors of SVR. In genotype‐4 patients, while failure to achieve an EVR at week 12 predicts non‐response, an RVR at week1 and week 4 98% guaranteed SVR. These findings further re‐enforce the value of week 12 in the course of IFN treatment. Genotype‐4 patients who show significant viral clearance (>1.17log viral load) by the first week of treatment and viral clearance >3log by week 4 are expected to show SVR and should therefore be assigned to a shorter drug regimen lasting for 24 weeks. Those unfortunate cases who do not achieve viral clearance by week 1 or week 4 should not be deprived from the treatment but rather given more time till week 12 before being classified as non‐responders.

A prospective cohort study of the incidence and risk factors for hepatitis C virus (HCV) infection was performed in 2171 pregnant women in three rural Egyptian villages who were HCV antibody (anti-HCV) and RNA (HCV-RNA) negative at baseline. During an average of 2.2 years follow up, 25 incident cases were observed, giving an estimated HCV incidence of 5.2/1000 person-years (PY). The infection rate correlated with community anti-HCV prevalence in pregnant women, while the perinatal incidence rate of 11.2/1000 PY was almost five times that of the non-perinatal rate (2.3/1000 PY). The data suggested iatrogenic perinatal risk factors were associated with infection in one village, while health education reduced infections in another. Among the 25 incident cases, eight were HCV-RNA negative when they were first found to be anti-HCV positive and one-third of the 15 viraemic cases with follow-up data available cleared their HCV-RNA after an average of 1.3 years. None of the 25 incident cases were jaundiced or had symptoms of hepatitis but elevated serum alanine aminotransferase levels confirmed hepatitis in nine. Our data suggest that asymptomatic HCV infections frequently occurred during the perinatal period but often cleared and that educating medical personnel on safe practices possibly reduced HCV transmission.

Summary. Recently, attention has been focussed on adiponectin and its changes in different types of chronic liver disease. Its relation to hepatic fibrosis and insulin resistance in post‐hepatitis liver disease is not clear. The aim of this study was to clarify the adiponectin changes in genotype 4 hepatitis C virus (HCV)‐infected patient in relation to liver histology and insulin resistance, and its usefulness as a predictor of hepatic fibrosis and response to treatment. Total adiponectin and its high molecular weight (HMW) form as well as insulin levels were studied in 92 chronic HCV, genotype 4 and 66 healthy control volunteers. Neither total adiponectin ( r = 0.101, P = 0.220) nor HMW adiponectin ( r = 0.081, P = 0.328) correlated with viral load. Total and not HMW adiponectin was significantly correlated with hepatic fibrosis and inflammation ( r = 0.267, P = 0.002, r = 0.278, P < 0.001, respectively).In addition, total adiponectin ( r = 0.224, P = 0.002) and HMW adiponectin ( r = 0.266, P < 0.0006) significantly correlated with insulin resistance. As fibrosis did not correlate with insulin resistance ( r = 0.081, P = 0.204), the correlation between total adiponectin and fibrosis was not mediated by insulin resistance. Multivariable regression analysis, (including pretreatment cases and controls) revealed that total adiponectin was significantly associated with gender, being lower among male subjects ( X 2 = 13.04, P = 0.0001). The multivariable regression model supported the lack of association between insulin resistance and total adiponectin levels ( X 2 = 1.88, P = 0.171), while non cirrhotics had significantly lower total adiponectin levels than cirrhotics ( X 2 = 10.90, P = 0.004) and lower level of inflammation significantly lower total adiponectin levels than more severe inflammation ( X 2 = 8.95, P = 0.003). Total or HMW adiponectin did not yield receiver operating characteristic (ROC) curves with area under the curve (AUC) >75%, thus the cutoff points have poor sensitivity/specificity as predictors of fibrosis. However, as a predictor of end‐of‐treatment response, the ROC curve of adiponectin index gave yield an AUC = 81.4%. We can conclude that total adiponectin level, in HCV genotype 4 patients, increases with progression of hepatic fibrosis regardless of insulin resistance. Its high molecular form does not have such correlation. The adiponectin changes are not related to viral load, insulin resistance or other demographic data suggesting that this change is histologically related. In spite of this, no adiponectin cutoff level had reasonable sensitivity/specificity for predicting hepatic fibrosis stage, while this may be used as a predictor for antiviral response possibly reflecting improvement in hepatic inflammation post treatment.

Objective: To assess trends in twinning over four decades using a population-based registry.Design: Ecological study to conduct trend analysis of twin pregnancies in a geographically defined area over 40 years.Setting: All pregnancies in the Cardiff and Vale of Glamorgan area Of South Wales from 1965 to 2004, as recorded in the Cardiff Birth Survey (CBS) database.Methods: Trends of the incidence of all twin pregnancies (>= 18 weeks of gestation) were calculated in 5-year increments, beginning with 1965-1969 and ending in 2000-2004. Natural twinning rates could only be calculated for the terminal five time periods (i.e., 1980-1984, 1985-1989, 1990-1994 1995-1999, and 2000-2004), when information regarding non-spontaneous (iatrogenic) twinning was first collected in the database. All results were adjusted for maternal age.Results: The total twinning rate was 13.1 per 1000 pregnancies in the 1st time period (1965-1969). Subsequently, there was a gradual reduction in twinning, reaching a nadir of 10.3 per 1000 for the time period 1980-1985 (Z = 3.15, P value < 0.00 1). This was followed by a gradual increase in twinning, reaching a maximum of 15.7 per 1000 for both 1995-1999 and 2000-2004 (Z = -5.18, P value < 0.000 1). After exclusion of the cases of iatrogenic pregnancies,, the natural twinning rate showed a continuous and gradual increase from 10 per 1000 spontaneous pregnancies in 1980-1984 to 13.3 per 1000 in 2000-2004 (Z= -5.08. P value < 0.0001).Conclusion: The data showed a gradual, continuous increase in natural twinning rates over the last two decades. Such an increase cannot be attributed to the rise in maternal age alone. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

AIM To assess hepatic fibrosis and factors associated with its progression in children with HCV infection. METHODS At the Hepatology Unit, Cairo University Children's Hospital, a single liver biopsy was performed to 43 children with HCV infection after an informed consent between 1998-2004. Their mean age at liver biopsy was 8.67 +/- 4.3 years. RESULTS Among the 43 patients' biopsies, 12 (27.9%) were having no fibrosis, 20 (46.5%) mild fibrosis and 11 (25.6%) moderate to severe fibrosis. The median time for development of fibrosis was estimated to be 5.5 years. Developing fibrosis was significantly associated with shorter duration from first detected ALT elevation to biopsy (12 mo vs 1.2 mo, P=0.015) and having higher levels of direct serum bilirubin (0.3 mg/dL vs 0.5 mg/dL, P=0.048). No association was found between fibrosis stage and the presence of co-morbid conditions (P=0.33). CONCLUSION Hepatic fibrosis was present in 72.1% of children with HCV infection. The development of fibrosis was associated with higher levels of direct serum bilirubin. There was no significant association between fibrosis and age, duration of infection, risk factors, co-morbid conditions and most biochemical parameters.

Prevalence and risk factors for hepatitis C virus (HCV) infection were studied in 2,587 pregnant women from three rural Egyptian villages in the Nile Delta being admitted to a prospective cohort study of maternal-infant transmission; 408 (15.8%) had antibodies to HCV (anti-HCV) and 279 (10.8%) also had HCV-RNA. Fewer than 1% gave a history of jaundice or liver disease. Risk factors for anti-HCV included increasing age, low socioeconomic status and a history of blood transfusion or injection therapy for schistosomiasis. Sub-analyses after stratification of subjects by village revealed risks associated with specific venues for medical care, having a previous delivery attended by a traditional birth assistant (TBA), receiving medical care in a temporary clinic located in a mosque, overnight admission to a private doctor's clinic, and circumcision by a TBA or a 'health barber'. Our results suggest HCV causes very little detected illness in young adult Egyptian women and some sources of HCV transmission in rural Egypt in the past were associated with the provision of medical care and varied by location. Prevention should be focused on providing appropriate resources and health education should be given to formal and informal health care providers and should be sufficiently broad to adjust for local variations in exposures.

The epidemiology of hepatitis E virus (HEV), an enterically-transmitted cause of acute viral hepatitis (AVH), is not fully understood. During outbreaks on the Indian subcontinent and elsewhere, HEV causes severe AVH with mortality rates around 20% during pregnancy. In Egypt, where prevalence of HEV antibodies (anti-HEV) in rural communities is very high, severe HEV-caused AVH in pregnant women has not been reported. This study examined a cohort of 2,428 pregnant women in the Nile Delta to assess prevalence of, and risk factors for, anti-HEV and correlated these with history of liver disease. Anti-HEV prevalence was 84.3%. Several risk factors associated with anti-HEV included older age, many siblings, not using soap to wash produce and frequent contact with cats. History of jaundice and liver disease was rare and not increased in those having anti-HEV. Our results confirm Egypt's high HEV endemicity and show that almost all women of childbearing age in these communities had prior HEV exposures without a history of liver disease. Reasons for the lack of clinical hepatitis remain unclear but could be the result of early childhood HEV exposures, producing long-lasting immunity and/or modify subsequent responses to exposure. Alternatively, the predominant HEV strain(s) in Egypt are less virulent than those in South Asia.