Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis

Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present systematic review and meta-analysis, we sought for assessing the efficacy and safety of Immune checkpoint inhibitors (ICIs) in patients with prostate cancer. PubMed, Scopus, Web of Science, and EMBASE databases were searched on Aguste 19, 2022. Thirty five studies met the eligibility criteria. The median overall survival (mOS) of all treatments was 14.1 months, with the longest and shortest mOS was seen among patients who received anti-CTLA-4 monotherapy and anti-PD-1/PD-L1+anti-CTLA-4 regimen at 24.9 and 9.2 months, respectively. Noteworthy, all types of adverse events had the lowest incidence in the anti-PD-1/PD-L1 monotherapy group. Considering the ICI monotherapy regimens, we found that fatigue, diarrhea, and infusion reaction had the highest incidence rates. Future studies evaluating the efficacy and safety of novel combination therapies with ICIs are warranted

Addressing the Younger Age at Onset in Breast Cancer Patients in Asia: An Age-Period-Cohort Analysis of Fifty Years of Quality Data from the International Agency for Research on Cancer

There is an established fact that Asian breast cancer patients are, on average, younger than their European counterparts. This study aimed to utilize the data from the Cancer Incidence in Five Continents I through XIII (published by the International Agency for Research on Cancer) to examine what contributes to the younger age at onset in the Asian population. Material and Methods. Data (number of breast cancer cases and corresponding population figures) for 29 registries in Europe and 9 registries in Asia for the period of 1953–2002 was accessioned and pooled to form two distinct populations, Asia and Europe. The age specific rates were defined and analyzed cross-sectionally (period wise) and longitudinally (cohort wise). The magnitude and the pattern of age specific rates were analyzed using the age-period-cohort analysis. The constrained generalized linear model with a priority assumption of cohort effect as contributing factor to changing rates was used to analyze the data. Result. During the last 50 years, the rate of breast cancer increased for both populations with an estimated annual percent change of 1.03% (with 95% CI of 1.029, 1.031) for Asia and 1.016% (95% CI of 1.015, 1.017) for Europe. There were stronger cohort effects in the magnitude of rates among the Asian population compared to the European population. The cohort effects, expressed as the rate ratio with cohort born in 1970 as reference, ranged from 0.06 (95% CI 0.05, 0.08) to 0.94 (95% CI 0.93, 0.96) for Asians and 0.35 (95% CI 0.33, 0.36) to 1.03 (95% CI 1.02, 1.04) for Europeans. The estimated longitudinal age specific rates (adjusted for cohort and period effects) showed similar patterns between the two populations. Conclusion. It was concluded that a strong cohort effect contributes to the younger age at onset among Asian breast cancer patients

Childhood Overweight and Obesity and Associated Factors in Iranian Children and Adolescents: A Multilevel Analysis; the CASPIAN-IV Study

Objective: The purpose of this paper is to explore multidimensional factors related to childhood obesity and overweight based on the data gathered on different aspects of the general health status were assessed among a large number of Iranian children and adolescents in the fourth phase of the “Childhood and Adolescence Surveillance and Prevention of Adult Non-communicable disease” survey. It also aims to determine the degree to which each ecological context contributes to childhood overweight/obesity.Method: A total of 14,880 students and their parents were recruited. They filled out a questionnaire on their relationship with peers, body image, and psychosocial environment of school, dietary habits, life-style habits, physical activity pattern and socioeconomic status (SES). Their height, weight, was measured and body mass index (BMI) was calculated. Obesity and overweight was defined based on the WHO growth chart. Multilevel modeling using three-level random intercept logistic regression models were used to assess predictors of overweight and obesity. In our hierarchical models, children (first level) were conceptualized as being nested within provinces (second level) and provinces within quad regions (third level).Result: From among the 13,486 recruited students, 9.7% were overweight and 11.9% were obese. In multivariate model (adjusted model), being boy (OR:1.58), living in urban area (OR:1.58), having positive family history of obesity (OR = 2.04), breakfast skipping (OR: 1.46), socioeconomic status (OR moderateSES/lowSES = 1.44 and OR highSES/lowSES = 1.89), and birth weight (BW) (OR normalBW/lowBW = 1.33 and OR highBW/lowBW = 1.8) were associated with childhood obesity. Increasing age was the only factor in the obesity model that had a significant preventive effect on the odds of becoming obese (OR = 0.96, P < 0.001). In multivariate model, living in urban area, increasing age, high and moderate SES, high BW and family history of obesity were the significant predictors of overweight.Conclusion: Our findings show that high BW, sociodemographic characteristics, breakfast skipping, and family history of obesity are associated with childhood obesity and overweight. Therefore, developing strategies that consider the effects of diverse sociodemographic and environmental factors on childhood overweight and obesity would be the most effective way to prevent and manage this multifactorial health concern

Efficacy and Safety of the Irinotecan, Capecitabine, and Oxaliplatin (IOX) Regimen in Metastatic Gastric Cancer: A Single Arm Phase II Trial

Background: Gastric cancer is one of the most common malignancies worldwide with a high case mortality rate. In metastatic gastric cancer, a proper combination of chemotherapy could increase the survival rate. The goal of this study is to evaluate the efficacy and safety of the combination regimen of irinotecan, oxaliplatin, and Xeloda in metastatic gastric cancer. Methods: A total of 45 patients with metastatic gastric cancer and good performance status according to the Eastern Cooperative Oncology Group (score: 0-1) received the irinotecan, oxaliplatin, and Xeloda chemotherapy regimen. Demographic data, responses to treatment, and adverse effects were gathered for all cases. Overall survival and progression-free survival rates for patients were calculated using the Kaplan-Meier estimate. Results: Patients’ mean age was 58.3 ± 11.3 years (range: 24-81). There were 73.4% male patients and 26.6% female patients. Anorexia and weight loss were the most common symptoms. Overall response rate was 50%. The majority of toxicities were anemia, nausea and vomiting (grades 1 and 2), diarrhea (grades 1 and 2), neutropenia, alopecia, and hand and foot syndrome. The one-year progression-free survival rate was 31.5 ± 7.5%, whereas the twoyear progression-free survival rate was zero. The one-year overall survival rate was 34.91 ± 8.5%. Patients had a two-year overall survival rate of 7.7 ± 6.6%. Diffuse type cancer was linked to an inferior outcome. Conclusion: Regardless of our limited number of patients, this combination could be a suitable regimen for metastatic gastric cancer in terms of low toxicity, acceptable response rate, and survival results

National and sub-national environmental burden of disease in Iran from 1990 to 2013-study profile

Development of national evidence-based public health strategies requires a deep understanding of the role of major risk factors (RFs) and the burden of disease (BOD). In this article, we explain the framework for studying the national and sub-national Environmental Burden of Disease (EBD) in Iran as a part of the National and Sub-national Burden of Disease (NASBOD) study.; The distribution of exposures to environmental RFs and their attributable effect size over 1990-2013 will be estimated through comprehensive reviews of either published or unpublished sources. Statistical modeling will be used to impute missing data in the distribution of RFs exposures for each district-year. National and sub-national BOD attributable to these RFs will be estimated in the following metrics: Prevalence, death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), and disability-adjusted life years lost (DALYs). The BOD attributable to the current distribution of exposures will be compared with a counterfactual exposure distribution scenario-here, the theoretical-minimum-risk exposure distribution. Inequalities in the distribution of exposure to RFs will be analyzed and manifested nationwide using geographic information systems.; The EBD study aims to provide an official report to Iranian Ministry of Health and Medical Education, to publish a series of articles on the exposure trends of the selected environmental RFs, to estimate the BOD attributable to these RFs, and to assess inequalities and its determinants in the distribution of exposure to RFs. Iran's territory is large with diverse population, socioeconomic, and geographic areas. Results of this comparative risk assessment study may pave the way for health policy makers to plan more comprehensive and cost-effective evidence-based strategies

Measuring Iran’s success in achieving Millennium Development Goal 4: a systematic analysis of under-5 mortality at national and subnational levels from 1990 to 2015

Background Child mortality as one of the key Millennium Development Goals (MDG 4—to reduce child mortality by two-thirds from 1990 to 2015), is included in the Sustainable Development Goals (SDG 3, target 2—to reduce child mortality to fewer than 25 deaths per 1000 livebirths for all countries by 2030), and is a key indicator of the health system in every country. In this study, we aimed to estimate the level and trend of child mortality from 1990 to 2015 in Iran, to assess the progress of the country and its provinces toward these goals. Methods We used three different data sources: three censuses, a Demographic and Health Survey (DHS), and 5-year data from the death registration system. We used the summary birth history data from four data sources (the three censuses and DHS) and used maternal age cohort and maternal age period methods to estimate the trends in child mortality rates, combining the estimates of these two indirect methods using Loess regression. We also used the complete birth history method to estimate child mortality rate directly from DHS data. Finally, to synthesise different trends into a single trend and calculate uncertainty intervals (UI), we used Gaussian process regression. Findings Under-5 mortality rates (deaths per 1000 livebirths) at the national level in Iran in 1990, 2000, 2010, and 2015 were 63·6 (95% UI 63·1–64·0), 38·8 (38·5–39·2), 24·9 (24·3–25·4), and 19·4 (18·6–20·2), respectively. Between 1990 and 2015, the median annual reduction and total overall reduction in these rates were 4·9% and 70%, respectively. At the provincial level, the difference between the highest and lowest child mortality rates in 1990, 2000, and 2015 were 65·6, 40·4, and 38·1 per 1000 livebirths, respectively. Based on the MDG 4 goal, five provinces had not decreased child mortality by two-thirds by 2015. Furthermore, six provinces had not reached SDG 3 (target 2). Interpretation Iran and most of its provinces achieved MDG 4 and SDG 3 (target 2) goals by 2015. However, at the subnational level in some provinces, there is substantial inequity. Local policy makers should use effective strategies to accelerate the reduction of child mortality for these provinces by 2030. Possible recommendations for such strategies include enhancing the level of education and health literacy among women, tackling sex discrimination, and improving incomes for families

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI