Sadaf Ghajarieh Sepanlou

Endoscopic retrograde cholangiopancreatography (ERCP) is a widely utilized procedure for diagnosing and treating biliary and pancreatic disorders. However, it carries a risk of post-ERCP pancreatitis (PEP). N-Acetylcysteine (NAC) has been proposed as a potential prophylactic agent due to its antioxidant properties, yet its efficacy remains debated. This systematic review and meta-analysis aimed to evaluate the effectiveness of NAC in preventing PEP in patients undergoing ERCP. We conducted a comprehensive literature search across multiple databases, including PubMed, Scopus, Web of Science, and EMBASE, for randomized controlled trials (RCTs) on humans published from January 2000 to end of August 2024. The primary outcome was the incidence of PEP in the group who received the NAC compared to the group receiving routine medication. Study selection and data extraction was performed according to PRISMA guidelines. Quality assessment was accomplished using risk of bias (RoB2) tool for RCTs. A total of four RCTs involving 773 patients were included in the final analysis. The meta-analysis demonstrated a non-significant lower incidence of post-ERCP pancreatitis in the NAC group compared to controls (Risk Ratio: 0.66; 95% Confidence Interval: 0.38–1.16). Sensitivity analyses indicated low robustness of these results, with moderate heterogeneity observed among studies (I2 = 55.89%). Egger test did not provide evidence of publication bias. The trim-and-fill correction suggested one potentially missing study on the left side of the funnel plot. Imputation for this potentially missing study yielded an effect size of RR: 0.57; 95% CI: 0.32—0.99), which was statistically significant this time. The results were additionally statistically non-significant stratified by severity of the PEP. While NAC shows promise in reducing the incidence of PEP, the current evidence does not support its routine use as a prophylactic agent. Further research is warranted to clarify its role and optimize preventive strategies for PEP.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a widely used procedure. Post-ERCP pancreatitis (PEP) remains a significant complication. This meta-analysis aimed to evaluate the efficacy of octreotide in reducing the incidence of PEP. Methods: A comprehensive review of randomized controlled trials (RCTs) was conducted across multiple databases to assess the impact of octreotide administration on post-ERCP outcomes, including acute pancreatitis (overall, mild, moderate, and severe), abdominal pain, and mortality. Pooled risk ratios (RR) were calculated using random-effects meta-analysis. Sensitivity analyses, Galbraith plots, Egger test, Begg funnel plots, and trim-and-fill correction were performed to assess the robustness of the findings, identify outliers, evaluate publication bias, and adjust for potentially missing studies. Results: The analysis included 21 RCTs for overall post-ERCP pancreatitis comprising 7229 patients, 15 RCTs for mild, moderate, and severe pancreatitis, 8 RCTs for abdominal pain, and 5 RCTs for mortality. Octreotide was associated with a significant reduction in the incidence of overall (RR: 0.63; 95% CI: 0.48-0.82) and moderate PEP (RR: 0.39; 95% CI: 0.22-0.67). However, no significant reduction was observed for mild and severe PEP, abdominal pain, or mortality. Evidence of publication bias was noted for overall and mild PEP, but trim-and-fill correction did not alter the significance of the overall pancreatitis result. Conclusion: Octreotide appears to be effective in reducing the risk of overall and moderate PEP. However, its impact on mild and severe PEP remains inconclusive. Further large-scale, high-quality RCTs are needed to refine clinical recommendations regarding its routine prophylactic use in ERCP.

Smoking and opium use are risk factors for gastrointestinal cancers, yet the extent to which cessation reduces cancer risk remains unclear, particularly in non-Western populations. This study analyzed data from the Golestan Cohort Study in northeastern Iran, comprising 50,045 adults aged 40–75 years followed for a median of 15 years. Participants were classified into never-users, current smokers or recent quitters (less than 5 years), and long-term quitters (more than 5 years). For esophageal cancer, long-term quitters demonstrated substantial risk reductions (HR for smoking: 0.68; 95% CI: 0.47–0.99; HR for opium: 0.33; 95% CI: 0.12–0.90), while current users and recent quitters of both smoking and opium indicated increased risks (HR for smoking: 1.53; 95% CI: 1.14–2.07; HR for opium: 1.50; 95% CI: 1.20–1.88). For stomach cancer, long-term smoking quitters showed a protective effect, with a 35% risk reduction though no significant risk reduction was observed for long-term opium cessation. For pancreatic cancer no significant risk reduction was noted among long-term quitters. This study highlights that cessation of smoking or opium use for more than 5 years can reduce the risk of esophageal cancer, while risk reduction for other types of gastrointestinal cancers requires longer cessation duration.

Background: Lung cancer remains a pressing health issue globally. This study investigates survival rates and the impact of pre-diagnostic factors on lung cancer incidence in Golestan Cohort Study (GCS). Method: The GCS, initiated in 2004 with enrollment concluding in 2008, comprises 49,783 individuals aged 40–75 from the Golestan province in northeastern Iran. Our analysis included all cases of lung, tracheal, and bronchial cancers diagnosed under ICD-10 codes C33-C34 from the study’s inception to 2022, tracking participants until death. A sensitivity analysis, excluding lung cancer cases diagnosed within the initial 24 months of follow-up, was performed to address the reverse causation bias from previously undiagnosed conditions at baseline. Results: Out of 49,783 participants in the study, 132 were diagnosed with lung cancer, of whom 130 died by the end of the study. The age and sex-standardized incidence rate stood at 20.39 per 100,000 person-years. The median survival post-diagnosis was approximately four months, with one-year and five-year survival rates at 18.67% and 1.56%, respectively. Sensitivity analyses identified advanced age, male sex, opiate use history, pack-years of cigarette smoking, and the utilization of non-gaseous energy sources as lung cancer risk factors. In contrast, high physical activity and a BMI of 25 or higher were inversely associated with lung cancer risk. Conclusion: Our study highlights the critical burden and low survival rates of lung cancer in resource-limited regions. Mitigating key risk factors and enhancing access to diagnostic and treatment services through targeted public health policies and comprehensive strategies are essential for ensuring equitable healthcare and improving lung cancer outcomes for underserved populations.

Brain cancer is an important public health concern in terms of its burden and the cost of its treatment. Evidence on determinants of brain cancer incidence and survival are sparse and inconsistent. We aimed to explore the pre-diagnostic factors for brain cancer incidence and survival in northeastern Iran. Data for the current study were derived from the Golestan Cohort Study, the largest cohort study in the Middle East on over 50,000 participants aged 40 to 75 years with a median follow-up of 15 years. Minimally adjusted and multiple Cox proportional hazards models were used to investigate the association of demographic and behavioral risk factors with brain cancer incidence and survival. Out of the 49,783 cancer free participants recruited at baseline, 77 patients were diagnosed with brain cancer and 62 patients were deceased till the end of the follow-up. Annual cancer mortality rate was 0.31 (95% Confidence Interval: 0.24 – 0.39), one-year survival was 38%, and the median survival was 0.72 years. In the multiple model, Turkmen ethnicity (Hazard Ratio = 0.42 (0.23–0.76)), urban residence (HR = 0.46 (0.25–0.84)), overweight or obesity (HR = 0.48 (0.25–0.93)), and history of animal contact (HR = 0.43 (0.19–0.96)) were associated with a better survival. Patients diagnosed with brain cancer had higher prevalence of hypertension, opium use, and smoking compared to cancer free participants. Our results indicate a complex interplay of demographic and life style risk factors influencing both the incidence and prognosis of brain cancer. Further research is mandated to inform policy makers of potentially effective preventive initiatives to reduce the burden of this cancer.

Background We aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting. Methods The PolyPars Study is a two-arm pragmatic cluster-randomised trial nested within the PARS cohort study, including all residents aged over 50 years in the entire district in southern Iran. The 91 villages underwent random allocation into two arms: the control arm, encompassing 45 clusters, was subjected to non-pharmacological intervention (educational training on healthy lifestyle), whereas the intervention arm, comprising 46 clusters, received the non-pharmacological interventions in conjunction with a once-daily polypill tablet. This tablet comprised two antihypertensive agents, a statin and aspirin. The primary outcome was the first occurrence of major cardiovascular events defined as a composite of hospitalisation for acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, non-fatal and fatal stroke, sudden death and heart failure. The Cox regression model, with shared frailty, was used to account for clustering effect. Results During December 2015–December 2016, a total of 4415 participants aged 50–75 years were recruited (2200 participants in the intervention arm and 2215 participants in the control arm). The overall median of follow-up duration was 4.6 years (interquartile interval 4.4–4.9). The achieved adherence rate to polypill in intervention arm was 86%. In the control group, 176 (8.0%) of 2215 participants developed primary outcome, compared with 88 (4.0%) of 2200 participants in the polypill group. We found substantial reduction in risk of primary outcome both in relative and absolute scales (HR 0.50, 95% CI 0.38 to 0.65; absolute risk reduction 4.0%, 95% CI 2.5% to 5.3%). No difference in serious adverse events was observed between the two groups. Conclusions The fixed-dose combination therapy using polypill can safely halve the risk of major cardiovascular diseases at the population level. Trial registration number NCT03459560.

Background Exploring the impact of national health expenditure and its allocation on neonate and child mortality can help policy makers implement strategies aimed at achieving target 3.2 of Sustainable Development Goals (SDGs). The aim of the current study is to explore the impact of selected indicators of national health accounts on neonate and under-5 mortality across 188 countries from 2000 to 2019. Methods and findings This study has an ecological design. Data on health expenditure was obtained from the Global Health Expenditure Database (GHED) for 188 countries from 2000 to 2019. The Global Burden of Disease study (GBD) 2019 data on neonatal and under 5 mortality rates at national levels from 2000 to 2019 were obtained from the website of the Global Health Data Exchange (GHDx) supported by the Institute for Health Metrics and Evaluation. The income groups were stratified based on the World Bank classification. We employed a mixed-effects regression model to investigate the association of different health account indicators with changes in neonatal and under-5 mortality rates over time across countries. We used the Multiple Change Points model to determine the turning points in the association of health expenditure per capita with mortality across countries in 2019. And finally, we estimated the observed-to-expected ratio of mortality based on the segmented regression model for all 188 countries in 2019. Increase in the current health expenditure in International dollar Purchasing Power Parity (Int$ PPP) per capita was associated with lower mortality among both neonates and children in all strata of countries. Reductions were very minimal among high-income countries and were generally more prominent in low-income countries and decreased along with increase in income. Reductions were more noteworthy for under-5 mortality rates. The percentage of domestic general government health expenditure and the percentage of compulsory financing arrangements out of current health expenditure were inversely associated with mortality, while the association of percentage of domestic private health expenditure and out-of-pocket expenditure out of current health expenditure with mortality was positive. Results showed that the reduction in neonatal mortality associated with each ten-dollar increase in current health expenditure per capita is significantly more prominent for per capita expenditures less that the cut-point of 480 Int$ PPP per capita. The respective figure for under-5 mortality was 386 Int$ PPP per capita. Ultimately, a total of 110 countries had observed versus expected ratio less than one for neonatal mortality and 118 countries for child mortality. Conclusions Increase in health expenditure is significantly associated with decrease in neonate and under-5 mortality especially among low and low-middle income countries. However, the association fades among countries in which health expenditure per capita is higher than the threshold. In all countries, improvement in neonate and under-5 mortality requires modifying the health system infrastructure to move towards universal health coverage. However, the COVID-19 pandemic may have influenced the health spending at national levels.

Background: Fixed-dose combination treatments reduce cardiovascular disease in primary prevention. We aim to explore whether those benefits differ in the presence of CKD. Methods: We conducted an individual participant data meta-analysis in 18,162 participants on the efficacy and safety of treatment for the primary prevention of cardiovascular disease. Combination therapies consisted of at least two BP-lowering drugs and a statin, with or without aspirin versus placebo or minimal care. Here, we examine the differential effect of fixed-dose combination treatment on the risk of developing cardiovascular disease in participants with a low eGFR (2; Chronic Kidney Disease Epidemiology Collaboration formula) compared with a normal eGFR (≥60 ml/min per 1.73 m²). The primary composite outcome was time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization. Results: At baseline, the mean level of eGFR was 76 ml/min per 1.73 m² (SD 17). In total, 3315 (18%) participants had low eGFR at baseline. During a median follow-up of 5 years, among participants with normal eGFR, the primary outcome occurred in 232 (3%) participants in the treatment group compared with 339 (5%) in the control group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P < 0.001). In participants with low eGFR, the primary outcome occurred in 64 (4%) participants in the treatment group compared with 130 (8%) in the control group (hazard ratio, 0.49; 95% confidence interval, 0.36 to 0.66; P < 0.001; P for interaction 0.047). The relative risk reduction among participants with low eGFR was larger for combination strategies, including aspirin compared with treatments without aspirin. Apart from dizziness, other side effects did not differ between treatment and control groups, regardless of the stage of their kidney function. Conclusions: A fixed-dose combination treatment strategy is effective and safe at preventing cardiovascular disease, irrespective of eGFR, but relative and absolute risk reductions are larger in individuals with low eGFR. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000251.mp3