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Objectives To review the evidence of the effects of centralization of cancer surgery on postoperative mortality. Methods We searched Medline, Embase, Cinahl, Cochrane and Scopus (up to November 2019) for studies that (i) assessed the effects of centralization of cancer surgery policies on in-hospital or 30-day mortality, or (ii) described changes in both postoperative mortality for a surgical intervention and degree of centralization using reduction in the number of hospitals or increases in the proportion of patients undergoing cancer surgery at high volume hospitals as proxy. PRISMA guidelines were followed. We estimated pooled odds ratios (OR) and conducted meta-regression to assess the relationship between degree of centralization and mortality. Results A total of 41 studies met our inclusion criteria of which 15 evaluated the effect of centralization policies on postoperative mortality after cancer surgery and 26 described concurrent changes in the degree of centralization and postoperative mortality. Policy evaluation studies mainly used before-after designs (n = 13) or interrupted time series analysis (n = 2), mainly focusing on pancreatic, oesophageal and gastric cancer. All but one showed some degree of reduction in postoperative mortality, with statistically significant effects demonstrated by six studies. The pooled odds ratio for centralization policy effect was 0.68 (95% Confidence interval: 0.54–0.85; I2 = 80%). Meta-regression analysis of the 26 descriptive studies found that an increase of the proportion of patients treated at high volume hospitals was associated with greater reduction in postoperative mortality. Conclusions Centralization of cancer surgery is associated with reduced postoperative mortality. However, existing evidence tends to be of low quality and estimates of the effect size are likely inflated. There is a need for prospective studies using more robust approaches, and for centralization efforts to be accompanied by well-designed evaluations of their effectiveness.

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational factors with ALS risk. Methods: We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases (n = 95) and randomly selected population referents (n = 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model. Results: We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79&ndash, 7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02&ndash, 7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14&ndash, 4.54) and paint removers (OR = 2.01, 95% CI 0.90&ndash, 4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70&ndash, 4.09) and 2.41 (95% CI 1.13&ndash, 5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63&ndash, 2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88&ndash, 9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies. Conclusions: Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology.

The aetiology of amyotrophic lateral sclerosis (ALS), a rare and extremely severe neurodegenerative disease, has been associated with magnetic fields exposure. However, evidence for such a relation in the general population is weak, although the previous null results might also be due to exposure misclassification, or a relationship might exist only for selected subgroups. To test such a hypothesis we carried out a population-based case-control study in two Northern and Southern Italy regions, including 703 ALS cases newly diagnosed from 1998 to 2011 and 2737 controls randomly selected from the residents in the study provinces. Overall, we found that a residence near high-voltage power lines, within the corridors yielding a magnetic fields of ≥0.1 μT, was not associated with an excess disease risk, nor did we identify a dose-response relationship after splitting the exposed corridor according to the 0.1, 0.2 and 0.4 μT cut-points of exposure. These results were confirmed taking into account age at onset, period of diagnosis, sex, geographical area, and length of exposure. Overall, despite the residual possibility of unmeasured confounding or small susceptible subgroups not identified in our study, these results appear to confirm that the exposure to magnetic fields from power lines occurring in the general population is not associated with increased ALS risk.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of the motor neurons. The etiology of ALS remains largely unknown, particularly with reference to the potential environmental determinants. Methods: We performed a population-based case-control study in four provinces from both Northern and Southern Italy in order to assess non-genetic ALS risk factors by collecting through tailored questionnaires information about clinical and lifestyle factors. We estimated ALS risk by calculating odds ratio (OR) with its 95% confidence interval (CI) using unconditional logistic regression models adjusted for sex, age and educational attainment. Results: We recruited 230 participants (95 cases and 135 controls). We found a possible positive association of ALS risk with trauma, particularly head trauma (OR = 2.61, 95% CI 1.19&ndash, 5.72), electric shock (OR = 2.09, 95% CI 0.62&ndash, 7.06), and some sports, although at a competitive level only. In addition, our results suggest an increased risk for subjects reporting use of private wells for drinking water (OR = 1.38, 95% CI 0.73&ndash, 2.27) and for use of herbicides during gardening (OR = 1.95, 95% CI 0.88&ndash, 2.27). Conversely, there was a suggestion of an inverse association with overall fish consumption (OR = 0.27, 95% CI 0.12&ndash, 0.60), but with no dose-response relation. Consumption of some dietary supplements, namely those containing amino acids and, in the Southern Italy population, vitamins and minerals such as selenium, seemed associated with a statistically imprecise increased risk. Conclusions: Our results suggest a potential etiologic role a number of clinical and lifestyle factors with ALS risk. However, caution is needed due to some study limitations. These include the small sample size and the low number of exposed subjects, which affect statistical precision of risk estimates, the potential for exposure misclassification, and the uncertainties about mechanisms underpinning the possible association between these factors and disease risk.

We much appreciate the positive comments and interest concerning our study on the environmental and occupational risk factors of amyotrophic lateral sclerosis (ALS) [...]

Some studies have reported an association between overexposure to selenium and risk of amyotrophic lateral sclerosis (ALS), a rare degenerative disease of motor neurons. From 1986 through 2015, we followed a cohort in Northern Italy that had been inadvertently consuming tap water with unusually high concentrations of inorganic hexavalent selenium from 1974 to 1985. We had previously documented an excess incidence of ALS in this cohort during 1986-1994. Here, we report extended follow-up of the cohort for an additional 21 years, encompassing 50,100 person-years of the exposed cohort and 2,233,963 person-years of the unexposed municipal cohort. We identified 7 and 112 incident ALS cases in the exposed and unexposed cohorts, respectively, yielding crude incidence rates of 14 and 5 cases per 100,000 person-years. A Poisson regression analysis, adjusting for age, sex and calendar year, produced an overall incidence rate ratio (IRR) for ALS of 2.8 (95% confidence interval (CI) 1.3, 6), with a substantially stronger IRR in 1986-1994 (8.2, 95% CI 2.7, 24.7) than in 1995-2015 (1.5, 95% CI 0.5, 4.7), and among women (5.1, 95% CI 1.8, 14.3) than men (1.7, 95% CI 0.5, 5.4). Overall, these results indicate an association between high exposure to inorganic selenium, a recognized neurotoxicant, and ALS incidence, with declining rates after cessation of exposure and stronger effects among women.

Aims In recent years, the prevalence of pregestational diabetes (PGDM) and the concern about the possibility of adverse pregnancy outcomes in affected women have been increasing. Routinely collected health data represent a timely and cost-efficient approach in PGDM epidemiological research. This study aims to evaluate the reliability of hospital discharge (HD) coding to identify a population-based cohort of pregnant women with PGDM and to assess trends in prevalence in two provinces of Northern Italy. Methods We selected all deliveries occurred in the period 1997–2010 with ICD-9-CM codes for PGDM in HD record and we matched up to 5 controls from mothers without diabetes. We used Diabetes Registers (DRs) as the gold standard for validation analysis. Results We selected 3800 women, 653 with diabetes and 3147 without diabetes. The agreement between HD records and DRs was 90.7%, with K = 0.58. We detected 350 false positives and only 1 false negative. Sensitivity was 99.3%, specificity 90.0%, positive predictive value 46.4% and negative predictive value 99.9%. Of the false positives, 48.6% had gestational diabetes and 2.3% impaired glucose tolerance. After the validation process, PGDM prevalence decreased from 4.4 to 2.0 per 1000 deliveries. Conclusions Our results show that HD facilitate detection of almost all PGDM cases, but they also include a large number of false positives, mainly due to gestational diabetes. This misclassification causes a large overestimation of PGMD prevalence. Our findings require accuracy evaluation of ICD-9-CM codes, before they can be widely applied to epidemiological research and public health surveillance related to PGDM.

Aluminum and tin are ubiquitous in the environment. In normal biological systems, however, they are present only in trace amounts and have no recognized biological functions in humans. High exposure to these metals can result in adverse health effects such as neurodegenerative diseases. In non-occupationally exposed subjects, diet is the primary source of exposure. In this study, we aimed at estimating dietary aluminum and tin intake in an Italian adult population. We measured aluminum and tin concentrations through inductively-coupled plasma mass spectrometry in 908 food samples. We also estimated dietary intake of these two metals, by using a validated semi-quantitative food-frequency questionnaire administered to 719 subjects (319 men and 400 women) recruited from the general population of the Emilia Romagna region, Northern Italy. We found the highest aluminum levels in legumes, sweets, and cereals, while the highest tin levels were in sweets, meat and seafood. The estimated median daily dietary intake of aluminum was 4.1 mg/day (Interquartile range – IQR: 3.3–5.2), with a major contribution from beverages (28.6%), cereals (16.9%), and leafy vegetables (15.2%). As for tin, we estimated a median intake of 66.8 μg/day (IQR: 46.7–93.7), with a major contribution from vegetables (mainly tomatoes) (24.9%), fruit (15.5%), aged cheese (12.2%), and processed meat (10.4%). This study provides an updated estimate of the dietary intake of aluminum and tin in a Northern-Italy adult population, based on data from a validated food-frequency questionnaire. The intake determined for this population does not exceed the established thresholds of tolerable intake.

Regular consumption of fish is generally recommended by authorities because fish is an important source of essential nutrients. However, the presence of potentially toxic contaminants in fish has raised many concerns about the food's safety for human health. In the present study, we used a validated semi-quantitative food frequency questionnaire to assess the dietary habits of a representative sample of 719 individuals (319 males and 400 females) aged 18-87 years residing in Northern Italy. We estimated weekly dietary intakes of Arsenic (As) and Mercury (Hg), and we compared them with safety standards set by the European Food Safety Authority. In this population, fish was the main contributor to As and Hg intake. The highest levels of As were in sardine, sole/flounder and cephalopods, and of Hg in the biggest, predatory fish. About the other foods, cereals were the second contributor to the intake of these elements, especially rice for As and bread for Hg, and high levels of As and Hg were also found in mushrooms, coffee and wine. Average weekly intake of both contaminants was below recommended safety limits.

Background/aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with still unknown aetiology. Among environmental factors, pesticides have been investigated due to their potential neurotoxic effects. Within a population-based case-control study conducted in two Italian regions, we aimed to investigate ALS risk due to passive residential exposure to pesticides using two methodologies. Methods The exposure assessment was carried with an individual questionnaire, which collected information of the entire residential history of subjects, focusing on rural residence or in the vicinity of agricultural areas. It was compared with assessment based on geographical information system (GIS), avoiding direct contact with study subjects. To do that, we computed the percentage (≥50%) of rural land use within the 100 m round buffer around each subjects’ residence, according to cover maps of two periods available from the Department of Agriculture, recent (2003–2009) and historical (1978–1989) ones. Risk for passive residential exposure to pesticides was computed using a sex and age adjusted logistic regression model for both methods, and their agreement was assessed using Cohen’s kappa (k). Results The odds ratio (OR) with their 95% confidence intervals (CI) for passive residential exposure to pesticides was 1.67 (95% CI 0.87 to 3.20) from the questionnaire-based assessment, while ORs from the GIS-based assessment were 1.05 (0.40 to 2.73) and 1.13 (0.49 to 2.63) for the recent and historical period, respectively. The agreement between two methods considering all participants was generally moderate to high, with k of 0.564 (95% CI: 0.361 to 0.767) and 0.648 (0.494–0.802) for recent and historical periods, respectively. Analyses divided between cases and controls yielded similar results, with k of 0.468 (0.133–0.803) in cases and 0.630 (0.382–0.879) in controls for recent period, and 0.642 (0.380–0.904) in cases and 0.652 (0.464–0.840) in controls for historical one. Conclusion Our results showed a slight increased risk of passive exposure to pesticides using the questionnaire-based assessment, with less conclusive results from the GIS-based one. The similar agreement either between periods and case/control status, suggested also that no substantial information bias and differential exposure misclassification occurred when assessing pesticides exposure in our population.

Starting from an analysis of contractual clauses included in a large-scale investment contract in land between Cameroon and a private company, this paper aims at inferring general conclusions on the multilevel regulatory framework applying to investment operations in land. After having identified how domestic law and international law interact at the contractual level, the study moves to the analysis of those provisions, namely umbrella clauses and stabilization clauses, which blur the lines between contract and treaty claims, and impact on the pursuit of host States’ public interest. The “chilling” effect of these clauses on host States has further triggered reflection onto whether international law, in its entirety, applies to investment operations and to what extent. Finally, beyond traditional treaty interpretation methods, this paper tries to offer an overview of different harmonization mechanisms, which might prove more effective in the accommodation between investment and non-investment obligations.

Background Epidemiologic studies have raised the possibility that some pesticide compounds induce the neurodegenerative disease amyotrophic lateral sclerosis (ALS), though the available evidence is not entirely consistent. Methods We conducted a population-based case-control study in two Italian populations to assess the extent to which residence in the vicinity of agricultural crops associated with the application of neurotoxic pesticides is a risk factor for ALS, using crop acreage in proximity to the residence as an index of exposure. Results Based on 703 cases and 2737 controls, we computed an ALS odds ratio of 0.92 (95% confidence interval 0.78-1.09) for those in proximity to agricultural land. Results were not substantially different when using alternative exposure categories or when analyzing specific crop types, with the exception of a higher risk related to exposure to citrus orchards and olive groves in Southern Italy, though based on few exposed subjects (N = 89 and 8, respectively). There was little evidence of any dose-response relation between crop proximity and ALS risk, and using long-term residence instead of current residence did not substantially change our estimates. Conclusions Though our index of exposure is indirect and subject to considerable misclassification, our results offer little support for the hypothesis that neurotoxic pesticide exposure increases ALS risk.

Several intervention studies have investigated the relation between potassium intake and blood-pressure, particularly in hypertensive subjects. However, uncertainties still exist about the existence and the amount of such an effect, and about the role of some potential effect-modifiers, including the baseline potassium intake and geographical area.We carried out a systematic review of the evidence concerning such relation in hypertensive subjects, performing a meta-analysis and a meta-regression of RCT with selective and validated long-term (≥4weeks) potassium supplementation. We also implemented 'unconventional' search strategies in order to identify all potentially interesting studies.Overall, potassium supplementation decreased systolic blood pressure of 4.48mmHg (95% CI 3.07-5.90) and diastolic blood pressure of 2.96mmHg (1.10-4.82). There was little evidence of dose-response relation between blood-pressure decrease and potassium supplementation, as assessed through total achieved potassium intake in the intervention groups, difference in achieved potassium intake, and study duration. However, lower (90mmol/day) potassium intake at baseline was associated with a higher blood-pressure lowering effect, as were higher sodium intake (particularly ≥4g/day), higher sodium-to-potassium ratio and the absence of any anti-hypertensive drug treatment. Trials conducted in Southern Europe showed the highest blood-pressure lowering effect compared with the remaining regions.Potassium supplementation in hypertensives was generally associated with decreased blood pressure, particularly in high sodium consumers, subjects not on hypertensive drug treatment, and those in the lowest category of potassium intake. An adequate dietary intake of potassium, in the order of 90mmol/day, should be achieved for blood pressure control.