Management of psychogenic non-epileptic seizures: a multidisciplinary approach.

The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.

Antidepressants and the risk of arrhythmia in elderly affected by a previous cardiovascular disease: a real-life investigation from Italy.

PURPOSE: The study aimed to fill existing knowledge gaps on the safety of antidepressant drugs (ADs) by estimating the risk of hospitalization for arrhythmia associated with use of selective serotonin reuptake inhibitors (SSRIs) and newer atypical ADs (NAAs) among elderly with previous cardiovascular (CV) events. METHODS: The cohort was composed by 199,569 individuals aged ≥ 65 years from five Italian healthcare territorial units who were discharged for cardiovascular outcomes in the years 2008-2010. The 17,277 patients who experienced hospital admission for arrhythmia during follow-up were included as cases. Odds of current ADs use among cases (i.e., 14 days before hospital admission) was compared with (i) odds of current use of 1:5 matched controls (between-patients case-control) and with (ii) odds of previous use during 1:5 matched control periods (within-patient case-crossover). The risk of arrhythmia associated with ADs current use was modelled fitting a conditional logistic regression. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS: Current users of SSRIs and NAAs were at increased risk of arrhythmia with case-control odds ratios (OR) of 1.37 (95% confidence interval, CI 1.18 to 1.58) and 1.41 (1.16 to 1.71) and case-crossover OR of 1.48 (1.20 to 1.81) and 1.72 (1.31 to 2.27). An increased risk of arrhythmia was associated with current use of trazodone (NAA) consistently in case-control and case-crossover designs. CONCLUSIONS: Evidence that current use of SSRIs and NAAs is associated to an increased risk of arrhythmia among elderly with CV disease was consistently supplied by two observational approaches.

Dietary acrylamide and the risk of pancreatic cancer in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Background: Occupational exposure to acrylamide was associated with excess mortality from pancreatic cancer, though in the absence of dose-risk relationship. Few epidemiological studies have examined the association between acrylamide from diet and pancreatic cancer risk. Patients and methods: We considered this issue in a combined set of 1975 cases of pancreatic cancer and 4239 controls enrolled in six studies of the Pancreatic Cancer Case-Control Consortium (PanC4). We calculated pooled odds ratios (ORs) and their 95% confidence intervals (CI) by estimating study-specific ORs through multivariate unconditional logistic regression models and pooling the obtained estimates using random-effects models. Results: Compared with the lowest level of estimated dietary acrylamide intake, the pooled ORs were 0.97 (95% CI, 0.79-1.19) for the second, 0.91 (95% CI, 0.71-1.16) for the third, and 0.92 (95% CI, 0.66-1.28) for the fourth (highest) quartile of intake. For an increase of 10 µg/day of acrylamide intake, the pooled OR was 0.96 (95% CI, 0.87-1.06), with heterogeneity between estimates (I2 = 67%). Results were similar across various subgroups, and were confirmed when using a one-stage modelling approach. Conclusions: This PanC4 pooled-analysis found no association between dietary acrylamide and pancreatic cancer.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).

BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.

Potential drug-drug interactions and radiodiagnostic procedures: an in-hospital survey.

OBJECTIVES: To evaluate the type, frequency, severity and predictors of potential Drug-Drug Interactions (DDIs) in a cohort of patients undergoing radiodiagnostic procedures. SETTING: Eight Radiology wards located in Tuscany (Italy). METHODS: All participants exposed to at least two medications were included in the analysis. DDIs were grouped according to their severity as 'minor', 'moderate' or 'major'. A logistic model was used to estimate Odds Ratios and 95% Confidence Intervals for all predictors of potential DDI. MAIN OUTCOME MEASURES: Type and predictors of potential DDI in a cohort of patients undergoing radiodiagnostic procedures. RESULTS: One-thousand-and-two subjects (57.6% females; mean age: 67.3 +/- 12.2) entered the analysis, and 46.1% of them incurred in a potential DDI (78.9% 'moderate' in severity). The combination of allopurinol and ACE-inhibitors was the most frequent (21/153) among major potential DDIs, while steroids were involved in all cases of potential DDI due to premedication. Co-morbidity, number of co-medications, advanced age and premedication use increased the risk of potential DDI; a protective role was found for positive history of allergy. When the analysis was restricted to subjects with premedication (n = 93), only 12.9% of them reported a potential DDI directly attributable to premedication drugs. CONCLUSIONS: Among patients undergoing radiological examination, types and predictors of potential DDIs appeared in agreement with other kind of in-hospital populations. Premedication revealed to be a proxy predictor for potential DDIs. Considering the poor capability of the prescriber in recognizing interactions, their systematic evaluation (using an informatics tool) in patients undergoing radiological examination might be helpful in preventing the occurrence of clinically relevant DDIs.

Tobacco smoking, alcohol consumption and pancreatic cancer risk: a case-control study in Italy.

In Italy, pancreatic cancer accounts for approximately 5% of cancer-related deaths. Tobacco smoking is the major established risk factor for this cancer, whereas the role of alcohol consumption is open to debate. Between 1991 and 2008, we conducted a hospital-based case-control study on pancreatic cancer in northern Italy. Cases were 326 patients (median age 63 years) with incident pancreatic cancer admitted to major general hospitals. Controls were 652 patients (median age 63 years) with acute non-neoplastic conditions admitted to the same hospital network of cases. Multiple logistic regression was used to estimate the odds ratios (OR) and the corresponding 95% confidence intervals (CI). Pancreatic cancer was associated to current smoking (OR=1.68; 95% CI: 1.13-2.48), and the risk rose with increasing number of cigarettes/day (OR=2.04; 95% CI: 1.14-3.66 for > or = 20 cigarettes/day). No association emerged for former smokers (OR=0.98; 95% CI: 0.66-1.45). Alcohol consumption was associated to increased pancreatic cancer risk, but ORs were significant only among heavy drinkers (ORs: 2.03 and 3.42 for 21-34 and > or = 35 drinks/week, respectively). Pancreatic cancer risk was 4.3-fold higher in heavy smokers (> or = 20 cigarettes/day) and heavy drinkers (> or = 21 drinks/week) in comparison with never smokers who drunk < 7 drinks/week, which is compatible with an additive effect of these exposures. In conclusion, we found that tobacco smoking and alcohol drinking are two independent risk factors for pancreatic cancer which may be responsible for approximately one third of these cancers in our population.

Macronutrients, fatty acids and cholesterol intake and stomach cancer risk.

BACKGROUND: Several case-control studies have examined the association between intake of selected macronutrients and stomach cancer, with inconsistent results regarding total energy, proteins, carbohydrates and fats. MATERIALS AND METHODS: We considered the relation between total energy, various macronutrients and fatty acids and gastric cancer using data from a case-control study conducted in northern Italy. Cases were 230 patients with incident, histologically confirmed stomach cancer. Controls were 547 frequency-matched patients, admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. Logistic regression models conditioned on age and sex and adjusted for selected covariates were used to estimate the odds ratios (ORs) of stomach cancer. RESULTS: The multivariate ORs were 0.65 [95% confidence interval (CI) 0.43-0.98] for the highest versus lowest tertile of vegetable fats and 0.66 (95% CI 0.44-0.97) for polyunsaturated fatty acids. No significant association was found for proteins, sugars, starch, total and animal fats, saturated and monounsaturated fatty acids and cholesterol. CONCLUSION: In conclusion, our study indicates that selected vegetable fats have a favorable effect on stomach cancer risk.

The role of foods and nutrients on oral and pharyngeal cancer risk.

The relation between selected aspects of diet and the risk of oral and pharyngeal cancer was considered in a few cohort studies and approximately 30 case-control studies. These studies reported consistent inverse associations with fruit and vegetable consumption. beta-carotene, vitamin C and selected flavonoids were also inversely related to risk, although it remains difficult to disentangle their potential effect from that of fruit and vegetables. Whole-grain cereals, but not refined grain ones, were also favorably related to the risk of oral and pharyngeal cancer. The results were not consistent for other foods, including meat, fish, eggs, milk and dairy products, but it is now possible to exclude a strong relation with oral and pharyngeal cancer risk. Data are also reassuring for coffee and tea, while hot maté drinking has been related to increased risk in studies from Argentina and Brazil. There is no consistent association with total fat intake, but monounsaturated fats (and olive oil) have resulted inversely related to risk. In developed countries, selected aspects of diet may account for 20% to 25% of oral and pharyngeal cancers. This proportion is likely greater in selected developing countries.

Dietary glycemic load and gastric cancer risk in Italy.

We investigated gastric cancer risk in relation to dietary glycemic index (GI) and glycemic load (GL), which represent indirect measures of carbohydrate absorption and consequently of dietary insulin demand, in a case-control study conducted in northern Italy between 1997 and 2007, including 230 patients with the incident, histologically confirmed gastric cancer and 547 frequency matched controls, admitted to the same hospitals as cases with acute non-neoplastic conditions. We used conditional logistic regression models, including terms for major recognised gastric cancer risk factors and non-carbohydrate energy intake. The odds ratios (ORs) in the highest vs lowest quintile were 1.9 (95% CI: 1.0-3.3) for GI and 2.5 (95% CI: 1.3-4.9) for GL. Compared with participants reporting low GL and high fruits/vegetables intake, the OR rose across strata of high GL and low fruits/vegetables, to reach 5.0 (95% CI: 2.2-11.5) for those reporting low fruits/vegetables intake and high GL. Our study may help to explain the direct relation observed in several studies between starchy foods and gastric cancer risk.

Macronutrients, fatty acids and cholesterol intake and endometrial cancer.

BACKGROUND: There is some evidence that dietary habits may influence the risk of endometrial cancer independently of body mass, although the role of diet on endometrial carcinogenesis is unclear. PATIENTS AND METHODS: We carried out a multicenter case-control study from 1992 to 2006 in Italy on 454 women with incident, histologically confirmed endometrial cancer (age range 18-79 years) and 908 controls (age range 19-79 years) admitted to hospitals for acute, non-neoplastic diseases. A validated food-frequency questionnaire was used to estimate macronutrients, fatty acids and cholesterol intake. Logistic regression models, conditioned on age and study centre, and adjusted for major known risk factor of endometrial cancer and residual of energy intake were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Significant direct associations were observed with intake of energy (OR = 1.7 for the highest versus the lowest quintile, 95% CI = 1.1-2.5), and cholesterol (OR = 2.1, 95% CI = 1.4-3.2), while a direct borderline association emerged with saturated fatty acids (OR = 1.3, 95% CI = 0.9-2.0). There was no association with proteins, sugars, starch, total fat and other selected fatty acids. CONCLUSION: Energy and cholesterol intake were associated with endometrial cancer.

Diabetes and endometrial cancer: effect modification by body weight, physical activity and hypertension.

Among 777 endometrial cancer cases and 1550 controls from Italy and Switzerland, odds ratio was 1.7 (95% confidence interval: 1.2-2.5) for diabetes, and 5.1 for obese diabetic women as compared with non-obese non-diabetic ones. Diabetes shows a supramultiplicative effect with body mass index, but not with physical activity or hypertension.