IL FUMO DI SIGARETTA E IL RISCHIO DI TUMORE DEL PANCREAS: DIVERSI APPROCCI DI ANALISI IN UNA POOLED-ANALYSIS

Background: To evaluate the dose\u2013response relationship between cigarette smoking and pancreatic cancer risk and to examine the effects of temporal variables. Aim: The aim of my PhD thesis is to explore the effect of selected smoking variable (including dose, duration and time since quitting) on the risk of pancreatic cancer using the two-stage and the multilevel analysis, and to compare these results with those obtained using the \u201cstandard\u201d aggregate analysis. Moreover, generalized additive models were used to analyse the relation between smoking and pancreatic cancer risk without any data constriction. Methods: Data from 12 case\u2013control studies, within the International Pancreatic Cancer Case\u2013Control Consortium (PanC4) and including 6507 pancreatic cases and 12 890 controls, were analyzed. In the aggregate analysis, smoking variables were categorized and odds ratios (ORs), and corresponding 95 confidence intervals (CIs), were calculated using logistic regression models adjusted for selected covariates (sex, age, ethnicity, education, body mass index, alcohol consumption, and history of diabetes and of pancreatitits) and study center. In the two-stage analysis, smoking variables were categorized, and summary ORs were calculated pooling study-specific ORs using random-effects models. Study-specific ORs were calculated using logistic regression models adjusted for the same covariates used for adjustment in the aggregate analysis. In the multilevel analysis, smoking variables were categorized and summary ORs were calculated using hierarchical models with two levels of hierarchy, considering study center as level 1, and subject as level 2. At level 2, models were adjusted the same covariates used for adjustment in the aggregate analysis. Finally, smoking variables were considered as continuous and generalized additive logistic regression were used to explore the nonlinear effects. Results - aggregate analysis: Compared with never smokers, the OR was 1.46 (95% confidence interval [CI] 1.36\u20131.57) for former smokers and 2.00 (96% CI : 1.83-2.19) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR = 3.17 for more than 40 cigarettes per day, P for trend <0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR = 2.02). Moreover, compared to current cigarette smokers, the risk decreased with increasing time since cigarette cessation, in fact the OR being 0.46 after 30 years. Results - two-stage analysis: Point estimates were similar to those obtained in the aggregate analysis, whereas interval ones were larger. There was substantial heterogeneity among studies, except for current smokers of less than 10 cigarette per day (p-value=0.0952) or more than 40 cigarette per day (p-value=0.2815), for current smokers who smoked for 20-<30 years (p-value=0.2309), and for ex-smokers who time since quitting 10-<15 years (p-value=0.0756) or 15-<20 years (p-value=0.0739). Results - multilevel analysis: Point ant interval estimates were similar to those obtained in the aggregate analysis. As regard number of cigarettes, risks were stronger among females, subjects with less than 65 years, and among subjects drinking 0-1 drinks of alcohol per day. No differences were found for duration and time since quitting. Though significant increasing trend in risk with increasing number of cigarettes, duration and time since quitting was observed, nonlinear relations were found. The risk of pancreatic cancer increased rapidly for each additional increment of one cigarette/day up to 25-30 cigarettes/day, and less rapidly for higher number of cigarettes/day. As regard duration, the risk increased rapidly for each year up to 25 years, then the risk increased less rapidly, plateaued at 35 years, and declined for subjects who smoked more than 40 years. Finally, a periodic effect was observed for years since quitting, although a decreased risk for each years was found. 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, with a nonlinear effect, increases with the number of cigarettes smoked and duration of smoking and decreases with time since quitting

Efficacy and safety of pharmacological treatments for patent ductus arteriosus closure: A systematic review and network meta-analysis of clinical trials and observational studies

Efficacy and safety profiles of different pharmacological interventions used to treat patent ductus arteriosus (PDA) are relatively unexplored. Integrating the findings of randomized clinical trials (RCTs) with those from observational studies may provide key evidence on this important issue. We aimed at estimating the relative likelihood of failure to close the PDA, need for surgical closure, and occurrence of adverse events among preterm and full-term infants treated with indomethacin, ibuprofen, or acetaminophen, placebo, or no treatment including both RCTs and observational studies. We searched PubMed, Embase, and the Register of Controlled Trials from inception to October 30, 2018. We first estimated proportions of subjects with failure to close the PDA, subjects in whom surgical closure was performed after pharmacological treatment, death, and subjects with selected adverse events (AEs). These estimates were obtained using frequentist random-effect meta-analysis of arm-specific proportions. We then compared active drugs with each other and with control (either placebo or no treatment) by summarizing results at the end of treatment reported in the papers, regardless of number of administration(s), dose, route and type of administration, and study design and quality. We also summarized primary outcome results separately at first, second and third cycles of treatment. These estimates were obtained using Bayesian random-effects network meta-analysis for mixed comparisons, and frequentist random-effect pairwise meta-analysis for direct comparisons. We included 64 RCTs and 24 observational studies including 14,568 subjects (5339 in RCTs and 9229 in observational studies, 8292 subjects received indomethacin, 4761 ibuprofen, 574 acetaminophen, and 941 control (including placebo or no intervention).The proportion of subjects with failure to close the PDA was 0.24 (95% Confidence Interval, CI: 0.20, 0.29) for indomethacin, 0.18 (0.14, 0.22) for ibuprofen, 0.19 (0.09, 0.30) for acetaminophen, and 0.59 (0.48, 0.69) for control. At end of treatment, compared to control, we found inverse associations between all active drugs and failure to close PDA (for indomethacin Odds Ratio, OR, was 0.17 [95% Credible Interval, CrI: 0.11-0.24], ibuprofen 0.19 [0.12-0.28], and acetaminophen 0.15 [0.09-0.26]), without differences among active drugs. We showed inverse associations between effective drugs and need for surgical closure, as compared to control (for indomethacin OR was 0.28 [0.15-0.50], ibuprofen 0.30 [0.16-0.54], and acetaminophen 0.19 [0.07-0.46]), without differences among drugs. Indomethacin was directly associated with intraventricular hemorrhage (IVH) (1.27; 1.00, 1.62) compared to ibuprofen, and to oliguria as compared to ibuprofen (3.92; 1.69, 9.82) or acetaminophen (10.8; 1.86, 93.1). In conclusion, active pharmacological treatment, with indomethacin, ibuprofen, or acetaminophen, is inversely associated with failure to close the PDA compared to non-treatment. Ibuprofen should be preferred to indomethacin to avoid occurrence of IVH or oliguria, acetaminophen should be preferred to indomethacin to avoid oliguria

Optic nerve head and fibre layer imaging for diagnosing glaucoma

Background The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma. Objectives To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage. Search methods We searched several databases for this review. The most recent searches were on 19 February 2015. Selection criteria We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or Data collection and analysis We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level. Main results We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear. Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study. The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio. Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people. Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD &lt; -6 db versus 0.64 (0.60 to 0.69) for MD &gt;=-6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P &lt; 0.0001 for the difference in relative DOR). Authors' conclusions The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base. We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data

The use of a non-biological, bridging, antiprotrusio cage in complex revision hip arthroplasty and periacetabular reconstructive oncologic surgery. Is still today a valid option?: A mid/long-term survival and complications’ analysis

Introduction: Burch–Schneider-like antiprotrusio cages (B-SlAC) still remain helpful implants to bridge severe periacetabular bone losses. The purpose of this study was to evaluate outcomes and estimate both cages’ failures and complication risks in a series of B-SlAC implanted in revision of failed total hip arthroplasties (THA) or after resection of periacetabular primary or secondary bone malignancies. Risk factors enhancing the chance of dislocations and infections were checked. Materials and methods: We evaluated 73 patients who received a B-SlAC from January 2008 to January 2018. Group A, 40 oncological cases (22 primary tumors; 18 metastases); Group B, 33 failed THAs. We compared both Kaplan–Meier estimates of risk of failure and complication with the cumulative incidence function, taking account the competing risk of death. Cox proportional hazards model was utilized to identify possible predictors of instability and infection. Harris hip score HHS was used to record clinical outcomes. Results: Medium follow-up was 80 months (24–137). Average final HHS was 61 (28–92), with no differences within the two groups (p &gt; 0.05). The probabilities of failure and complications were 57% and 26%, respectively, lower in the oncologic group than in the rTHA group (p =0.176; risk 0.43) (p = 0.52; risk 0.74). Extended ileo-femoral approach and proximal femur replacement (p =0.02, risk ratio = 3.2; p = 0.04, rr = 2.1) were two significant independent predictors for dislocations, while belonging to group B (p = 0.04, rr = 2.6) was predictable for infections. Conclusion: Burch–Schneider-like antiprotrusio cages are a classical non-biological acetabular reconstruction method that surgeons should bear in mind when facing gross periacetabular bone losses, independently of their cause. However, dislocation and infection rates are high. Whenever possible, we suggest preserving the proximal femur in revision THA, and to use a less-invasive postero-lateral approach to reduce dislocation rates in non-oncologic cases

Using alternative or direct anthropometric measurements to assess risk for malnutrition in nursing homes.

AbstractObjectiveThe aim of this study was to use the Malnutrition Universal Screening Tool (MUST) to assess the applicability of alternative versus direct anthropometric measurements for evaluating the risk for malnutrition in older individuals living in nursing homes (NHs).MethodsWe conducted a cross-sectional survey in 67 NHs in Tuscany, Italy. We measured the weight, standing height (SH), knee height (KH), ulna length (UL), and middle-upper-arm circumference of 641 NH residents. Correlations between the different methods for calculating body mass index (BMI; using direct or alternative measurements) were evaluated by the intraclass correlation coefficient and the Bland-Altman method; agreement in the allocation of participants to the same risk category was assessed by squared weighted kappa statistic and indicators of internal relative validity.ResultsThe intraclass correlation coefficient for BMI calculated using KH was 0.839 (0.815–0.861), whereas those calculated by UL were 0.890 (0.872–0.905). The limits of agreement were ±6.13 kg/m2 using KH and ±4.66 kg/m2 using UL. For BMI calculated using SH, 79.9% of the patients were at low risk, 8.1% at medium risk, and 12.2% at high risk for malnutrition. The agreement between this classification and that obtained using BMI calculated by alternative measurements was “fair-good.”ConclusionWhen it is not possible to determine risk category by using SH, we suggest using the alternative measurements (primarily UL, due to its highest sensitivity) to predict the height and to compare these evaluations with those obtained by using middle-upper-arm-circumference to predict the BMI

A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study

Inter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly, no studies have focused on children. The STOP Pain project aimed to evaluate the risk factors that contribute to clinical response and adverse drug reactions to opioids by means of a systematic review and a clinical investigation on paediatric oncological patients

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

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

The role of a Mediterranean diet on the risk of oral and pharyngeal cancer.

BACKGROUND: The Mediterranean diet has a beneficial role on various neoplasms, but data are scanty on oral cavity and pharyngeal (OCP) cancer. METHODS: We analysed data from a case-control study carried out between 1997 and 2009 in Italy and Switzerland, including 768 incident, histologically confirmed OCP cancer cases and 2078 hospital controls. Adherence to the Mediterranean diet was measured using the Mediterranean Diet Score (MDS) based on the major characteristics of the Mediterranean diet, and two other scores, the Mediterranean Dietary Pattern Adherence Index (MDP) and the Mediterranean Adequacy Index (MAI). RESULTS: We estimated the odds ratios (ORs), and the corresponding 95% confidence intervals (CI), for increasing levels of the scores (i.e., increasing adherence) using multiple logistic regression models. We found a reduced risk of OCP cancer for increasing levels of the MDS, the ORs for subjects with six or more MDS components compared with two or less being 0.20 (95% CI 0.14-0.28, P-value for trend &lt;0.0001). The ORs for the highest vs the lowest quintile were 0.20 (95% CI 0.14-0.28) for the MDP score (score 66.2 or more vs less than 57.9), and 0.48 (95% CI 0.33-0.69) for the MAI score (score value 2.1 or more vs value less 0.92), with significant trends of decreasing risk for both scores. The favourable effect of the Mediterranean diet was apparently stronger in younger subjects, in those with a higher level of education, and in ex-smokers, although it was observed in other strata as well. CONCLUSIONS: Our study provides strong evidence of a beneficial role of the Mediterranean diet on OCP cancer