ESTIMATES OF CANCER POPULATION ATTRIBUTABLE FRACTIONS FOR MULTIPLE RISK FACTORS FROM A NETWORK OF ITALIAN CASE-CONTROL STUDIES

Introduction. Attributable fraction (AF), proposed by Levin, quantifies the reduction in the disease prevalence that could be achieved by eliminating the exposure (or risk factor) of interest from the population. Disease etiology involves multiple risk factors that may act simultaneously in the occurrence of disease and the optimal approach to quantify the individual and the joint effects of different risk factors on the disease burden is one of the goals in epidemiological research. Adjusted AFs quantify the effect of one risk factor after controlling of other factors (i.e., risk factors that may act together to cause disease, adjustment variables or confounders). Adjusted AFs may add up more than the joint AF (i.e., the AF for eliminating all risk factors from the population) and in some situation may add up to more than 1, leading to the conclusion that adjusted AFs should not be used to the purpose of partitioning the joint effect into individual contributions. Eide and Gefeller proposed a way to accomplish this task. Sequential AFs quantify the additional effect of one risk factor on the disease risk after the preceding risk factors have already been removed in a specified order from the population. However, sequential AFs depend on the order in which risk factors are removed from the population. Average AFs overcome this shortcoming by averaging sequential AFs for a risk factor over all orders by which risk factors can be removed from the population. Average AFs quantify the additional effect of one risk factor on the disease risk after the preceding factors selected randomly have already been removed from the population. Objective. This work aims to illustrate the main methodologies to estimate AFs and corresponding confidence intervals in presence of multiple risk factors with a focus on case-control study design. Moreover, we provide AF estimates for the major risk factors using Italian case-control data on oral cavity and breast cancers. Modification of case-control study design. In the original notation, sequential and average AFs could not be used in case-control study design, since the ratio of controls to cases in the sample is fixed a priori and the resulting AF estimates will be biased. Ferguson et al. proposed a prevalence-based weighting approach to correct the imbalance between controls and cases. The method consists in weighting the likelihood function of the model used to estimate sequential and average AFs for the disease prevalence. Variance estimation. The main approaches for estimating AF confidence intervals (CIs) are based on asymptotic approximation (Delta method) and simulations (Monte Carlo method). Ferguson proposed a method based on Monte Carlo simulations for constructing average AF variance. They also proposed the \u201caverisk\u201d R package for calculating average AFs and corresponding CIs in both prospective and case-control studies. In this work, we proposed a modification of the Ferguson\u2019s method to account for sequential AF variability on the total variability. Variances comparison. We compared our and Ferguson\u2019s methods to estimate average AF variance using simulated data. We generate two classes of simulated dataset. Each class included four scenarios according to different correlation structure: from independence (scenario 1) to strong correlation among risk factors (scenario 4). The two classes differed in the prevalence and strength of the association between risk factors. In particular, the first class had a high prevalence and modest relative risks, whereas the second class had a low prevalence and huge relative risks. For both classes of simulated data, standard deviation increment (i.e., the relative difference between our and Ferguson\u2019s methods) became gradually larger increasing the number of independent risk factors (from two to ten). Conversely, standard deviation increment decreased incrementing the number of correlated risk factors. Although in some situations (i.e., for correlated risk factors) the contribution of our method could have a substantial relative impact on total AF variability (up to 88%), the absolute standard deviation differences between two methods were very small (less than 0.15) indicating a limited contribution of our method than the Feguson\u2019s one. Application to real data. We estimated average AFs using a case-control study conducted in Italy on 946 oral cavity cases and 2492 controls. Risk factors considered for AF estimation were smoking, alcohol drinking, red meat intake, vegetables intake, fruit intake, and family history of oral cavity cancer. The final model included also terms for sex, age, study centre, years of education, BMI, and non-alcohol energy intake to account for possible confounding effect. We set a prevalence of oral cavity cancer according to statistics from the consortium of Italian Cancer Registry (AIRTUM) to adjust average AFs for case-control data structure. Eighty-eight percent (95% CI: 78%; 98%) of oral cavity cases were attributable to the considered risk factors. In particular, the average AF for smoking was 0.34 (95% CI: 0.27; 0.41), indicating that 34% of oral cavity cases would not has occurred if smoking was randomly removed from the population over all possible risk factor removal orders. For the remaining risk factors, average AFs were 0.27 (95% CI: 0.17; 0.37) for alcohol drinking, 0.11 (95% CI: 0.06; 0.17) for low vegetables intake, 0.08 (95% CI: 0.02; 0.15) for low fruit intake, 0.06 (95% CI: 0.01; 0.12) for high red meat intake, and 0.009 (95% CI: -0.001; 0.02) for family history. We analyzed a further case-control study on 2569 breast cancer cases and 2588 controls. We set a prevalence of breast cancer to adjust average AFs for case-control data structure. The final model included alcohol drinking, parity, breastfeeding, use of oral contraceptives (OCs), and family history of breast cancer as risk factors; study centre, age, years of education, smoking, age at menarche and use of hormonal replacement therapy (HRT) as adjusting factors. The joint AF was 0.49 (95% CI: 0.35; 0.63) indicating that approximately half of the breast cancer cases would not has occurred if all risk factors were simultaneously eliminated from the population. In particular, average AFs were 0.27 (95% CI: 0.16; 0.39) for parity, 0.12 (95% CI: 0.06; 0.18) for alcohol drinking, 0.04 (95% CI: -0.02; 0.10) for breastfeeding (No or <4 months), 0.04 (95% CI: 0.03; 0.06) for family history of breast cancer, and 0.01 (95% CI: -0.01; 0.03) for OCs users. Conclusions. Sequential and average AFs are useful tools to apportion exposure-specific contributions in a population exposed to multiple risk factors. Sequential and average AFs share some mathematical properties such as component-additivity, symmetry, marginal rationality, and internal marginal rationality. Average AFs, however, do not represent the actual amount of disease ascribable for each risk factors because they assume that risk factors are removed from the population in a random order. Nevertheless, average AFs could be useful parameters to estimate the average burden of disease for each risk factors across all possible removal orders. In this work, we proposed an alternative approach to estimate the average AF confidence interval accounting for sequential AF variability on the total AF one. We compared the performance between our and Fergusons\u2019 methods to estimate AF variance. Although our method could have a relative impact on total AF variability, the absolute standard deviation differences suggest a limited contribution of our method. However, this topic should be further analyzed

Upper limb work-related musculoskeletal disorders in operating room nurses: A multicenter cross-sectional study

This study aimed to evaluate the association between personal and job characteristics and the risk of upper limb work-related musculoskeletal disorders (WMSDs) among operating room nurses (ORNs). To this end, we collected data from 148 ORNs working at 8 Italian hospitals and measured any upper limb disabilities experienced in the previous year using the Italian version of the disabilities of the arm, shoulder and hand (DASH) questionnaire. The associations between personal and job characteristics and risk of upper limb WMSDs were estimated by unconditional logistic regression models. The prevalence of upper limb WMSDs was 45.9%. Multivariate analysis showed the \u201cfemale gender\u201d and \u201cmonthly hours spent working as a scrub nurse\u201d to be directly associated with a higher DASH score (adjusted OR for gender = 5.37, 95% CI: 1.65\u201317.51, p &lt; 0.01; adjusted OR for monthly hours as scrub nurse = 3.09, 95% CI: 1.33\u20137.19, p &lt; 0.01). Overall, our findings indicate that a full-time job (&gt;120 h/month) as a scrub nurse significantly increases the risk of developing upper limb WMSDs among female ORNs. Thus, to reduce such risk in this particularly sensitive population, we recommend urgent implementation of ergonomic interventions on surgical equipment alongside job rotation and medical surveillance programs

Association between Nutrient-Based Dietary Patterns and Bladder Cancer in Italy

Limited knowledge is available on dietary patterns and bladder cancer risk. We analyzed data from an Italian case-control study carried out between 2003 and 2014, including 690 incident bladder cancer cases and 665 hospital-controls. We derived nutrient-based dietary patterns applying principal component factor analysis on 28 selected nutrients. We categorized factor scores according to quartiles, and estimated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) through logistic regression models, adjusted for major confounding factors. We identified four dietary patterns named "Animal products", "Vitamins and fiber", "Starch-rich", and "Animal unsaturated fatty acids". We found an inverse association between the "Vitamins and fiber" pattern and bladder cancer (OR = 0.70, 95% CI: 0.48-0.99, IV versus I quartile category). Inverse relationships of borderline significance were also found for the "Animal products" and the "Animal unsaturated fatty acids" dietary patterns. No significant association was evident for the "Starch-rich" pattern. The current study allowed us to identify major dietary patterns in this Italian population. Our study confirms available evidence and shows that scoring high on a fruit-and-vegetables pattern provides beneficial effects on bladder cancer risk

Red meat and cancer risk in a network of case-control studies focusing on cooking practices

Background Consumption of red meat has been related to increased risk of several cancers. Cooking methods could modify the magnitude of this association, as production of chemicals depends on the temperature and duration of cooking. Methods We analyzed data from a network of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463 colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian, 1294 prostate and 767 renal cancer cases. Controls included 11 656 patients admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence intervals (CIs) were estimated by multiple logistic regression models, adjusted for known confounding factors. Results Daily intake of red meat was significantly associated with the risk of cancer of the oral cavity and pharynx (OR for increase of 50 g/day = 1.38; 95% CI: 1.26-1.52), nasopharynx (OR = 1.29; 95% CI: 1.04-1.60), larynx (OR = 1.46; 95% CI: 1.30-1.64), esophagus (OR = 1.46; 95% CI: 1.23-1.72), colon (OR = 1.17; 95% CI: 1.08-1.26), rectum (OR = 1.22; 95% CI:1.11-1.33), pancreas (OR = 1.51; 95% CI: 1.25-1.82), breast (OR = 1.12; 95% CI: 1.04-1.19), endometrium (OR = 1.30; 95% CI: 1.10-1.55) and ovary (OR = 1.29; 95% CI: 1.16-1.43). Fried meat was associated with a higher risk of cancer of oral cavity and pharynx (OR = 2.80; 95% CI: 2.02-3.89) and esophagus (OR = 4.52; 95% CI: 2.50-8.18). Risk of prostate cancer increased for meat cooked by roasting/grilling (OR = 1.31; 95% CI: 1.12-1.54). No heterogeneity according to cooking methods emerged for other cancers. Nonetheless, significant associations with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97; 95% CI: 1.30-3.00) and stomach (OR = 1.86; 95% CI: 1.20-2.87). Conclusions Our analysis confirmed red meat consumption as a risk factor for several cancer sites, with a limited impact of cooking methods. These findings, thus, call for a limitation of its consumption in populations of Western countrie

History of cholelithiasis and cancer risk in a network of case-control studies

Background We analyzed the relationship between cholelithiasis and cancer risk in a network of case-control studies conducted in Italy and Switzerland in 1982-2009. Methods The analyses included 1997 oropharyngeal, 917 esophageal, 999 gastric, 23 small intestinal, 3726 colorectal, 684 liver, 688 pancreatic, 1240 laryngeal, 6447 breast, 1458 endometrial, 2002 ovarian, 1582 prostate, 1125 renal cell, 741 bladder cancers, and 21284 controls. The odds ratios (ORs) were estimated by multiple logistic regression models. Results The ORs for subjects with history of cholelithiasis compared with those without were significantly elevated for small intestinal (OR=3.96), prostate (OR=1.36), and kidney cancers (OR=1.57). These positive associations were observed ≥10 years after diagnosis of cholelithiasis and were consistent across strata of age, sex, and body mass index. No relation was found with the other selected cancers. A meta-analysis including this and three other studies on the relation of cholelithiasis with small intestinal cancer gave a pooled relative risk of 2.35 [95% confidence interval (CI) 1.82-3.03]. Conclusion In subjects with cholelithiasis, we showed an appreciably increased risk of small intestinal cancer and suggested a moderate increased risk of prostate and kidney cancers. We found no material association with the other cancers considere

Diabetes mellitus and the risk of bladder cancer : an Italian case-control study

Diabetes mellitus has been associated with an increased risk of bladder cancer, although the evidence is still open to discussion.Methods:We examined this association using data from a multicentre Italian case-control study, conducted between 2003 and 2014 on 690 bladder cancer cases and 665 frequency-matched hospital controls. Odds ratios (ORs) for diabetes were estimated by unconditional multiple logistic regression models, after allowance for major known risk factors for bladder cancer.Results:One hundred and twelve (16.2%) cases and 57 (8.6%) controls reported a diagnosis of diabetes mellitus, corresponding to a multivariate OR of 2.09 (95% confidence interval (CI): 1.46-3.01). Bladder cancer risk increased with duration of diabetes (OR 1.92 for 1-<5 years, 1.63 for 5-<10 years, 2.39 for 10-<15 years, and 2.58 for 6515 years). The increased risk of bladder cancer was consistent in strata of age and education, whereas it was somewhat lower (although not significantly) in women (OR 1.18), in never (OR 1.31) and current (OR 1.42) smokers, and in subjects with a body mass index <25 kg m-2 (OR 1.48).Conclusion:The present study provides further support of a role of diabetes in bladder cancer aetiology, although some residual confounding by tobacco, body mass index, or other unmeasured covariates may partly explain the association observed

Mediterranean diet and bladder cancer risk in Italy

Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms; however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54\u20130.98) for MDS of 4\u20135 and 0.66 (95% CI, 0.47\u20130.93) for MDS of 6\u20139 (p for trend = 0.02) compared to MDS = 0\u20133. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1\u2013pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer

&#947;-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation

Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1-and ASCT-associated immunodeficiency might increase the risk for \u3b3-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with \u3b3-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12135 copies/mL) and 18 patients (median 417 copies/106 PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other \u3b3-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of \u3b3-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT

Perinatal care in SARS-CoV-2 infected women: the lesson learnt from a national prospective cohort study during the pandemic in Italy

Background: Despite the growing importance given to ensuring high-quality childbirth, perinatal good practices have been rapidly disrupted by SARS-CoV-2 pandemic. This study aimed at describing the childbirth care provided to infected women during two years of COVID-19 emergency in Italy. Methods: A prospective cohort study enrolling all women who gave birth with a confirmed SARS-CoV-2 infection within 7 days from hospital admission in the 218 maternity units active in Italy during the periods February 25, 2020-June 30, 2021, and January 1-May 31, 2022. Perinatal care was assessed by evaluating the prevalence of the following indicators during the pandemic: presence of a labour companion; skin-to-skin; no mother-child separation at birth; rooming-in; breastfeeding. Logistic regression models including women' socio-demographic, obstetric and medical characteristics, were used to assess the association between the adherence to perinatal practices and different pandemic phases. Results: During the study period, 5,360 SARS-CoV-2 positive women were enrolled. Overall, among those who had a vaginal delivery (n = 3,574; 66.8%), 37.5% had a labour companion, 70.5% of newborns were not separated from their mothers at birth, 88.1% were roomed-in, and 88.0% breastfed. These four indicators showed similar variations in the study period with a negative peak between September 2020 and January 2021 and a gradual increase during the Alpha and Omicron waves. Skin-to-skin (mean value 66.2%) had its lowest level at the beginning of the pandemic and gradually increased throughout the study period. Among women who had a caesarean section (n = 1,777; 33.2%), all the indicators showed notably worse outcomes with similar variations in the study period. Multiple logistic regression analyses confirm the observed variations during the pandemic and show a lower adherence to good practices in southern regions and in maternity units with a higher annual number of births. Conclusions: Despite the rising trend in the studied indicators, we observed concerning substandard childbirth care during the SARS-CoV-2 pandemic. Continued efforts are necessary to underscore the significance of the experience of care as a vital component in enhancing the quality of family-centred care policies