Childhood infectious diseases and risk of non-Hodgkin's lymphoma according to the WHO classification: A reanalysis of the Italian multicenter case-control study.

Since 1960, incidence of non-Hodgkin's lymphoma (NHL) has been increasing in most industrialized countries, but causes of this trend remain unclear. A role of the decreased exposure to infectious agents during childhood has been proposed. Our study evaluates the association between common childhood infectious diseases and the risk of NHL and its major subtypes by a reanalysis of the Italian multicenter case-control study. After exclusion of next-of-kin interviews, 1,193 cases, diagnosed between 1990 and 1993, and 1,708 population-based controls were included in the analyses. OR estimates were obtained by logistic regression, adjusting for gender, age, residence area, education, smoking habit and exposure to radiations, pesticides and aromatic hydrocarbons. Among B-cell lymphomas (n = 1,102) an inverse association was observed for rubella (OR = 0.80, 95% CI: 0.65-0.99), pertussis (OR = 0.74, 95% CI: 0.62-0.88) and any infection (OR = 0.75, 95% CI: 0.61-0.93). A negative trend by number of infections was observed, which was more evident among mature B-cell lymphoma (OR = 0.66 for three infections or more, 95% CI: 0.48-0.90). Our results indicate a potential protective role of common childhood infections in the etiology of B-cell NHL.

[Safety in surgery]. / Sicurezza in chirurgia. Lunga vita alla checklist, ma non solo checklist.

The effectiveness of the World Health Organization's (WHO) surgical safety checklist (SSCL) in decreasing mortality and morbidity of surgical procedures was firstly suggested in 2009; the checklist is now strongly recommended internationally for adoption as a highly effective yet economically simple intervention. However, since 2009 several published studies have reported inconsistent results, besides many issues concerning local implementation. Drawing on the recently published experience carried out in Ontario, a concise overview of the current debate is presented, with some comments on implications for the national healthcare system in Italy. More generally, the need to include the implementation of the SSCL in a larger effort addressing safety in surgery is pointed out.

[Patient-reported outcomes: definition and measurement]. / Esiti riferiti dal paziente: cosa sono e come si misurano.

The concept of "patient-reported outcomes" have been proposed by the Food and Drug Administration in the year 2000, in order to describe one of the different and potential sources of information on the drug's safety and effectiveness. It represents an "umbrella" term, which covers a multiplicity of meanings and primarily identifies a conceptual approach and a methodology specifically oriented to the patients' point of view on outcomes, instead of the traditional clinical and professional perspective. The patient-reported outcomes measures are frequently self-completed questionnaires. The measures can be classified in general and specific. The first one, general, relates to the assessment of the quality of life or the health status, in the general population or in subgroups with particular health problems (eg. SF-36 Health Survey, EQ-5D). The second one, specific, mainly relates to the assessment of particular types of symptoms (eg. pain, anxiety, fear, depression) and functions (eg. daily living activities), in population's subgroups with definite health problems, undergoing or not to a healthcare procedure (eg. Adult Asthma Quality of Life Questionnaire, Kidney Disease Quality of Life Instrument, Oxford Hip Score, Oxford Knee Score). For the selection of an instrument a series of criteria needs to be taken into account, among which the psychometric properties, the expert judgement, the interpretability, the acceptability, and the feasibility of the entire process.

[Patient-reported outcomes: the experience of United Kingdom's NHS and suggestions for the Italian NHS]. / Esiti riferiti dal paziente: l'esperienza del SSN del Regno Unito e le riflessioni per il SSN italiano.

This paper describes the applications of the patient-reported outcome measures, focusing on the National Health Service (NHS) in the United Kingdom. Over the years the use of some related measures has widened, moving from research to clinical practice, and, only recently, to the healthcare quality assessment. The program launched by the United Kingdom Department of Health in April 2009 falls into the latter one, and requires the collection of patient-reported outcome measures for selected surgical procedures (hip or knee replacement, inguinal hernia, varicose veins) within all the health facilities financed by the National Health Service. Several of questionnaires are administered before and after the procedure, thus allowing to assess the health outcomes reported by the patient. From 2009 to 2013, the total number of questionnaires analyzed was high and steadily growing; in the period April 2009-March 2010 184.818 pre-procedure and 134.768 post-procedure questionnaires were completed by the patients and returned, with a 17% and 11% increase, respectively, compared to the previous period (April 2009-March 2010). The analysis of the United Kingdom's experience offers some reflections for the Italian Health Service with regard to some issues, such as the feasibility and the resources, the most appropriate methodology, and the professional culture.

Childhood infectious diseases and risk of leukaemia in an adult population.

Our study is aimed at investigating the association between common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing leukaemia in an adult population. A reanalysis of a large population-based case-control study was carried out. Original data included 1,771 controls and 649 leukaemia cases from 11 Italian areas. To contain recall bias, the analysis was restricted to subjects directly interviewed and with a good quality interview (1,165 controls and 312 cases). Odds ratios (ORs) and their related 95% confidence intervals (95% CIs) were estimated by unconditional polychotomous logistic regression model adjusting for age, gender and occupational and lifestyle exposures. A protective effect of at least one infection (OR = 0.66, 95% CI: 0.45-0.97), measles (OR = 0.57, 95% CI: 0.39-0.82) and pertussis (OR = 0.66, 95% CI: 0.45-0.98) was observed for chronic lymphoid leukaemia (CLL). The number of infections was strongly inversely associated with the risk of CLL (p = 0.002, test for trend). With regard to the other types of leukaemia, only a protective effect of pertussis was observed for AML (OR = 0.52, 95% CI: 0.32-0.87). Our results pointed out a protective role of childhood infectious diseases on the risk of CLL in adults. Although a specific antioncogenic effect of some infectious disease, especially measles, cannot be ruled out, the observed decrease of risk with increasing number of infections suggests that a more general "hygiene hypothesis" could be the most likely explanation of the detected association. The protective role of pertussis remains to be elucidated.

Risk of leukemia and multiple myeloma associated with exposure to benzene and other organic solvents: evidence from the Italian Multicenter Case-control study.

BACKGROUND: While there is a general consensus about the ability of benzene to induce acute myeloid leukemia (AML), its effects on chronic lymphoid leukemia and multiple myeloma (MM) are still under debate. We conducted a population-based case-control study to evaluate the association between exposure to organic solvents and risk of myeloid and lymphoid leukemia and MM. METHODS: Five hundred eighty-six cases of leukemia (and 1,278 population controls), 263 cases of MM (and 1,100 population controls) were collected. Experts assessed exposure at individual level to a range of chemicals. RESULTS: We found no association between exposure to any solvent and AML. There were elevated point estimates for the associations between medium/high benzene exposure and chronic lymphatic leukemia (OR = 1.8, 95% CI = 0.9-3.9) and MM (OR = 1.9, 95% CI = 0.9-3.9). Risks of chronic lymphatic leukemia were somewhat elevated, albeit with wide confidence intervals, from medium/high exposure to xylene and toluene as well. CONCLUSIONS: We did not confirm the known association between benzene and AML, though this is likely explained by the strict regulation of benzene in Italy nearly three decades prior to study initiation. Our results support the association between benzene, xylene, and toluene and chronic lymphatic leukemia and between benzene and MM with longer latencies than have been observed for AML in other studies.

Effects on Clinical Outcomes of a 5-Year Surgical Safety Checklist Implementation Experience: A Large-scale Population-Based Difference-in-Differences Study.

The adoption of a surgical checklist is strongly recommended worldwide as an effective practice to improve patient safety; however, several studies have reported mixed results and a number of issues are still unresolved. The main objective of this study was to explore the impact of the first 5-year period of a surgical checklist-based intervention in a large regional health care system in Italy (4 500 000 inhabitants). We conducted a retrospective longitudinal study on 1 166 424 patients who underwent surgery in 48 public hospitals between 2006 and 2014. The adherence to the checklist was measured between 2011 and 2013 through a computerized database. The effects of the intervention were explored through multivariable logistic regression and difference-in-differences (DID) approaches, based on current administrative data sources. In-hospital and 30-days mortality, 30-days readmissions and length-of-stay (LOS) ⩾8 days were the observed outcomes. Adherence to the checklist showed marked variations across hospitals (0%-93.3%). A pre/post analysis detected statistically significant differences between surgical interventions performed in hospitals with higher adherence to the checklist (⩾75% of the surgeries) and those performed in other hospitals, as for the 30-days readmissions rate (odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.94-0.98) and LOS ⩾ 8 days rate (OR: 0.88; 95% CI: 0.87-0.89). These findings were confirmed after risk adjustment and DID analysis. No association was observed with mortality outcomes. On the whole, our study attained mixed results. Although a protective effect of the surgical checklist use could not be proved over the first 5 years of this regional implementation experience, our research offers some methodological insights for practical use in the evaluation process of large-scale implementation projects.

Alcohol consumption and risk of leukemia: A multicenter case-control study.

A population-based case-control study of 649 leukemia cases and 1771 controls carried out in 11 Italian areas, offered the opportunity to evaluate the relationship between alcohol consumption and leukemia risk. For all leukemias, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL), we found a non-significantly inverse association for moderate levels of total alcohol and wine intake, but increased risks at high levels, with, in most cases, significant trend effects (odd ratios (OR) for all leukemias in the lowest quartile of total alcohol consumption [0.1-9.0 g/day of ethanol] versus never-drinker = 0.73; 95% confidence intervals (95% CI) = 0.51-1.03; OR in the highest quartile [> 31.7 g/day] = 1.15; 95% CI = 0.82-1.63; p of the linear trend test = 0.007). For chronic myeloid leukemia (CML), we found a non-significantly positive association for all levels of total alcohol and wine intake, and a significant positive linear trend effect (p = 0.03) for wine intake (OR for 0.1-9.0 g/day of ethanol intake from wine = 1.34; 95% CI = 0.61-2.94; OR in the highest quartile of wine intake [> 27.7 g/day] = 2.13; 95% CI = 1.01-4.50). No consistent dose-response was detected analysing duration of alcohol consumption for any leukemia subtypes. In conclusion, even though our study did not show a clear association between alcohol intake and leukemia risk, some of the patterns of the risk estimates (a possible J-shaped dose-response curve between alcohol intake and ALL, AML, and CLL risks, and the positive association between alcohol and CML), may be suggestive.

[End-of-life and palliative care: the experience of the Tuscany region, Italy]. / Assistenza di fine vita e cure palliative: l'esempio della Regione Toscana.

This paper summarizes a research of the Regional Agency for Health in Tuscany (Florence, Italy) on end-of-life and palliative care. The evolving concepts and definitions at the international level as well as some relevant experiences of research and intervention are reported. The national context is described through recent legislation and the state-of-the art of health services. The experience of Tuscany is discussed with respect to regulation, health services and significant experiences in epidemiological research, education, and cultural promotion. The population needs for palliative care are estimated on the basis of mortality rates and hospital admissions in the last year of life. Seventy-five percent of people dying in 2003 had at least one hospital admission in the 12 previous months, while 42.1 percent of deaths occurred in hospital (more than half of them in Internal Medicine or Intensive Care Units).

[Qualitative research: which priority for scientific journals?]. / Ricerca qualitativa: quale priorità per le riviste scientifiche?

Quantitative and qualitative approaches in scientific research should not be looked at as separate or even opposed fields of thinking and action, but could rather offer complementary perspectives in order to build appropriate answers to increasingly complex research questions. An open letter recently published by the BMJ and signed by 76 senior academics from 11 countries invite the editors to reconsider their policy of rejecting qualitative research on the grounds of low priority and challenge the journal to develop a proactive, scholarly and pluralistic approach to research that aligns with its stated mission. The contents of the letter, the many voices raised by almost fifty rapid responses and the severe but not closed responses of the editors outline a stimulating debate and hopefully prelude some "change in emphasis", ensuring that all types of research relevant to the mission of the BMJ (as well as other core journals) are considered for publication and providing an evolving landmark for scientific and educational purposes.

Non-Hodgkin's lymphoma and type of tobacco smoke.

BACKGROUND: In recent decades, the incidence of non-Hodgkin's lymphoma (NHL) has increased in all industrialized countries. Tobacco smoke contains several recognized or putative carcinogenic compounds that differ in concentration depending on which of the two main types, blond or black, is consumed. This investigation sought to evaluate the association between NHL and type of tobacco smoked (blond, black, or mixed), focusing on the Working Formulation (WF) subgroups. METHODS: Reanalysis of Italian data from a recent multicenter population-based case-control study. The 1450 cases of NHL and 1779 healthy controls from 11 Italian areas with different demographic and productive characteristics were included in the study, corresponding to approximately 7 million residents. Odds ratios (ORs) adjusted for age, gender, residence area, educational level, and type of interview were estimated by unconditional logistic regression model. RESULTS: A statistically significant association [OR = 1.4, 95% confidence interval (CI) 1.1-1.7] was found for blond tobacco exposure and NHL risk. A dose-response relationship was limited to men younger than 52 years (chi(2) for trend = 9.95, P < 0.001). Subjects starting smoking at an early age showed a higher risk in men younger than 65 years, whereas no clear trend was evident for the other age and gender subgroups. The analysis by WF categories showed the highest risks for follicular lymphoma in blond (OR = 2.1, 95% CI 1.4-3.2) and mixed (OR = 1.8, 95% CI 1.1-3.0) tobacco smokers and for large cell within the other WF group (OR = 1.6, 95% CI 1.1-2.4) only for blond tobacco. CONCLUSIONS: Smoking blond tobacco could be a risk factor for NHL, especially follicular lymphoma.

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

BACKGROUND: Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. METHODS: We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE). RESULTS: Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. CONCLUSIONS: Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.

Assessing pain in hospital in-patients: a cross-sectional study in Tuscany, Italy.

Guidelines Towards a Pain-Free Hospital, published in 2001 in Italy, determined an increasing spread of No-Pain Hospital Committees across the country and supported a more effective pain control in hospital. However, few hospitals adopted such protocols. To date, a thorough investigation on quality of pain management documentation is lacking. The present survey aimed to evaluate the quality of pain management documentation reported in medical and hospital discharge records. The study reviewed records of 2,459 patients discharged every Wednesday of November 2006 in 29 Tuscany hospitals. Among 2,459 patients, 51.5 % were males. Patients were aged between 0 and 90 years or above and were mostly (24.93 %) between 70 and 79 years; most of them (47.1 %) were hospitalized in Medicine ward. At hospital admission, less than half of examined records (40.3 %) reported pain-related items, and only 8.1 % reported how it was treated. During hospitalization, 39.6 % of the records reported the use of scales for measuring pain intensity and 49.7 % reported the pharmacological therapy. The present study highlights the lack of an exhaustive documentation of pain recording and management in the hospital setting. Therefore, healthcare providers should pay close attention to this relevant issue, and the quality of such documentation should be constantly monitored.

Occupational exposure to solvents and the risk of lymphomas.

BACKGROUND: A number of studies have shown possible associations between occupational exposures, particularly solvents, and lymphomas. The present investigation aimed to evaluate the association between exposure to solvents and lymphomas (Hodgkin and non-Hodgkin) in a large population-based, multicenter, case-control study in Italy. METHODS: All newly diagnosed cases of malignant lymphoma in men and women age 20 to 74 years in 1991-1993 were identified in 8 areas in Italy. The control group was formed by a random sample of the general population in the areas under study stratified by sex and 5-year age groups. We interviewed 1428 non-Hodgkin lymphoma cases, 304 Hodgkin disease cases, and 1530 controls. Experts examined the questionnaire data and assessed a level of probability and intensity of exposure to a range of chemicals. RESULTS: Those in the medium/high level of exposure had an increased risk of non-Hodgkin lymphoma with exposure to toluene (odds ratio = 1.8; 95% confidence interval = 1.1-2.8), xylene 1.7 (1.0-2.6), and benzene 1.6 (1.0-2.4). Subjects exposed to all 3 aromatic hydrocarbons (benzene, toluene, and xylene; medium/high intensity compared with none) had an odds ratio of 2.1 (1.1-4.3). We observed an increased risk for Hodgkin disease for those exposed to technical solvents (2.7; 1.2-6.5) and aliphatic solvents (2.7; 1.2-5.7). CONCLUSION: This study suggests that aromatic and chlorinated hydrocarbons are a risk factor for non-Hodgkin lymphomas, and provides preliminary evidence for an association between solvents and Hodgkin disease.

Personal use of hair dyes and hematolymphopoietic malignancies.

In the context of a population-based case-control study in Italy, the authors investigated the possible association between the personal use of hair dyes and non-Hodgkin's lymphoma (NHL), leukemia, multiple myeloma, and Hodgkin's disease. They collected all incident cases of hematolymphopoietic malignancies; the control group was formed with a random sample of the general population. Overall, the authors interviewed 2,737 research subjects and 1,779 control subjects. Among women, the authors found no association between ever using hair dyes and the risk of hematolymphopoietic malignancies. However, for permanent hair dyes, the authors observed a slightly increased risk of lymphocytic leukemia (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 0.8-2.2) and of follicular subtypes of NHL (OR= 1.3; 95% CI = 0.8-2.0). Women who used black hair dye colors were at an increased risk of developing leukemia (OR = 1.9; 95% CI = 1.0-3.4), in particular chronic lymphocytic leukemia (OR = 3.0; 95% CI = 1.1-7.5). In spite of the lack of information on the timing and frequency of hair dye use and the imprecision of the ORs, associations were suggested between leukemia and permanent black hair dye use and follicular NHL and the use of permanent hair dyes.

Non-Hodgkin's lymphoma, leukemia, and exposures in agriculture: results from the Italian multicenter case-control study.

BACKGROUND: The etiology of non-Hodgkin's lymphoma (NHL) and leukemia is still largely unknown, but exposure to chemicals, in particular pesticides, has been suggested to be a risk factor. METHODS: A large population-based case-control study was conducted in Italy with the aim of investigating the associations between pesticide exposure and NHL, and solvents and leukemia. Data presented in this article refer to 1,575 interviewed cases and 1,232 controls in the nine agricultural study areas. RESULTS: Exposure to nitro-derivatives and phenylimides among fungicides, hydrocarbon derivatives and insecticide oils among insecticides, and the herbicide amides are the chemical classes observed to be associated with the pathologies under investigation. CONCLUSIONS: The results of the case-control study suggest an increased risk for NHL and leukemia, and some chemical classes of pesticides, although few are statistically significant and some are based on few exposed cases. The results also show that men and women experience both similar and different risks for the same environmental agricultural exposures. Am. J. Ind. Med. 44:627-636, 2003.