Use of pharmacological treatments by a sample of Italian patients affected by alcohol use disorders

Title: USE OF PHARMACOLOGICAL TREATMENTS BY A SAMPLE OF ITALIAN PATIENTS AFFECTED BY ALCOHOL USE DISORDERS Author name(s): R. Agabio; E.M. Diana; D. Grazzini; R. Pirastu; G.L. Gessa Institution: Department of Biochemical Sciences, Section of Neuroscience, Preclinical and Clinical Pharmacology, University of Cagliari, Italy Text Background: It has often been reported that the majority of patients affected by Alcohol Use Disorders (AUDs) do not receive any pharmacological treatment. This study was aimed at investigating the use of the medications available in Italy (disulfiram, naltrexone, acamprosate, and γ-hydroxybutyric acid) by a sample of outpatients affected by AUDs. Methods: Four trained psychologists interviewed outpatients affected by AUDs in an area of Sardinia, Italy, of approximately 550.000 adult inhabitants. Results: A total sample of 208 outpatients affected by AUDs was interviewed (~1/3 of total outpatients affected by AUDs of that area). Their main features were: 166 males (79.5%); mean age=48.6±0.6 year; duration of AUDs=15.8±0.7 years; number of drinks per drinking days=19.4±1.3; number of criteria of DSM-IV-Tr=5.8±0.1. Before the admission into specific services, 13 patients (6.2%) had already received medication for AUDs; 7 patients (3.4%) had received disulfiram and 6 patients (2.9%) γ-hydroxybutyric acid. Over the same period, 22 patients (10.6%) had already attended self-help groups and 4 patients (1.9%) had received thiamine (Vitamine B1). After the admission into specific medical settings for the treatment of AUDs, 113 patients (54.3%) received medication for AUDs: 58 patients (27.9%) received disulfiram, 65 patients (31.2%) γ-hydroxybutyric acid, 2 patients (1.0%) naltrexone, and 6 patients (2.9%) acamprosate. In the same period, 54 patients (26.0%) frequented self-help associations, and 21 patients (10.1%) received thiamine. Conclusions: The results of this study confirm that the number of patients who receive a treatment for AUDs continues to be surprisingly low. Despite the long duration and the high level of severity of the AUDs, the majority of patients affected by AUDs did not receive any treatment before their admission in specific medical settings for the treatment of AUDs (10% of patients frequented self-help groups, 6% received a medication for AUDs, and 2% thiamine). After the admission into specific medical settings, the number of patients who received a treatment increased: 26% frequented self-help associations, 54% received a specific medication, and 10% received thiamine. However, approximately half of the patients did not receive any pharmacological treatment even if they frequented medical settings for the treatment of AUDs. Additional work is needed to understand the reasons of such a scarce use of treatments. Acknowledgements: This study was supported by a grant from Regione Autonoma della Sardegna

Lung cancer mortality in a cohort of workers in a petrochemical plant: occupational or residential risk?

Gela area is an Italian polluted site qualifying for remediation because of widespread contamination from a petrochemical complex. This study investigates mortality and morbidity of the cohort of employees in Gela petrochemical plant with the aim of disentangling the health effect of work and residence. Work experience was classified in terms of job title, while an ad hoc mobility model was applied to define qualitative categories of residence in Gela as probable residents and probable commuters. Mortality rate ratio for lung cancer was 1.60 (90% CI 1.01-2.53) in workers probable resindents compared to probable commuters. For the same comparison, Hospital Discharge Prevalence Ratio for COPD was 1.39 (0.94-2.07). The crude categories of work and residence limits the interpretation of the causal nature of the study results. Despite several limitations, the results for respiratory pathologies are compatible with an etiological role of the documented contamination.The purpose of the present study is to examine the role of environmental (non occupational) exposures in lung cancer risk among petrochemical workers at a large petrochemical plant built on the Sicilian coast in the immediate vicinity of the town of Gela, Italy in 1960. The cohort included workers employed in the Gela petrochemical plant in 1960-1993. We looked at mortality rates for the period 1960-2002. An internal comparison was performed between two categories of workers with different likelihood of residence in Gela during the period of employment. The rate ratio of mortality from lung cancer comparing "probable residents" with "possible non residents," adjusted for age, calendar period, andjob classification (only blue collar, only white collar and both), was 1.66 (90% Confidence Interval 1.07-2.58). Although the information collected is quite sparse and no inferences can be made about risk sources, the results show a possible excess of residential/environmental risk from lung cancer mortality for those workers more likely to have been residents in Gela

Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data

BACKGROUND AND OBJECTIVES: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. METHODS: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. RESULTS: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an extended reference interval that takes into account the differences in platelet count observed in different geographic areas. CONCLUSIONS: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy

[Deprivation indices in small-area studies of environment and health in Italy].

The use of deprivation indices in small-area studies of environment and health is described, with particular reference to the Italian context. Deprivation indices can represent a proxy for individual deprivation and/or contextual deprivation. In Italy, deprivation indices have been constructed using Census variables. They are applied at census tract level in studies with a local basis; in national based studies, they can be used at municipality level. In SENTIERI Project (Mortality study of residents in Italian polluted sites) an ad hoc deprivation index at municipal level was used (DI SENTIERI). Its strength and weaknesses are discussed. In addition, suggestions about the use of socioeconomic indices in small area studies of environment and health are given

Mendelian randomisation identifies priority groups for prophylactic EBV vaccination

BACKGROUND: Epstein Barr virus (EBV) infects ~ 95% of the population worldwide and is known to cause adverse health outcomes such as Hodgkin’s, non-Hodgkin’s lymphomas, and multiple sclerosis. There is substantial interest and investment in developing infection-preventing vaccines for EBV. To effectively deploy such vaccines, it is vital that we understand the risk factors for infection. Why particular individuals do not become infected is currently unknown. The current literature, describes complex, often conflicting webs of intersecting factors—sociodemographic, clinical, genetic, environmental-, rendering causality difficult to decipher. We aimed to use Mendelian randomization (MR) to overcome the issues posed by confounding and reverse causality to determine the causal risk factors for the acquisition of EBV. METHODS: We mapped the complex evidence from the literature prior to this study factors associated with EBV serostatus (as a proxy for infection) into a causal diagram to determine putative risk factors for our study. Using data from the UK Biobank of 8422 individuals genomically deemed to be of white British ancestry between the ages of 40 and 69 at recruitment between the years 2006 and 2010, we performed a genome wide association study (GWAS) of EBV serostatus, followed by a Two Sample MR to determine which putative risk factors were causal. RESULTS: Our GWAS identified two novel loci associated with EBV serostatus. In MR analyses, we confirmed shorter time in education, an increase in number of sexual partners, and a lower age of smoking commencement, to be causal risk factors for EBV serostatus. CONCLUSIONS: Given the current interest and likelihood of a future EBV vaccine, these factors can inform vaccine development and deployment strategies by completing the puzzle of causality. Knowing these risk factors allows identification of those most likely to acquire EBV, giving insight into what age to vaccinate and who to prioritise when a vaccine is introduced

Indoor exposure to environmental tobacco smoke and dampness: respiratory symptoms in Sardinian children- DRIAS study

Indoorexposuresathome,environmentaltobaccosmoke(ETS)andmould/dampnessadverselyaffect respiratoryhealthofchildren.DisturbiRespiratorinell’InfanziaeAmbienteinSardegna(DRIAS) (RespiratorySymptomsinchildrenandtheEnvironmentinSardegna,Italy)aimsatrelatingthe prevalenceofrespiratoryandallergicsymptomstoindoorexposuresinSardinianchildren. DRIAS,across-sectionalinvestigationofrespiratorysymptoms/diseases,usedamodifiedversionof ISAACquestionnaire,included4122childrenattending29primaryschoolsintheschoolyear 2004–2005. If bothparentssmoketheprevalenceforcurrentwheezeandcurrentasthmaisalmostdoubledin comparisonwithneversmokers,forpersistentcoughandphlegmaroleissuggestedwhenonlymother smokes.Amongmotherssmokinginpregnancy,theprevalenceofcurrentwheezeandcurrentasthmais increased. ExposuretoETSandfamilyatopyhaveajointeffectresultinginanalmosttriplingof prevalenceforcurrentwheezeandmorethanfourtimesforcurrentasthma.Exposureto‘‘dampness’’ (mouldordampness)bothduringthefirstyearoflifeandcurrentlyisassociatedwithincreased prevalenceofcurrentwheeze,persistentcoughorphlegmandcurrentrhino-conjunctivitis;ifexposure is onlyduringthefirstyearoflifeadoublingormoreofprevalenceisobservedforcurrentwheeze, current asthma,andpersistentcoughorphlegm. DRIASresultsaddevidencetothecausalroleofchildhoodexposuretoETSinthedevelopmentof respiratorysymptoms(cough,phlegm,andwheezing)andasthma.ThejointeffectofETSandfamily atopyiscorroborated.Theresultsstrengthentheevidenceforacausalassociationbetween‘‘dampness’’ and respiratoryhealth,pointingtoitspossibleindependentroleincausingasthma,along-lasting exposureentailsadoubledprevalenceforbothasthmaticandbronchitissymptoms

LTF and DEFB1 polymorphisms are associated with susceptibility toward chronic periodontitis development

Objectives: Chronic periodontitis is a common pathological condition that affects the supporting tissue of the teeth, leading to progressive alveolar bone destruction and teeth loss. The disease is caused by bacteria and derives from an altered host immune and inflammatory response, also involving different factors such as the oral hygiene, smoking, and genetic background. The innate immune response, the first line of host defense, could also play an important role in the susceptibility to chronic periodontitis. In this study, we evaluated the possible association between periodontal disease and seven genetic variations within DEFB1 and LTF genes, encoding for \u3b2-defensins 1 and lactoferrin (two members of oral innate immune system), in an Italian isolated population. Subjects and Methods: DEFB1 5\u2032UTR g. -52G>A (rs1799946), g. -44C>G (rs1800972), g. -20G>A (rs11362), 3\u2032UTR c*5G>A (rs1047031), c*87A>G (rs1800971), LTF p.Ala29Thr (rs1126477), and p.Lys47Arg (rs1126478) single nucleotide polymor- phisms (SNPs) were analyzed in 155 healthy individuals and 439 chronic periodontitis patients from North-East Italy. Results: Significant associations were found between periodontitis and g. -20G>A (rs11362) and g. -44C>G (rs1800972) SNPs in DEFB1 gene as well as p.Ala29Thr (rs1126477) and p.Lys47Arg (rs1126478) SNPs in LTF gene. Discussion: Our results suggest the involvement of DEFB1 and LTF genetic variations in the susceptibility toward development of periodontitis

Cancer incidence in Italian contaminated sites

INTRODUCTION: The incidence of cancer among residents in sites contaminated by pollutants with a possible health impact is not adequately studied. In Italy, SENTIERI Project (Epidemiological study of residents in National Priority Contaminated Sites, NPCSs) was implemented to study major health outcomes for residents in 44 NPCSs. METHODS: The Italian Association of Cancer Registries (AIRTUM) records cancer incidence in 23 NPCSs. For each NPCSs, the incidence of all malignant cancers combined and 35 cancer sites (coded according to ICD-10), was analysed (1996-2005). The observed cases were compared to the expected based on age (5-year period,18 classes), gender, calendar period (1996-2000; 2001-2005), geographical area (North-Centre and Centre-South) and cancer sites specific rates. Standardized Incidence Ratios (SIR) with 90% Confidence Intervals were computed. RESULTS: In both genders an excess was observed for overall cancer incidence (9% in men and 7% in women) as well as for specific cancer sites (colon and rectum, liver, gallblad-der, pancreas, lung, skin melanoma, bladder and Non Hodgkin lymphoma). Deficits were observed for gastric cancer in both genders, chronic lymphoid leukemia (men), malignant thyroid neoplasms, corpus uteri and connective and soft-tissue tumours and sarcomas (women). DISCUSSION: This report is, to our knowledge, the first one on cancer risk of residents in NPCSs. The study, although not aiming to estimate the cancer burden attributable to the environment as compared to occupation or life-style, supports the credibility of an etiologic role of environmental exposures in contaminated sites. Ongoing analyses focus on the interpretation of risk factors for excesses of specific cancer types overall and in specific NPCSs in relation to the presence of carcinogenic pollutants

Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

<b>Background</b><p></p> It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.<p></p> <b>Methods</b><p></p> Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.<p></p> <b>Results</b><p></p> There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.<p></p> <b>Conclusions</b><p></p> Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes