Disease control of acromegaly does not prevent excess mortality in the long term: results of a nationwide survey in Italy.

OBJECTIVE: This study aimed to assess the long-term outcome of patients with acromegaly. DESIGN: This is a multicenter, retrospective, observational study which extends the mean observation period of a previously reported cohort of Italian patients with acromegaly to 15 years of follow-up. METHODS: Only patients from the centers that provided information on the life status of at least 95% of their original cohorts were included. Life status information was collected either from clinical records or from the municipal registry offices. Standardized mortality ratios (SMRs) were computed comparing data with those of the general Italian population. RESULTS: A total of 811 patients were included. There were 153 deaths, with 90 expected and an SMR of 1.7 (95% CI 1.4-2.0, p < 0.001). Death occurred after a median of 15 (women) or 16 (men) years from the diagnosis, without gender differences. Mortality remained elevated in the patients with control of disease (SMR 1.3, 95% CI 1.1-1.6). In the multivariable analysis, only older age and high IGF1 concentrations at last available follow-up visit were predictors of mortality. The oncological causes of death outweighed the cardiovascular ones, bordering on statistical significance with respect to the general population. CONCLUSIONS: Mortality remains significantly high in patients with acromegaly, irrespectively of disease status, as long as the follow-up is sufficiently long with a low rate of patients lost to follow-up. Therapy strategy including radiotherapy does not have an impact on mortality. Oncological causes of death currently outweigh the cardiovascular causes.

Cyberbullying and problematic social media use: an insight into the positive role of social support in adolescents-data from the Health Behaviour in School-aged Children study in Italy.

OBJECTIVES: The global spread of electronic devices has made cyberbullying and problematic social media use (PSMU) emerging public health concerns. This study aimed to investigate the prevalence of cyberbullying and PMSU among adolescents in northwestern Italy. We also explored the association between cyberbullying and PSMU and whether this association was moderated by social support. STUDY DESIGN: Data were collected as part of the Italian 2018 Health Behaviour in School-aged Children (HBSC) study in the Piedmont region; 186 school classes participated, comprising 3022 children aged 11, 13 and 15 years. The prevalence of cyberbullying and PSMU were estimated in subgroups of age and gender. Multivariate logistic regression was used to investigate the association between cyberbullying and PSMU, before and after taking into account social support. RESULTS: Girls reported higher cyber-victimisation and PSMU than boys (9.1% vs 6.0% and 10.2% vs 6.1%, respectively), and the risk of cyber-victimisation was higher in the presence of PSMU. This risk was attenuated in the presence of social support. CONCLUSIONS: PSMU is an important driver of cyberbullying, although social support can mediate these behaviours. Public health interventions are needed to guide adolescents how to use social media appropriately and to prevent cyberbullying and the mental health problems they can provoke.

Transposition of cardiovascular outcome trial effects to the real-world population of patients with type 2 diabetes.

BACKGROUND: Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. We herein transposed CVOT results to the population of patients with type 2 diabetes (T2D) seen in routine clinical practice and who may receive the medications tested in CVOTs. METHODS: We implemented the post-stratification approach based on aggregate data of CVOTs and individual data of a target population of diabetic outpatients. We used stratum-specific estimates available from CVOTs to calculate expected effect size for the target population by weighting the average of the stratum-specific treatment effects according to proportions of a given characteristic in the target population. Data are presented as hazard ratio (HR) and 95% confidence intervals. RESULTS: Compared to the target population (n = 139,708), the CVOT population (n = 95,816) was younger and had a two to threefold greater prevalence of cardiovascular disease. EMPA-REG was the CVOT with the largest variety of details on stratum-specific effects, followed by TECOS, whereas DECLARE and PIONEER-6 had more limited stratum-specific information. The post-stratification HR estimate for 3 point major adverse cardiovascular event (MACE) based on EMPA-REG was 0.88 (0.74-1.03) in the target population, compared to 0.86 (0.74-0.99) in the trial. The HR estimate based on LEADER was 0.88 (0.77-0.99) in the target population compared to 0.87 (0.78-0.97) in the trial. Consistent results were obtained for SUSTAIN-6, EXSCEL, PIONEER-6 and DECLARE. The effect of DPP-4 inhibitors observed in CVOTs remained neutral in the target population. CONCLUSIONS: Based on CVOT stratum-specific effects, cardiovascular protective actions of glucose lowering medications tested in CVOTs are transferrable to a much different real-world population of patients with T2D.

Prevalence of cocaine use and cocaine use disorder among adult patients with attention-deficit/hyperactivity disorder: A systematic review and meta-analysis.

We conducted this systematic review and meta-analysis (registered with PROSPERO CRD42020142039) of the literature to estimate the lifetime prevalence of cocaine use and cocaine use disorder among adult patients with attention-deficit/hyperactivity disorder (ADHD). The literature search was performed on the electronic databases PubMed and PsychINFO without date or language restrictions. Additional studies were identified by hand searching of citations. Inclusion criteria were: studies involving adult patients with ADHD and reporting cocaine use and/or cocaine use disorders. Data were pooled in the meta-analyses using a generalized linear mixed model with random effects. Statistical heterogeneity was assessed using the Cochran Q test. Sensitivity analyses were conducted. Twelve studies were included in the review: six in the meta-analysis of cocaine use and nine in the meta-analysis of cocaine use disorder. The estimated prevalence of cocaine use was 26.0% (95% CI 0.18-0.35) and the estimated prevalence of cocaine use disorder was 10.0% (95% CI 0.08-0.13). Heterogeneity in both meta-analyses was high but decreased to non-significance in the meta-analysis on cocaine use disorder after excluding the outlier study. In conclusion, one out of four adult patients with ADHD use cocaine and one out of ten develop a lifetime cocaine use disorder. Since cocaine use can lead to more severe and complex disorders of impaired systemic functioning, adult patients with ADHD should be assessed for cocaine use disorder and promptly referred for treatment.

Graft factors as determinants of postoperative delirium after liver transplantation.

Post-operative delirium (POD) is a frequent complication after surgery, occurring in 15-20% of patients. POD is associated with a higher complications rate and mortality. Literature on POD after liver transplantation (LT) is limited, with the few available studies reporting an incidence of 10-47%. The aim of this study was analyzing pattern, risk factors and clinical impact of POD after LT. Data on donor and recipient characteristics, postoperative course and POD of consecutive adult LT recipients from March 2016 to May 2018 were prospectively collected and retrospectively analyzed. Risk factors for POD were analyzed using univariable logistic regression and Lasso regression. Kaplan-Meier method was used for survival analysis. 309 patients underwent LT during study period; 3 were excluded due to perioperative death. Incidence of POD was 13.4% (n = 41). The median day of onset was 5th (IQR [4-7]) with a median duration of 4 days (IQR [3-7]). Several risk factors, related to the severity of liver disease and graft characteristics, were identified. Graft macrovesicular steatosis was the only factor independently associated with POD at multivariable analysis (OR 1.27, CI 1.09-1.51, p = 0.003). POD was associated with a higher rate of severe postoperative complications and longer intensive care unit and hospital stay, but did not significantly impact on patient and graft survival. Incidence of POD after LT is comparable to that observed after general surgery and graft factors are strongly associated with its onset. These results help identifying a subset of patients to be considered for preventive interventions.

Adjuvant mitotane therapy is beneficial in non-metastatic adrenocortical carcinoma at high risk of recurrence.

Objective Many patients with adrenocortical carcinoma (ACC) suffer from tumor recurrence despite radical surgery. Evidence on the post-operative use of mitotane is controversial and no predictors of response are available. We aimed to assess whether adjuvant mitotane treatment may prolong survival in patients with non-metastatic ACC following complete resection and whether ACC patients at high risk of recurrence may benefit from treatment. Design and methods We retrospectively reviewed data from 152 non-metastatic ACC patients followed at the San Luigi Gonzaga Hospital: 100 patients were treated with adjuvant mitotane and 52 patients were left untreated following surgery. We assessed a number of potential predictive factors of recurrence and death. Mitotane effect was explored stratifying patients by staging (stage I-II vs stage III), hormone secretion (yes vs no) and Ki67 index. Results The non-treated group had a higher risk of recurrence (HR: 2.79, 95%CI: 1.58-4.91; P < 0.001) than mitotane-treated group, while overall survival was not significantly different between groups. Hormone secretion, elevated Weiss score and elevated Ki67 index confer a higher risk of both recurrence and death and stage III ACC of death. Adjuvant mitotane treatment reduced significantly the risk of death in patients with elevated Ki67 index (P = 0.005) and in patients with stage III ACC (P = 0.02). Conclusions Adjuvant mitotane may prolong recurrence-free survival in radically resected ACC patients with acceptable toxicity and may also prolong overall survival in a subgroup of ACC patients at high risk of recurrence.

Self-reported recurrent pain and medicine use among 15-year-olds: results from the HBSC Italian study.

BACKGROUND: The prevalence of adolescent pain varies considerably across epidemiological studies, and little information is available on pain-related behaviours among adolescents, including medicine use. The aims of this study were: [1] to examine the prevalence of recurrent pain among 15-year-old adolescents in Italy; [2] to investigate the association between recurrent pain and medicine use among boys and girls; and [3] to evaluate the consistency of these associations across Regions. METHODS: The World Health Organization (WHO) collaborative International Health Behaviour in School-aged Children 2013/2014 study collected self-reported data on pain and medicine use from 13611 15-year-old adolescents in 21 Italian Regions. We used multi-level multivariate logistic regression, stratified by gender, to analyse the association between recurrent pain and medicine use for headache, stomachache, nervousness and difficulties in getting to sleep. RESULTS: On average, across all Regions, almost 45% of adolescents reported recurrent headache, more than 30% reported recurrent backache and approximately 30% reported recurrent stomachache. Although the prevalence of both pain and medicine use was much higher among girls, the association between pain and medicine use was similarly strong in adolescents of both genders. Adolescents with recurrent pain proved more likely to use medicines also for non-corresponding pain, nervousness and difficulties in getting to sleep. The association between recurrent pain and medicine use was consistent across Regions despite large inter-regional differences in the prevalence of both phenomena. CONCLUSIONS: Recurrent pain in adolescence is common nationwide. Adolescents with recurrent pain are more likely to use medicines in general. Recurrent pain and medicine use should be addressed by adolescent health policies.

Geographical and epidemiological analysis of oncological incidence in paediatric and adolescent ages in a municipality of North-Western Italy: Vercelli, years 2002-2009.

INTRODUCTION: This study of the geographical incidence on the oncological mortality in young age (0-44 years) in the City of Vercelli, was aimed to address the concerns of the population and the request of municipal administrators. A detailed and sophisticated study for a City of medium-small size is due for the presence of various sources of pressure, such as a MSW incinerator just a few kilometres from the city and an intensive agricultural activity that characterizes the entire area. MATERIALS AND METHODS: The study is based on the census analysis of the population, and of the hospital admission cards, and it considers epidemiological standardized estimators and spatial analysis through Bayesian models, as well. RESULTS: Both approaches highlight Major risks for the area south of the city for major tumours such as total cancer in women (SIR / SMR significant excess of about 50%), colorectal (mean increments SMR / SIR between 3 and 4 times), ovary (mean increments SMR / SIR between 3:04 and times), and nervous system (increases 3 times for both indicators). CONCLUSION: These results deserve further studies through inferential case-control and cohort analysis, given the marginal role of the possible occupational hazards in the aetiology of juvenile cancer disorders.

A molecular exploration of human DNA/RNA co-extracted from the palmar surface of the hands and fingers.

"Touch DNA" refers to the DNA that is left behind when a person touches or comes into contact with an item. However, the source of touch DNA is still debated and the large variability in DNA yield from casework samples suggests that, besides skin, various body fluids can be transferred through contact. Another important issue concerning touch DNA is the possible occurrence of secondary transfer, but the data published in the literature in relation to the background levels of foreign DNA present on the hand surfaces of the general population are very limited. As the present study aimed at better understanding the nature and characteristics of touch DNA, samples were collected from the palmar surface of the hands and fingers ("PHF" samples) of 30 male and 30 female donors by tape-lifting/swabbing and subjected to DNA/RNA co-extraction. Multiplex mRNA profiling showed that cellular material different from skin could be observed in 15% of the PHF samples. The total amount of DNA recovered from these samples (median 5.1 ng) was significantly higher than that obtained from samples containing skin cells only (median 1.6 ng). The integrity of the DNA isolated from the donors' hands and fingers as well as the prevalence of DNA mixtures were evaluated by STR typing and compared with reference STR profiles from buccal swabs. DNA integrity appeared significantly higher in the male rather than in the female subsample, as the average percentage of the donors' alleles effectively detected in PHF profiles was 75.1% and 60.1%, respectively. The prevalence of mixtures with a foreign DNA contribution ≥20% was 19.2% (30.0% in the female PHF samples and 8.3% in the male PHF samples). The obtained results support the hypothesis that transfer of cellular material different from skin may underlie the occasional recovery of quality STR profiles from handled items. These results also suggest that gender may represent an important factor influencing the propensity of individuals to carry and transfer DNA through hand contact, possibly because of the differences in personal and hygiene habits between males and females.

Anti-inflammatory genes associated with multiple sclerosis: a gene expression study.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system caused by a complex interaction between multiple genes and environmental factors. HLA region is the strongest susceptibility locus, but recent huge genome-wide association studies identified new susceptibility genes. Among these, BACH2, PTGER4, RGS1 and ZFP36L1 were highlighted. Here, a gene expression analysis revealed that three of them, namely BACH2, PTGER4 and ZFP36L1, are down-regulated in MS patients' blood cells compared to healthy subjects. Interestingly, all these genes are involved in the immune system regulation with predominant anti-inflammatory role and their reduction could predispose to MS development.

Cancer risk among farmers in the Province of Vercelli (Italy) from 2002 to 2005: an ecological study.

BACKGROUND: As the link between agricultural pesticides and numerous types of human cancers is wellknown. Farmers living in the Province of Vercelli (Italy) were observed to verify if they have a higher cancer risk than the rest of the local employed population. Literature showed a well-known excess of cancer morbidity and mortality in the Province of Vercelli, but only few studies focused on cancer incidence in local farmers. Studying farmers could allow to assess the causal importance respectively of environmental pressure and professional exposure factors in explaining cancer excesses in the above-mentioned area. MATERIALS AND METHODS: The present ecological study considered all cancer new cases recorded among the mean employed population with a range of age from 25 to 84 years and resident in the Province of Vercelli during the four-year period 2002-2005. Cancer odds ratios, by gender and type of cancer, between farmers and non-farmers were calculated. RESULTS: Farmers showed a higher risk for the following tumors: colorectal (OR 2.38, IC95%: 1,76-2,87), leaukaemia (OR 2.65, IC95%:2,12-2,89), digestive system (OR 2.16, IC95% 1,92-2,33), lymphoma OR 2.08, IC95%:1,99-2,23), melanoma (OR 2.90, IC95%:2,54-3,15), myeloma OR 3.55, IC95%:3,23-3,70), pancreas OR 3.38, IC95%:3,14-3,61), lung (1.59, IC95%:1,12-2,38) and kidney (2.70, IC95%:2,41-2,99). Males showed a higher risk for lung cancer, females for liver neoplasm, melanoma and lymphoma. CONCLUSIONS: Farmers showed a higher risk for several cancers. Further studies are needed, in order to examine in detail the issue, to encourage the use of personal protective equipment and to promote a more responsible pesticides use.

Monocytes and CD4+ T cells contribution to the under-expression of NR4A2 and TNFAIP3 genes in patients with multiple sclerosis.

We recently found a gene signature for multiple sclerosis (MS) that reverted to normal during pregnancy in MS patients and included NR4A2 and TNFAIP3, key molecules in anti-inflammatory processes. Here we focus on the expression levels of these two genes in monocytes and CD4+ T cells from healthy controls and treatment-naïve RRMS patients. Our findings show that monocytes play a key role in the dysregulated anti-inflammatory response, being the expression of both genes down-regulated in these cells in RRMS patients with respect to healthy individuals. CD4+ T cells seem to have only a marginal part, because we can observe only a slight down-regulation in NR4A2.

Surgical remission of Cushing's syndrome reduces cardiovascular risk.

OBJECTIVE: Recent studies have questioned the reversibility of complications of Cushing's syndrome (CS) after successful surgical treatment. The aim of this study was to assess the outcome of patients with CS who achieved disease remission compared with those patients with persistent hypercortisolism and matched controls. DESIGN: A retrospective study of 75 patients with CS followed at an academic center. METHODS: Cardiovascular risk profile was evaluated in 51 patients with CS in remission (group 1) and 24 patients with persistent disease (group 2) and compared with 60 controls. Mortality of patients with CS was compared with the background population. RESULTS: In group 1, the frequency of cardiovascular risk factors dropped after disease remission even if it remained higher at the last follow-up than in the control group. In group 2, the frequency of cardiovascular risk factors remained unchanged during follow-up. The rate of cardiovascular and thromboembolic events was higher in group 2 than in group 1, as was the mortality rate (two deaths in group 1 and nine in group 2; ratio of two SMRs, 0.11; 95% CI, 0.011-0.512). Survival was significantly longer in group 1 than in group 2 (87 months, 80-98 vs 48 months, 38-62; P<0.0001). CONCLUSIONS: Successful surgical treatment of hypercortisolism significantly improves cardiovascular risk and may reduce the mortality rate. Patients with persistent disease have increased morbidity and mortality when compared with patients in remission.

Posthepatectomy liver failure after simultaneous versus staged resection of colorectal cancer and synchronous hepatic metastases.

BACKGROUND: Posthepatectomy liver failure (PHLF) is the third most frequent complication and the major cause of postoperative mortality after resection of colorectal cancer liver metastases (CRLM). In case of synchronous resectable CRLM, it is still unclear if surgical strategy (simultaneous versus staged resection of colorectal cancer and hepatic metastases) influences the incidence and severity of PHLF. The aim of this study was to evaluate the impact of surgical strategy on PHLF and on the early and long-term outcome. PATIENTS AND METHODS: Retrospective study on 106 consecutive patients undergoing hepatectomy for synchronous CRLM between 1997 and 2012. RESULTS: Of 106 patients, 46 underwent simultaneous resection and 60 had staged hepatectomy. The rate of PHLF was similar between groups (16.7% vs 15.2%; p=1) and subgroup analysis restricted to patients undergoing major hepatectomy confirmed this observation (31.8% vs 23.8%; p=0.56). Propensity-score analysis showed that preoperative total bilirubin level and the amount of intra-operative blood transfusion were independently associated with an increased risk of PHLF. Nevertheless, the risk of severe PHLF (grade B - C) was increased in patients who underwent simultaneous resection and major hepatectomy (OR: 4.82; p=0.035). No significant differences were observed in severe (Dindo - Clavien 3 - 4) postoperative morbidity (23.9% vs 20.0%; p=0.64) and survival (3 and 5-year survival: 55% and 34% vs 56% and 33%; p=0.83). CONCLUSIONS: The risk of PHLF is not associated with surgical strategy in the treatment of synchronous CRLM. Nevertheless, the risk of severe PHLF is increased in patients undergoing simultaneous resection and major hepatectomy.

Geographical and epidemiological analysis of oncological mortality in a Municipality of North-Western Italy Vercelli years 2000-2009.

BACKGROUND: We performed a geographic analysis study on mortality in the town of Vercelli, in order to respond to the concerns of the population and some local administrators. Main reason to carry out a detailed and sophisticated study for a city of medium-small size was represented by the presence of various sources of environmental and industrial pressure (i.e. old-generation incinerator for solid urban waste, industrial site for chemicals production, intense agricultural activity of rice production…). METHODS: The study analyzed census, ISTAT death cards, both from the epidemiological point of view with admirers that SMR standardized spatial analysis using Bayesian models. RESULTS: Overall, both approaches highlighted major risks for the area south of the capital for major cancers such as colorectal and lung and increases worthy of investigation for the young-adult age groups in both genders. And being processed a similar study that considers the incidence oncology. CONCLUSIONS: The imminent elaboration of the cartography by oncological incidence will allow us to confirm, or less, the areas in excess for the death data, and in the meanwhile observe any excesses for low mortality pathologies (e.g., thyroid) or neoplasies whose present therapies allowed complete recovery and/or very long survivals (e.g. leukaemia, lymphomas and testicle).

[Assessment of the impact of cancer in the Vercelli Local Health Authority from 2002 to 2009]. / Incidenza oncologica nell'ASL VC di Vercelli dal 2002 al 2009.

The object of the study is to provide an epidemiological overview of the impact of neoplasms in an area that has no cancer registry. A descriptive study was conducted within the Local Health Authority of Vercelli. To estimate the number of cases, hospital discharge documents (including passive mobility) were used and integrated with the archives of pathology. The number of cases was calculated on the basis of SIR (specific rates of the Vercelli Local Health Authority divided by age in the years 2002-2009 in comparison with new cases of cancer in the city of Turin from 2005 to 2007, used as standard population). All readings were expressed including intervals of confidence at 95%. For tumors of low lethality for males, extending the period of observation confirms the excess for bladder cancer (SIR = 1.1, 1.07 to 1.21) and lymphoma aggregate (SIR = 1.4, 1.2 to 1.6). for females: thyroid (SIR = 1.5, 1.3 to 1.65) and lymphomas (SIR = 1.25, 1.1 to 1.4). In addition to these tumors in both sexes is observed to decrease colorectal cancer but excess for leukemias and brain. The extension of the study is intended as the base for the creation of a cancer register that will be established, naturally integrating further sources of information. In all cases, data observed indicated several epidemiological peculiarities in the region, probably linked to specific characteristics of local exposure, which should be addressed in terms of Public Health.

Familial environment in high- and middle-low-income municipalities: a survey in Italy to understand the distribution of potentially obesogenic factors.

OBJECTIVES: To explore the familial and social environment in high- and middle-low-income municipalities in Italy to evaluate the distribution of potentially obesogenic factors. A hybrid methodological approach was chosen. A survey of 1215 Italian children was performed to collect information regarding child, family and peer characteristics; additionally, income data were derived from national estimates based on zip codes. STUDY DESIGN: A cross-sectional study conducted via computer-assisted telephone interviews (CATI). METHODS: A CATI facility was used to interview 1215 Italian children aged 6-10 years. Information regarding family composition; body mass index (BMI) of the child, father and mother; mother's perception of the child's weight; levels of physical activity of the child, father and mother; time spent watching television or playing video games; use of social networks; leisure-time habits; and dietary habits of peers was collected. Income per year per person was obtained from the Italian National Institute of Statistics estimates. Municipalities were divided into two groups: one representing the highest ranking income from the total Italian income distribution, and one representing middle-low incomes. Differences between middle-low-income and high-income groups for child and parent BMIs, social networks, and dietary and leisure-time habits were compared using Wilcoxon and McNemar tests, as appropriate. Multivariate analysis was conducted using logistic regression. RESULTS: In total, 604 high-income children and 611 middle-low-income children were identified. A significant difference in father's BMI was found between middle-low- and high-income groups: 10.5% of fathers in middle-low-income municipalities were obese, compared with 3.8% in high-income areas (P < 0.001). On the contrary, this analysis found no association between income group and the mother's BMI. In this sample, middle-low-income children participated in less physical activity than high-income children (22.7% vs 34.8% participated in sporting activities for more than 3 h per week, P < 0.001), and spent more time in sedentary activities, such as watching television. However, middle-low-income children were not isolated and were surrounded by a wider social network than high-income children (80.4% vs 69% had more than three friends, P < 0.001). CONCLUSIONS: Significant differences were found in the distribution of obesogenic behaviours between middle-low- and high-income municipalities, suggesting that social factors as well as the physical environment should be considered in the development of health policies and interventions to reduce childhood obesity.