The involvement of early stage breast cancer patients during oncology consultations in Italy: a multi-centred, randomized controlled trial of a question prompt sheet versus question listing

OBJECTIVES: To investigate, prior to an oncology consultation, the use of a pre-prepared list of evidence based questions, Question Prompt Sheet (QPS), compared with a Question List (QL), a patient self-generated list of questions. DESIGN: Multi-centred, randomised controlled trial. SETTING: Secondary-care patients attending three outpatient oncology clinics in Northern Italy. PARTICIPANTS: 308 women completed the study. Inclusion criteria were an age between 18 and 75 years, a recent diagnosis of early stage, non-metastatic breast cancer, adequate Italian language skills, no previous oncology visits and no evidence of cognitive impairment. INTERVENTION: Patients received the QPS or the QL prior to the consultation, completed it without suggestion or coaching session and delivered back before the visit.The consultations were audio-recorded and analysed for the number and content of questions. Multilevel linear models were used to compare the two groups. OUTCOME MEASURES: The primary outcome was the comparison of questions asked between QPS and QL group. Secondary outcomes included satisfaction about questions asked, satisfaction with decision, and level of anxiety. RESULTS: Patients in the QPS and QL group asked 13 and 16 questions respectively. The difference was not significant (b=1.7, CI -0.3 to 3.6, p=0.10). A mean of 22 questions was selected in the QPS, while a mean of 2 questions was written in the QL. Patients in the QPS group were significantly less satisfied (t=3.60, p<0.01) with questions asked but wanted less additional information (t=2.20, p<0.05). Levels of patient decisional satisfaction were equivalent between groups. Similarly, anxiety levels were equal between groups prior to the consultation and decreased in similar way after the consultation. CONCLUSIONS: Both interventions have similar impact on patients' participation in terms of question asking during the consultation. Future research is needed in order to explore which components of the interventions are really useful and efficacious. TRIAL REGISTRATION: ClinicalTrials.gov NCT01510964

The Olfactory System Revealed: Non-Invasive Mapping by using Constrained Spherical Deconvolution Tractography in Healthy Humans

Although the olfactory sense has always been considered with less interest than the visual, auditive or somatic senses, it does plays a major role in our ordinary life, with important implication in dangerous situations or in social and emotional behaviors. Traditional Diffusion Tensor signal model and related tractography have been used in the past years to reconstruct the cranial nerves, including the olfactory nerve (ON). However, no supplementary information with regard to the pathways of the olfactory network have been provided. Here, by using the more advanced Constrained Spherical Deconvolution (CSD) diffusion model, we show for the first time in vivo and non-invasively that, in healthy humans, the olfactory system has a widely distributed anatomical network to several cortical regions as well as to many subcortical structures. Although the present study focuses on an healthy sample size, a similar approach could be applied in the near future to gain important insights with regard to the early involvement of olfaction in several neurodegenerative disorders

New results on rewrite-based satisfiability procedures

Program analysis and verification require decision procedures to reason on theories of data structures. Many problems can be reduced to the satisfiability of sets of ground literals in theory T. If a sound and complete inference system for first-order logic is guaranteed to terminate on T-satisfiability problems, any theorem-proving strategy with that system and a fair search plan is a T-satisfiability procedure. We prove termination of a rewrite-based first-order engine on the theories of records, integer offsets, integer offsets modulo and lists. We give a modularity theorem stating sufficient conditions for termination on a combinations of theories, given termination on each. The above theories, as well as others, satisfy these conditions. We introduce several sets of benchmarks on these theories and their combinations, including both parametric synthetic benchmarks to test scalability, and real-world problems to test performances on huge sets of literals. We compare the rewrite-based theorem prover E with the validity checkers CVC and CVC Lite. Contrary to the folklore that a general-purpose prover cannot compete with reasoners with built-in theories, the experiments are overall favorable to the theorem prover, showing that not only the rewriting approach is elegant and conceptually simple, but has important practical implications.Comment: To appear in the ACM Transactions on Computational Logic, 49 page

Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

<p>Abstract</p> <p>Background</p> <p>Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk.</p> <p>Methods</p> <p>A case-control study design was used to test the association between prostate cancer risk and the polymorphisms <it>TNF-A</it>-308 A/G (rs 1800629), <it>RANTES</it>-403 G/A (rs 2107538), <it>IL1-A</it>-889 C/T (rs 1800587) and <it>MCP-1 </it>2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area.</p> <p>Results</p> <p>Diagnosis of prostate cancer was significantly associated with <it>TNF-A </it>GA + AA genotype (OR, 1.61; 95% CI, 1.09–2.64) and <it>RANTES </it>GA + AA genotype (OR, 1.44; 95% CI, 1.09–2.38). A alleles in <it>TNF-A </it>and <it>RANTES </it>influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and <it>IL1-A </it>or <it>MCP-1 </it>polymorphisms.</p> <p>Conclusion</p> <p>Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development.</p

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR &lt;0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted &lt;4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (&lt;10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR&gt;6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS &lt;50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR&lt;0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mechanism of Action for rTMS: A Working Hypothesis Based on Animal Studies

Experiments in rodents have elucidated some of the molecular mechanisms underlying repetitive transcranial magnetic stimulation (rTMS). These studies may be useful in a translational perspective so that future TMS studies in rodents can closely match human TMS protocols designed for therapeutic purposes. In the present work we will review the effects of rTMS on glutamate neurotransmission which in turn induce persistent changes in synaptic activity. In particular, we will focus on the role of NMDA and non-NMDA transmission and on the permissive role of BDNF-TrKB interaction in the rTMS induced after-effects