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Objective: The first instruments developed to evaluate specific logotherapeutic dimensions were the Purpose In Life (PIL) and the Seeking Of Noetic Goals (SONG) tests, designed to reflect Frankl's concepts of, respectively, meaning in life attainment and will to meaning. This study aims to perform the Italian cultural adaptation and the psychometric validation of the PIL and SONG questionnaires. Methods: We administered the PIL and SONG, culturally adapted into the Italian language, to 266 cancer patients. The psychometric validation appraised construct validity, internal consistency, test-retest reliability, known-group validity, and convergent validity of the two questionnaires with respect to one another. Results: The factorial analysis indicates that the original single-factor solution can be maintained for both instruments (proportion of variance explained by the first factor 77% and 71% for the PIL and SONG, respectively). The results show excellent internal consistency (Cronbach's alpha of 0.91 for the PIL and 0.90 for the SONG) and test-retest reliability (intraclass correlation coefficient of 0.92 for the PIL and 0.81 for the SONG). As expected, males, believers, patients nearer to the diagnosis, and patients not undergoing psychological therapy have higher PIL and lower SONG scores, while expectations for age were not confirmed. The average level for the PIL was 107.3, while for the SONG, it was 66.1, and a negative correlation (−0.47) between PIL and SONG scores indicates good convergent validity of the two instruments. Conclusion: Italian versions of the PIL and SONG are adequate and reliable self-report instruments for evaluating purpose in life and the motivation to find purpose for cancer patient populations. [ABSTRACT FROM AUTHOR]

CONTEXT: The End-of-Life Preferences Interview (ELPI) was developed with the purpose of supporting physicians in communicating with advanced cancer patients. OBJECTIVES: This study aimed to evaluate ELPI feasibility and compare home care/hospice (HC-H) vs. outpatient (OU) care settings. METHODS: Twenty-eight physicians were trained in the use of the ELPI and were asked to apply the new instrument in their daily clinical practice for two months. ELPI feasibility was evaluated through three indices: the percentage of eligible patients, the percentage of patients to whom the ELPI was proposed, and the percentage of completed interviews. RESULTS: The 23 physicians participating in the data collection screened 633 patients, and 156 of them (25%, 95% confidence interval 21%-28%) were judged to be eligible. Eligibility in HC-H was lower than that in the OU setting (18% vs. 46%; P<0.0001), whereas the differences were reduced when looking at patients to whom the ELPI was proposed (12% vs. 20%; P=0.017) and who completed the ELPI (8% vs. 18%; P<0.001). The percentage of eligible patients refusing the interview was very low in the entire sample (1.9%). CONCLUSION: Results indicate that discussing end-of-life preferences in an earlier disease phase, such as in the OU setting, could be preferable but that its accomplishment in this setting may be more difficult, mainly as a result of organizational reasons. This observation could indicate that the system is not yet ready to offer patients such an opportunity and although communication on these sensitive issues cannot be reduced to a procedure, the ELPI can become a useful tool to help physicians in accomplishing this difficult task. [ABSTRACT FROM AUTHOR]

The overall aim of the present study was to further develop an evidence-based platform for the content of an international cancer pain classification system. Data from a multicentre, observational longitudinal study of cancer patients were analysed. Analyses were carried out in 2 samples: (A) Cross-sectional data of patients on opioids at inclusion, and (B) patients just admitted to palliative care. Outcome measures in the models we investigated were pain on average, worst pain, and pain relief at inclusion, and at day 14, respectively. Uni- and multivariate regression models were applied to test the explicative power on pain outcomes of a series of known pain domains, including incident pain, psychological distress, neuropathic pain, pain localisation, sleep disturbances, total morphine equivalent daily dose (MEDD), and cancer diagnosis. In the 2 analyses, 1529 (A) and 352 (B) patients were included, respectively. Incident pain, pain localisation, MEDD, use of nonsteroidal antiinflammatory drugs, and sleep were associated with one or more of the pain outcomes in analysis A, while initial pain intensity, initial pain relief, incident pain, localisation of pain, cancer diagnosis, and age were predictors in the longitudinal analysis. Identified domains explained 16% to 24% of the variability of the pain outcome. Initial pain intensity emerged as the strongest predictor of pain outcome after 2 weeks, and incident pain was confirmed to be a relevant domain. The regression models explained only a minor part of the variability of pain outcomes. [ABSTRACT FROM AUTHOR]

In this paper we describe the coupling of a corona-charged aerosol detector (CAD) to packed column supercritical fluid chromatography (pSFC). The CAD can be coupled to pSFC by connecting the outlet of the back pressure regulator (BPR) directly to the inlet of the detector. To reduce the noise and increase the reproducibility, the transfer line (1 m × 0.25 mm i.d. stainless steel) was placed in a thermostatic bath at 45 °C. Limits of detection (LODs) ranged from 3 to 11.5 ng loaded on column, with an average value of 4.5 ng (from 0.6 to 2.3 mg/L, with an average value of 0.9 mg/L for 5 μL injection). To reduce differences in response at different mobile-phase compositions, mobile-phase flow compensation was performed by placing a T-piece before the BPR. In this way, the differences in response were significantly reduced from a factor of 2-3 to a factor of 1.2-1.7. Compared to CAD application without flow compensation, the average LOD was higher by a factor of ∼1.8. However, the nearly uniform response in gradient analysis with mobile-phase flow compensation far outweighed the slight increase in the LOD. The performance of the pSFC-CAD combination was illustrated by the analysis of selected pharmaceutically related compounds. In addition, a comparison with UV detection was made. Measurement of analytes at a relative concentration of 0.05% versus the main component was demonstrated. [ABSTRACT FROM AUTHOR]

The aim of this review was to evaluate the methods of pain measurement in controlled clinical trials in oncology published between 1999 and 2002. An electronic literature search strategy was used according to established criteria applied to the Medline database and PubMed search engine. Articles were selected to include only studies that had chronic cancer pain as the primary or secondary objective of a controlled clinical trial. A specific evaluation scheme was used to examine how pain measurement methods were chosen and implemented in the study procedures. The search strategy identified 613 articles, and 68 were selected for evaluation. Most articles (69%) chose unidimensional pain measurement tools, such as visual analogue scales, numerical rating scales and verbal rating scales, whereas others used questionnaires. The implementation of the pain assessment method was problematic in many studies, especially as far as time frame of pain assessment (70%), administration modalities (46%), and use of non-validated measurement methods (10%). Design of study and data analysis were often unclear about the definition of pain outcome measure (40%), patient compliance with pain assessment (98%), and impact of missing data (56%). Statistical techniques were seldom appropriate to the type of data collected and often inadequate to describe the pain variable under study. It is clear from this review that most authors were aware of the need of valid pain measurement tools to be used in clinical trials. However, too often these tools were not appropriately used in the trial, or at least their use was not described with sufficient accuracy in the trial methods. © 2005 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

Abstract: The influence of GC speed on the separation capability of a chromatographic system is reported measuring a series of parameters including separation measure (S), peak capacity (n), peak width (), analysis time, t b (determined on the last eluting compound) and separation measure/analysis time ratio (S/t b) determined by analyzing a bergamot essential oil sample and a standard mixture of pesticides. Conventional GC, fast GC (with 10m (FGC10) and 5m (FGC5) narrow-bore columns), and direct resistively-heated ultra fast module-GC (UFM-GC) were the GC speed approaches used. The influence of different heating rates with a constant flow for FGC5, FGC10, and UFM-GC and with variable flows for UFM-GC on S, n, , S/t b, and t b was also studied. The results of this study show that: [(a)] separation capability of the chromatographic system (i.e. S and n) and analysis time depend on the GC approaches. Within each GC approach, S and n and analysis time depend on the heating rates, although to a different extent, and S and n decrease much less than the gain in analysis time, in particular when fast heating rates are applied; [(b)] in UFM-GC, the loss of separation capability with heating rate can also be partially compensated by the choice of an appropriate flow rate that, within each heating rate, may contribute to increase S while reducing t b; [(c)] within a specific GC approach, the chromatographic system (column and stationary phase) and conditions (heating and flow rates) must be such to achieve a suitable S-value when two analytes must be separated with a given resolution in a minimum analysis time. [Copyright &y& Elsevier]

INTRODUCTION: This study compares the relative prognostic power of clinical variables and quality-of-life (QoL) measures in a population of terminal cancer patients. METHODS: A prospective cohort study in 58 Italian Palliative Care Units. Of the 601 randomly selected terminal cancer patients, 574 were followed until death in order to compare clinical and QoL variables (using the Therapy Impact Questionnaire (TIQ) as predictors of survival, and assess whether their combined implementation makes prediction more accurate. RESULTS: The clinical variables most strongly associated with survival were dyspnoea, cachexia, Katz's ADL, oliguria, dysphagia, dehydration, liver and acute kidney failure and delirium (hazard ratios (HR) ranging from 2.10 to 3.01). Only the first four kept their strength once introduced in the Cox model (HRs ranging from 1.95 to 2.22). In the TIQ primary scale the strongest predictors were physical wellbeing, fatigue, functional status and cognitive status (HRs ranging from 1.42 to 1.71), but only fatigue showed an independent prognostic relevance (90% of selection). In the TIQ global scales, the Physical Symptom Index showed a stronger association with survival (HR 1.71) than the Therapy Impact Index (HR 1.47). The former marginally improved the prognostic power of the model when added to clinical variables. Internal validation confirmed that the results were not spurious. CONCLUSIONS: In terminal cancer patients, clinical variables are better predictors of survival than QoL. The large residual variability not accounted for by the model (approximately 70%) suggests that survival is also influenced by factors unlikely to be identified in a survey. [ABSTRACT FROM AUTHOR]

Abstract Background Progression of heart failure is associated with interstitial changes in the heart and in areas distant from the heart. Enhanced expression of metalloproteinases 2 and 9 and of metalloproteinases tissue inhibitors 1 and 2 have been found in ventricular tissue of patients with heart failure. Our aim was to determine whether increased activity of metalloproteinase-2, metalloproteinase-9 and of metalloproteinases tissue inhibitor-1 and metalloproteinases tissue inhibitor-2 were also present in plasma of patients with heart failure. Design Levels of metalloproteinase-2, metalloproteinase-9 and of metalloproteinase tissue inhibitor-1 and metalloproteinases tissue inhibitor-2 were measured in venous blood of 51 patients with heart failure, and were compared with levels of 52 control subjects. Samples collected from patients and control subjects were assayed for gelatinolytic activity (zymography) and for protein levels. Results Compared with the control subjects, the patients with heart failure had a significant increase in activity levels (mean ± SE, ng mL-1 ) of prometalloproteinase-9 (95·1 ± 11·2 and 38·9 ± 4·5* ), activ. metalloproteinase-9 (18·4 ± 2·5 and 10·9 ± 1·3* ), and of prometalloproteinase-2 (571·4 ± 26·1 and 456·8 ± 21·1* ) (respectively: patients and control sub jects; * P < 0·05). Metalloproteinases tissue inhibitor-1, but not metalloproteinases tissue inhibitor-2 protein values were higher in the patients. Among the patients, clinical status and New York Heart Association (NYHA) class did not correlate with the metalloproteinase concentrations. Positive correlations with left ventricular volumes, and negative correlations with lipid values were obtained for prometalloproteinase-2; positive correlations with total number of white cells and neutrophils were obtained for... [ABSTRACT FROM AUTHOR]

Objective: Patients with unstable angina fall within a wide therapeutic and prognostic spectrum, and, in general, have access to specialty care and invasive procedures. Today, when hospital admissions for unstable angina outnumber those for myocardial infarction worldwide, and growing economic pressures are being placed on healthcare systems, cardiologists should re-examine clinical strategies for treating unstable angina in light of healthcare cost accounting. This study examines the number of patients with unstable angina hospitalised in our centre and the services supplied to them to determine the ‘real’ cost regarding diagnostic and therapeutic procedures for these patients compared with the reimbursement rates established by the diagnosis-related group (DRG) system. Design and Setting: A patient schedule was drawn up to prospectively register the number and types of cardiac processes carried out during hospitalisation for all patients with unstable angina in the period between 1 March and 30 May 1996. The time (in minutes) actually spent by both physicians and nurses for each process was carefully recorded in order to calculate the ‘activity budget’. An ‘economic budget’ was calculated for each cardiac process, taking into account salaries, materials, equipment maintenance, depreciation and indirect medical and nonmedical costs for hospitalisation in the coronary care unit and ward. Results: 53 out of 318 patients (16%) were discharged with a diagnosis of unstable angina. According to the DRG system, patients were allocated to 4 DRGs: DRG 140 (medically treated unstable angina; 18 patients); DRG 124 (unstable angina with angiography; 16 patients); DRG 122 (unstable angina evolving into myocardial infarction; 6 patients); DRG 112 (unstable angina with angioplasty; 13 patients). The mean cost for a hospitalised patient with unstable angina was 2911 euro (EUR): (DRG 140 = EUR1403.4; DRG 124 = EUR1462.2; DRG 122 = EUR3178.1; DRG 112 = EUR6658.3). The differences in costs were essentially related to the procedures involved in medical care; DRGs involving expensive cardiac processes had higher costs. Furthermore, these data show a marked discrepancy between ‘real’ costs and current DRG reimbursements. Conclusions: The data show the standard management of unstable angina in our centre. Calculating the true costs of unstable angina is the first step towards maximising resources and optimising benefits. Our experience suggests that the use of this system is an essential means of creating an efficient management system for a cardiology unit. It should also be used to gather all the information necessary to establish whether reimbursement rates are covering real costs and to initiate the reduction of deficits or the utilisation of surpluses. [ABSTRACT FROM AUTHOR]

Purpose: Explore clinical factors associated with higher pain intensity and future pain in patients with bone metastases to identify patients who can benefit from closer follow-up or pain-modifying interventions.Methods: This is a secondary analysis of 606 patients with bone metastases included in a multicenter longitudinal study. The dependent variables were "average pain" and "worst pain" in the last 24 h (0-10 NRS). Twenty independent variables with potential association to pain intensity were selected based on previous literature. Cross-sectional analyses were performed with multiple linear regression to explore factors associated with pain intensity at baseline. Longitudinal data were analyzed with a generalized equation models to explore current factors associated with pain intensity at the next visit in 1 month.Results: Current pain intensity (p < 0.001), sleep disturbances (p 0.01 and 0.006), drowsiness (p 0.003 and 0.033) and male gender (p 0.045 and 0.001) were associated with higher average and worst pain intensity in 1 month. In addition, breakthrough pain was related to higher worst pain intensity (p 0.003) in 1 month. The same variables were also associated with higher average pain intensity at baseline.Conclusion: Higher current pain intensity, sleep disturbances, drowsiness, male gender, and breakthrough pain are factors associated with higher pain intensity in patients with bone metastases at the next follow-up in 1 month. These factors should be assessed in clinical practice and may aid clinicians in identifying patients that can benefit from closer follow-up or interventions to prevent lack of future pain control. TRIAL REGISTRATION IN CLINICALTRIALS.GOV : NCT01362816. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the use of pain assessment methods in clinical trials is presented.

Background More than 60 per cent of patients treated surgically for primary retroperitoneal sarcoma survive for at least 5 years. Extended surgical resection has been proposed for primary disease, but long-term morbidity data are lacking. A cross-sectional study was conducted to assess the long-term morbidity of patients undergoing surgery for retroperitoneal sarcoma. Methods Patients operated on between January 2002 and December 2011 were eligible for the study. Long-term morbidity was evaluated based on a semistructured clinical interview. Lower limb function was assessed by means of the Lower Extremity Functional Scale ( LEFS), a self-report questionnaire with a total score ranging from 0 (low functioning) to 80 (high functioning). Pain was investigated by means of the Brief Pain Inventory - Short Form, with pain intensity scores reported on a scale from 0 (no pain) to 10 (worst pain). Results Some 243 patients underwent surgery, and 101 of 160 patients who were alive at the time of the investigation responded to the study invitation letter. Finally, 95 patients were enrolled in the study. Sensory impairment of the limbs was reported in 72 patients (76 per cent). The median LEFS score was 60 (i.q.r. 43-73). Mean scores for the pain intensity items varied from 1·23 to 2·68. In multivariable analysis, there was no difference in median levels of creatinine at survey between patients who did or did not undergo nephrectomy (difference between median values 13 (95 per cent c.i. −4 to 30) µmol/l; P = 0·170). Conclusion Severe chronic pain and lower limb motor impairment after multivisceral resection for retroperitoneal sarcomas are rare. Long-term renal function is not significantly impaired when nephrectomy is performed. [ABSTRACT FROM AUTHOR]

MICCINESI G., BIANCHI E., BRUNELLI C. & BORREANI C. (2012) European Journal of Cancer Care 21, 623-633 End-of-life preferences in advanced cancer patients willing to discuss issues surrounding their terminal condition The aim of the present study is to describe end-of-life preferences of advanced cancer patients willing to talk about death issues. Eighty-eight advanced cancer patients were interviewed through End of Life Preferences Interview (ELPI), a 23-item interview covering a wide range of end-of-life care issues. Most interviewed subjects were home care patients and their median survival after ELPI administration was 69 days. In total, 100% of responders expressed the will to receive some kind of information on the disease process and/or the treatments proposed. Approximately 77% declared to be willing to talk about what it is important at the end of life in case of worsening of their conditions and 31% prefer to be left alone in difficult moments. Approximately 67% choose home as the preferred place of death and 63% think it is preferable to die in a state of unconsciousness induced by drugs. About half of responders declare to believe in any kind of life after death and 40% consider very important to find any meaning at the end of life. ELPI can be a useful instrument to adapt the model of care to the specific needs and values of each patient. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few studies have focused on neuropsychiatric symptoms like hallucinations or delusions occurring in the early posttransplant period. The aim of this study was to estimate the percentage of patients reporting neuropsychiatric symptoms in the immediate postoperative phase, to describe the phenomenology, and to evaluate the emotional impact of such disorders. Method: We studied 94 consecutive patients who underwent orthotopic liver transplant (OLT) for hepatocellular carcinoma at least 30 days prior. The presence of neuropsychiatric symptoms were retrospectively evaluated through a semistructured interview. Results: Overall 49 patients (52%) reported various postoperative neuropsychiatric symptoms. None of the demographic and clinical variables showed significant associations, except for barbiturate administration; patients using barbiturates showed a lower percentage of neuropsychiatric symptoms. It was a time-limited phenomenon that in most cases resolved by day 7 after transplantation. Interestingly, the most frequent emotion perceived was surprise and not fear; a nontrivial amount of patients reported happiness, while many patients reported no emotion. Conclusions: The results of this study suggested the usefulness of a registry of the neurological and psychiatric complications after OLT that may help to clarify the pathogenic mechanisms of such complications and implement uniform protocols of prevention and treatment. In fact, better knowledge of the phenomenology of neuropsychiatric symptoms in OLT recipients could allow easier symptom recognition and therapy adjustments on the basis of the emotional impact of such symptoms on patients, family, and caregivers, as well as increase patients’ awareness and capability to face this experience. [Copyright &y& Elsevier]

Background: This study aims to propose an initial development of the FACT-Liver Transplant (FACT-LT) scale to assess the major physical and emotional concerns of patients before and after Orthotopic Liver transplant (OLT) due to acute and chronic liver failure and hepatocellular carcinoma. Methods: The FACT-LT was developed in two phases. In Phase I, items were generated: 1) through interviews with 10 OLT experts and 15 candidates for or recipients of both oncological and non-oncological OLT which identified relevant topics; 2) from the FACIT item bank. In Phase II, a questionnaire to assess item frequency, applicability, and comprehension was administered to 20 OLT experts and, to assess item difficulty, embarrassment and content irrelevance, to 30 transplant recipients or candidate patients (15 oncological, 15 non-oncological). Results: In Phase I, 44 items were formulated/reviewed, and 30 items were maintained. All the healthcare professionals interviewed rejected the recommendation to develop two different modules for cancer and non-cancer patients. In Phase II, the majority of the experts and patients expressed an overall satisfaction with the questionnaire, indicating that the items were relevant, comprehensible and not embarrassing (range 75% - 99%). The first version of the FACT-LT includes 28 items defining four QOL domains: 5 items relating to Physical Well-Being, 8 to Functional Well-Being, 13 to Emotional Well-Being, and 2 to Social/Family Well-Being. Conclusion: The preliminary results obtained were promising; however further studies are needed, in order to proceed with a FACT-LT validation process. [ABSTRACT FROM AUTHOR]

The loss of an eye is a highly traumatic event, with severe psychological and physical implications. From November 1996 to June 2002, 32 patients underwent eye enucleation and placement of a hydroxyapatite orbital implant wrapped in autologous fascia lata; this was then fixed to the four rectus muscles. Motility was noted in all reconstructed sockets, without implant related complications. The immediate post-operative period was uncomplicated and all patients were discharged within 48 to 72 h after surgery. The orbital implant remained well positioned without dehiscence and motility was satisfactory. The follow-up ranged from 8 months to more than 5 years. [ABSTRACT FROM AUTHOR]

In the last few years, palliative care for advanced and terminal cancer patients has undergone considerable evolution. We determined the characteristics of patients admitted to the 4-bed Palliative Care Unit (PCU) of the National Cancer Institute (NCI) of Milan in 1987, 1993 and 2000 to evaluate how our diagnostic and therapeutic approaches have changed over the years. We reviewed the charts of every patient admitted to the PCU in 1987, 1993, and the first ten months of 2000. We recorded demographic data; the primary tumor sites; the main reason for admission; the types of therapies administered (oncologic, analgesic, surgical, neurosurgical analgesic procedures, and supportive therapy); the type and number of cardiological, radiological and endoscopic examinations, as well as specialist consultations; the duration of stay and eventual death on the Unit. There were no significant differences regarding gender, age, primary tumor site and death in hospital of the patients admitted during these years. The time spent in hospital increased over time (P = 0.006). A significant increase was observed in the percentage of patients admitted for supportive therapy (P < 0.001) and investigation concerning the stage of the disease (P < 0.001). There was a significant decrease in admission for invasive analgesic procedures (P < 0.001), as well as for pain diagnosis and/or uncontrolled pain. Uncontrolled pain remained the most frequent reason for admission. Over the years, during hospitalization, 7% to 12% of the patients underwent radiotherapy,1% to 9% had computerized tomography, and 4% to 8% had palliative surgery. More than 50% of the patients received intravenous hydration; a few patients received hypodermoclysis in 1987. Over time, there was a significant increase in "as needed" administration of nonsteroidal anti-inflammatory drugs and a significant reduction in their regular administration (from 24% in 1987 and 1993 to 3% in 2000) (P < 0.001). The use of codeine, tramadol and methadone increased (P < 0.001), whereas the use of oral morphine, buprenorphine and oxycodone decreased in 2000 (P < 0.001). There was a reduction in the use of antidepressants (no significant constant trend) and a significant increase in the use of anticonvulsants, laxatives and pamidronate (P < 0.001). Regularly administered hypnotics decreased in 1993 and increased in 2000 (P < 0.001). Over these years, no significant differences were found in the routes of opioid administration, in route switching and in the mean maximum oral opioid dose (ranging from 108 to 126 mg/day). The percentage of patients undergoing percutaneous cordotomy significantly decreased in 1993 and 2000 (P < 0.001). Over time, there was an increase in requests for specialist consultations, which was significant for neurological, cardiological and oncological consults (P < 0.001). Although the characteristics of the patients admitted to the PCU did not change over these years, there have been significant modifications in our therapeutic approaches, above all in the use of supportive therapy, adjuvant drugs, opioids and neurosurgical invasive procedures. Moreover, a major collaborative interaction with other specialists of the NCI took place with the aim to tailor treatment for each single patient. [ABSTRACT FROM AUTHOR]

Objective FNA biopsy is considered as the most accurate method for the selection of patients with thyroid nodules that need for surgery or for the wait and see management. The aim of the present study is to clarify the risk of malignancy for the cytological data classified according to the 2014 Italian reporting system. Methods We report a retrospective analysis of 4043 patients in our institution's experience during the period April 2014 through December 2016 with the Italian reporting system for thyroid cytology. Results The diagnostic incidences of the 4043 cases were as follows: 9.8% TIR1; 1.3% TIR1C; 70% TIR2; 6.6% TIR3A; 4.5% TIR3B; 2.4% TIR4; 5.2% TIR5. A repeated aspiration was carried out in 68 out of 269 cases (25%) classified as TIR3A. A total of 407 cases with cytology underwent surgical resection. A malignant neoplasm was detected in 261 out of 407 (64%) cases. Regarding TIR3B, surgical excision was undertaken in 109 cases, which included 42 high-risk lesions and 67 Hürthle cell neoplasms. The risk of malignancy was significantly higher in the former compared to the latter (50% vs 9%; P<.05). Conclusions This investigation emphasises the reliability of the 2014 Italian Reporting System concerning the mutual frequency of the diagnostic categories. The risk of malignancy is perfectly within the range of the estimated values. [ABSTRACT FROM AUTHOR]

We examined the contribution of arterial wave reflection to early abnormalities in left ventricular relaxation, whether this association was modified by gender or hypertension and the role of reflected wave timing and amplitude. We studied a cohort of normotensive and untreated essential hypertensive Taiwanese participants (675 men, 601 women, mean age 52 years). Doppler flow and applanation tonometry were performed to assess carotid-femoral pulse wave velocity (PWV) and augmentation index (AI). Diastolic parameters including the ratio between the peak velocity of early and late diastolic mitral inflow (E/A), E-deceleration time and left atrial (LA) diameter were measured by echocardiography. In multivariate models predicting E/A, women were more likely to have lower E/A than men (β=−0.08, P<0.001). AI was significantly associated with lower E/A in both men (β=−0.09, P=0.005) and women (β=−0.12, P<0.001) independent of PWV. Inclusion of AI in the overall model reduced the gender difference in E/A by 61% and rendered it nonsignificant. There was a significant interaction between AI and hypertension (P=0.02). The inverse association between AI and E/A was significant only in normotensive men and women, and only for the amplitude but not timing of the reflected wave. In conclusion, the contribution of wave reflection to left ventricular diastolic dysfunction was independent of arterial stiffness, more pronounced in normotensive individuals and explained a significant portion of the gender difference in diastolic function. [ABSTRACT FROM AUTHOR]

This study was performed to describe the impact of preventive options on the psychological condition of BRCA1/ BRCA2 carriers. A sample of 52 cancer-affected (C-A) and 27 cancer-unaffected (C- UN) women were enrolled after gene test disclosure ( T0). Psychological evaluations were performed at T0 and 15 months later ( T1). The surgical options were more likely to be chosen in C-A women (62%), although a consistent proportion of C- UN women (30%) also opt for these preventive measures. At the baseline, both samples had average anxiety and depression scores below the cut-off value, restrained average cancer worry scores and a risk perception consistent with the risk percentage provided during genetic counselling. The longitudinal results indicated no clinically meaningful variations in the anxiety and depression scores in either of the two samples. Statistically significant reductions in cancer-risk perception emerged in women who chose surgery in both C-A and C- UN women. In BRCA1/ BRCA2 mutation carriers, surveillance does not influence their initial psychological condition, whereas prophylactic surgery has a significant impact in reducing the perceived risk and worry about getting sick. C-A and C-UN women have to be considered as two separate populations of BRCA mutation carriers requiring personalized approaches to risk management. [ABSTRACT FROM AUTHOR]

Abstracts: Inflammatory and immunologic mechanisms are important for the initiation and the progression of atherosclerotic lesions. OxLDL and HSP-60 antigens are involved in the pathogenesis of atherosclerotic disease by triggering immune cells within the plaques. Through the MHC pentamer assays, we investigated the presence of OxLDL- and HSP-60-specific CD8 + T lymphocytes in twenty HLA-A2-positive patients suffering from coronary artery disease (10 NSTEMI and 10 stable angina). Similarly, 10 age- and sex-matched healthy subjects were enrolled as controls. Biological samples were collected within 6 h of admission to hospital, at 30 days and at 180 days. OxLDL- and HSP-60-specific CD8 + T lymphocytes were never detectable in the peripheral blood from all the healthy controls. On the contrary, at each scheduled time point, both of these specific cells could be detected in peripheral blood from all enrolled patients. More in detail, the flow cytometric analysis of MHC-1 pentamer OxLDL-specific CD8 + T lymphocytes revealed a sharp and significant increase at the hospital admission, within 6 h from the chest pain onset, followed by an evident decline to lower levels at 30 days and at 180 days from the enrollment in the study. On the contrary, although MHC-1 pentamer HSP-60 CD8 + T lymphocytes were detectable in enrolled patients, almost no variance could be detectable during the follow-up scheduled evaluations. On the whole, this finding indicates that HSP-60- and OxLDL-specific CD8 + T lymphocytes could play a role in the maintenance or worsening of the atherosclerotic coronary disease. [ABSTRACT FROM AUTHOR]

Objectives The effects of vitamin D on the heart have been studied in patients with cardiac disease, but not in healthy persons. We investigated the relation between vitamin D status and left ventricular ( LV) structure and function in community-dwelling subjects without heart disease. Design The relationship between concentrations of 25-hydroxyvitamin D [25( OH)D], a marker of vitamin D reserve, and LV transthoracic echocardiography measures was analysed in 711 participants in the Baltimore Longitudinal Study of Aging who were without cardiac disease. Results Mean 25(OH)D in the study population was 32.3 ± 11.4 ng mL−1; only 15.5% of subjects had moderate or severe vitamin D deficiency [25(OH)D < 20 ng mL−1]. Adjusting for age, body mass index, cardiovascular disease risk factors, physical activity, calcium and parathyroid hormone, 25(OH)D was positively correlated with LV thickness (β 0.095, SE 0.039, P < 0.05) and LV mass index (β 7.5, SE 2.6, P < 0.01). A significant nonlinear relation between 25(OH)D and LV concentric remodelling was observed. LV remodelling was more likely in participants with 25(OH)D levels <30 ng mL−1 [odds ratio (OR) 1.24; 95% confidence interval (CI) 0.83-1.85] or ≥38 ng mL−1 (OR 1.73; 95% CI 1.13-2.65), compared with those with 30-37 ng mL−1 25(OH)D. Consistently, LV relative wall thickness was significantly lower ( P for trend=0.05), and LV diastolic internal diameter index ( P for trend<0.05) and end-diastolic volume index ( P for trend<0.05) were significantly higher in subjects with 30-37 ng mL−1 25(OH)D compared to the rest of the study population. There was a significant interaction between 25(OH)D and hypertension on the risk of LV hypertrophy ( P < 0.05). Conclusions In a population-based sample of predominantly vitamin D-sufficient subjects without heart disease, LV geometry was most favourable at intermediate 25( OH)D concentrations. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cell (VSMC) viability and homeostasis is regulated by cell-matrix and cell-cell contact: disruption of these interactions are responsible of a switch from a mature to a high proliferative phenotype. VSMCs migration, rate of growth and apoptosis, and the extent of their extracellular matrix (ECM) deposition can be also modulated by proatherogenic peptides. Among them, ATII induces the transactivation of IGF IR, which, together with the binding protein IGFBP3, represents a determinant of cell survival, growth and proliferation. Aim of our in vitro study was to verify the role of elective cell-cell bond in modulating the response to ATll. Thus, we evaluated viability, proliferation, IGF IR, IGFBP3 expression and the long term survival and production of ECM in a provisional tissue. A7rS cell-tine was used in adherent cultures or incubated in agarose-coated culture plates to inhibit cell-matrix interactions. Cells, treated or not with ATII 100 nM, were evaluated for apoptosis rate, cell cycle, IGF IR and IGFBP3 protein expression. Fibrin provisional tissue was developed polymerizing a fibrin solution containing A7r5 cells with thrombin. Histological stainings for ECM components were performed on sections of provisional tissue. An exclusive cell-cell contact resulted in the formation of floating clustered cells with a 10% higher apoptosis rate and an 8% reduction of "S" phase of the cell cycle, compared to monolayer cell cultures. ATII did not affect the cell survival in both culture conditions, but promoted a 10% decrease in "S" phase and an increases IGF IR expression only in adherent cells, while suspended cell aggregates were resistant to ATII administration; IGFBP3 was reduced both in ATII treated adherent cells and in floating clustered cells, irrespective of the treatment. VSMC conditioning in agarose-coated plates before seeding in fibrin provisional matrix reduced, but not abolished, the cell ability to colonize the clot and to produce ECM. This study demonstrates that the elective cell-cell contact induces a quiescent status in cells lacking of cell-matrix interactions and reduces the responsiveness to ATll. Therefore, preserved cell-cell contact may counteract vascular remodeling induced by proatherogenic stimuli. [ABSTRACT FROM AUTHOR]

Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% Cl 70-80) of the follow-up period in the intent- to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P< 0.00 1) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opiold titration phase in patients with moderate-to-severe cancer pain. [ABSTRACT FROM AUTHOR]

Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% Cl 70-80) of the follow-up period in the intent- to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P< 0.00 1) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opiold titration phase in patients with moderate-to-severe cancer pain. [ABSTRACT FROM AUTHOR]

A number of controlled studies have recently demonstrated the role of disodium pamidronate in the prevention of skeletal complications in patients with metastatic bone disease due to breast cancer and multiple myeloma. They have also shown that it relieves pain and is well tolerated. The aim of this open prospective study was to evaluate the acceptability of a new schedule of pamidronate infusion and to assess pain, analgesic consumption and the Karnofsky Performance Status (KPS) in patients with metastatic bone pain treated with pamidronate in association or not with chemotherapy, radiotherapy, and hormone therapy. Patients with different types of cancer and at least one painful bone metastasis were treated with two cycles of 60 mg intravenous (iv) pamidronate weekly for three consecutive doses, with a 3-week interval between the two cycles (six infusions over 7 weeks), followed by one infusion every 3 weeks for a total of 24 infusions. Two hundred patients were enrolled in the study, of whom 94 received at least the first six infusions; 25 patients received all 24 infusions. Pamidronate was well tolerated in the majority of the patients both during the first six infusions and during the whole study period. In the patients under study, pain intensity decreased compared with T[sub 0] after the first two infusions (second week of treatment). The mean equivalent daily dose of oral morphine required ranged from 21.5 to 41.5 mg/day and was low and stable during the study. For the patients who remained in the study, the KPS remained around 70 during the whole treatment period and intrasubject analysis showed a substantial stability of the KPS within each subject. A first fracture occurred within 321 days in 25% of the whole population under study. Pamidronate represents a further valid therapy to add to an already consolidated list of therapies such as radiotherapy, chemotherapy, hormone therapy and orthopaedic intervention in the pain management of patients with bone metastases. Future studies are necessary to evaluate the role of pamidronate and the appropriate schedule in patients with advanced or terminal cancer who are no longer being treated with oncological therapies. [ABSTRACT FROM AUTHOR]

Objective: Sulfonylureas block the activation of vascular potassium-dependent ATP channels and impair the vasodilating response to ischcmia in nondiabetic individuals, but it is not know whether this occurs in type 2 diabetic patients under chronic treatment with these drugs. Glimepiride, a new sulfonylurea, apparently has no cardiovascular interactions. The aim of our study was to compare the effect of the widely used compound glibenclamide, the pancreas-specific glimepiride, and diet treatment alone on brachial artery response to acute forearm ischemia.Research Design and Methods: Brachial artery examination was performed by a high-resolution ultrasound technique on 20 type 2 diabetic patients aged mean +/- SD) 67 +/- 2 years and on 18 nondiabetic patients matched for age, hypertension, and dislipidemia. Diabetic subjects underwent three separate evaluations at the end of each 8-week treatment period, during which they received glibenclamide, glimepiride, or diet alone according to crossover design. Scans were obtained before and after 4.5 min of forearm ischemia. Postischemic vasodilation and hyperemia were expressed as percent variations in vessel diameter and blood flow.Results: Postischemic vasodilation and hyperemia were, respectively, 5.42 +/- 0.90 and 331 +/- 38% during glibenclamide, 5.46 +/- 0.69 and 326 +/- 28% during glimepiride, and 5.17 +/- 0.64 and 357 +/- 35% during diet treatment (NS). These results were similar to those found in the nondiabetic patients (6.44 +/- 0.68 and 406 +/- 42%, NS).Conclusions: In type 2 diabetic patients, the vasodilating response to forearm ischemia was the same whether patients were treated with diet treatment alone or with glibenclamide or glimepiride at blood glucose-lowering equipotent closes. [ABSTRACT FROM AUTHOR]

As part of a large multicentre study on palliative care units in Italy, carried out between 1 January and 30 June 1995, we describe the place, circumstances and `quality of death' of patients admitted to home palliative care. Data presented refer to 401 patients (67% of the 601 patients randomly selected for evaluation). Of these 401 patients 303 (76%) died at home. According to the Support Team Assessment Schedule (STAS) pain was fairly well controlled during the final week of life, while the control of other symptoms appeared to be less satisfactory. Invasive procedures were undertaken on 56% of patients, while in hospital the percentage increased to 75%. Twenty-five per cent of patients were totally pharmacologically sedated during the final 12 h of life. Neither the number of symptoms nor other factors were apparently associated with the decision to sedate the patient. The wide variations in the frequency of sedation among centres suggest that the choice to sedate the patient may reflect the provider's behaviour or services' policy rather than the patients' preference or needs. The definition of common criteria and guidelines for sedation of patients should be one of the topics for discussion among palliative care teams. [ABSTRACT FROM AUTHOR]

Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages. Mstn co-localized with α-smooth muscle actin (α-SMA) staining and with some CD45+ cells, indicating Mstn expression in VSMCs and bloodstream-derived leukocytes. In vitro, Mstn was tested in VSMCs and monocytes. In A7r5 VSMCs, Mstn downregulated proliferation and Smoothelin mRNA, induced cytoskeletal rearrangement, increased migratory rate and MCP-1/CCR2 expression. In monocytes (THP-1 cells and human monocytes), Mstn acted as a chemoattractant and increased the MCP-1-dependent chemotaxis, F-actin, α-SMA, MCP-1 and CCR2 expression; in turn, MCP-1 increased Mstn mRNA. Mstn induced JNK phosphorylation both in VSMCs and monocytes. Our results indicate that Mstn is overexpressed in abdominal aortic wall deterioration, affects VSMCs and monocyte biology and sustains a chronic inflammatory milieu. These findings propose to consider Mstn as a new playmaker in atherosclerosis progression. [ABSTRACT FROM AUTHOR]

Resveratrol (Rsv) is a natural antioxidant polyphenol with vasoprotective properties. We evaluated whether Rsv affects the inflammatory response in an experimental model of elastase-induced abdominal aortic aneurysm. Thirty male rats were subjected to aneurysm induction and treated or not with Rsv. Circulating levels of CD62L- monocyte subset, monocyte CD 143 surface expression, MMP-9 plasma activity and TNFOL serum levels were lower in Rsv-treated rats. In conclusion, Rsv acts as an anti-inflammatory compound and could be of great relevance to improve the immune response in AAA patients. [ABSTRACT FROM AUTHOR]

Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system. [ABSTRACT FROM AUTHOR]