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Adelaide Mozzi,1 Michela Meregaglia,2 Carlo Lazzaro,3 Valentina Tornatore,4 Maurizio Belfiglio,4 Giovanni Fattore,1,2 1Department of Policy Analysis and Public Management, 2Centre for Research on Health and Social Care Management (CeRGAS), Bocconi University, 3Studio di Economia Sanitaria, Milan, 4AbbVie srl, Campoverde Di Aprilia, Latina, Italy Abstract: Weights associated with the EuroQol 5-Dimension 3-Level (EQ-5D-3L) instrument represent preferences for health states elicited from general population's samples. Weights have not been calculated for every country; however, empirical research shows that cross-country differences exist. This empirical study aims at investigating the impact of recently developed Italian weights in comparison with UK and US scores on health-related utility calculation using a sample of patients with Crohn's disease. The study is based on a survey on health-related quality of life in patients (n=552) affected by active Crohn's disease conducted in Italy from 2012 to 2013. Utilities computed through the Italian algorithm (mean: 0.76; SD: 0.20; median: 0.81) are generally higher than US (mean: 0.69; SD: 0.22; median: 0.77) and UK (mean: 0.57; SD: 0.32; median: 0.69) utilities, except for extremely severe health states where US values outweigh the Italian ones. UK preference weights generate the highest number of negative results. All the three value distributions are left-skewed due to very low scores associated with the most serious health states (ie, three or four levels equal to 3). As expected, despite the tariff set considered, more severe disease (Harvey Bradshaw Index >16) reduces the mean conditional EQ-5D-3L index (P16) reduces the mean conditional EQ-5D-3L index (P

Objective: The role of self-monitoring of blood glucose (SMBG) in type 2 diabetes is still a matter of debate. In the framework of a nationwide outcomes research program, we investigated the frequency of SMBG and its association with metabolic control and quality of life (QoL).Research Design and Methods: The study involved 3,567 patients with type 2 diabetes who were recruited by 101 outpatient diabetes clinics and 103 general practitioners. Patients completed a questionnaire investigating SMBG practice and QoL (diabetes-related stress, diabetes health distress, diabetes-related worries, and Centers for Epidemiologic Studies-Depression scale).Results: Data on SMBG were available for 2,855 subjects (80% of the entire study population). Overall, 471 patients (17%) stated that they tested their blood glucose levels at home > or =1 time per day, 899 patients (31%) tested their blood glucose levels > or =1 time per week, and 414 patients (14%) tested their blood glucose levels <1 time per week, whereas 1,071 patients (38%) stated that they never practiced SMBG. A higher frequency of SMBG was associated with better metabolic control among subjects who were able to adjust insulin doses, whereas no relationship was found in all other patients, irrespective of the kind of treatment. Multivariate analyses showed that an SMBG frequency > or =1 time per day was significantly related to higher levels of distress, worries, and depressive symptoms in non-insulin-treated patients.Conclusions: Our findings suggest that SMBG can have an important role in improving metabolic control if it is an integral part of a wider educational strategy devoted to the promotion of patient autonomy. In patients not treated with insulin, self-monitoring is associated with higher HbA(1c) levels and psychological burden. Our data do not support the extension of SMBG to this group. [ABSTRACT FROM AUTHOR]

Objective: In the context of the QuED (Quality of Care and Outcomes in Type 2 Diabetes) project, we evaluated the longitudinal changes over 3 years in quality of life (QoL) in patients with type 2 diabetes according to the presence or the development of erectile dysfunction (ED).Research Design and Methods: Patients were requested to fill in a questionnaire investigating the presence of ED and QoL (SF-36 Health Survey, depression symptoms [Center for Epidemiologic Studies-Depression], and quality of sexual life) every 6 months for 3 years. The analyses were based on multilevel models, adjusted for patient clinical and sociodemographic characteristics.Results: The study involved 1,456 patients, of whom 34% reported frequent erectile problems at baseline; 192 developed ED during the follow-up. No changes in QoL measures were detected in patients without ED; in those with ED at baseline, a worsening in all SF-36 scales was observed, reaching statistical significance for physical functioning (P = 0.03). Among patients who developed ED during the study, a deterioration in all SF-36 dimensions and a worsening in depressive symptoms preceded the development of ED. The onset of ED was associated with a further marked worsening in physical functioning (P = 0.0008), general health perception (P = 0.02), and social functioning (P = 0.04) on SF-36 subscales, as well as in the summary physical and mental components scores (P = 0.04 and P = 0.07, respectively). The development of ED was also associated with a highly significant increase in depressive symptoms (P = 0.001) and a marked decrease in quality of sexual life (P < 0.0001).Conclusions: This longitudinal study documents for the first time the impact of ED onset on several aspects of QoL in patients with type 2 diabetes. The study also shows that QoL tended to further decrease during 3 years in patients with ED at baseline but not in those without this condition. [ABSTRACT FROM AUTHOR]

Objective: To evaluate an opportunistic screening strategy addressed to individuals with one or more cardiovascular risk factor, based on the Diabetes Risk Score (DRS) as the initial instrument, for the identification of individuals with type 2 diabetes or impaired glucose tolerance (IGT).Research Design and Methods: The DRS, a simple self-administered questionnaire, was completed by individuals identified by general practitioners and presenting with one or more cardiovascular risk factor. All patients underwent a 2-h oral glucose tolerance test (OGTT). The optimal DRS cutoff was calculated by applying the receiver-operating characteristic curve.Results: Overall, 1,377 individuals aged between 55 and 75 years received an OGTT and completed the DRS. Mean DRS values showed a marked variation according to glucose metabolism categories, as follows: 8.7 +/- 3.0 in normoglycemic individuals, 9.5 +/- 3.1 in individuals with impaired fasting glucose, 9.9 +/- 3.3 in individuals with IGT, and 12.0 +/- 3.5 in individuals with type 2 diabetes. The receiver-operating characteristic curve showed that, with a cutoff of 9, the sensitivity of DRS in detecting individuals with glucose abnormalities (type 2 diabetes or IGT) was 77% and the specificity 45%. The use of the DRS as an initial screening instrument, followed by the measurement of fasting blood glucose in individuals with a score > or =9 and by the OGTT in individuals with a fasting blood glucose between 5.6 and 6.9 mmol/l, would lead to the identification of 83% of the case subjects with type 2 diabetes and 57% of the case subjects with IGT, at a cost of an OGTT in 38% of the sample and a fasting blood glucose in 64%.Conclusions: The DRS can represent a valid inexpensive instrument for opportunistic screening and a useful alternative to indiscriminate fasting blood glucose measurement, not readily available in general practice. [ABSTRACT FROM AUTHOR]

Objective: The role of general practice and diabetes clinics in the management of diabetes is still a matter of debate. Methodological flaws in previous studies may have led to inaccurate conclusions when comparing the care provided in these different settings. We compared the care provided to type 2 diabetic patients attending diabetes outpatient clinics (DOCs) or being treated by a general practitioner (GP) using appropriate statistical methods to adjust for patient case mix and physician-level clustering.Research Design and Methods: We prospectively evaluated the process and intermediate outcome measures over 2 years in a sample of 3,437 patients recruited by 212 physicians with different specialties practicing in 125 DOCs and 103 general practice offices. Process measures included frequency of HbA(1c), lipids, microalbuminuria, and serum creatinine measurements and frequency of foot and eye examinations. Outcome measures included HbA(1c), blood pressure, and total and LDL cholesterol levels.Results: Differences for most process measures were statistically significantly in favor of DOCs. The differences were more marked for patients who were always treated by the same physician within a DOC and if that physician had a specialty in diabetology. Less consistent differences in process measures were detected when patients followed by GPs were compared with those followed by physicians with a specialty other than diabetology. As for the outcomes considered, patients attending DOCs attained better total cholesterol levels, whereas no major differences emerged in terms of metabolic control and blood pressure levels between DOCs and GPs. Physicians' specialties were not independently related to patient outcomes.Conclusions: Being followed always by the same physician in a DOC, particularly if the physician had a specialty in diabetes, ensured better quality of care in terms of process measures. In the short term, care provided by DOCs was also associated with better intermediate outcome measures, such as total cholesterol levels. [ABSTRACT FROM AUTHOR]

Objective: Within the context of a large, nationwide outcomes research program in type 2 diabetes, we assess the prevalence of self-reported erectile dysfunction and evaluate its impact on quality of life.Research Design and Methods: The study involved 1,460 patients enrolled by 114 diabetes outpatient clinics and 112 general practitioners. Patients were asked to complete a questionnaire investigating their ability to achieve and maintain an erection. Various aspects of quality of life were also assessed depressive using the following instruments: SF-36 Health Survey, diabetes health distress, psychological adaptation to diabetes, depressive symptoms (CES-D scale), and quality of sexual life.Results: Overall, 34% of the patients reported frequent erectile problems, 24% reported occasional problems, and 42% reported no erectile problems. After adjusting for patient characteristics, erectile dysfunction was associated with higher levels of diabetes-specific health distress and worse psychological adaptation to diabetes, which were, in turn, related to worse metabolic control. Erectile problems were also associated with a dramatic increase in the prevalence of severe depressive symptoms, lower scores in the mental components of the SF-36, and a less satisfactory sexual life. A total of 63% of the patients reported that their physicians had never investigated their sexual problems.Conclusions: Erectile dysfunction is extremely common among type 2 diabetic patients and is associated with poorer quality of life, as measured with generic and diabetes-specific instruments. Despite their relevance, sexual problems are seldom investigated by general practitioners and specialists. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between beliefs of physicians relative to intensive metabolic control in type 2 diabetes and levels of HbA1c obtained in a sample of their patients.Research Design and Methods: Physicians' beliefs were investigated through a questionnaire sent to a sample of self-selected clinicians participating in a nationwide initiative aimed at assessing the relationship between the quality of care delivered to patients with type 2 diabetes and their outcomes. At the same time, physicians were asked to collect clinical data on a random sample of their patients, stratified by age (<65 vs. > or = 65 years). Mean HbA1c levels in the study population were thus evaluated according to target fasting blood glucose (FBG) used by their physicians.Results: Of 456 physicians, 342 (75%) returned the questionnaire. Among the responders, 200 diabetologists and 99 general practitioners (GPs) recruited 3,297 patients; 2,003 of whom were always followed by the same physician and 1,294 of whom were seen by different physicians in the same structure on different occasions. Only 14% of the respondents used target FBG levels < or = 6.1 mmol/l, whereas 38% pursued values >7.8 mmol/l, with no statistically significant difference between diabetologists and GPs. The analysis of the relationship between FBG targets and metabolic control, restricted to those patients always seen by the same physician, showed a strong linear association, with mean HbA1c values of 7.0 +/- 1.6 for patients in the charge of physicians pursuing FBG levels < or = 6.1 mmol/l and 7.8 +/- 1.8 for those followed by physicians who used target values >7.8 mmol/l. After adjusting for patients' and physicians' characteristics, the risk of having HbA1c values > 7.0% was highly correlated with physicians' beliefs. Patients followed by different physicians in the same unit showed a risk of inadequate metabolic control similar to that of patients followed by physicians adopting a nonaggressive policy.Conclusions: Doctors adopt extremely heterogeneous target FBG levels in patients with type 2 diabetes, which in turn represent an important independent predictor of metabolic control. To improve patient outcomes, physicians-centered educational activities aimed at increasing the awareness of the potential benefits of a tight metabolic control in patients with type 2 diabetes are urgently needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: To investigate if the tumour infiltrating lymphocytes (TILs) are able to predict the sentinel lymph node (SLN) positivity, the disease-free survival (DFS) and overall survival (OS) in clinical stages I-II AJCC primary cutaneous melanoma (PCM). METHODS: The study included consecutive patients with PCM, all diagnosed, treated and followed up prospectively. Logistic regression was used to investigate the association between DFS, OS, SLN positivity and Breslow thickness, Clark level, TIL, ulceration, lesion site, gender, regression and age. RESULTS: From November 1998 to October 2008, 1251 consecutive patients with PCM were evaluated. Median age was 51 (range 15-96) with 32.2% (N=393) of them older than 60; 44.8% of them were males. Of the whole series, a total of 404 patients with primary vertical growth phase (VGP) melanoma and no clinical evidence of metastatic disease underwent SLN biopsy. Of these, 74 (18.8%) had a positive SLN. In a multivariate analysis, primary melanoma on the extremities versus that on the axial locations (truncal and head/neck) (OR 0.49, 95% CI 0.25-0.98, p 0.04) and TILs (TILs versus no TILs) (OR 0.47, 95%CI 0.25-0.90, p 0.02) were predictive for lower probability of SLN involvement, while thickness (>4mm versus 0-1mm) (OR 24, 19, 95% CI 4.91-119.13, p<.001) was predictive for higher risk of SLN positivity. A multivariate stepwise analysis confirmed these results. The histological status of the SLN was the most significant predictor of DFS and OS. Patients with a negative SLN had a 5-year DFS of 75.9%, compared with 35.2% in patients with a positive SLN (p<.0001) and a 5-year OS of 88.7% versus 42.9%, respectively (p<.0001). CONCLUSIONS: Our study demonstrates that the absence of TILs predicts SLN metastasis, in multivariate analysis the SLN positivity predicts DFS and OS. [ABSTRACT FROM AUTHOR]

Background: Older adults suffer from increased rates of dysphagia and dysphonia, both of which have a profound effect on quality of life and are often underdiagnosed. We sought to better understand the prevalence of these complaints and the potential utility of a patient-reported screening program in a geriatrics clinic., Methods: Using an IRB-approved cross-sectional survey and retrospective cohort design, we recruited participants from a population of new patients seeking care at an academic geriatrics clinic. We used three validated questionnaires to assess self-reported dysphagia, dysphonia, and pill dysphagia: the Eating-Assessment Tool-10 (EAT-10), the Voice Handicap Index-10 (VHI-10), and the PILL-5. Patients who screened positive on any questionnaire were offered referral to a laryngologist for additional evaluation. Patients who screened positive on the PILL-5 were also offered referral to our geriatric pharmacist., Results: Among our 300 patients surveyed, the mean age was 76 (SD 8.46). A total of 82 (27.3%) patients screened positive (73 on EAT-10, 10 on PILL-5, 13 on VHI-10) and were offered referral, of which 36 accepted. These positive screening patients took more prescription medications ( p  = .024) and had a higher GDS score ( p  < .001) when compared to the patients who screened negative., Conclusions: Many new patients seeking generalized care at our center screened positively for dysphagia and/or dysphonia on validated questionnaires. Geriatric patients may benefit from integrating screening for these disorders to identify the need of further evaluation. It is unknown if these survey tools are appropriate in a non-otolaryngology clinic., Level of Evidence: III., Competing Interests: The authors have no conflict of interest to declare., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Purpose: To assess the risk of tonsillar regrowth and post-operative complications associated with intracapsular tonsillectomy (IT) when performed by a single surgeon using a standardized technique., Materials and Methods: The current study was conducted as a retrospective chart review of all IT performed by a single surgeon between November 11, 2009 and July 22, 2020 at the Cleveland Clinic and the Cleveland Clinic Beachwood Family Health and Surgery Center . Data collection included patient demographics, surgical data, post operative results, complications, and available long-term follow-up data., Results: There were 221 ITs performed between November 2009 and July 2020. The post operative bleeding rate was 3.5 %. A single adult patient required re-operation for bleeding. Rate of tonsillar regrowth was 3.9 % (n = 7) and 1.1 % (n = 2) required re-operation (total tonsillectomy). No patients in the current study developed post-operative dehydration or had excessive post-operative pain requiring an emergency department visit or hospitalization., Conclusions: The current study demonstrated similar rates of post operative bleeding after IT when compared to established rates following TT. The current study's regrowth rate was 3.9 % with a low 1.1 % rate of re-operation. This study adds to a growing body of literature supporting the use of IT due to lower complication rates when compared to TT, including post-operative bleeding, dehydration, and pain, with minimal rate of re-operation for bleeding or regrowth., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Organ preservation (OP) treatment for advanced laryngeal cancer has increased compared to primary total laryngectomy. Our study compares oncologic and functional outcomes between these approaches., Study Design: Retrospective cohort study., Setting: Single tertiary care institution., Methods: Retrospective review of patients receiving primary total laryngectomy or OP for laryngeal cancer between 1/1/2000 and 12/31/2018., Results: A total of 118 patients received primary total laryngectomy and 119 received OP. Overall survival was similar between total laryngectomy and OP. When stratified by T stage, disease-free survival was worse among T3 patients receiving OP versus total laryngectomy. In T3 patients, 28 OP patients experienced local recurrence (28.9%) compared to 3 total laryngectomy patients (7.1%; p < 0.01). In total, 20 OP patients with local recurrence received salvage surgery. These patients had similar overall survival to patients who underwent initial total laryngectomy (TL). About 14 OP patients with local recurrence did not receive salvage surgery. About 89 (75.4%) TL patients achieved normal diet as compared to 64 (53.8%) OP patients (p < 0.001). In TL patients, 106 (89.8%) received primary or secondary tracheoesophageal-prosthesis, 82 (77.4%) of whom achieved completely understandable speech., Conclusions: There was no difference in survival by treatment in T4 patients, possibly because of strict patient selection. However, disease-free survival was worse in T3 patients receiving OP, likely due to a high local recurrence rate. Approximately 40% of patients with local recurrence were not eligible for salvage laryngectomy. TL patients had comparable swallowing and speech outcomes with OP patients., Level of Evidence: 3 Laryngoscope, 133:1122-1131, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: We sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy., Methods: Retrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis., Results: Assessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease-free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS., Conclusion: Gestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Introduction: Rare diseases have a high social and health impact. Since 2005, AIFA has been funding independent clinical research. The objective of this paper is to describe data on independent research on rare diseases financed by the Agency., Methods: With reference to studies financed by AIFA between 2005-2018 the following data have been collected: financial characteristics, study design, therapeutic area, population included, completion status, availability of study results publications, publication characteristics and conclusions. Data have been analyzed in order to provide information on characteristics and scientific productivity of clinical studies on rare diseases., Results: Between 2005 and 2018, AIFA published 9 Calls for Funding of Independent Research and financed 282 clinical studies, 111 (about 40%) of which were on a rare disease and/or a rare tumor for a total of € 43,455,438. Studies were interventistic in 93.6% (mainly phase II or III). The most represented therapeutic area was oncology (19.9%), followed by neurology (17.1%), and onco-hematology (16.2%). 28.8% of clinical studies enrolled fragile population (children, elderly, pregnant women). Fourty eight studies (43.2%) completed according to protocol, 8 (7.2%) completed with reduced sample size, 18 (16.2%) were prematurely terminated, while 37 of them are still ongoing. In the subgroup of 74 closed studies at least a scientific publication is available for 49 of them. A total of 81 papers are available including two publications related to ongoing studies (range 1-8; mean 1.5; median 1). Cumulative Impact Factor is 619.269 (range for single paper 0.17-34.492)., Discussion: A good percentage of clinical studies financed by AIFA were on rare diseases and/or rare tumors. Clinical trials were less likely to complete according to protocol than observational ones, in agreement with literature data; on the other hand once completed, clinical trials were more likely to publish research findings. Overall, 66.2% of closed studies has at least one publication; this percentage is higher if we consider the subgroup of clinical trials and if we consider clinical trials completed according to study protocol (95.3%).

Introduction: The unmet therapeutic needs lead to accelerated registration of new oncology drugs, even with incomplete information of the benefit-risk ratio., Methods: In Italy the Onco-AIFA Register was established to monitor oncology drugs when used according to authorized indications and to assure their appropriate use in clinical practice. In the Abruzzo region, an observational longitudinal study (ProMoFIA&#95;Oncologici) was performed to evaluate in standard clinical practice all patients treated with these new oncology drugs for any indication., Results: During the period 2008-2011, 3435 patients were observed: in 62.2% of patients, the use of these drugs was eligible also for the Onco-AIFA Register; in 22.7% it was in-label but not monitored in the Onco-AIFA; in 15.1% the use was off-label., Discussion: The study findings showed a widespread use of the new oncology drugs beyond the Onco-AIFA indications, as well as their off-label use.

Aims and Background: At the Oncology Department of the Chieti and Ortona Hospitals, the pharmacist designated by the Abruzzo Region to oversee the obligatory monitoring of innovative oncological drugs listed in the database of the Italian Medicines Agency (AIFA) collaborates with oncologists to educate them about evidenced-based prescribing for off-label uses of drugs and to optimize the efficiency of spontaneous reporting of adverse drug reaction (ADR) local system., Methods: The contribution of the pharmacist as a member of the healthcare team was evaluated using the following indices: the percentage of off-label prescriptions of the innovative drugs monitored, the number of reported ADRs, and the percentage of pharmacist suggestions actually implemented by physicians., Results: In the course of 3 years (2008-2010), the pharmacist monitored a total of 843 patients treated with 716 appropriate uses and 127 off-label uses of drugs, oversaw a reduction in the latter from 28.3% in 2008 to 9.6% in 2010, and contributed to almost tripling the number of reported ADRs, from 10 in 2008 to 27 in 2010. In 2010, the pharmacist identified 60 potentially inappropriate prescribing cases, and proposed more appropriate prescriptions for each case: 68.3% (41) of the suggestions were implemented by the physicians and only 31.7% (19) were not. According to answers to a questionnaire administered at the end of the 2010 to evaluate the usefulness of this particular collaboration, physicians are interested in continuous and extensive collaboration., Conclusions: This article demonstrates that a pharmacist, active in the department as part of the heath-care team, can facilitate evidenced-based prescribing for off-label uses of drugs and improve spontaneous reporting of ADRs.

Gemcitabine is a commonly used chemotherapeutic agent for a variety of tumors. Although this nucleoside analog antineoplastic agent is similar in structure to cytarabine, central nervous system toxicities have rarely been attributed to gemcitabine. The posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible neurological and radiological findings that has been associated with use of chemotherapeutic and more recently novel targeted therapies. We describe one case of a 41-year-old woman with PRES under treatment for leiomyosarcoma because of the probable association with gemcitabine. Our case, to our knowledge, represents the seventh published report of this particular toxicity. Naranjo algorithm, efficacious method for assessing the causality of adverse drug reactions (ADRs) from a case report, suggests a direct casual relationship. PRES is probably a rare complication of gemcitabine, but the oncologist should take it into careful consideration, because PRES is reversible with treatment of current hypertension or removal of the causative agent. However, failure to quickly recognize the syndrome and discontinue the offending agent may result in profound and permanent central nervous system dysfunction or death.

Purpose: Whether combination chemotherapy offers an advantage over sequential therapy in metastatic breast cancer (MBC) is still an unsettled issue. Polychemotherapy regimens containing taxanes has been shown to increase overall survival (OS), time to tumor progression (TTP), and overall response rate (ORR) when compared with regimens that did not contain a taxanes, while taxane-based doublets have a statistically significant benefit over single-agent taxane only for progression-free survival. However, the term "taxanes" generally includes both paclitaxel and docetaxel, drugs with different clinical activity. Aim of this work is to compare OS, TTP, and ORR in patients with MBC receiving docetaxel alone or in combination with chemotherapy using a formal meta-analysis., Methods: We performed a systematic review of all published trials comparing docetaxel alone or in combination with other chemotherapeutic agents in MBC., Results: Three randomized clinical trials including 1,313 patients were retrieved. A significant reduction of risk ratio was found in TTP (P ≤ 0.0001) but not in OS (P = 0.48) or ORR (P = 0.10) for patients treated with a chemotherapy agent plus docetaxel compared with docetaxel alone. Treatment with docetaxel alone is associated with a lower incidence of grade 3 diarrhea and stomatitis (diarrhea, P = 0.011; stomatitis, P = 0.0004)., Conclusion: Combination chemotherapy regimens with docetaxel show a statistically significant advantage for TTP, but not for OS and ORR in MBC. This review confirms that it is unlikely that any single agent or combination chemotherapy regimen will emerge as superior in MBC, due to its heterogeneous nature.

Aims and Background: Cancer in young patients (15-39 years) is unique for the distribution of types, therapeutic options and clinical evolution. Administrative databases represent well-documented tools in epidemiology, and in oncology they are very important in those realities without cancer registries. Our study aimed to analyze the occurrence, outcomes and burden of cancer in young patients through the analysis of hospital discharge records., Methods: Hospital discharge databases and civil registries were analyzed through record linkage technique. Annual incidence rate (AIR), standardized incidence rate (SR), overall survival, hospitalization rate, and mean number of hospitalizations were evaluated., Results: Among 2,330,459 young adults, 1846 new cancer patients had been hospitalized in the analyzed period. The SR was 69.3/100,000/year: 1051, 56.9%, were females (AIR 91.0 and SR 76.0) and 795, 43.1%, were males (AIR 67.6 and SR 62.5). Hematological disease was more frequent in males than females (25.5% vs 14.7%, P <0.0001), whereas solid tumors were more frequent among females (85.3% vs 74.5, P <0.0001). The distribution by diagnostic group showed that among females breast cancer was the most frequent (n = 272, SR 17.2), whereas among males genitourinary tract cancer (n = 245, SR 19.2), especially testicular cancer (n = 187, SR 15.1), was the most frequent. Metastatic disease at diagnosis was already present in 198 patients with a solid cancer (13.3%), whereas 213 (11.5%) developed metastasis in the following years. At 12 months from the diagnosis, 87 of 1488 patients with solid cancers and 35 of 358 patients with hematologic disease failed: overall survival was 94% and 90%, respectively. Patients with a new diagnosis of cancer had produced 6663 hospitalizations, 4640 (69.6%) of which were due to solid tumors, 3992 (59.9%) produced by patients over 29 years old, and 3606 (54.1%) by females. The percentage of day hospital admissions increased proportionally with patient age: 25.7% of all hospitalizations among older adolescents (15-20 years) and 32.9% among young adults of 34-39 years., Conclusions: Administrative data have clear advantages in terms of availability and large numbers. Comparison of our results with the literature showed that a health care delivery database can provide useful information for clinical-epidemiologic evaluations in oncology as well as for the analysis of health services utilization.

Background: To determine interobserver variability in clinical target volume (CTV) of supra-diaphragmatic Hodgkin's lymphoma., Materials and Methods: At the 2008 AIRO (Italian Society of Radiation Oncology) Meeting, the Radiation Oncology Department of Chieti proposed a multi-institutional contouring dummy-run of two cases of early stage supra-diaphragmatic Hodgkin's lymphoma after chemotherapy. Clinical history, diagnostics, and planning CT imaging were available on Chieti's radiotherapy website (www.radioterapia.unich.it). Participating centers were requested to delineate the CTV and submit it to the coordinating center. To quantify interobserver variability of CTV delineations, the total volume, craniocaudal, laterolateral, and anteroposterior diameters were calculated., Results: A total of 18 institutions for case A and 15 institutions for case B submitted the targets. Case A presented significant variability in total volume (range: 74.1-1,157.1 cc), craniocaudal (range: 6.5-22.5 cm; median: 16.25 cm), anteroposterior (range: 5.04-14.82 cm; median: 10.28 cm), and laterolateral diameters (range: 8.23-22.88 cm; median: 15.5 cm). Mean CTV was 464.8 cc (standard deviation: 280.5 cc). Case B presented significant variability in total volume (range: 341.8-1,662 cc), cranio-caudal (range: 8.0-28.5 cm; median: 23 cm), anteroposterior (range: 7.9-1.8 cm; median: 11.1 cm), and laterolateral diameters (range: 12.9-24.0 cm; median: 18.8 cm). Mean CTV was 926.0 cc (standard deviation: 445.7 cc)., Conclusion: This significant variability confirms the need to apply specific guidelines to improve contouring uniformity in Hodgkin's lymphoma.

Objective: To investigate the influence of socioeconomic status (SES) on Breslow thickness, disease-free survival, and overall survival in patients with stage I-II primary cutaneous melanoma (PCM)., Patients and Methods: The study consists of all consecutive patients who were diagnosed as having PCM and were treated and followed up at our hospital between November 1, 1998, and July 31, 2009. Pathologic and sociodemographic characteristics of the patients were obtained. We categorized SES into 3 levels: low (manual employees and skilled/unskilled workers, including farmers, with primary education level), middle (nonmanual employees and clerks with middle education level), and high (professionals, executives, administrators, and entrepreneurs with tertiary education)., Results: A total of 1443 consecutive patients were evaluated. In a multivariate logistic regression analysis, sex (female vs male: odds ratio [OR], 1.37; 95% confidence interval [CI], 1.08-1.75), SES (high vs middle: OR, 1.27; 95% CI, 0.96-1.69; high vs low: OR, 1.73; 95% CI, 1.26-2.38), age (<60 vs ≥60 years: OR, 1.35; 95% CI, 1.03-1.78), and family context (single vs living with relatives: OR, 1.37; 95% CI, 0.97-1.94) were the strongest correlates of Breslow thickness. Compared with high SES, the risk of melanoma-related death, adjusted for age and sex, was 7 times higher (hazard ratio, 7.44; 95% CI, 3.27-16.93) and almost 2 times higher (hazard ratio, 1.88; 95% CI, 1.04-3.39) in patients with low SES living alone or living with relatives, respectively., Conclusion: In patients with PCM, low SES is associated with thicker melanoma and a poorer clinical outcome.

Aims and Background: In 2007, an Italian Research Network proposed to the Ministry of Health a concerted action aimed at developing a specific pathway for the analytical and clinical validation of new biomarkers for early cancer diagnosis. The action, funded by the Italian Ministry of Health within the Integrated Program in Oncology (PIO) and coordinated by the National Cancer Institute of Bari, started in 2008 involving 37 national research teams., Methods: To monitor the methodological and analytical needs of the studies proposed by the research teams of PIO as well as to explore the plausibility of planning external quality assessment programs for early cancer biomarker detection, the coordinating team developed an ad hoc questionnaire that was submitted to each research team., Results: From the collected data it emerged that about 70% of the biomarkers under investigation were analyzed according to nonroutine laboratory practices. The biological material utilized for biomarker assessment consisted of solid tissue (normal or pathological) in 31% of studies, serum in 21%, urine in 15%, plasma in 15%, and whole blood in 11%. Specific training of personnel directly involved in the program was reported by 18% of the teams. In 2008, only 6% of laboratories involved in PIO participated in both external quality assessment and internal quality control schemes specifically designed for the biomarkers under consideration. Standard operating procedures for the determination of about half (52%) of the biomarkers proved to be lacking in at least one phase of the biomarker assessment process., Conclusions: On the basis of these results, we decided to give priority to the application of a four-phase process for the analytical validation of new potential biomarkers by setting up and applying standard operating procedures and developing external quality assessment and internal quality control schemes as specific steps of the workflow.

A critical appraisal of the recent legislation on clinical trials is proposed, together with some reflections on the implications on the practice and principles of clinical experimentation. The possible role and contribution of Ethical Committees is discussed.

In 2007, an Italian cancer research group proposed a specific concerted action aimed at the "analytical and clinica validation of new biomarkers for early diagnosis: Network, resources, methodology, quality control, and data analysis." The proposal united 37 national operative units involved in different biomarker studies and it created a strong coordinative body with the necessary expertise in methodologies, statistical analysis, quality control, and biological resources to perform ad hoc validation studies for new biomarkers of early cancer diagnosis. The action, financed by the Italian Ministry of Health within the Integrated Oncology Program (PIO) coordinated by NCI-Istituto Tumori Bari, started in 2007 and activated 7 projects, each of which focused on disease-specific biomarker studies. Overall, the 37 participating units proposed studies on 50 biomarkers, including analytical and clinical validation procedures. Clusters of units were specifically involved in research of early-detection biomarkers for cancers of the lung, digestive tract, prostate/bladder, and nervous system, as well as female cancers. Furthermore, a cluster involved in biomarkers for bioimaging and infection-related cancers was created. The first investigators' meeting, "Analytical and clinical validation of new biomarkers for early diagnosis," was held on 9 September 2008 in Bari. During this meeting, methodological aspects, scientific programs and preliminary results were presented and discussed.

Trastuzumab, a monoclonal antibody against the HER2 receptor, is currently approved as a part of adjuvant therapy for patients with HER2-overexpressing breast tumors. The Short-HER study is a phase III randomized, multicentric Italian trial aimed at testing the optimal duration of adjuvant trastuzumab. In this trial, 2500 patients with HER2-positive breast cancer will be randomized to receive the following: (arm A, long) 4 courses of anthracycline- based chemotherapy (doxorubicin/cyclophosphamide or epidoxorubicin/cyclophosphamide) followed by 4 courses of docetaxel or paclitaxel in combination with trastuzumab, followed by 14 additional courses of trastuzumab administered every 3 weeks (for a total of 18 3-weekly doses of trastuzumab); or (arm B, short) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab (for a total of 9 weekly doses of trastuzumab) followed by 3 courses of 5-fluorouracil/epirubicin/cyclophosphamide. The primary objective is disease-free survival.

Background and Aim: In the context of the QuED Study we assessed whether a quality of care summary score was able to predict the development of cardiovascular (CV) events in patients with type 2 diabetes., Methods and Results: The score was calculated using process and intermediate outcome indicators (HbA1c), blood pressure, low-density lipoprotein cholesterol, microalbuminuria) and ranged from 0 to 40. Overall, 3235 patients were enrolled, of whom 492 developed a CV event after a median follow-up of 5 years. The incidence rate (per 1000 person-years) of CV events was 62.4 in patients with a score < or =10, 54.8 in those with a score between 15 and 20, and 39.8 in those with a score >20. In adjusted multilevel regression models, the risk to develop a CV event was 89% greater in patients with a score of < or =10 (rate ratio [RR]=1.89; 95% confidence interval [CI] 1.43-2.50) and 43% higher in those with a score between 10 and 20 (RR=1.43; 95% CI 1.14-1.79), as compared to those with a score >20. A difference between centers of 5 points in the mean quality score was associated with a difference of 16% in CV event risk (RR=0.84; 95% CI 0.72-0.98)., Conclusion: Our study documented for the first time a close relationship between a score of quality of diabetes care and long-term outcomes.

Background and Objectives: The objective of this study was to investigate correlates of risk for having microalbuminuria in individuals with one or more cardiovascular risk factors., Design, Setting, Participants, & Measurements: The study involved 1919 individuals who attended general practice settings, were aged 55 to 75 yr, and did not have a history of cardiovascular events or diabetes but had one or more cardiovascular risk factors. A tree-based regression technique and multivariate analysis were used to identify distinct, homogeneous subgroups of patients with different likelihood of having microalbuminuria; interaction between correlates of microalbuminuria and risk for microalbuminuria was also investigated., Results: The prevalence of microalbuminuria was 5.9%. Patients who did not have hypertension and had postload glycemia < 140 mg/dl showed the lowest prevalence of microalbuminuria (1.9%) and represented the reference class. The likelihood of microalbuminuria was seven times higher in men with hypertension and homeostatic model assessment levels in the upper tertile and four times higher in women with the same characteristics. Individuals with hypertension and lower homeostatic model assessment levels and normotensive individuals with postload glycemia > or = 140 mg/dl had a more than three-fold increased likelihood of having microalbuminuria. Treatment with statins was associated with a 54% reduction in the likelihood of having microalbuminuria, whereas levels of triglycerides > 150 mg/dl and fibrinogen levels in the upper tertile were associated with a significantly higher risk for microalbuminuria., Conclusions: The likelihood of having microalbuminuria in a population-based study of elderly individuals is strongly related to the interaction between the components of the metabolic syndrome, particularly hypertension, insulin resistance, and impaired glucose tolerance.