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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%).

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 (P<0.0001). Kendall's rank correlation between EQ Visual Analog Scale score and EQ-5D-3L index is positive (P<0.0001), even though patients tend to value their health-related quality of life more when responding to EQ-5D-3L questions than on EQ Visual Analog Scale. Regardless of the tariff set considered, ordinary least-square results highlight that more severe disease (Harvey Bradshaw Index >16) reduces the mean conditional EQ-5D-3L index (P<0.0001). Results reveal remarkable differences among the three national tariff sets and especially when severe health states occur, suggesting the need for country-specific preference weights when evaluating utilities, which can be problematic since they have not been calculated for every country yet.

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.

Background: No study has so far addressed whether differences do exist in the management of cancer pain between patients receiving usual care by primary specialists and those receiving early palliative/supportive intervention., Patients and Methods: A multicentre cross-sectional study in 32 Italian Hospitals has included 1450 patients, receiving analgesic therapy for cancer pain: 602 with access to primary specialist alone (standard care, SC) and 848 with early access to a palliative/supportive care (ePSC) team, concomitant with primary oncology care., Results: Statistically significant differences in the analgesic drug administration according to care model have been evident: non-opioids were more frequently used in SC (9.5% versus 2%; P<0.001), while strong opioids in ePSC group (80% versus 63%; P<0.001). The number of patients with severe pain was lower in ePSC compared with SC group (31% versus 17%; P<0.001). Results of multivariate analysis have shown that ePSC integrated with primary oncologic care (relative risk 0.69; 95% confidence interval 0.48-0.99; P=0.045) was an independent factor associated with a 31% reduced risk of suffering from severe pain., Conclusions: An ePSC team provides the most effective standard of analgesic therapy for cancer pain. A randomized clinical trial is needed to confirm these findings.

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.

Background: clinical guidelines can improve quality of care summarising available knowledge and proposing recommendations for health care decisions. Being up to date is one of their quality requisites. Little experience is available on when and how guidelines should be updated. We report on the update process of evidence-based clinical recommendations on anticancer drugs., Methods: three multidisciplinary panels, supported by methodology experts, updated the recommendations. The methodologists were in charge of the qualitative and quantitative synthesis of the evidence. The panels were responsible for the final decision about risk/benefit profile of the drugs and strength of the recommendations. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used., Results: six recommendations out of 15 were completely updated in 8 months time. In four cases, the strength of the recommendation changed; in two of them, we moved from a weak to a strong positive one. Despite the increased certainty about the positive risk/benefit profile, this was translated in a change in the strength of the recommendation only in one case out of three. Three recommendations were refined making them more clinically specific., Conclusions: accumulation of evidence is an opportunity for guideline panels to refine methodological rigour, clinical relevance and to foster consensus on recommendations. This requires time and resource investments.

Background: No study has so far addressed whether differences do exist in the management of cancer-related pain in patients admitted to oncology and non-oncology settings., Patients and Methods: A multicentre cross-sectional study in 48 Italian hospitals has enrolled 819 patients receiving analgesic therapy for cancer-related pain. Demographics and clinical and analgesic therapy information have been prospectively collected by standardized forms. Adequacy of pain management has been evaluated by the Pain Management Index (PMI)., Results: Differences in the analgesic drug administration according to settings of care have been evident, non-opioids more frequently being administered in non-oncology units (19.6% versus 7.0%; P < 0.0001), while strong opioids are more frequently used in the oncology units (69.5% versus 51.9%; P < 0.0001). The number of patients receiving inadequate therapy (PMI < 0) has lowered in oncology compared with non-oncology units (11.3% versus 18.8%; P = 0.0024). Results of multiple logistic regression analysis have shown that the admission to non-oncology setting [odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.15-2.67; P = 0.0096] and the absence of metastatic disease (OR = 1.60, 95% CI = 1.04-2.44; P = 0.0317) were independent factors associated with an increased risk of receiving an inadequate analgesic therapy., Conclusion: Oncology wards provide the most adequate standard of analgesic therapy for cancer-related pain.

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.

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.

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.

Purpose: In the area of anticancer drugs, the legitimate search for effective interventions can be jeopardized by the strong pressure for accelerated approval, which may hinder the full assessment of their benefit-risk profile. We aimed to produce drug-specific recommendations using an explicit approach that separates the judgments on quality of evidence from the judgment about strength of recommendations., Materials and Methods: We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system to develop recommendations for the use of specific anticancer drugs/regimens; 12 clinical questions relevant to adjuvant treatment of breast (three), colorectal (four) and lung (five) cancer have been assessed by multidisciplinary panels supported by a group of methodologists., Results: For nine of 12 questions, recommendations were produced (one strong and six weak in favor and one weak and one strong against the index treatment); for the remaining three questions no specific course of action could be recommended. The perceived benefits to risk balance of the treatment was the most important and statistically significant (P < .01) predictor of panels' recommendations and of their strength, whereas panelists' personal (age, sex) and professional (specialty) characteristics were not statistically associated., Conclusion: Because the GRADE system sets out an explicit process going from evaluation of the quality of evidence and benefit-risk profile to the judgment of the strength of recommendations, in this experience, it proved very useful to combine methodologic rigor with the interdisciplinary participation that is important in the definition of evidence based clinical policies.

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.

Purpose: We evaluated the predictors of the incidence of erectile dysfunction in patients with type 2 diabetes mellitus and identified subgroups of patients in whom the interaction between clinical and psychological characteristics determined an increase in the risk of erectile dysfunction., Materials and Methods: The study was based on 670 individuals. The presence of erectile dysfunction and the severity of depressive symptoms were investigated with a questionnaire filled in every 6 months for 3 years. Poisson regression was used to calculate incidence rates. To evaluate interactions among the different variables and identify distinct and homogeneous subgroups in terms of incidence of erectile dysfunction, RECursive Partitioning and AMalgamation method was used., Results: Overall erectile dysfunction developed in 192 men with type 2 diabetes, with an incidence rate of 166.3 per 1,000 person-years. Age, insulin treatment, hemoglobin A1c greater than 8.0%, total cholesterol greater than 3.88 mmol/l and severity of depressive symptoms represented independent predictors of erectile dysfunction. RECursive Partitioning and AMalgamation analysis identified 5 classes with a marked variation in the risk of erectile dysfunction. Patients with low levels of depressive symptoms and hemoglobin A1c 8.0% or less showed the lowest risk of erectile dysfunction. Compared with this subgroup patients with higher levels of depressive symptoms and treated with insulin had a 3-fold risk of erectile dysfunction. Age, smoking, high cholesterol levels and neuropathy were globally predictive variables associated with an increased risk of erectile dysfunction., Conclusions: The incidence of erectile dysfunction is predicted by modifiable risk factors. Even in diabetes, psychological problems can contribute to the pathogenesis of erectile dysfunction, in addition to organic causes.

Background and Objectives: Clinical trials have shown that high dose chemotherapy (HDT) with peripheral stem cell autotransplantation is presently the best treatment for patients with symptomatic multiple myeloma (MM). In the context of an outcomes research project, we analyzed the feasibility of this strategy in clinical practice in a large cohort of consecutive, unselected patients with newly diagnosed MM and looked at the major determinants of response of patients enrolled in a HDT with tandem autotransplantation (Total Therapy I, TTI) program., Design and Methods: Two hundred and fourteen patients were treated outside of a clinical trial and regularly followed-up at our Center for symptomatic MM. Ninety-seven patients (45%) received conventional chemo-radiotherapy regimens, 110 (51%) entered the TTI program and the remaining 7 patients (3.3%) were enrolled in other programs involving HDT with autotransplantation., Results: Patients enrolled in HDT with tandem autotransplantation programs were 14 years younger and less likely to have co-morbidities than patients treated with conventional therapy. Median overall survivals of the two groups were 60 and 33 months, respectively. Thirteen percent of the patients enrolled in the TTI program did not receive the first HDT with autotransplantation, mostly because of disease progression, and another 16% did not proceed to the second HDT with autotransplantation mainly because of infections or drug-related complications. Most patients achieved complete remission after the second autotransplantation, with acceptable toxicity. However, only patients with a major reduction of the myeloma burden at the end of induction therapy enjoyed significantly prolonged event-free and overall survivals., Interpretation and Conclusions: Approximately one third of patients with newly diagnosed symptomatic MM completed the TTI program. These data suggest the need to improve the induction therapy in order to increase both the number of patients able to proceed to autotransplantation programs and to enhance the rate of early response.

Background: This study evaluated the impact on overall survival (OS) of 2 versus 5 years adjuvant tamoxifen in early breast carcinoma patients after 12 years of follow-up., Methods: Women with breast carcinoma T1-3, N0-3, M0, aged 50-70 years, were eligible for this multicenter randomized Phase III trial. Patients event-free after 2 years of tamoxifen therapy (TAM) were randomly assigned to stop or continue TAM (20 mg/day) for an additional 3 years. The primary endpoint was disease-free survival. Secondary endpoints included OS and toxicity., Results: From 1989 through 1996, 1901 patients were randomly assigned either to stop treatment (n = 958) or to continue TAM (n = 943). Overall, 98% of patients alive at the previous report (n = 1611) had updated information about OS, of whom 549 had died. The median duration of postrandomization follow-up was 115 months (interquartile range, 86-137). No statistically significant differences between the two arms were detected in the whole population (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.86-1.22) and in estrogen receptor (ER)-positive patients (HR, 0.90; 95% CI, 0.72-1.13). In the latter group, survival curves started to diverge after 90 months, showing a trend in favor of the 5-year arm. In younger (age < or =55 yrs) ER-positive patients longer TAM was associated with a 44% decrease in the risk of death (HR, 0.56; 95% CI, 0.31-1.00), while no clear benefit was documented in women older than 55 years of age (HR, 0.98; 95% CI, 0.77-1.25)., Conclusions: The benefits of longer TAM on OS start to emerge only after 9 years from diagnosis and seem to be more relevant in younger ER-positive women.

In the context of a nationwide outcomes research program on Type 2 diabetes, we investigated physician and patient practices related to foot care. Patients filled in a questionnaire investigating whether they had received information about foot care, how often they had had their feet examined in the last year, and how often they usually checked their feet. Analyses were adjusted for patient case-mix and physician-level clustering. Overall, 3564 patients were recruited by 125 diabetes outpatient clinics (DOCs) and 103 general practitioners (GPs), of whom 6.8% suffered form lower limb complications. The presence of foot complications was correlated with insulin treatment, cigarette smoking, low levels of school education, and the presence of other diabetic complications. More than 50% of the patients reported that they had not had their feet examined by their physician and 28% referred that they had not received foot education. Patients with lower levels of school education and income, as well as overweight individuals, were less likely to receive foot education. Physicians tended to perform foot examination more often in males, low-income patients, those with foot complications, and those treated with insulin, but not in patients with the highest risk of foot complications, that is, those with diabetic neuropathy or peripheral vascular disease (PVD). GPs tended to perform foot examination less frequently than diabetologists do. Foot self-examination was not performed by 33% of the patients. Those individuals who had received foot education or had had their feet examined were more likely to check their feet regularly. A substantial proportion of Type 2 diabetic patients is not offered adequate foot care, even in the presence of major risk factors for lower limb complications. Patient knowledge and practices are strongly related to physicians' attitudes.

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.

Aims: In the framework of a nationwide outcomes research programme, we assessed the impact of self-monitoring of blood glucose (SMBG) on metabolic control over 3 years in patients with Type 2 diabetes mellitus (DM2) not treated with insulin., Methods: The study involved 1896 patients who completed, at 6-month intervals for 3 years, a questionnaire investigating SMBG practice. Clinical information was collected by participating clinicians at the same time intervals. The predictive value of SMBG frequency on long-term metabolic control was estimated using multilevel analysis. The impact of SMBG on metabolic control was also evaluated in distinct and homogeneous subgroups of patients showing different likelihood of performing SMBG, identified using a tree-growing technique (RECPAM)., Results: Overall, 22% of the patients were on diet alone and 78% were treated with oral agents; 41% practiced SMBG > or = 1/week (10.3% > or = 1/day). The analysis of metabolic control according to the frequency of SMBG failed to show any significant impact of this practice on HbA1c levels over 3 years. Similarly, changes in SMBG frequency during the study were not related to significant changes in HbA1c levels. RECPAM analysis led to the identification of eight classes, characterized by substantial differences in the likelihood of performing SMBG with a frequency of at least 1/week. Nevertheless, in none of the RECPAM classes identified, did SMBG predict a better metabolic control over 3 years of follow-up. In those RECPAM classes indicating that SMBG was mainly performed to avoid hypoglycaemic episodes, SMBG was associated with a decrease in the frequency of hypoglycaemic episodes during the study., Conclusions: In a large sample of non-insulin-treated Type 2 diabetic patients, the performance and frequency of SMBG did not predict better metabolic control over 3 years. We could not identify any specific subgroups of patients for whom SMBG practice was associated with lower HbA1c levels during the study.

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.

Background: Clinical trials demonstrate significant benefit from cholesterol management for patients with type 2 diabetes. The aim of this work was to explore the correlates of lipid management in patients with type 2 diabetes, including the subjective beliefs of physicians, setting of care, and patient-related factors., Methods: This longitudinal outcomes research study involved 2359 patients with type 2 diabetes recruited by 111 general practitioners and 214 physicians practicing in diabetes clinics. Physicians' beliefs were assessed through a questionnaire administered when the study started in 1998. Main outcome measures were total cholesterol (TC) and LDL cholesterol (LDL-C) levels over 3 years and the proportion of patients treated with lipid-lowering drugs (LLDs)., Results: Less than one-third of the physicians (27%) stated that they routinely started pharmacologic therapy for TC values > or =200 mg/dL (more aggressive), whereas 46% considered a TC level > or =240 mg/dL as the threshold for the initiation of treatment (less aggressive). During 3 years of observation, mean TC and LDL-C levels decreased from 215 +/- 40 mg/dL to 203 +/- 37 mg/dL and from 135 +/- 36 mg/dL to 126 +/- 35 mg/dL respectively, while the proportion of patients treated with LLDs increased from 13.2% to 24.6%; in particular, among individuals cared for by the more aggressive physicians, 30.0% were taking LLDs after 3 years, while only 17.7% of those followed by the less aggressive physicians and 18.1% of those followed by >1 physician were being treated with LLDs. Multilevel analysis showed that physicians' beliefs were an independent predictor of TC levels over the 3-year period. In patients treated with LLDs, TC levels decreased on average by 14%, and LDL-C levels decreased by 20%., Conclusion: Our data show that physicians' beliefs in more aggressive management strategies will result in better mean TC values over a 3-year period.

In the context of an Italian nation-wide outcomes research program on type 2 diabetes, we investigated the contribution of both patient and setting-related factors to patient satisfaction with their relationship with their physicians. The level of patient satisfaction was measured using the American Board of Internal Medicine (ABIM) 14 patient satisfaction questionnaire. The main results were obtained using multilevel analysis, a statistical technique that takes into account the clustered nature of our data. Overall, 3563 patients were recruited by 101 diabetologists and 103 general practitioners (GPs). Information on patients' satisfaction was available for 2515 patients (71% of the whole sample). Patients' satisfaction was related to patient characteristics and attitudes, but not with physician's sex, age, speciality, and setting of care. In particular, patients who were less likely to delegate to physicians responsibility for diabetes management and those perceiving a lower degree of involvement in disease management showed lower levels of satisfaction. Lower satisfaction scores were also related to lower levels of school education, more severe clinical conditions, and lower psychological adaptation to diabetes. However, patients reporting higher levels of diabetes related worries and more frequent encounters with health care providers showed higher levels of satisfaction. In conclusion, patient satisfaction with physicians' humanness and communication skills is strongly related to personal characteristics, attitudes, expectations, and perceived health. In deciding the best decision-making approach to adopt in individual patients, it is of primary importance to measure how the patient perceives and engages in relationships.

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.

Purpose: To compare 2 with 5 years of adjuvant tamoxifen therapy in the treatment of early breast cancer., Patients and Methods: Women with breast carcinoma T1-3, N0-3, M0, who were between 50 and 70 years of age, were eligible irrespective of menopausal status, tumor grade, or estrogen receptor (ER) status. Patients who were event-free after 2 years of tamoxifen therapy were randomly assigned to stop or continue tamoxifen therapy for an additional 3 years. The primary end point was length of disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity., Results: From 1989 through 1996, 1,901 patients were randomly assigned either to stop treatment (n = 958) or to receive tamoxifen for 3 additional years (n = 943). The median duration of postrandomization follow-up was 52 months. We found no statistically significant differences between the 5-year arm and the 2-year arm in terms of DFS (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.76 to 1.08) and OS (HR, 1.16; 95% CI, 0.92 to 1.46). In ER-positive patients, a statistically significant prolongation of DFS related to longer treatment duration was observed (HR, 0.74; 95% CI, 0.59 to 0.93), whereas no difference in OS could be detected (HR, 0.98; 95% CI, 0.72 to 1.32). No differences in terms of endometrial cancers, cardiac or cerebrovascular events, or fractures were detected, whereas a doubling in the risk of thromboembolic events was found in the 5-year arm., Conclusion: Our results confirm previous research that shows that 5 years of tamoxifen decreases recurrence compared to 2 years in patients with ER-positive tumors.

Purpose: We estimated the prevalence of erectile dysfunction in patients with type 2 diabetes and identified subgroups of patients in which the interaction among clinical, psychological and sociodemographic characteristics determined an increased likelihood of erectile dysfunction., Materials and Methods: The presence of erectile dysfunction was based on patient self-reporting. Clinical information was collected by participating physicians. The severity of depressive symptoms was investigated using the Center for Epidemiological Studies Depression scale. To evaluate interactions among the variables investigated and identify distinct, homogeneous subgroups of patients with different odds ratios for erectile dysfunction a tree growing technique was used., Results: In the 1,460 patients studied the prevalence of severe and mild-moderate erectile dysfunction was 34% and 24%, respectively. While severe erectile dysfunction was mainly related to the severity of diabetes, mild-moderate dysfunction was independent of clinical variables and only associated with the severity of depressive symptoms. The tree growing technique led to the identification of 6 classes characterized by a marked difference in the prevalence of severe erectile dysfunction of between 19% and 65%. Patients on diet alone showed the lowest prevalence of erectile dysfunction and were considered the reference category, while patients treated with insulin who had neuropathy represented the subgroup with the highest likelihood of erectile dysfunction (OR = 7.2, 95% CI 3.9 to 13.2). In patients treated with oral agents the odds ratio for erectile dysfunction was 2.7 (95% CI 1.8 to 3.9) for those with severe depressive symptoms and 1.9 (95% CI 1.3 to 2.7) for current/former smokers with low depressive symptoms. Patient age, retinopathy and cardiac-cerebrovascular disease were globally predictive variables associated with an increased likelihood of erectile dysfunction., Conclusions: Our data illustrate the interplay of clinical and psychological factors in determining the risk of erectile dysfunction in type 2 diabetes and can help identify those for whom much greater attention is needed to detect erectile problems.

Background: A large body of evidence supports the need for reducing the cardiovascular burden of diabetes. Only indirect and occasional data describe the adequacy of routine management of hypertension in patients with diabetes. The aim of this study was to explore the interplay of some potential key determinants of quality of antihypertensive care, including the settings, physicians' beliefs about blood pressure (BP) control, and patient-related factors., Methods: We evaluated physicians' beliefs about BP control using questionnaire responses at study entry. A sample of 3449 patients with type 2 diabetes mellitus, of whom 1782 (52%) were considered to have hypertension, was recruited by 212 physicians practicing in 125 diabetes outpatients clinics (DOCs) and 106 general practitioners (GPs). We evaluated the type and number of antihypertensive agents used and the BP values at study entry and after 1 year of follow-up. We used multilevel analysis to investigate correlates of poor BP control (> or =160/90 mm Hg)., Results: Only 16% of GPs and 14% of DOC physicians targeted BP values of less than 130/85 mm Hg. At study entry, 6% of the patients had values below 130/85 mm Hg, whereas 52% showed values of 160/90 mm Hg or greater. Only 12% of subjects were treated with more than 2 drugs at study entry, compared with 16% at the 1-year follow-up (P =.001). Multilevel analysis showed that patients attending DOCs had a more than 2-fold increased risk for inadequate BP control, compared with those treated by GPs. The risk for poor BP control was 2 times higher for patients treated by male physicians compared with those treated by female physicians, and it was halved when the physician responsible for the diabetes care specialized in diabetology or endocrinology., Conclusion: In a model situation of comorbidity, the overall quality of care depends on structural and organizational factors, which are likely to be more influential than existing guidelines.

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.

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.

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.

Background: Several studies have investigated the possible role of the adjuvant chemotherapy after curative resection for gastric cancer failing to show a clear indication; previous meta-analyses suggested small survival benefit of adjuvant chemotherapy, but the statistical methods used were open to criticisms., Materials and Methods: Randomised trials were identified by means of Medline and CancerLit and by selecting references from relevant articles. Systematic review of all randomised clinical trials of adjuvant chemotherapy for gastric cancer compared with surgery alone, published before January 2000, were considered. Pooling of data was performed using the fixed effect model. Death for any cause was the study endpoint. The hazard ratio and its 95% confidence intervals (95% CI), derived according to the method of Parmar, were the statistics chosen for summarising the relative benefit of chemotherapy versus control., Results: Overall 20 articles (21 comparisons) were considered for analysis. Three studies used single agent chemotherapy, seven combination of 5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU without anthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82, 95% CI: 0.75-0.89, P < 0.001). Association of Anthracyclines to 5-FU did not show a statistically significant improvement when compared with the effect of the other regimens., Conclusions: Chemotherapy produces a small survival benefit in patients with curatively resected gastric cancer. However, taking into account the limitations of literature based meta-analyses, adjuvant chemotherapy is still to be considered as an investigational approach.

Background: Institutional and physician-related factors can influence the way in which physicians interpret research results. The aim of this study was to determine what physicians know about, and their opinions of, hormone treatment in breast cancer patients, and the factors comprising their medical decision-making., Materials and Methods: A questionnaire was mailed to a random sample of physicians inquiring as to their preferences with respect to adjuvant tamoxifen, and the usual duration of the treatment applied in various clinical scenarios (according to a woman's menopausal status, the oestrogen receptor status and the stage of disease)., Results: Of 500 physicians identified, 38% returned the questionnaire. Of the non-responders, a random sample of 60 physicians was interviewed by phone. The total number of available questionnaires was 250 (50%). About 3/4 of the doctors would prescribe tamoxifen in older ER+ women and 30%-40% in post-menopausal ER-patients, but only 2/5 would do so in younger ER+ women. The vast majority of physicians considered five years as standard for ER+ patients. Nevertheless, about 1/4 of the doctors chose a shorter treatment duration for node-negative, pre-menopausal patients. A minority of physicians used tamoxifen for longer than five years. Older clinicians were less likely to prescribe tamoxifen, particularly for low-risk patients., Conclusions: According to the data of the recent EBCTG overview, an additional 20,000 lives could be saved worldwide each year if tamoxifen were given to all early breast cancer patients with hormone-sensitive disease, irrespective of age and disease stage, and for a minimum of five years. Our study, involving a representative sample of physicians practicing in Italy, shows that tamoxifen is not used optimally, with a substantial under-use in younger women and women with node-negative disease.

Objective: To assess the efficacy, safety and extent of perceived indications of acarbose, a new antidiabetic agent, under routine clinical practice conditions in an unselected Northern Italian population of type II diabetic patients., Methods: The study population was assigned to three different groups according to the physician's clinical judgement: group A (acarbose considered as an elective treatment); group B (acarbose considered to be of uncertain benefit): group C (acarbose deemed not to be appropriate). Group B patients were randomized either to continue their standard treatment or to add acarbose to it. Patients with type II diabetes mellitus were recruited from 17 diabetes outpatient clinics from one Italian region (Lombardy). A total of 1027 patients were recruited (group A: 283; group C: 494; group B: 250, of whom 124 were randomly assigned to standard treatment + acarbose and 126 to standard treatment alone). Acarbose was administered for 1 year at a median dose of 100 mg 3 times daily. Drug efficacy was evaluated in terms of mean HbAlc, pre- and post-prandial glycaemic values. Additional endpoints were the proportion of patients with HbA1c levels below 8% at the end of the study period and the proportion of subjects who needed a modification in the standard treatment. The safety and tolerability profiles of the drug were also investigated. Data on HbA1c, fasting and post-prandial blood glucose levels were analysed over time using repeated-measures analysis [Generalized Estimating Equation (GEE) models]., Results: The analysis of Group B showed that, after treatment for 1 year, the mean reduction in HbA1c levels in the acarbose group with respect to the control group was 0.30% (95% confidence limits -0.60 +0.02; P = 0.07), while the mean reduction in post-prandial glycaemia was 17 mg-dl(-1) (95% c.l. -33.5 -0.8; P = 0.04). No difference resulted for fasting blood glucose levels. When looking at the baseline HbA1c levels, it emerged that the mean benefit associated with the use of acarbose was 0.14% (95% c.l. -0.6 +0.28; P = 0.5) in patients with HbAlc levels below 8%, 0.28% (95% c.l. -0.6 +0.05; P = 0.09) in those with values between 8% and 9.9% and 0.65% (95% c.l. -1.36 +0.06; P = 0.07) in those with values > or =10%. Only patients treated with diet+/-oral anti-diabetic agents (OAA) benefited from acarbose treatment (mean benefit = 0.37%, 95% c.l. -0.65 -0.08), while no effect was shown for insulin-treated subjects. The proportion of patients with HbA1c below 8% increased from 31% to 44% in the acarbose group and from 40% to 45% in the control group (absolute difference between baseline and end-of-study values = 8.0% in favour of acarbose-treated patients; P = 0.058). Patients treated with acarbose were significantly more likely to undergo a dose reduction in concomitant diabetic treatments compared with the control group; they were also less likely to require an increase in the dose of standard treatment and to start insulin during the study period. One third of the patients could not assume the drug for the whole study period, mainly due to gastrointestinal side-effects., Conclusions: The design adopted in this study allowed an integrated evaluation of the overall effectiveness of acarbose in clinical practice. The benefits of the drug in an unselected population of non-insulin-dependent diabetes mellitus (NIDDM) patients are significant but of marginal clinical relevance. Only a better definition of the subgroups of patients who are more likely to benefit from long-term treatment, particularly through possible postponement of secondary OAA failure, will allow a reliable definition of the cost-effectiveness of this complementary component of anti-diabetic strategy.

We set out to describe patterns of care of an Italian diabetic population, with reference to the recommendations of the St Vincent Declaration. We investigated different aspects of care received by 2707 patients, of whom 2196 in the charge of 35 Diabetes Outpatient Clinics (DOCs) and 511 cared for by 49 General Practitioners (GPs). Data were collected by interviewing the patients, their physicians and by reviewing medical records. Our data show that diabetes care in Italy differs in many aspects from the recommendations of the St Vincent Declaration. Glycated haemoglobin measurement was lacking in 50% of the patients in the charge of GPs and in 15% of those attending DOCs. While the control of cardiovascular risk factors was satisfactory, information on albumin excretion was not available in one third of the patients. Overall, 79% of the patients had had an eye examination in the previous 12 months. More than one-third of the patients had not received adequate information on different aspects of care, with wide variations according to the setting of care. Forty-two per cent of the patients attending DOCs and 14% of those cared for by GPs practised blood glucose self-monitoring; similarly, insulin therapy self-management was performed by 50% and 19% of the patients attending DOCs and GPs, respectively. Our data call for vigorous efforts aimed at improving the awareness of the potential for reducing major diabetic complications. Therefore, it is essential to promote the incorporation of clearly defined clinical practice guidelines at each level of care.

Peripheral neuropathy is one of the most common and disabling long-term sequelae of diabetes mellitus. Aldose reductase inhibitors (ARIs) have been proposed and are increasingly used in many countries for the prevention and treatment of diabetic neuropathy. The aim of this study was to review existing evidence on the effectiveness of ARIs in the treatment of peripheral diabetic neuropathy, with particular reference to the type and clinical relevance of the end point used and to the consistency of results across studies. Thirteen randomized clinical trials (RTCs) comparing ARIs with placebo, published between 1981 and 1993 were included in the meta-analysis. Nerve conduction velocity (NCV) was the only end point reported in all trials. Treatment effect was thus evaluated in terms of NCV mean difference in four different nerves: median motor, median sensory, peroneal motor, and sural sensory. A statistically significant reduction in decline of median motor NCV was present in the treated group as compared to the control group (mean 0.91 ms-1; 95% CI 0.41-1.42 ms-1). For peroneal motor, median sensory, and sural sensory nerves results did not show any clear benefit for patients treated with ARIs. When the analysis was limited to trials with at least 1-year treatment duration, a significant effect was present for peroneal motor NCV (mean 1.24 ms-1; 95% CI 0.32-2.15 ms-1) and a benefit of borderline statistical significance was also present for median motor NCV (mean 0.69 ms-1; 95% CI-0.07-1.45 ms-1). A heterogeneous picture emerged when looking at the results of different studies and serious inconsistencies were also present in the direction of treatment effects among nerves in the same studies. Although the results of 1-year treatment on motor NCV seem encouraging, the uncertainty about the reliability of the end-point employed and the short treatment duration do not allow any clear conclusion about the efficacy of ARIs in the treatment of peripheral diabetic neuropathy.

The aim of this study was to describe the epidemiology of self-monitoring of blood glucose and to identify specific characteristics of those subgroups of diabetic patients treated with insulin that are most likely to monitor their blood glucose according to medical recommendations. Data were collected on 1384 insulin-treated patients, enrolled from 35 diabetic outpatient clinics and 49 general practitioners' offices between December 1993 and June 1994. Seventeen Italian regions out of 20 were included in the study. Our data show that 418 (31%) diabetic patients treated with insulin had never practised blood glucose self-monitoring. In addition, only 242 patients (18.2%) self-monitored their glycemia with a mean frequency of at least once a day (29.7% among insulin-dependent diabetes mellitus (IDDM) and 13.9%, among insulin-treated non-insulin-dependent diabetes mellitus (NIDDM-IT) patients). Patients' characteristics associated with a higher probability of practising blood glucose self-monitoring were age below 50 years, being treated at a diabetic outpatient clinic, hypertension, need of three or more insulin injections per day, history of hypoglycemic episodes, ability to self-manage insulin doses. Our study calls for vigorous efforts aimed at promoting the incorporation of clearly-defined educational programs at each level of care, in order to improve the motivation and self-care of diabetic patients. Furthermore, studies are necessary to identify subgroups of diabetic patients that truly need to self-monitor blood glycemia, and to assess the efficacy of the practice of self-monitoring of blood glucose in improving metabolic control and reducing acute and long-term diabetic complications.

To assess appropriateness of surgical care delivered to breast cancer patients in Italy and quantify the use of unnecessary radical procedures, a retrospective charts review of patients treated in 1988-1989 was conducted. A series of 1724 consecutive patients (median age 61 years; range 17-89) treated in 63 hospitals selected from within 8 regions with newly diagnosed operable breast carcinoma was evaluated. Overall, 541 (38%) patients had inappropriate surgery with more than two thirds of it being accounted for by the use of unnecessary mutilating Halsted mastectomy. Substantial geographic variation emerged in the overall rates of appropriateness (range 88-52%) which were not substantially affected by allowance for imbalances in patient- and hospital-related variables. Despite the important contribution given by Italian clinical researchers to the demonstration that less radical surgery can be as good as more radical procedures, still a substantial proportion of breast cancer patients are treated too aggressively. Besides pointing to the urgent need of interventions aimed at facilitating the process of technology transfer in order to promote more appropriate surgical care, these results suggest that efforts to increase patients' participation into treatment decision and awareness about alternative treatment options are warranted.

Objective: To assess whether and how the characteristics of hospitals' surgical staff can predict utilization of breast conserving surgery. We anticipated that the use of the procedure was more frequent in hospitals with a greater proportion of younger and female surgeons on their staff., Setting: Sixty-two hospitals with different level of organization for the care of cancer patient from eight Italian regions were included., Design: We collected information on the personal characteristics (age and sex) of all surgeons on the staff of the participating centers. A concurrent pattern of care study was undertaken, in order to assess the utilization of breast conserving procedures., Results: The use of conservative surgery was 16%, 20%, 31%, in centers with 0%, < 20% and 20-50% female surgeons respectively (p = 0.003), while no associations emerged between the mean age of the surgical staff and the use of conservative surgery. This relationship also held true after adjusting for other patients' characteristics, such as stage of disease, age and presence of comorbidity. However, overall the use of patient-related and staff-related characteristics to predict the number of breast conserving surgeries performed in each area was able to explain only 16% of the observed variability in the use of breast conserving surgery., Conclusions: Even though in this study a large proportion of the observed variation in the use of breast conserving surgery was still left unexplained, this finding suggests that assessing the relationship between doctors' characteristics and the use of scientific evidence is an important topic for health service research and can be of some help in exploring variations in clinical practice styles.