Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.

BACKGROUND: For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS: In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS: Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79­1·02] during years 5­9 and 0·75 [0·62­0·90] in later years; breast cancer mortality RR 0·97 [0·79­1·18] during years 5­9 and 0·71 [0·58­0·88] in later years). The cumulative risk of recurrence during years 5­14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5­14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89­1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13­3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83­1·36), ischaemic heart disease 0·76 (0·60­0·95, p=0·02), and endometrial cancer 1·74 (1·30­2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5­14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION: For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING: Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.

[Current status of the studies on breast cancer outcomes. A review of the literature]. / Andamento e stato della ricerca sul cancro della mammella: una analisi della letteratura.

Breast cancer is the most frequent neoplasm among women. The Outcomes Research could be a useful tool in managing this kind of tumour. A recent review of the literature evaluates the interest for this kind of research and the possible future evolution.

How to conduct a randomized trial.

Randomized controlled clinical trials represent the gold standard of research into health-care interventions but conducting a randomized trial requires careful planning, structures and procedures. The conduct of a clinical trial is a collaborative effort between investigators, participants and a range of professionals involved both centrally and locally in the coordination and execution of the study. In this article, the key steps to conducting a randomized controlled trial are summarized.

[Memorandum for the management of clinical trials]. / Pro-memoria per la gestione della sperimentazione clinica.

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.

Quality of diabetes care predicts the development of cardiovascular events: results of the QuED study.

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.

Low versus high dose erythropoiesis-stimulating agents in hemodialysis patients with anemia: A randomized clinical trial.

The increased risks of death and adverse events with erythropoiesis-stimulating agent (ESA) therapy targeting a higher hemoglobin level are established. It is uncertain whether the adverse effects of ESA therapy are related to dose and are mitigated when a fixed low ESA dose is used. We conducted a multicenter, prospective randomized open-label, blinded-endpoint (PROBE) trial to evaluate fixed low versus high dose ESA therapy on patient outcomes. We intended to recruit 2104 hemodialysis patients >18 years with anemia or receiving ESA treated at dialysis clinics in Italy. The intervention was fixed low (4000 IU epoetin alfa equivalent weekly) or high (18,000 IU epoetin alfa equivalent weekly) dose ESA for 12 months. Primary outcomes were serum transferrin, ferritin, albumin, C-reactive protein and ESA dose. Secondary outcomes were the composite of death or cardiovascular event, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, cardiovascular hospitalization, and quality of life. Study recruitment was terminated after inclusion of 656 participants with convergence of ESA dose between groups during follow up. Fixed low dose ESA had uncertain effects on serum ferritin (delta of delta (DD) 3.9 ng/ml, 95% CI -85.0 to 92.8), transferrin (9.2 mg/dl, -6.3 to 24.8), transferrin saturation (3.7%, -5.0 to 12.3), serum albumin (-0.03 g/dl, -0.2 to 0.1), or C-reactive protein (-0.6 mg/l, -3.3 to 2.1). In addition, fixed dose therapy had inconclusive effects on the composite endpoint of mortality and cardiovascular events (hazard ratio [HR] 0.95, 95% CI 0.66 to 1.37), death (0.98, 0.64 to 1.52), nonfatal myocardial infarction (0.52, 0.18 to 1.52), nonfatal stroke (no events), hospital admission for cardiovascular causes (0.93, 0.50 to 1.72) or health-related quality of life. A fixed low ESA dose in hemodialysis patients has uncertain effects on serum parameters, mortality, cardiovascular events, and quality of life. Hemoglobin targets may be so entrenched in nephrology practice that a trial of ESA dose is no longer possible.

Use of the diabetes risk score for opportunistic screening of undiagnosed diabetes and impaired glucose tolerance: the IGLOO (Impaired Glucose Tolerance and Long-Term Outcomes Observational) 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.

Longitudinal assessment of quality of life in patients with type 2 diabetes and self-reported erectile dysfunction.

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.

Impact of physicians' beliefs and practices on cholesterol levels in patients with type 2 diabetes: a longitudinal assessment.

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.

Feasibility and outcome of tandem stem cell autotransplants in multiple myeloma.

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.

Are Type 2 diabetic patients offered adequate foot care? The role of physician and patient characteristics.

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.

Role of organizational factors in poor blood pressure control in patients with type 2 diabetes: the QuED Study Group--quality of care and outcomes in type 2 diabetes.

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.

Erectile dysfunction and quality of life in type 2 diabetic patients: a serious problem too often overlooked.

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.

Quality of care and outcomes in type 2 diabetic patients: a comparison between general practice and diabetes clinics.

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.

Correlates of satisfaction for the relationship with their physician in type 2 diabetic patients.

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.

Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer.

BACKGROUND: Systematic reviews have found that luteinizing hormone-releasing hormone (LHRH) agonists are effective in treating premenopausal women with early breast cancer. METHODS: We conducted long-term follow-up (median 12 years) of 2706 women in the Zoladex In Premenopausal Patients (ZIPP), which evaluated the LHRH agonist goserelin (3.6 mg injection every 4 weeks) and tamoxifen (20 or 40 mg daily), given for 2 years. Women were randomly assigned to receive each therapy alone, both, or neither, after primary therapy (surgery with or without radiotherapy/chemotherapy). Hazard ratios and absolute risk differences were used to assess the effect of goserelin treatment on event-free survival (breast cancer recurrence, new tumor or death), overall survival, risk of recurrence of breast cancer, and risk of dying from breast cancer, in the presence or absence of tamoxifen. RESULTS: Fifteen years after the initiation of treatment, for every 100 women not given tamoxifen, there were 13.9 (95% confidence interval [CI] = 17.5 to 19.4) fewer events among those who were treated with goserelin compared with those who were not treated with goserelin. However, among women who did take tamoxifen, there were 2.8 fewer events (95% CI = 7.7 fewer to 2.0 more) per 100 women treated with goserelin compared with those not treated with goserelin. The risk of dying from breast cancer was also reduced at 15 years: For every 100 women given goserelin, the number of breast cancer deaths was lower by 2.6 (95% CI = 6.6 fewer to 2.1 more) and 8.5 (95% CI = 2.2 to 13.7) in those who did and did not take tamoxifen, respectively, although in the former group the difference was not statistically significant. CONCLUSIONS: Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy. In women who did not take tamoxifen, there was a large benefit of goserelin treatment on survival and recurrence, and in women who did take tamoxifen, there was a marginal potential benefit on these outcomes when goserelin was added.

Identifying patients at risk for microalbuminuria via interaction of the components of the metabolic syndrome: a cross-sectional analytic study.

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.

Clinical and psychological predictors of incidence of self-reported erectile dysfunction in patients with type 2 diabetes.

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.

Twelve-year mortality results of a randomized trial of 2 versus 5 years of adjuvant tamoxifen for postmenopausal early-stage breast carcinoma patients (SITAM 01).

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.