Associations Between Glycemic Control, Depressed Mood, Clinical Depression, and Diabetes Distress Before and After Insulin Initiation: An Exploratory, Post Hoc Analysis.

INTRODUCTION: Although depression is often associated with poor glycemic control in patients with type 2 diabetes mellitus (T2DM), this observation has been inconsistent. This exploratory, post hoc analysis investigated associations between depression parameters and glycemic control using data from a 24-month, prospective, observational, non-interventional study evaluating glycemic response following insulin initiation for T2DM. METHODS: We analyzed data from a 24-month, prospective, observational study that evaluated glycemic response in patients with T2DM who initiated insulin therapy (N = 985) in 5 European countries. Secondary measures included patient-reported diagnosis of depression at baseline, severity of depressed/anxious mood (EuroQol (EQ)-5D item) and diabetes-related distress (Psychological Distress domain of the Diabetes Health Profile, DHP-18). The latter two measures were assessed at baseline and 5 time points throughout the study. Glycemic control was measured by glycated hemoglobin (HbA1c) at these same time points. Analyses employed t tests to assess the unadjusted baseline difference in HbA1c between patients with and without the respective depression parameter. The potential effect of demographic and clinical confounding variables was controlled through a linear model structure. Patient HbA1c levels were analyzed by presence/absence of a history of diagnosed depression, depressed mood, and diabetes-related distress. RESULTS: Patients with higher depression parameters or distress at baseline had significantly higher rates of microvascular complications at baseline. Patients with a history of diagnosed depression or high diabetes-related distress had higher HbA1c than patients without. HbA1c of patients with or without depressed mood was not significantly different at baseline. The proportion of patients with depressed mood declined after insulin initiation, whereas the proportion of patients with high diabetes-related distress did not significantly change. HbA1c improved following insulin initiation, regardless of presence/absence of studied depression/distress parameters at baseline. CONCLUSION: History of diagnosed depression, diabetes-related distress, and depressed mood were associated with a higher rate of microvascular complications. Diagnosed depression and diabetes-related distress also showed higher HbA1c at baseline when insulin was initiated. Insulin therapy improved glycemic control, while preexisting depressed mood declined and diabetes-related distress remained unchanged.

Evaluation of insulin initiation on resource utilization and direct costs of treatment over 12 months in patients with type 2 diabetes in Europe: results from INSTIGATE and TREAT observational studies.

OBJECTIVES: To describe the changes in resource utilization in seven European countries (Germany, Greece, Portugal, Romania, Sweden, Spain, and Turkey) and direct costs in four European countries (Germany, Spain, Sweden, and Greece) over the first 12 months of insulin treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: INSTIGATE and TREAT (2005-2010) were non-interventional, prospective, observational studies in patients with T2DM and initiating insulin for the first time. A 6-month retrospective data capture was conducted at baseline (insulin initiation) followed by prospective data collections at ∼3, 6, and 12 months. Statistical analyses were descriptive; estimated costs are presented as nominal values. RESULTS: This study presents data for 1450 patients. Overall, in the first 6 months after insulin initiation, the use and cost of blood glucose monitoring and insulin increased, while the cost of oral diabetic medication decreased. Contributors to total direct costs differed between countries. Ranges of total mean direct costs over the 6-month period before insulin initiation were €489.10-€658.50 (Greece-Spain); 0-6 months after insulin initiation, €573.40-€1084.70 (Greece-Spain); and 6-12 months after insulin initiation, €495.80-€859.30 (Greece-Germany). Thus, the mean cost of treatment increased in all countries in the first 6 months after insulin initiation and then returned to baseline except in Germany. LIMITATIONS: Overall, 15% of patients were lost to follow-up over 12 months. Costs were not pro-rated to account for variation of visits. Participating centres may not have been fully representative of all levels of care. CONCLUSIONS: Contributors to total cost differed between countries, potentially reflecting local clinical practice patterns and insulin regimens. In each country, mean direct total costs of T2DM care increased during the first 6 months after insulin initiation and decreased thereafter.

Effects of 12-month tadalafil therapy for erectile dysfunction on couple relationships: results from the DETECT study.

INTRODUCTION: Erectile dysfunction (ED) is distressing and can affect a couple's relationship. AIM: To investigate partner awareness of ED, relationship problems, and the effects of tadalafil treatment over 12 months. METHODS: The Determinants of Continued Use of Tadalafil study is a prospective 12-month European observational study in patients with ED initiating or changing treatment to on-demand tadalafil. A total of 1,900 patients were enrolled in eight countries. Assessments were made on predefined treatment outcomes in a routine clinical setting. MAIN OUTCOME MEASURES: At baseline, 1, 6, and 12 months, patients were asked about relationship problems (unspecified), partner awareness and support of consultation, and partner sexual problems. Data were analyzed for patients continuing tadalafil at 12 months. RESULTS: At baseline, 96% of patients had a partner, 80% of partners supported an ED consult, and 73% were aware of the consultation. Relationship problems were reported by 17% of patients at baseline. At 12 months, 84% of patients were still taking tadalafil. Of these, 19% reported relationship problems at baseline. After 12 months of treatment with tadalafil, 4% of patients still reported perceived problems. Factors associated with no relationship problems at 12 months were: at baseline, no previous ED treatment, partner in poor health; and at 12 months a lower ED severity. If the partner was felt to have a sexual problem at 12 months, relationship improvement was less likely. Further, 3% of patients developed relationship problems during treatment. Factors associated with developing a relationship problem were: a history of pelvic surgery at baseline, a different partner at 12 months than at baseline, and a partner with a sexual problem at 12 months. CONCLUSIONS: Improvement of ED with tadalafil was associated with reduced relationship problems, suggesting that problems were associated with ED and resolved with treatment.

Evaluation of patient expectations and treatment satisfaction after 1-year tadalafil therapy for erectile dysfunction: the DETECT study.

INTRODUCTION: Erectile dysfunction (ED) is a self-reported condition and satisfaction with sexual performance is individual, subjective, and multi-factorial. Treatment success depends on several outcomes. Tadalafil is a long-acting, selective inhibitor of phosphodiesterase 5 that has been shown to be effective at treating men with ED. AIM: To investigate patient's ED treatment expectations at baseline; patient satisfaction with tadalafil treatment after 12 months; factors associated with satisfaction; and effect of early tadalafil treatment satisfaction on tadalafil continuation at 12 months. METHODS: The Determinants of Continued Use of Tadalafil study is a 12-month, prospective, pan-European, noninterventional, observational study, which enrolled 1,900 patients with ED wishing to initiate or change their treatment to tadalafil. Assessments were made on predefined treatment outcomes in a routine clinical setting. MAIN OUTCOME MEASURES: International Index of Erectile Function-erectile function domain scores (at baseline, 1, 6, and 12 month visit), ED Inventory of Treatment Satisfaction (EDITS) scores (after 1, 6, and 12 months), and patient expectation questionnaire (at baseline visit) were analyzed for these patients. RESULTS: Data were available from 1,567 patients (82%) after 12 months, with similar baseline characteristics as the initial cohort. Treatment expectations identified as important included: erection hardness and ability to maintain erection through intercourse completion (>92% of patients); confidence, partner satisfaction, and naturalness (>84% of patients); rapid effect and long duration of treatment (>75% of patients). Continued tadalafil use from 1,319 (84%) patients at 12 months were reported. Total EDITS scores for those continuing treatment was 85.9 (95% CI: 85.1-86.7). Increased satisfaction was associated with higher effectiveness, number of sexual attempts, partner support, good relationships, and good drug tolerance. Treatment satisfaction at 1 month was best predictive of treatment continuation at 12 months. CONCLUSIONS: Eighty-four percent of patients reported continued use of tadalafil after 12 months. High satisfaction after first month of treatment was the best predictor of treatment continuation.

Therapeutic response after first month of tadalafil treatment predicts 12 months treatment continuation in patients with erectile dysfunction: results from the DETECT study.

INTRODUCTION: The DETECT study is a prospective, 12-month, European, multicenter, observational study of patients with erectile dysfunction (ED) initiating or changing treatment to tadalafil in routine clinical practice. AIM: To determine the effectiveness of tadalafil and the factors associated with the continuation of treatment for ED at 12 months. METHODS: The DETECT study included 1,900 men aged 18 years and older with a history of ED and who were initiating or changing treatment to tadalafil. MAIN OUTCOME MEASURES: Sexual function at baseline, 1, 6, and 12 months was assessed using the International Index of Erectile Function-erectile function (IIEF-EF) domain. Factors associated with treatment continuation at 12 months were evaluated using multivariate regression analysis. RESULTS: At 12 months, 1,319 (84%) of 1,567 patients who completed the questionnaire reported continued use of tadalafil. Among these patients, tadalafil was highly effective: 94%, 95%, and 71% with severe, moderate, and mild ED at baseline, respectively, improved by at least one IIEF-EF category and 65% had normal EF. Five factors were associated with tadalafil continuation at 12 months: (i) ED severity at 1 month (based on IIEF-EF domain score); (ii) tolerance to treatment at 1 month; (iii) age younger than 60 years; (iv) number of sexual attempts in the first month; and (v) no history of pelvic surgery. Patient and partner factors at baseline were not significantly associated with continued tadalafil use. CONCLUSIONS: Tadalafil is an effective treatment for ED in routine clinical practice. The therapeutic response and treatment tolerance after 1-month treatment are the most important factors influencing tadalafil continuation.

The influence of age on treatment outcomes in men with erectile dysfunction treated with two regimens of tadalafil: results of the SURE study.

OBJECTIVE: To evaluate whether patterns of sexual activity and efficacy over time to two dosing regimens of tadalafil differ with ageing in men with erectile dysfunction (ED). PATIENTS AND METHODS: The SURE study was a multicentre, crossover, open-label study. In all, 4262 men with ED were randomly assigned to treatment with tadalafil 20 mg on-demand before sexual activity, or three times per week for 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternative regimen for 5-6 weeks. This post hoc analysis evaluated the pattern of sexual attempts, efficacy and safety of these two regimens of tadalafil across several age groups. RESULTS: The mean number of sexual attempts per week decreased from a range of 2.6-2.8 at age < or = 40 years to 1.9 at age >70 years. Age did not significantly influence the time of sexual activity after dosing. A high percentage of attempts occurred >4 h after dosing for all age groups ( approximately 70% for men taking tadalafil three times per week and approximately 50% for men taking tadalafil on-demand). For all age groups, most attempts took place in the late evening. The mean per-patient rate of successful attempts was similar for each interval up to 36 h after dosing and decreased with increasing age (> or =75% at age < or = 60 years, > or = 68% at age >60 to < or = 70 years, and > or = 60% at age >70 years). Tadalafil was well tolerated at all ages. CONCLUSIONS: Patterns of sexual activity with tadalafil 20 mg, taken on-demand or three times per week, were similar in the different age groups. Tadalafil was effective up to 36 h after dosing for all age groups.

Efficacy and safety of two dosing regimens of tadalafil and patterns of sexual activity in men with diabetes mellitus and erectile dysfunction: Scheduled use vs. on-demand regimen evaluation (SURE) study in 14 European countries.

AIM: The aim of this article is to evaluate the efficacy and safety of 20-mg tadalafil taken on demand or three times per week and its effect on the sexual activity of patients with diabetes mellitus and erectile dysfunction (ED). METHODS: The scheduled use vs. on-demand regimen evaluation (SURE) was a randomized, crossover, open-label study with 4,262 patients in 14 European countries. The efficacy measures for the 762 patients with diabetes and ED included changes from baseline in the erectile function (EF) domain of the International Index of Erectile Function (IIEF), and the proportion of "yes" responses to patient Sexual Encounter Profile (SEP) questions 2 (SEP2) and 3 (SEP3). The treatment satisfaction was measured with responses to SEP question 4 (SEP4) and SEP question 5 (SEP5), and sexual attempts data were collected. Patient preference for either regimen was determined by the treatment preference question (TPQ). RESULTS: At end point on both regimens, the mean IIEF EF domain score was 22, and >40% of the patients had a normal EF domain score (> or =26). The proportion of "yes" responses was > or =73% for SEP2 (penetration), > or =58% for SEP3 (successful intercourse), >46% for SEP4 (hardness of erection), and > or =45% for SEP5 (overall satisfaction). Efficacy was maintained up to 36 hours post-dosing. More than 70% of sexual attempts while on the three-times-per-week regimen and approximately 50% of the attempts on the on-demand treatment occurred >4 hours post-dosing. Tadalafil was well tolerated, with dyspepsia and headache as the most frequent adverse events reported. Treatment preference was 57.2% for on demand and 42.8% for three times per week. CONCLUSIONS: Tadalafil, when taken on demand or three times per week, is efficacious and safe in men with diabetes and ED.

Treatment-seeking behavior of erectile dysfunction patients in Europe: Results of the Erectile Dysfunction Observational Study.

INTRODUCTION: The Erectile Dysfunction Observational Study (EDOS) is a 6-month, pan-European prospective, observational study of health outcomes designed to assess patients' profiles and characteristics and the effectiveness of erectile dysfunction (ED) treatment in routine clinical practice. AIM: To present baseline characteristics and treatment-seeking behavior of a large sample of ED patients recruited in real-life clinical settings. METHODS: Men aged 18 years and older who visited a physician to initiate or change any ED treatment were enrolled in EDOS. They were assessed at baseline, 3 months, and 6 months as part of their normal course of care in nine European countries. MAIN OUTCOME MEASURES: Sexual health outcomes using the short form of the Psychological and Interpersonal Relationship Scales. Treatment effectiveness and satisfaction were assessed using the International Index of Erectile Function questionnaire, Global Assessment Questions, and further single-item questions. RESULTS: Of the 8,186 patients enrolled by 904 investigators (69% general practitioners [GPs]) across nine European countries, 8,055 patients were eligible for analysis at baseline; 63.9% were ED treatment-naive. Of the total patient population, mean age was 56.5 years, mean body mass index (BMI) was 27.2 kg/m2, 18.3% were obese (BMI > 30 kg/m2), 42.5% had severe ED, and there was a high frequency of comorbidities and concomitant medication use. A similar proportion of the treatment-naive patients were seen by GPs (62.9%) and specialists (65.8%). In the treatment-naive group, there was a higher frequency of severe ED among ex-smokers, obese patients, and in those who drank no alcohol or excessive amounts of alcohol. CONCLUSIONS: Unmet need of treatment in ED is high; 66% of patients had experienced ED symptoms for 1 year or longer when they were looking for treatment. Severity seems to be related to treatment seeking.

Integrated analysis examining first-dose success, success by dose, and maintenance of success among men taking tadalafil for erectile dysfunction.

OBJECTIVES: To examine, in a post-hoc, integrated analysis, the first-dose success, cumulative success by dose, and maintenance of success among men taking tadalafil. Early treatment success is important to men with erectile dysfunction. METHODS: In five double-blind, placebo-controlled, 12-week studies, men were randomized to placebo (n = 308), tadalafil 10 mg (n = 321), or tadalafil 20 mg (n = 258) as a fixed dose. The Sexual Encounter Profile (SEP) diary questions assessed success from three perspectives: (a) first-dose success; (b) cumulative proportion of men with first success by dose; and (c) maintenance of success among men with first-dose success. RESULTS: With the first dose, significantly greater proportions of men taking tadalafil 10 and 20 mg versus placebo achieved successful erection (SEP-Q1: 85% and 90% versus 66%, respectively), successful penetration (SEP-Q2: 74% and 79% versus 47%, respectively), successful intercourse (SEP-Q3: 56% and 67% versus 31%, respectively), and were satisfied overall with their sexual experience (SEP-Q5: 36% and 47% versus 15%, respectively; all P <0.001). The proportion of men achieving first success increased with continued dosing, reaching a plateau between doses 4 and 8 at approximately 95% (SEP-Q2), 90% (SEP-Q3), and 81% (SEP-Q5). For men with first-dose success, the subsequent success rate during the 12-week period was significantly greater for men taking tadalafil 10 and 20 mg versus placebo (all P <0.001; SEP-Q2: 85% and 91% versus 75%; and SEP-Q3: 81% and 88% versus 64%, respectively). CONCLUSIONS: Most men taking tadalafil achieved successful erection, penetration, and intercourse after one dose and maintained the success over time. Because success increased with continued use, men who do not respond initially should continue treatment to increase the likelihood of treatment success.

Effect of raloxifene combined with monofluorophosphate as compared with monofluorophosphate alone in postmenopausal women with low bone mass: a randomized, controlled trial.

Raloxifene effectively reduces the incidence of vertebral fractures in patients with postmenopausal osteoporosis. Recent data suggest that low-dose monofluorophosphate (MFP) plus calcium reduces the vertebral fracture rate in postmenopausal women with moderate osteoporosis. The objective of this study was to evaluate the combination of raloxifene and MFP in the treatment of postmenopausal women with osteopenia, osteoporosis and severe osteoporosis. A total of 596 postmenopausal women with osteopenia, osteoporosis and severe osteoporosis (mean femoral neck T-score of -2.87 SD) were randomized to treatment with 60 mg/day raloxifene HCl and 20 mg/day fluoride ions (as MFP) or 20 mg/day fluoride and placebo for 18 months. All patients received calcium (1000 mg/day) and vitamin D (500 IU/day) supplements. Changes in bone mineral density (BMD), as primary endpoint, and the rate of osteoporotic fractures and biochemical markers, as secondary endpoints, were assessed. As compared with MFP, raloxifene plus MFP was associated with significantly greater mean increases in the BMD of the femoral neck (1.37% versus 0.33%; P=0.004), total hip (0.89% versus -0.42%; P<0.001) and lumbar spine (8.80% versus 5.47% P<0.001). In the raloxifene plus MFP group, 16 patients sustained 17 osteoporotic fractures, as compared with 22 patients sustaining 34 incident osteoporotic fractures in the MFP group ( P=0.313). One patient in the raloxifene plus MFP group sustained multiple osteoporotic fractures, as compared with eight patients in the MFP group ( P=0.020). MFP alone significantly increased the serum bone alkaline phosphatase (bone ALP) and the urinary C-terminal crosslinking telopeptide of type I collagene (U-CTX). The addition of raloxifene in the combination arm blunted the rise in bone ALP, which remained nevertheless significant, and abolished the increase in U-CTX. The combination of raloxifene with MFP was generally well tolerated. This study demonstrates that, in postmenopausal women with osteopenia, osteoporosis and severe osteoporosis, the combination therapy of raloxifene plus MFP favorably influences the BMD and the bone formation and resorption balance, and may reduce the risk of multiple osteoporotic fractures compared to MFP alone.