Search

To assess cardiovascular, glycaemic, weight and safety outcomes of long-term treatment with dulaglutide 1.5 mg compared with placebo in patients with a baseline HbA1c of less than 7% versus 7% or higher.Intention-to-treat analyses were performed on REWIND participants with a baseline HbA1c measurement, using Cox proportional hazards regression and mixed model for repeated measures. Subgroup analyses with factors for baseline HbA1c categories and their interaction with treatment group, as well as analyses within the HbA1c subgroups, were conducted. Additionally, sensitivity analyses were performed for baseline HbA1c subgroups of 6.5% or less and more than 6.5%.Of the 9876 eligible participants, 3921 and 5955 had a baseline HbA1c of less than 7% and 7% or higher, respectively. Mean baseline HbA1c was 6.3% and 8.0% and the mean duration of diabetes was 9.0 and 11.6 years in the respective subgroups. The less than 7% subgroup was slightly older and less frequently insulin-treated. There was no evidence of a differential dulaglutide treatment effect on body mass index (BMI) reduction, cardiovascular or safety outcomes of interest between the baseline HbA1c subgroups. Treatment-by-baseline HbA1c group interaction was significant for HbA1c change from baseline (P .001), with a greater reduction in the subgroup with higher baseline HbA1c values. Sensitivity analyses by baseline HbA1c subgroups of 6.5% or less and more than 6.5% showed similar results.The reduced incidence of cardiovascular events, and the reduction in BMI in participants treated with once-weekly dulaglutide, were independent of the baseline HbA1c level. Conversely, participants with a higher baseline HbA1c level had greater reductions in HbA1c. Dulaglutide has a positive benefit-risk profile and can be considered in patients with comparatively well-controlled HbA1c levels seeking optimal metabolic control and cardiovascular benefits.

This post hoc analysis investigated the effect of dulaglutide on cardiovascular disease (CVD) risk factors in subgroups of participants at increased CVD risk in the AWARD-11 study.Participants who received once weekly dulaglutide 1.5, 3.0 or 4.5 mg for 52 weeks were categorized according to their baseline Framingham CVD risk category [low (N = 295), medium (N = 481) and high (N = 1054) risk], as well as their baseline CVD risk according to the REWIND study eligibility criteria (N = 953). Serum lipids and vital signs were assessed at baseline and at 52 weeks. Data were analysed as least squares mean percentage change from baseline for lipids and least squares mean change from baseline for vital signs.Demographic and baseline clinical characteristics were balanced across doses within the CVD risk groups. In the high Framingham CVD risk and REWIND-like groups, dulaglutide resulted in dose-related decreases in total cholesterol (≤6.0%), non-high-density lipoprotein cholesterol (≤8.8%), very-low-density lipoprotein cholesterol (≤19.4%) and triglycerides (≤21.5%), with little change in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Systolic and diastolic blood pressure decreased up to 5.6 mmHg and 1.6 mmHg, respectively, and heart rate increased up to 2 beats/min.This post hoc analysis suggests the magnitude of the favourable effects of dulaglutide 3.0 mg and 4.5 mg on several cardiometabolic CVD risk factors was similar to, if not greater than, those of dulaglutide 1.5 mg among participants with type 2 diabetes and increased CVD risk.gov Identifier: NCT03495102.

OBJECTIVE: To retrospectively compare the long-term clinical, functional, and cost outcomes for early RA patients (symptoms

Background:Background: Weight management is considered a key therapeutic strategy in type 2 diabetes mellitus. However, little is known about the impact of weight loss or body mass index (BMI) reduction on type 2 diabetes-related healthcare costs. Abstract: Objective:Objective: The aim of this study was to estimate the economic impact of change in BMI among patients with type 2 diabetes mellitus from the Spanish healthcare system perspective. Abstract: Methods:Methods: The ECOBIM study is an observational, non-interventional study in which data on BMI change and costs incurred by patients with type 2 diabetes were collected cross-sectionally and retrospectively for a 12-month period. Generalized linear mixed models were applied to estimate the effects of (i) BMI change in general (one-slope model); (ii) BMI gain and no BMI gain (two-slope model); and (iii) BMI gain and no BMI gain among obese and non-obese patients (four-slope model). Abstract: Results:Results: We studied 738 patients with a mean (SD) age of 66 (11) years and BMI of 30.6 (5.2) kg/m. During the 12-month study period, 41.2% of patients gained BMI (BMI gainers) and 58.8% experienced either loss (52.2%) or no change (6.6%) in BMI (non-BMI gainers). One-unit gain (or loss) in BMI was significantly (p < 0.001) associated with a 2.4% cost increase (or decrease) &lsqb;one-slope model&rsqb;. Every unit gain in BMI was associated with a 20.0% increase in costs among BMI gainers while losing one unit was associated with an 8.0% decrease in costs among non-BMI gainers (two-slope model, p < 0.01). The economic benefit associated with reducing one BMI unit was 9.4% cost decrease in obese and 2.7% in non-obese patients (4-slope model). Abstract: Conclusion:Conclusion: An increase in BMI among patients with type 2 diabetes was associated with increased 1-year direct healthcare costs. A reduction in BMI was associated with appreciable short-term economic benefits, especially in obese patients.

To examine insulin regimens and factors that affect glycaemic control at 6 months after initiation of insulin therapy in patients with type 2 diabetes mellitus.Information on patients requiring insulin initiation as part of usual care was collected in a prospective, observational, open-label study in five European countries. Univariate and multiple regression analyses were used to investigate factors associated with HbA1c achieved at 6 months.Mean HbA1c for all patients at baseline was 9.6 ± 1.8%. Long/intermediate-acting insulin only was most commonly initiated in France and Spain, while long/intermediate or pre-mixed formulations were initiated in Greece and UK. This was consistent with guidelines used in those countries and there was little change in insulin regimen at 6 months in these countries. In Germany, short-acting insulin only was favoured at baseline and there was a shift towards basal/bolus regimens at 6 months, which reflected the local guidelines for insulin initiation in Germany. Mean HbA1c reduction was greatest in Germany (-2.3%), which was the only country to achieve a mean of7% at 6 months. In all countries, HbA1c achieved at 6 months was associated with baseline HbA1c. Differences between countries were seen for influence of factors such as BMI, duration of diabetes, insulin regimen, insulin dose and number of oral anti-diabetes drugs on HbA1c achieved. Explained variability for the factors ranged from 5.6% to 22.9%.Differences in insulin regimen were observed between countries, and appeared to reflect the guidelines and treatment regimens used.

ObjectiveInitial GH-induced catch up growth is highly variable in short children born small for gestational age (SGA) and mainly influenced by age at start of therapy and GH dose. This study compared the first year growth-promoting effect of an individually adjusted GH dose (IAD) versus a fixed high GH dose (FHD) in pre-pubertal children born SGA with severe short stature.DesignThis was a randomized, open-label, multi-center study.MethodsThe FHD group received 0.067 mg/kg per day GH throughout the 12-month study. The IAD group initially received 0.035 mg/kg per day GH; at 3 months the Cologne growth-prediction model for first year change in height SDS was applied; if predicted change was ResultsIn the IAD group, 38 out of the 80 patients required the higher GH dose from month 3. From an ANCOVA for non-inferiority, mean difference in change in height SDS between IAD and FHD groups was −0.24 (95% confidence interval (CI) −0.35: −0.12), the CI for height SDS being above the pre-defined non-inferiority margin of −0.5. GH dose reductions due to IGF-I SDS >0.5 and IGFBP-3 SDS ConclusionWith a mean treatment group difference of 1 cm in 12-month growth response, although statistically significant, the IAD group was considered non-inferior compared with the FHD group. Early growth prediction can be used to tailor the dose to the individual patient's needs, resulting in lower overall GH dose.

Bleeding in the calf or ankle joint may lead to ankle equinus deformity, particularly in childhood and during adolescence. We assessed the long-term functional and radiographic results after Achilles tendon lengthening for ankle equinus deformity in hemophiliacs.Between 1975 and 1986, 30 hemophilic patients with pes equinus were surgically managed by Achilles tendon lengthening. Of these, 23 were followed up prospectively twice a year for an average of 13 (1-24) years. The mean age at operation was 29 (12-46) years. The clinical results were documented according to the score of the Advisory Committee of the World Federation of Hemophilia (WFH), while radio-graphs were evaluated using the Pettersson score. On average, preoperative ankle equinus deformity was 21 (5-55) degrees. Mean range of motion was 21 (5-42) degrees prior to surgery.At the first postoperative examination 1 year after surgery, 21/23 cases were improved, and 9/21 reached dorsiflexion to at least neutral position. At the last follow-up, ankle equinus deformity was 10 (4-20) degrees on average. 20/23 patients still showed significant improvement compared to their condition before surgery. 7 patients still had complete correction of the equinus deformity, while mean range of motion decreased constantly over the observation period. The clinical score was significantly improved 1 year after surgery and diminished only slightly afterwards. Radio-graphic outcome deteriorated, with scores rising from 4.3 (1-10) points preoperatively to 7.3 (3-12) points at last follow-up.Most patients treated for hemophilic pes equinus by Achilles tendon lengthening experienced long-term benefit concerning the equinus deformity, but gradually lost overall movement of the ankle joint. Progression of the ankle arthropathy cannot be hindered.

In this study the long-term value of corrective osteotomy around the knee was evaluated by means of clinical and radiographic parameters. Between 1974 and 1984 we performed 52 corrective osteotomies in the vicinity of the knee on patients affected by haemophilic arthropathy. Forty-two patients (45 osteotomies) were adequately followed-up at an average 11.6 years postoperatively. Using the clinical score of the Advisory Committee of the World Federation of Haemophilia, 38 patients showed a postoperative improvement, five remained clinically unchanged and two showed deterioration. Range of motion of the knee joint did not significantly improve postoperatively. The radiographic Pettersson score showed only a marginal decrease by an average 0.003 points at the time of follow-up. Only one patient needed subsequent joint replacement of both knees, on the left side 13 years after osteotomy and on the right side 8 years after osteotomy. Even in cases of marked radiographic joint destruction, corrective osteotomy shows acceptable long-term clinical results, underlining the feasibility of this management option in the treatment of haemophilic arthropathy of the knee. Although moderate cartilage degenerations in the femoropatellar complex and in the contralateral compartment can be tolerated, this therapy should primarily be contemplated for those patients where damage is unicompartmental and a corresponding axial deviation is found. Particularly the younger patient can benefit from this treatment option in that joint replacement may possibly wholly be avoided or at least postponed to a later stage of life.

To quantify wear processes by measuring the retention force changes and the fitting tolerance at different prefabricated attachment systems to estimate the wear constancy and applicability in clinical practice.Seven prefabricated attachment systems (Dalbo-Classic, Dalbo-PLUS, Dalbo-Z, Mini-Gerber-PLUS, Stufenexzenter, SpharoLock, and Degussa-Kugelankersystem) with different construction and alloy composition were tested. Twenty samples of each system were subjected to 10,000 insertion-separation cycles in a wear simulator with a periodontium-simulating specimen holder. The simulator was designed to record the force needed to insert and to separate the attachment and the distance moved during the insertion and separation cycles.All types of anchors showed wear that led to a loss or to an increase in retention force at the beginning of the wear simulation. Anchors with a plastic retention insert showed the slightest changes in retention force. The wear does not have an effect on the fitting tolerance.Anchor systems that possess an adjustable matrix should be preferred. They allow decreasing or increasing the retention force of an anchor if this force is changed by wear. There is no risk of a loss of support if forces in occlusal direction are exerted because there is no clinically relevant change in the fitting tolerance.

Objective: The present study was performed to examine the efficacy of a selective treatment according to the guidelines for the prevention of recurrence in calcium oxalate stone patients and to assess risk factors for stone recurrence. Methods: To investigate the effect of specific diagnostic and therapeutic measures, 134 recurrent calcium oxalate stone formers participated in a prospective study for two years with regular follow-ups of at least every six months. Depending on the results of analysis of 24-hour urine, nutrition record and metabolic situation, selective recommendations were given concerning diet and medication. Results: Throughout the follow-up period, 57 (43%) of the patients experienced relapses. In recurrence-free patients, the significant increase in urinary volume, as well as urinary pH, potassium and citrate excretion, three indexes of compliance with alkalization, resulted in a significant decrease in the calculated risk of calcium oxalate stone formation. In patients with recurrences during follow-up, the relative supersaturation with calcium oxalate increased significantly, mainly due to the significant rise in urinary oxalate excretion exceeding the significant increases in urinary volume, pH, potassium and citrate excretion. Multiple logistic regression analysis revealed previous ESWL treatment and a history of multiple stones as independent predictors of the risk for recurrence. Conclusions: The results indicate that compliance with drinking advice and alkalization therapy was highest among both, patients with and without recurrences, compared with all other therapeutic measures. The increase in oxalate excretion is identified as the major urinary risk factor for relapse during follow-up in recurrent calcium oxalate stone disease.

In a prospective pilot study, subjective and objective parameters of the health status were assessed in 148 male patients (mean age 56 +/- 8.4 years) before and 4 months after successful coronary angioplasty (PTCA). Restenosis was defined as residual diameter stenosis > 50%. Although 96 patients (65%) had not developed restenosis at 4 months' invasive follow-up, subjective assessment of general well-being was unchanged in 26% or worse in 71%; overall anginal status and exercise performance had however improved. Of 71 men younger than 60 years who had no restenosis at follow-up, 4 men retired and 13 remained on medical leave. The striking disparity between subjective and objective parameters was not related to significant differences of age, exercise capacity, and left ventricular ejection fraction, as well as to baseline characteristics (previous myocardial infarction, extent of coronary heart disease, comorbidity) compared with 52 patients with restenosis. Thus, despite documented sustained success after PTCA, the majority of patients failed to resume the status of subjective well-being.

Dietary risk factors for hyperoxaluria in calcium oxalate stone formers.BackgroundHyperoxaluria is a major predisposing factor in calcium oxalate urolithiasis. The aim of the present study was to clarify the role of dietary oxalate in urinary oxalate excretion and to assess dietary risk factors for hyperoxaluria in calcium oxalate stone patients.MethodsDietary intakes of 186 calcium oxalate stone formers, 93 with hyperoxaluria (≥0.5 mmol/day) and 93 with normal oxalate excretion (