Long-term outcomes of biodegradable polymer versus durable polymer drug-eluting stents in patients with diabetes a pooled analysis of individual patient data from 3 randomized trials

BACKGROUND There is ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. Biodegradable polymer drug-eluting stents (BP-DES) may potentially improve clinical outcomes in these high-risk patients. We sought to compare long-term outcomes in patients with diabetes treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). METHODS We pooled individual patient-level data from 3 randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4 and LEADERS) comparing biodegradable polymer DES with durable polymer SES. Clinical outcomes out to 4years were assessed. The primary end point was the composite of cardiac death, myocardial infarction and target-lesion revascularization. Secondary end points were target lesion revascularization and definite or probable stent thrombosis. RESULTS Of 1094 patients with diabetes included in the present analysis, 657 received biodegradable polymer DES and 437 durable polymer SES. At 4years, the incidence of the primary end point was similar with BP-DES versus SES (hazard ratio=0.95, 95% CI=0.74-1.21, P=0.67). Target lesion revascularization was also comparable between the groups (hazard ratio=0.89, 95% CI=0.65-1.22, P=0.47). Definite or probable stent thrombosis was significantly reduced among patients treated with BP-DES (hazard ratio=0.52, 95% CI=0.28-0.96, P=0.04), a difference driven by significantly lower stent thrombosis rates with BP-DES between 1 and 4years (hazard ratio=0.15, 95% CI=0.03-0.70, P=0.02). CONCLUSIONS In patients with diabetes, biodegradable polymer DES, compared to durable polymer SES, were associated with comparable overall clinical outcomes during follow-up to 4years. Rates of stent thrombosis were significantly lower with BP-DES.

Long-term outcome of the unrestricted use of everolimus-eluting stents compared to sirolimus-eluting stents and paclitaxel-eluting stents in diabetic patients: The Bern–Rotterdam diabetes cohort study

BACKGROUND Newer generation everolimus-eluting stents (EES) improve clinical outcome compared to early generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). We investigated whether the advantage in safety and efficacy also holds among the high-risk population of diabetic patients during long-term follow-up. METHODS Between 2002 and 2009, a total of 1963 consecutive diabetic patients treated with the unrestricted use of EES (n=804), SES (n=612) and PES (n=547) were followed throughout three years for the occurrence of cardiac events at two academic institutions. The primary end point was the occurrence of definite stent thrombosis. RESULTS The primary outcome occurred in 1.0% of EES, 3.7% of SES and 3.8% of PES treated patients ([EES vs. SES] adjusted HR=0.58, 95% CI 0.39-0.88; [EES vs. PES] adjusted HR=0.29, 95% CI 0.13-0.67). Similarly, patients treated with EES had a lower risk of target-lesion revascularization (TLR) compared to patients treated with SES and PES ([EES vs. SES], 5.6% vs. 11.5%, adjusted HR=0.68, 95% CI: 0.55-0.83; [EES vs. PES], 5.6% vs. 11.3%, adjusted HR=0.51, 95% CI: 0.33-0.77). There were no differences in other safety end points, such as all-cause mortality, cardiac mortality, myocardial infarction (MI) and MACE. CONCLUSION In diabetic patients, the unrestricted use of EES appears to be associated with improved outcomes, specifically a significant decrease in the need for TLR and ST compared to early generation SES and PES throughout 3-year follow-up.

Long-term outcomes of dental implants with a titanium plasma-sprayed surface: a 20-year prospective case series study in partially edentulous patients

BACKGROUND Long-term studies of ≥10 years are important milestones to get a better understanding of potential factors causing implant failures or complications. PURPOSE The present study investigated the long-term outcomes of titanium dental implants with a rough, microporous surface (titanium plasma sprayed [TPS]) and the associated biologic and technical complications in partially edentulous patients with fixed dental prostheses over a 20-year follow-up period. MATERIALS AND METHODS Sixty-seven patients, who received 95 implants in the 1980s, were examined with well-established clinical and radiographic parameters. Based on these findings, each implant was classified as either successful, surviving, or failed. RESULTS Ten implants in nine patients were lost during the observation period, resulting in an implant survival rate of 89.5%. Radiographically, 92% of the implants exhibited crestal bone loss below 1 mm between the 1- and 20-year follow-up examinations. Only 8% yielded peri-implant bone loss of >1 mm and none exhibited severe bone loss of more than 1.8 mm. During the observation period, 19 implants (20%) experienced a biologic complication with suppuration. Of these 19 implants, 13 implants (13.7%) had been treated and were successfully maintained over the 20-year follow-up period. Therefore, the 20-year implant success rate was 75.8 or 89.5% depending on the different success criteria. Technical complications were observed in 32%. CONCLUSION The present study is the first to report satisfactory success rates after 20 years of function of dental implants with a TPS surface in partially edentulous patients.

Long-term stability of early implant placement with contour augmentation

In this prospective case series study, 20 patients with an implant-borne single crown following early implant placement with simultaneous contour augmentation were followed for 6 years. Clinical, radiologic, and esthetic parameters were assessed. In addition, cone beam computed tomography (CBCT) was used at 6 years to examine the facial bone wall. During the study period, all 20 implants were successfully integrated, and the clinical parameters remained stable over time. Pleasing esthetic outcomes were noted, as assessed by the pink esthetic scores. None of the implants developed mucosal recession of 1 mm or more. The periapical radiographs yielded stable peri-implant bone levels, with a mean DIB of 0.44 mm at 6 years. The CBCT scans showed that all 20 implants had a detectable facial bone wall at 6 years, with a mean thickness of around 1.9 mm. In summary, this prospective case series study demonstrated stable peri-implant hard and soft tissues for all 20 implants, and pleasing esthetic outcomes overall. The follow-up of 6 years confirmed that the risk for mucosal recession is low with early implant placement. In addition, contour augmentation with guided bone regeneration (GBR) was able to establish and maintain a facial bone wall in all 20 patients.

Long-term stability of contour augmentation with early implant placement following single tooth extraction in the esthetic zone: a prospective, cross-sectional study in 41 patients with a 5- to 9-year follow-up

BACKGROUND Early implant placement with simultaneous contour augmentation is documented with short- and medium-term studies. The long-term stability of contour augmentation is uncertain. METHODS In this prospective, cross-sectional study, 41 patients with an implant-borne single crown were examined twice, in 2006 and 2010. Clinical, radiologic, and esthetic parameters were assessed at both examinations. In addition, a cone beam computed tomographic (CBCT) image was obtained during the second examination to assess the dimensions of the facial bone wall. RESULTS All 41 implants demonstrated ankylotic stability without signs of peri-implant infection at both examinations. The clinical parameters remained stable over time. Satisfactory esthetic outcomes were noted, as assessed by the pink and white esthetic score (PES/WES) indices. Overall, the PES scores were slightly higher than the WES scores. None of the implants developed mucosal recession over time, as confirmed by values of the distance between implant shoulder and mucosal margin and cast measurements. The periapical radiographs yielded stable peri-implant bone levels, with a mean distance between implant shoulder and first visible bone-implant contact value of 2.18 mm. The CBCT analysis demonstrated a mean thickness of the facial bone wall ≈2.2 mm. In two implants (4.9%) no facial bone wall was detectable radiographically. CONCLUSIONS This prospective cross-sectional study demonstrates stable peri-implant hard and soft tissues for all 41 implants examined and satisfactory esthetic outcomes overall. The follow-up of 5 to 9 years confirmed again that the risk for mucosal recession is low with early implant placement. In addition, contour augmentation with guided bone regeneration was able to establish and maintain a facial bone wall in 95% of patients.

Long-term comparison of everolimus-eluting stents with sirolimus- and paclitaxel-eluting stents for percutaneous coronary intervention of saphenous vein grafts

Aims: Newer-generation everolimus-eluting stents (EES) have been shown to improve clinical outcomes compared with early-generation sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) in patients undergoing percutaneous coronary intervention (PCI). Whether this benefit is maintained among patients with saphenous vein graft (SVG) disease remains controversial. Methods and results: We assessed cumulative incidence rates (CIR) per 100 patient years after inverse probability of treatment weighting to compare clinical outcomes. The pre-specified primary endpoint was the composite of cardiac death, myocardial infarction (MI), and target vessel revascularisation (TVR). Out of 12,339 consecutively treated patients, 288 patients (5.7%) underwent PCI of at least one SVG lesion with EES (n=127), SES (n=103) or PES (n=58). Up to four years, CIR of the primary endpoint were 58.7 for EES, 45.2 for SES and 45.6 for PES with similar adjusted risks between groups (EES vs. SES; HR 0.94, 95% CI: 0.55-1.60, EES vs. PES; HR 1.07, 95% CI: 0.60-1.91). Adjusted risks showed no significant differences between stent types for cardiac death, MI and TVR. Conclusions: Among patients undergoing PCI for SVG lesions, newer-generation EES have similar safety and efficacy to early-generation SES and PES during long-term follow-up to four years.

Long-term outcomes of patients receiving zotarolimus-eluting stents in ST elevation myocardial infarction, non-ST elevation acute coronary syndrome, and stable angina: data from the Resolute program

BACKGROUND Outcome data are limited in patients with ST-segment elevation acute myocardial infarction (STEMI) or other acute coronary syndromes (ACSs) who receive a drug-eluting stent (DES). Data suggest that first generation DES is associated with an increased risk of stent thrombosis when used in STEMI. Whether this observation persists with newer generation DES is unknown. The study objective was to analyze the two-year safety and effectiveness of Resolute™ zotarolimus-eluting stents (R-ZESs) implanted for STEMI, ACS without ST segment elevation (non-STEACS), and stable angina (SA). METHODS Data from the Resolute program (Resolute All Comers and Resolute International) were pooled and patients with R-ZES implantation were categorized by indication: STEMI (n=335), non-STEACS (n=1416), and SA (n=1260). RESULTS Mean age was 59.8±11.3 years (STEMI), 63.8±11.6 (non-STEACS), and 64.9±10.1 (SA). Fewer STEMI patients had diabetes (19.1% vs. 28.5% vs. 29.2%; P<0.001), prior MI (11.3% vs. 27.2% vs. 29.4%; P<0.001), or previous revascularization (11.3% vs. 27.9% vs. 37.6%; P<0.001). Two-year definite/probable stent thrombosis occurred in 2.4% (STEMI), 1.2% (non-STEACS) and 1.1% (SA) of patients with late/very late stent thrombosis (days 31-720) rates of 0.6% (STEMI and non-STEACS) and 0.4% (SA) (P=NS). The two-year mortality rate was 2.1% (STEMI), 4.8% (non-STEACS) and 3.7% (SA) (P=NS). Death or target vessel re-infarction occurred in 3.9% (STEMI), 8.7% (non-STEACS) and 7.3% (SA) (P=0.012). CONCLUSION R-ZES in STEMI and in other clinical presentations is effective and safe. Long term outcomes are favorable with an extremely rare incidence of late and very late stent thrombosis following R-ZES implantation across indications.

Long-term Results of a 12-Week Comprehensive Ambulatory Cardiac Rehabilitation Program

PURPOSE: To evaluate the long-term outcome of a 12-week outpatient cardiac rehabilitation (CR) program. METHODS: In a prospective single-center interventional cohort study, 201 consecutive patients (133 patients after acute coronary syndrome, 32 patients after heart surgery, and 36 patients with heart failure) attending a 12-week comprehensive outpatient CR program were evaluated for exercise capacity, cardiovascular risk factors (CvRFs), and quality of life at entry, end, and 1.4 years after completion of the program (followup). RESULTS: Physical exercise capacity improved significantly from program entry to program end and remained at this level at followup (P ≤ .006). CvRFs at followup were significantly reduced with regard to smoking prevalence and blood lipids (P < .001). At program end and followup, MacNew heart disease–specific emotional, physical, and social quality of life were improved significantly compared with those at program entry (P < .001). Use of cardioprotective medication remained equally high over the entire study period. However, significantly fewer patients reached blood pressure (<140/90 mm Hg, P = .034) and body mass index (<30 kg/m2, P = .017) goals at followup than at program end. CONCLUSION: The 12-week comprehensive outpatient CR program was successful at reducing important CvRFs long-term.

Chronic NSAID use and long-term decline of renal function in a prospective rheumatoid arthritis cohort study

OBJECTIVES Non-steroidal anti-inflammatory drugs (NSAIDs) may cause kidney damage. This study assessed the impact of prolonged NSAID exposure on renal function in a large rheumatoid arthritis (RA) patient cohort. METHODS Renal function was prospectively followed between 1996 and 2007 in 4101 RA patients with multilevel mixed models for longitudinal data over a mean period of 3.2 years. Among the 2739 'NSAID users' were 1290 patients treated with cyclooxygenase type 2 selective NSAIDs, while 1362 subjects were 'NSAID naive'. Primary outcome was the estimated glomerular filtration rate according to the Cockroft-Gault formula (eGFRCG), and secondary the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formula equations and serum creatinine concentrations. In sensitivity analyses, NSAID dosing effects were compared for patients with NSAID registration in ≤/>50%, ≤/>80% or ≤/>90% of assessments. FINDINGS In patients with baseline eGFRCG >30 mL/min, eGFRCG evolved without significant differences over time between 'NSAID users' (mean change in eGFRCG -0.87 mL/min/year, 95% CI -1.15 to -0.59) and 'NSAID naive' (-0.67 mL/min/year, 95% CI -1.26 to -0.09, p=0.63). In a multivariate Cox regression analysis adjusted for significant confounders age, sex, body mass index, arterial hypertension, heart disease and for other insignificant factors, NSAIDs were an independent predictor for accelerated renal function decline only in patients with advanced baseline renal impairment (eGFRCG <30 mL/min). Analyses with secondary outcomes and sensitivity analyses confirmed these results. CONCLUSIONS NSAIDs had no negative impact on renal function estimates but in patients with advanced renal impairment.

Cholesteatoma surgery in children: long-term results of the inside-out technique

OBJECTIVE To present the anatomical and functional results of the inside-out technique applied in pediatric cholestetaoma surgery and to evaluate functionality with good hearing results against radicality with lower recurrence rate. METHODS Retrospective analysis and evaluation of the postoperative outcome in a consecutive series of 126 children or 130 ears operated between 1992 and 2008. With the inside-out technique, cholesteatoma is eradicated from the epitympanum toward the mastoid and, as a single stage procedure, functional reconstruction of the middle ear is achieved by tympanoossiculoplasty. RESULTS In 89.2% of all cases, the ear was dry postoperatively. 80.9% of the ears reached a postoperative air-bone gap of 30 dB or less and the median air conduction hearing threshold was 29 dB; in 60.9% of all cases, hearing was postoperatively improved. The recurrence rate was 16.2% in a mean postoperative follow-up 8.5 years. Altogether, 48 ears (36.9%) underwent revision surgery. The complication rate was 3.1% and involved only minor complications. CONCLUSION The inside-out technique allows a safe removal of cholesteatoma from the epitympanum toward the mastoid with a single-stage reconstruction of the ossicular chain. For this reason we support our individual approach, which allows creation of the smallest possible cavity for the size of the cholesteatoma. Our results confirm that the inside-out technique is effective in the treatment of pediatric cholesteatoma.

The long-term stability of self-esteem: Its time-dependent decay and nonzero asymptote

How stable are individual differences in self-esteem? We examined the time-dependent decay of rank-order stability of self-esteem and tested whether stability asymptotically approaches zero or a nonzero value across long test–retest intervals. Analyses were based on 6 assessments across a 29-year period of a sample of 3,180 individuals aged 14 to 102 years. The results indicated that, as test–retest intervals increased, stability exponentially decayed and asymptotically approached a nonzero value (estimated as .43). The exponential decay function explained a large proportion of variance in observed stability coefficients, provided a better fit than alternative functions, and held across gender and for all age groups from adolescence to old age. Moreover, structural equation modeling of the individual-level data suggested that a perfectly stable trait component underlies stability of self-esteem. The findings suggest that the stability of self-esteem is relatively large, even across very long periods, and that self-esteem is a trait-like characteristic.

Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: effects on feed intake, milk production, and metabolism.

Elevation of ketone bodies in dairy cows frequently occurs in early lactation, usually concomitantly with a lack of energy and glucose. The objective of this study was to induce an elevated plasma β-hydroxybutyrate (BHBA) concentration over 48 h in mid-lactating dairy cows (i.e., during a period of positive energy balance and normal glucose plasma concentrations). Effects of BHBA infusion on feed intake, metabolism, and performance were investigated. Thirteen cows were randomly assigned to 1 of 2 infusion groups, including an intravenous infusion with Na-dl-β-OH-butyrate (1.7 mol/L) to achieve a plasma concentration of 1.5 to 2.0 mmol/L of BHBA (HyperB; n=5), or an infusion of 0.9% saline solution (control; n=8). Blood was sampled before and hourly during the 48 h of infusion. In the liver, mRNA transcripts related to gluconeogenesis (pyruvate carboxylase, glucose 6-phosphatase, mitochondrial phosphoenolpyruvate carboxykinase), phosphofructokinase, pyruvate dehydrogenase complex, and fatty acid synthesis (acetyl-coenzyme A carboxylase, fatty acid synthase) were measured by real-time PCR. Glyceraldehyde-3-phosphate dehydrogenase and ubiquitin were used as housekeeping genes. Changes (difference between before and after 48-h infusion) during the infusion period were evaluated by ANOVA with treatment as fixed effect, and area under the curve of variables was calculated on the second day of experiment. The plasma BHBA concentration in HyperB cows was 1.74 ± 0.02 mmol/L (mean ± SE) compared with 0.59 ± 0.02 mmol/L for control cows. The change in feed intake, milk yield, and energy corrected milk did not differ between the 2 experimental groups. Infusion of BHBA reduced the plasma glucose concentration (3.47 ± 0.11 mmol/L) in HyperB compared with control cows (4.11 ± 0.08 mmol/L). Plasma glucagon concentration in HyperB was lower than the control group. All other variables measured in plasma were not affected by treatment. In the liver, changes in mRNA abundance for the selected genes were similar between 2 groups. Results demonstrate that intravenous infusion of BHBA decreased plasma glucose concentration in dairy cows, but this decrease could not be explained by alterations in insulin concentrations or key enzymes related to gluconeogenesis. Declined glucose concentration is likely functionally related to decreased plasma glucagon concentration.