Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial

OBJECTIVES This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial. BACKGROUND The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES. METHODS The LEADERS trial was a 10-center, assessor-blind, noninferiority, "all-comers" trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat. RESULTS At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority <0.0001, p for superiority = 0.069). The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death, any MI, and all-cause revascularization (297 [35.1%] vs. 339 [40.4%], RR: 0.84 [95% CI: 0.71 to 0.98], p for superiority = 0.023). A significant reduction in very late definite ST from 1 to 5 years was evident with the BES (n = 5 [0.7%] vs. n = 19 [2.5%], RR: 0.26 [95% CI: 0.10 to 0.68], p = 0.003), corresponding to a significant reduction in ST-associated clinical events (primary endpoint) over the same time period (n = 3 of 749 vs. n = 14 of 738, RR: 0.20 [95% CI: 0.06 to 0.71], p = 0.005). CONCLUSIONS The safety benefit of the biodegradable polymer BES, compared with the durable polymer SES, was related to a significant reduction in very late ST (>1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220).

Comparison of zotarolimus- and everolimus-eluting coronary stents: final 5-year report of the RESOLUTE all-comers trial

BACKGROUND Newer-generation drug-eluting stents that release zotarolimus or everolimus have been shown to be superior to the first-generation drug-eluting stents. However, data comparing long-term safety and efficacy of zotarolimus- (ZES) and everolimus-eluting stents (EES) are limited. RESOLUTE all-comers (Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) trial compared these 2 stents and has shown that ZES was noninferior to EES at 12-month for the primary end point of target lesion failure. We report the secondary clinical outcomes at the final 5-year follow-up of this trial. METHODS AND RESULTS RESOLUTE all-comer clinical study is a prospective, multicentre, randomized, 2-arm, open-label, noninferiority trial with minimal exclusion criteria. Patients (n=2292) were randomly assigned to treatment with either ZES (n=1140) or EES (n=1152). Patient-oriented composite end point (combination of all-cause mortality, myocardial infarction, and any revascularizations), device-oriented composite end point (combination of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization), and major adverse cardiac events (combination of all-cause death, all myocardial infarction, emergent coronary bypass surgery, or clinically indicated target lesion revascularization) were analyzed at 5-year follow-up. The 2 groups were well-matched at baseline. Five-year follow-up data were available for 98% patients. There were no differences in patient-oriented composite end point (ZES 35.3% versus EES 32.0%, P=0.11), device-oriented composite end point (ZES 17.0% versus EES 16.2%, P=0.61), major adverse cardiac events (ZES 21.9% versus EES 21.6%, P=0.88), and definite/probable stent thrombosis (ZES 2.8% versus EES 1.8%, P=0.12). CONCLUSIONS At 5-year follow-up, ZES and EES had similar efficacy and safety in a population of patients who had minimal exclusion criteria. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00617084.

A 5-year review of teeth filled with the noninstrumentation technology

AIM: The aim of this Case Series was to evaluate the radiographic quality of root fillings performed 5 years previously using the noninstrumentation technology (NIT)-obturation method and to assess radiographically the outcome of these root canal treatments. METHODOLOGY: Seventeen patients requiring root canal treatment participated in this study and were re-evaluated after 5 years. After instrumentation with K-Flexofiles, Calcium-Hydroxide inter-appointment dressing, re-entry and copious irrigation with NaOCl, the teeth were root filled using the NIT. RESULTS: Immediately after obturation the root fillings were (-0.78 +/- 0.11 mm) short when taking the radiographic apex as a reference point. After 60 months these values were -0.85 +/- 0.11 mm. No statistical difference was found (P > 0.05). In the periapical region, PAI rating 1 and 2 increased from 20.1% to 75.6% after 60 months. CONCLUSIONS: * This prospective Case Series demonstrated the performance of the NIT-obturation method in vivo. * Root canals filled by the reduced-pressure method using sealer combined with gutta-percha cones showed good radiographic quality. * Periapical healing after 5 years was comparable with conventional filling techniques.

Dermatopathology in sub-Saharan Africa: a systematic 5-year analysis of all histopathological diagnoses from the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania.

BACKGROUND Proper diagnosis of skin diseases relies on dermatopathology, the most important diagnostic technique in dermatology. Unfortunately, there are few dermatopathology institutions in sub-Saharan Africa, where little is known about the spectrum of histopathological features observed. OBJECTIVES To investigate the spectrum of dermatopathological diagnoses made in a sub-Saharan African reference centre of a large, mainly rural area. PATIENTS/METHODS To retrospectively evaluate all dermatopathological diagnoses made over a period of 5 years at the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania. RESULTS There were a total of 1554 skin biopsy specimens. In 45% of cases, there were inflammatory diseases, most frequently lichenoid conditions. Cutaneous neoplasms represented 30.4% of all diagnoses, with Kaposi's sarcoma (KS) and, less frequently, squamous cell carcinoma (SCC) being the two most common neoplastic conditions. The latter also reflected the intensive management of persons with albinism in the RDTC. The distribution of histological diagnoses seemed to correlate with the overall clinical spectrum of cutaneous diseases managed in the RDTC. CONCLUSIONS In this African study inflammatory conditions are the main burden of skin diseases leading to a diagnostic biopsy. Our findings provide further evidence that KS, primarily related to the high prevalence of HIV infection is an epidemiological problem. Both SCC and basal cell carcinoma represent another relatively common malignant cutaneous neoplasms, reflecting the presence of specific populations at risk. The challenging spectrum of histological diagnoses observed in this specific African setting with basic working conditions shows that development of laboratory services of good standards and specific training in dermatopathology are urgently needed.

5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.

BACKGROUND In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1·44% (95% CI 0·51-2·38) with APBI and 0·92% (0·12-1·73) with whole-breast irradiation (difference 0·52%, 95% CI -0·72 to 1·75; p=0·42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3·2% with APBI versus 5·7% with whole-breast irradiation (p=0·08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7·6% versus 6·3% (p=0·53). The risk of severe (grade 3) fibrosis at 5 years was 0·2% with whole-breast irradiation and 0% with APBI (p=0·46). INTERPRETATION The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING German Cancer Aid.

Temporomandibular disorders/myoarthropathy of the masticatory system. Costs of dental treatment and reimbursement by Swiss federal insurance agencies according to the Health Care Benefits Ordinance (KLV)

The goal of the study was to calculate the direct costs of therapy for patients with MAP. This retrospective study included 242 MAP patients treated at the Department of Prosthodontics of the University of Bern between 2003 and 2006. The following parameters were collected from the clinical charts: chief complaint, diagnosis, treatment modalities, total costs, costs of the dental technician, number of appointments, average cost per appointment, length of treatment, and services reimbursed by health insurance agencies. The average age of the patients was 40.4 ± 17.3 years (76.4% women, 23.6% men). The chief complaint was pain in 91.3% of the cases, TMJ noises (61.2%) or limitation of mandibular mobility (53.3%). Tendomyopathy (22.3%), disc displacement (22.4%), or a combination of the two (37.6%) were more often diagnosed than arthropathy alone (7.4%). Furthermore, 10.3% of the MAP patients had another primary diagnosis (tumor, trauma, etc.). Patients were treated with counseling and exercises (36.0%), physiotherapy (23.6%), or occlusal splints (32.6%). The cost of treatment reached 644 Swiss francs for four appointments spread over an average of 21 weeks. In the great majority of cases, patients can be treated with inexpensive modalities. 99.9% of the MAP cases submitted to the insurance agencies were reimbursed by them, in accordance with Article 17d1-3 of the Swiss Health Care Benefits Ordinance (KLV) and Article 25 of the Federal Health Insurance Act (KVG). The costs of treatment performed by dentists remain modest. The more time-consuming services, such as providing information, counseling and instructions, are poorly remunerated. This aspect should be re-evaluated in a future revision of the tariff schedule.

Usage of complementary medicine across Switzerland. Results of the Swiss Health Survey 2007

QUESTIONS UNDER STUDY: This study investigated the use among the Swiss adult population and regional dissemination of various methods of complementary medicine (CM) provided by physicians or therapists in Switzerland. METHODS: Data of the Swiss Health Survey 2007 were used, which comprised a telephone interview followed by a written questionnaire (18,760 and 14,432 respondents, respectively) and included questions about people's state of health, health insurance and usage of health services. Users and non-users of CM were compared using logistic regression models. RESULTS: The most popular CM methods were homeopathy, osteopathy, acupuncture and shiatsu/foot reflexology. 30.5% of women and 15.2% of men used at least one CM method in the 12 months preceding the survey. Lake Geneva region and central Switzerland had more CM users than the other regions. Women, people between 25 and 64 years of age and people with higher levels of education were more likely to use CM. 53.5% of the adult population had a supplemental health insurance for CM treatments. 32.9% of people with such an insurance used CM during the 12 months preceding the survey, and so did 12.0% of people without additional insurance. CONCLUSIONS: Almost one fourth of the Swiss adult population had used CM within the past 12 months. User profiles were comparable to those in other countries. Despite a generally lower self-perceived health status, elderly people were less likely to use CM.

Clinical performance of a sutureless aortic bioprosthesis: five-year results of the 3f Enable long-term follow-up study.

OBJECTIVE Sutureless valves are designed to facilitate surgical implantation, including less-invasive techniques in aortic valve replacement, by maintaining surgical precision of implantation compared with transcatheter techniques. Long-term clinical experience with sutureless valves is lacking. We report the 5-year follow-up results of an international, prospective, multicenter study evaluating the clinical performance and safety of the 3f Enable valve (Medtronic Inc, Minneapolis, Minn). METHODS Between March 2007 and December 2009, 141 patients (54 male; mean age, 76.1±5.7 years) undergoing aortic valve replacement with the 3f Enable valve were enrolled in 10 European sites. The mean follow-up was 2.76 years (range, 2 days to 5.1 years; total, 388.7 patient-years). Echocardiographic valvular hemodynamic and morphologic analyses were performed by an independent core laboratory. RESULTS The mean systolic gradient was 10.4±4.4 mm Hg at discharge and 7.7±4.1 mm Hg at 5 years. The mean effective orifice area was 1.7±0.5 cm2 at discharge and 1.6±0.2 cm2 at 5 years. Freedom from all-cause and valve-related mortality was 87.6%±2.9% and 96.8%±1.6% at 1 year (113 patients at risk) and 77.0%±7.5% and 93.8%±4.8% at 5 years (24 patients at risk), respectively. Six patients underwent reoperation (4 because of major paravalvular leakage and 2 because of endocarditis). Freedom from reoperation was 95.4%±1.9% at 1 year and 95.4%±6.1% at 5 years. No structural valve deterioration occurred during the follow-up period. CONCLUSIONS The sutureless 3f Enable valve represents a safe and effective treatment for aortic valve stenosis, providing an excellent hemodynamic profile. This study represents the longest follow-up study for a sutureless bioprosthesis. Sutureless valves may become an option for all patients with indicated biological aortic valve replacement.

Viral load versus CD4⁺ monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa: a cohort-based modelling study.

OBJECTIVES Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4⁺ to monitor ART. We assessed the benefit of replacing CD4⁺ by viral load monitoring. DESIGN A mathematical modelling study. METHODS A simulation model of HIV progression over 5 years in children on ART, parameterized by data from seven South African cohorts. We simulated treatment programmes with 6-monthly CD4⁺ or 6- or 12-monthly viral load monitoring. We compared mortality, second-line ART use, immunological failure and time spent on failing ART. In further analyses, we varied the rate of virological failure, and assumed that the rate is higher with CD4⁺ than with viral load monitoring. RESULTS About 7% of children were predicted to die within 5 years, independent of the monitoring strategy. Compared with CD4⁺ monitoring, 12-monthly viral load monitoring reduced the 5-year risk of immunological failure from 1.6 to 1.0% and the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with CD4⁺ compared with 12% with viral load monitoring switched to second-line ART. Differences became larger when assuming higher rates of virological failure. When assuming higher virological failure rates with CD4⁺ than with viral load monitoring, up to 4.2% of children with CD4⁺ compared with 1.5% with viral load monitoring experienced immunological failure; the mean time spent on failing ART was 27.3 months with CD4⁺ monitoring and 6.0 months with viral load monitoring. Conclusion: Viral load monitoring did not affect 5-year mortality, but reduced time on failing ART, improved immunological response and increased switching to second-line ART.

Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable-Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization: 2-Year Results of the BIOSCIENCE Trial.

BACKGROUND No data are available on the long-term performance of ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES). We reported 2-year clinical outcomes of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation) trial, which compared BP-SES with durable-polymer everolimus-eluting stents (DP-EES) in patients undergoing percutaneous coronary intervention. METHODS AND RESULTS A total of 2119 patients with minimal exclusion criteria were assigned to treatment with BP-SES (n=1063) or DP-EES (n=1056). Follow-up at 2 years was available for 2048 patients (97%). The primary end point was target-lesion failure, a composite of cardiac death, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. At 2 years, target-lesion failure occurred in 107 patients (10.5%) in the BP-SES arm and 107 patients (10.4%) in the DP-EES arm (risk ratio [RR] 1.00, 95% CI 0.77-1.31, P=0.979). There were no significant differences between BP-SES and DP-EES with respect to cardiac death (RR 1.01, 95% CI 0.62-1.63, P=0.984), target-vessel myocardial infarction (RR 0.91, 95% CI 0.60-1.39, P=0.669), target-lesion revascularization (RR 1.17, 95% CI 0.81-1.71, P=0.403), and definite stent thrombosis (RR 1.38, 95% CI 0.56-3.44, P=0.485). There were 2 cases (0.2%) of definite very late stent thrombosis in the BP-SES arm and 4 cases (0.4%) in the DP-EES arm (P=0.423). In the prespecified subgroup of patients with ST-segment elevation myocardial infarction, BP-SES was associated with a lower risk of target-lesion failure compared with DP-EES (RR 0.48, 95% CI 0.23-0.99, P=0.043, Pinteraction=0.026). CONCLUSIONS Comparable safety and efficacy profiles of BP-SES and DP-EES were maintained throughout 2 years of follow-up. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443104.

Performance of dental implants after staged sinus floor elevation procedures: 5-year results of a prospective study in partially edentulous patients

OBJECTIVES: The aim of this prospective study was to evaluate the 5-year performance and success rate of titanium screw-type implants with the titanium plasma spray (TPS) or the sand-blasted, large grit, acid-etched (SLA) surface inserted in a two-stage sinus floor elevation (SFE) procedure in the posterior maxilla. MATERIAL AND METHODS: A total of 59 delayed SFEs were performed in 56 patients between January 1997 and December 2001, using a composite graft with autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) or synthetic porous beta-tricalcium phosphate (beta-TCP). After a healing period averaging 7.75 months, 111 dental implants were inserted. After an additional 8-14-week healing period, all implants were functionally loaded with cemented crowns or fixed partial dentures. The patients were recalled at 12 and 60 months for clinical and radiographic examination. RESULTS: One patient developed an acute infection in the right maxillary sinus after SFE and did not undergo implant therapy. Two of the 111 inserted implants had to be removed because of a developing atypical facial pain, and 11 implants were lost to follow-up and were considered drop-outs. The remaining 98 implants showed favorable clinical and radiographic findings at the 5-year examination. The peri-implant soft tissues were stable over time; the mean probing depths and mean attachment levels did not change during the follow-up period. The measurement of the bone crest levels (DIB values) indicated stability as well. Based on strict success criteria, all 98 implants were considered successfully integrated, resulting in a 5-year success rate of 98% (for TPS implants 89%, for SLA implants 100%). CONCLUSION: This prospective study assessing the performance of dental implants inserted after SFE demonstrated that titanium implants can achieve and maintain successful tissue integration with high predictability for at least 5 years of follow-up in carefully selected patients.

A 5-year comparison of performance of sentinel and mandatory notification surveillance systems for measles in Switzerland

A sensitive, specific and timely surveillance is necessary to monitor progress towards measles elimination. We evaluated the performance of sentinel and mandatory-based surveillance systems for measles in Switzerland during a 5-year period by comparing 145 sentinel and 740 mandatory notified cases. The higher proportion of physicians who reported at least one case per year in the sentinel system suggests underreporting in the recently introduced mandatory surveillance for measles. Accordingly, the latter reported 2-36-fold lower estimates for incidence rates than the sentinel surveillance. However, these estimates were only 0.6-12-fold lower when we considered confirmed cases alone, which indicates a higher specificity of the mandatory surveillance system. In contrast, the sentinel network, which covers 3.5% of all outpatient consultations, detected only weakly and late a major national measles epidemic in 2003 and completely missed 2 of 10 cantonal outbreaks. Despite its better timeliness and greater sensitivity in case detection, the sentinel system, in the current situation of low incidence, is insufficient to perform measles control and to monitor progress towards elimination.

Unprotected left main stenting in the real world: two-year outcomes of the French left main taxus registry

BACKGROUND: Cardiac surgery is the reference treatment for patients with left main (LM) disease, although percutaneous coronary intervention with drug-eluting stents is emerging as a possible alternative. The objective of this registry was to evaluate the 2-year outcome of elective percutaneous coronary intervention for unprotected LM disease with paclitaxel-eluting stents. METHODS AND RESULTS: A total of 291 patients were prospectively included from 4 centers. Acute myocardial infarction and cardiogenic shock were the only exclusion criteria. Patients were 69+/-11 years old, 29% were diabetic, and 25% had 3-vessel disease. For distal LM lesions (78%), the provisional side-branch T-stenting approach was used in 92% of cases and final kissing balloon inflation in 97%. Angiographic success was obtained in 99.7% of cases. At 2-year follow-up, the total cardiac death rate was 5.4% (1 EuroSCORE point was associated with a 15% [95% confidence interval 2.9% to 28.2%, P=0.013] higher risk of cardiac death), target-lesion revascularization was 8.7%, and incidence of Q-wave or non-Q-wave myocardial infarction was 0.9% and 3.1%, respectively. The combined end point occurred in 15.8% of cases and stroke in 0.7%. The incidence of definite and probable LM stent thrombosis was 0.7%, whereas the incidence of any stent thrombosis was 3.8%, with a higher risk in patients with side-branch stenting in the presence of LM bifurcation lesions (hazard ratio 9.6, 95% confidence interval 1.2 to 77.7, P=0.035). CONCLUSIONS: Unprotected LM stenting with paclitaxel-eluting stents, with a strategy of provisional side-branch T-stenting for distal lesions, provides excellent acute angiographic results and good mid-term clinical outcomes, with a 15.8% rate of major adverse cardiac events at 2-year follow-up.

The 10-year anniversary of the European Association for Cardiovascular Prevention and Rehabilitation: achievements and challenges

On the occasion of the 2014 European Society of Cardiology annual congress in Barcelona the European Association for Cardiovascular Prevention and Rehabilitation (EACPR) will celebrate its 10-year anniversary, having been initiated in Munich in 2004. In this article each EACPR president gives their personal recollections and views on the main achievements under their leadership and discusses the challenges for preventive cardiology that still lay ahead.

Construction and first validation of the comprehensive inventory of mindfulness (CHIME)

Introduction: Measuring trait mindfulness and change in mindfulness may be a crucial prerequisite for the evaluation and further development of mindfulness based interventions for the treatment of mental disorders. This endeavour is nontrivial as current measures cover varying aspects and mindfulness and may have problems regarding validity. This presentation describes the development and validation of a questionnaire for the comprehensive assessment of mindfulness: the Comprehensive Inventory of Mindfulness Experiences (CHIME). Method: The factor structure, reliability, and validity of the CHIME were established in a community sample (N = 298) and a sample of MBSR group participants (N = 161). Results: Factor-analytical procedures supported an eight-factor structure. The structure was tested in a further confirmatory sample (N = 202). The questionnaire and its subscales exhibited good reliability (internal consistency and retest-reliability). Analysis of the measurement invariance of the single items over groups differing in age, gender, meditation experience, and symptom load pointed to the absence of systematic differences in the items' semantic understanding. Parameters reflecting construct validity, criterion validity, and incremental validity as well as change sensitivity were all at least satisfactory. Conclusions: The CHIME is a self-report measure with favorable psychometric properties based on all aspects of mindfulness that are included in current mindfulness scales. This scale may be helpful in the evaluation and further development of mindfulness based interventions.