Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis

In a 5-year study involving 119 postmenopausal women, zoledronic acid 4 mg given once-yearly for 2, 3 or 5 years was well tolerated with no evidence of excessive bone turnover reduction or any safety signals. BMD increased significantly. Bone turnover markers decreased from baseline and were maintained within premenopausal reference ranges. INTRODUCTION: After completion of the core study, two consecutive, 2-year, open-label extensions investigated the efficacy and safety of zoledronic acid 4 mg over 5 years in postmenopausal osteoporosis. METHODS: In the core study, patients received 1 to 4 mg zoledronic acid or placebo. In the first extension, most patients received 4 mg per year and then patients entered the second extension and received 4 mg per year or calcium only. Patients were divided into three subgroups according to years of active treatment received (2, 3 or 5 years). Changes in BMD and bone turnover markers (bone ALP and CTX-I) were assessed. RESULTS: All subgroups showed substantial increases in BMD and decreases in bone markers. By the end of the core study, 37.5% of patients revealed a suboptimal reduction (< 30%) of bone ALP levels. After subsequent study drug administration during the extensions, there was no evidence of progressive reduction of bone turnover markers. Furthermore, increased marker levels after treatment discontinuation demonstrates preservation of bone remodelling capacity. CONCLUSIONS: This study showed that zoledronic acid 4 mg once-yearly was well tolerated and effective in reducing biomarkers over 5 years. Detailed analysis of bone marker changes, however, suggests that this drug regimen causes insufficient reduction of remodelling activity in one third of patients.

Tooth loss over five years

Objectives: To assess the ability to predict tooth loss on the basis of clinical and radiographic parameters. Methods: Clinical and radiographic data from a five year prospective cohort were studied to identify cause of progressive tooth loss in older subjects. Results: 363 subjects with a baseline mean age of 67.1 years (S.D. + 4.7, range : 60-75), and 51.4% women were studied including 59.5% never smokers, and 33.0% current smokers. At baseline the subjects had, on average, 22.4 teeth (S.D. + 6.4). Self-assessed tooth loss risk was identified by 16.0 % of subjects while 34% of subjects lost teeth. Tooth loss due to caries was found in 24.7% (178 teeth), periodontitis in 15.4% (133 teeth), peri-apical lesions 5.9% (32 teeth), combined periodontal/peri-apical in 3.4% (18 teeth), and teeth irrational to treat in 7.5% (58 teeth) of the subjects. 122 of the extracted teeth (34%) should have been possible to save but were extracted. At year five severe caries, periodontitis, peri-apical lesions, periodontal/peri-apical, irrational to treat were found in 6.3%, 7.2%, 2.6%, 4.6%, and 1.2% of subjects, respectively. Signs of osteoporosis increased by 11.2 % (Klemetti index). Linear regression analysis failed to include smoking habits as being explanatory. Explanatory factors were researcher prediction of extraction needs, subject self assessment of risk and change in ostoporosis status (r2 = 0.39, ANOVA, F=22.6, p< 0.001). Conclusions: Caries and periodontitis are primary causes for extraction. Progressive osteoporosis is associated with tooth loss. Radiographs, and subjects self-assessment of risk for tooth loss are robust predictors.

The UNESCO Convention on Cultural Diversity: An Appraisal Five Years after Its Entry into Force

The United Nations Educational Scientific and Cultural Organization (UNESCO) adopted in 2005 the first legally binding international instrument on culture. The Convention on the Protection and Promotion of the Diversity of Cultural Expressions was agreed upon with an overwhelming majority and after the swiftest ratification process in the history of the UNESCO entered into force on 18 March 2007. Now, five years later and with some 125 Members committed to implementing the Convention, not only observers with a particular interest in the topic but also the broader public may be eager to know what has happened and in how far has the implementation progress advanced. This is the question that animates this paper and which it seeks to answer by giving a brief background to the UNESCO Convention, clarifying its legal and political status and impact, as well as by looking at the current implementation activities in the domestic and international contexts.

The UNESCO Convention on Cultural Diversity : An Appraisal Five Years after its Entry into Force

The United Nations Educational Scientific and Cultural Organization (UNESCO) adopted in 2005 the first legally binding international instrument on culture. The Convention on the Protection and Promotion of the Diversity of Cultural Expressions was agreed upon with an overwhelming majority and after the swiftest ratification process in the history of the UNESCO entered into force on 18 March 2007. Now, five years later and with some 125 Members committed to implementing the Convention, not only observers with a particular interest in the topic but also the broader public may be eager to know what has happened and in how far has the implementation progress advanced. This is the question that animates this paper and which it seeks to answer by giving a brief background to the UNESCO Convention, clarifying its legal and political status and impact, as well as by looking at the current implementation activities in the domestic and international contexts.

Separation of the Ribbon from globally distributed energetic neutral Atom Flux using the first five Years of Ibex Observations

The Interstellar Boundary Explorer (IBEX) observes the IBEX ribbon, which stretches across much of the sky observed in energetic neutral atoms (ENAs). The ribbon covers a narrow (~20°-50°) region that is believed to be roughly perpendicular to the interstellar magnetic field. Superimposed on the IBEX ribbon is the globally distributed flux that is controlled by the processes and properties of the heliosheath. This is a second study that utilizes a previously developed technique to separate ENA emissions in the ribbon from the globally distributed flux. A transparency mask is applied over the ribbon and regions of high emissions. We then solve for the globally distributed flux using an interpolation scheme. Previously, ribbon separation techniques were applied to the first year of IBEX-Hi data at and above 0.71 keV. Here we extend the separation analysis down to 0.2 keV and to five years of IBEX data enabling first maps of the ribbon and the globally distributed flux across the full sky of ENA emissions. Our analysis shows the broadening of the ribbon peak at energies below 0.71 keV and demonstrates the apparent deformation of the ribbon in the nose and heliotail. We show global asymmetries of the heliosheath, including both deflection of the heliotail and differing widths of the lobes, in context of the direction, draping, and compression of the heliospheric magnetic field. We discuss implications of the ribbon maps for the wide array of concepts that attempt to explain the ribbon's origin. Thus, we present the five-year separation of the IBEX ribbon from the globally distributed flux in preparation for a formal IBEX data release of ribbon and globally distributed flux maps to the heliophysics community.

Simple training tool is insufficient for appropriate diagnosis and treatment of malnutrition: A pre-post intervention study in a tertiary center.

OBJECTIVES To improve malnutrition awareness and management in our department of general internal medicine; to assess patients' nutritional risk; and to evaluate whether an online educational program leads to an increase in basic knowledge and more frequent nutritional therapies. METHODS A prospective pre-post intervention study at a university department of general internal medicine was conducted. Nutritional screening using Nutritional Risk Score 2002 (NRS 2002) was performed, and prescriptions of nutritional therapies were assessed. The intervention included an online learning program and a pocket card for all residents, who had to fill in a multiple-choice questions (MCQ) test about basic nutritional knowledge before and after the intervention. RESULTS A total of 342 patients were included in the preintervention phase, and 300 were in the postintervention phase. In the preintervention phase, 54.1% were at nutritional risk (NRS 2002 ≥3) compared with 61.7% in the postintervention phase. There was no increase in the prescription of nutritional therapies (18.7% versus 17.0%). Forty-nine and 41 residents (response rate 58% and 48%) filled in the MCQ test before and after the intervention, respectively. The mean percentage of correct answers was 55.6% and 59.43%, respectively (which was not significant). Fifty of 84 residents completed the online program. The residents who participated in the whole program scored higher on the second MCQ test (63% versus 55% correct answers, P = 0.031). CONCLUSIONS Despite a high ratio of malnourished patients, the nutritional intervention, as assessed by nutritional prescriptions, is insufficient. However, the simple educational program via Internet and usage of NRS 2002 pocket cards did not improve either malnutrition awareness or nutritional treatment. More sophisticated educational systems to fight malnutrition are necessary.

Reduction of inappropriate medications among older nursing-home residents: a nurse-led, pre/post-design, intervention study

Background: Medication-related problems are common in the growing population of older adults and inappropriate prescribing is a preventable risk factor. Explicit criteria such as the Beers criteria provide a valid instrument for describing the rate of inappropriate medication (IM) prescriptions among older adults. Objective: To reduce IM prescriptions based on explicit Beers criteria using a nurse-led intervention in a nursing-home (NH) setting. Study Design: The pre/post-design included IM assessment at study start (pre-intervention), a 4-month intervention period, IM assessment after the intervention period (post-intervention) and a further IM assessment at 1-year follow-up. Setting: 204-bed inpatient NH in Bern, Switzerland. Participants: NH residents aged ≥60 years. Intervention: The intervention included four key intervention elements: (i) adaptation of Beers criteria to the Swiss setting; (ii) IM identification; (iii) IM discontinuation; and (iv) staff training. Main Outcome Measure: IM prescription at study start, after the 4-month intervention period and at 1-year follow-up. Results: The mean±SD resident age was 80.3±8.8 years. Residents were prescribed a mean±SD 7.8±4.0 medications. The prescription rate of IMs decreased from 14.5% pre-intervention to 2.8% post-intervention (relative risk [RR] = 0.2; 95% CI 0.06, 0.5). The risk of IM prescription increased nonstatistically significantly in the 1-year follow-up period compared with post-intervention (RR = 1.6; 95% CI 0.5, 6.1). Conclusions: This intervention to reduce IM prescriptions based on explicit Beers criteria was feasible, easy to implement in an NH setting, and resulted in a substantial decrease in IMs. These results underscore the importance of involving nursing staff in the medication prescription process in a long-term care setting.

Facial esthetics in children with unilateral cleft lip and palate 3 years after alveolar bonegrafting combined with rhinoplasty between 2 and 4 years of age

OBJECTIVES To evaluate facial esthetics in patients with unilateral cleft lip and palate (UCLP) after alveolar bone grafting combined with rhinoplasty between 2 and 4 years of age. DESIGN Retrospective case-control study. SETTING The Department of Pediatric Surgery, Institute of Mother and Child, Warsaw, Poland. MATERIAL AND METHODS Photographs of full faces and cropped images of five nasolabial components: nasal deviation, nasal form, nasal profile, vermillion border, and inferior view were assessed by 5 professional and 14 layraters in 29 children (23 boys and 6 girls; mean age = 5.3 years, SD 0.5; Early-grafted group) and 30 children (20 boys and 10 girls; mean age = 5.5 years, SD 1.0; Non-grafted group) with complete unilateral cleft lip and palate repaired with a one-stage closure. The groups differed regarding the timing of alveolar bone grafting: in the Early-grafted group, alveolar bone grafting in combination with rhinoplasty (ABG-R) was performed between 2 and 4 years of age (mean age = 2.3 years; SD 0.6); in the Non-grafted group, the alveolar defect was grafted after 9 years of age. No primary nose correction was carried out in any group. To rate esthetics, a modified five-grade esthetic index of Asher-McDade was used, where grade 1 means the most esthetic and grade 5 - the least esthetic outcome. RESULTS Esthetics of full faces and of all nasolabial elements in the Early-grafted group was significantly better than in Non-grafted group. The scores in the Early-grafted group ranged from 2.30 to 2.66 points, whereas in the Non-grafted group ranged from 2.66 to 3.17 points. All intergroup differences were statistically significant (p < 0.05). CONCLUSIONS Three years post-operatively, early alveolar bone grafting combined with rhinoplasty is favorable for facial esthetics in children with UCLP, but a longer follow-up is needed to assess whether the improvement was permanent.

Differences in coronary risk factors, procedural characteristics, mortality and stent thrombosis between two all-comers percutaneous coronary intervention registries from Europe and Japan: a patient-level data analysis of the Bern-Rotterdam and j-Cypher registries

Aims: The reported rate of stent thrombosis (ST) after drug-eluting stent (DES) implantation varies among registries. To investigate differences in baseline characteristics and clinical outcome in European and Japanese all-comers registries, we performed a pooled analysis of patient-level data. Methods and results: The j-Cypher registry (JC) is a multicentre observational study conducted in Japan, including 12,824 patients undergoing SES implantation. From the Bern-Rotterdam registry (BR) enrolled at two academic hospitals in Switzerland and the Netherlands, 3,823 patients with SES were included in the current analysis. Patients in BR were younger, more frequently smokers and presented more frequently with ST-elevation myocardial infarction (MI). Conversely, JC patients more frequently had diabetes and hypertension. At five years, the definite ST rate was significantly lower in JC than BR (JC 1.6% vs. BR 3.3%, p<0.001), while the unadjusted mortality tended to be lower in BR than in JC (BR 13.2% vs. JC 14.4%, log-rank p=0.052). After adjustment, the j-Cypher registry was associated with a significantly lower risk of all-cause mortality (HR 0.56, 95% CI: 0.49-0.64) as well as definite stent thrombosis (HR 0.46, 95% CI: 0.35-0.61). Conclusions: The baseline characteristics of the two large registries were different. After statistical adjustment, JC was associated with lower mortality and ST.

Gingival labial recessions and the post-treatment proclination of mandibular incisors

INTRODUCTION A prerequisite for development of gingival recession is the presence of alveolar bone dehiscence. Proclination of mandibular incisors can result in thinning of the alveolus and dehiscence formation. OBJECTIVE To assess an association between proclination of mandibular incisor and development of gingival recession. METHODS One hundred and seventeen subjects who met the following inclusion criteria were selected: 1. age 11-14 years at start of orthodontic treatment (TS), 2. bonded retainer placed immediately after treatment (T0), 3. dental casts and lateral cephalograms available pre-treatment (TS), post-treatment (T0), and 5 years post-treatment (T5), and 4. post-treatment (T0) lower incisor inclination (Inc_Incl) <95° or >100.5°. Two groups were formed: non-proclined (N = 57; mean Inc_Incl = 90.8°) and proclined (N = 60; mean Inc_Incl = 105.2°). Clinical crown heights of mandibular incisors and the presence of gingival recession sites in this region were assessed on plaster models. Fisher's exact tests, t-tests, and regression models were computed for analysis of inter-group differences. RESULTS The mean increase of clinical crown heights (from T0 to T5) of mandibular incisors ranged from 0.75 to 0.83mm in the non-proclined and proclined groups, respectively (P = 0.273). At T5, gingival recession sites were present in 12.3% and 11.7% patients from the non-proclined and proclined groups, respectively. The difference was also not significant (P = 0.851). CONCLUSIONS The proclination of mandibular incisors did not increase a risk of development of gingival recession during five-year observation in comparison non-proclined teeth.

Simultaneous bilateral hip replacement reveals superior outcome and fewer complications than two-stage procedures: a prospective study including 1819 patients and 5801 follow-ups from a total joint replacement registry

Background Total joint replacements represent a considerable part of day-to-day orthopaedic routine and a substantial proportion of patients undergoing unilateral total hip arthroplasty require a contralateral treatment after the first operation. This report compares complications and functional outcome of simultaneous versus early and delayed two-stage bilateral THA over a five-year follow-up period. Methods The study is a post hoc analysis of prospectively collected data in the framework of the European IDES hip registry. The database query resulted in 1819 patients with 5801 follow-ups treated with bilateral THA between 1965 and 2002. According to the timing of the two operations the sample was divided into three groups: I) 247 patients with simultaneous bilateral THA, II) 737 patients with two-stage bilateral THA within six months, III) 835 patients with two-stage bilateral THA between six months and five years. Results Whereas postoperative hip pain and flexion did not differ between the groups, the best walking capacity was observed in group I and the worst in group III. The rate of intraoperative complications in the first group was comparable to that of the second. The frequency of postoperative local and systemic complication in group I was the lowest of the three groups. The highest rate of complications was observed in group III. Conclusions From the point of view of possible intra- and postoperative complications, one-stage bilateral THA is equally safe or safer than two-stage interventions. Additionally, from an outcome perspective the one-stage procedure can be considered to be advantageous.