Real-World Safety and Effectiveness of Canagliflozin Treatment for Type 2 Diabetes Mellitus in Japan: SAPPHIRE, a Long-Term, Large-Scale Post-Marketing Surveillance.

INTRODUCTION: This long-term post-marketing surveillance (SAPPHIRE) collected information on the safety and effectiveness of canagliflozin (approved dose 100 mg) prescribed to patients with type 2 diabetes mellitus (T2DM) in real-world practice in Japan. METHODS: Patients with T2DM who were prescribed canagliflozin between December 2014 and September 2016 were registered and observed for up to 3 years. Safety was evaluated in terms of adverse drug reactions (ADRs). Effectiveness was assessed in terms of glycaemic control. Data were also analysed across age subgroups (< 65, ≥ 65 to < 75, and ≥ 75 years old) and the estimated glomerular filtration rate (eGFR) categories for chronic kidney disease (G1-G5 based on eGFR) at baseline. RESULTS: A total of 12,227 patients were included in the safety analyses and 11,675 in effectiveness analyses. Overall, 7104 patients were treated with canagliflozin for ≥ 3 years. The mean age, haemoglobin A1c (HbA1c), and eGFR at baseline were 58.4 ± 12.5 years, 8.01 ± 1.49%, and 80.04 ± 21.85 mL/min/1.73 m2, respectively. There were 1836 ADRs in 1312 patients (10.73%) and 268 serious ADRs in 225 patients (1.84%). The most common ADRs were those related to volume depletion (1.39%), genital infection (1.34%), polyuria/pollakiuria (1.23%), and urinary tract infection (1.19%). The frequencies of ADRs tended to increase with age and stage of chronic kidney disease. The reductions in mean HbA1c after starting canagliflozin were maintained for up to 3 years with a mean change of - 0.68% (n = 6345 at 3 years). Maintained reductions in mean HbA1c were observed in each age subgroup and in patients with G1-G3b renal function. CONCLUSION: This surveillance in real-world clinical practice showed that canagliflozin provides sustained glucose-lowering effects in patients with T2DM, including elderly patients and patients with moderate renal impairment, without new safety concerns beyond those already described in the Japanese package insert. TRIAL REGISTRATION: JapicCTI-153048.

Canagliflozin is a sodium­glucose cotransporter 2 (SGLT2) inhibitor that lowers blood glucose levels by increasing urinary glucose excretion. It was approved for the management of blood glucose levels in patients with type 2 diabetes mellitus following clinical trials. However, clinical trials may not fully represent the safety or effectiveness of a drug in real-world clinical practice. Therefore, a 3-year post-marketing surveillance was performed in Japan to obtain safety and effectiveness data for a large group of 12,227 patients with type 2 diabetes mellitus and various demographic/clinical characteristics. Safety and effectiveness data were collected for up to 3 years while patients were treated with canagliflozin. Adverse drug reactions occurred in 10.73% of patients. The most common types of adverse drug reactions were those related to volume depletion (body fluid decreased), followed by genital infection, polyuria/pollakiuria (increased urination), and urinary tract infection. Adverse drug reactions tended to be more common in elderly patients and in patients with renal impairment. As expected, canagliflozin was associated with improvements in haemoglobin A1c, a marker of blood glucose control, in patients with type 2 diabetes, including in elderly patients and patients with moderate renal impairment. In this surveillance in real-world clinical practice, long-term treatment with canagliflozin raised no new safety concerns beyond the information already included in the Japanese package insert. Canagliflozin provides sustained glucose-lowering effects.

Rationale, design, demographics and baseline characteristics of the randomized, controlled, Phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia.

BACKGROUND: Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4-62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia. METHODS: Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30-5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months. CONCLUSIONS: This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.

Therapeutic potential of topically administered γ-AlOOH on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like lesions in Balb/c mice.

Boehmite (γ-AlOOH) has a wide range of applications in a variety of industrial and biological fields. However, little is known about its potential roles in skin diseases. The current study investigated its effect on atopic dermatitis (AD). Following characterization, cytotoxicity, pro-inflammatory response and oxidative stress associated with boehmite were assessed, using TNF-α-induced keratinocytes and mast cells. In addition, therapeutic effects of boehmite, topically administered to Balb/c mice induced by 2,4-dinitrochlorobenzene (DNCB), were evaluated. Expression of cytokines (TLSP, IL-25 and IL-33) and the generation of ROS from keratinocytes induced by TNF-α were significantly inhibited by boehmite without affecting cell viability. MAPKs (ERK, JNK and p38) required for cytokine expression were suppressed by boehmite treatment. Up-regulation of cytokines (TSLP, IL-4, IL-5, IL-13, RANTES) in human mast cells treated with phorbol 12-myristate 13-acetate and calcium ionophore was also suppressed by boehmite. Boehmite improved the AD severity score, epidermal hyperplasia and transepidermal water loss in DNCB-induced AD-like lesions. Moreover, Th2-mediated cytokine expression, mast cell hyperplasia and destruction of the skin barrier were improved by boehmite treatment. Overall, we demonstrated that boehmite may potentially protect against AD.

Vx3-Functionalized Alumina Nanoparticles Assisted Enrichment of Ubiquitinated Proteins from Cancer Cells for Enhanced Cancer Immunotherapy.

A simple and effective strategy was developed to enrich ubiquitinated proteins (UPs) from cancer cell lysate using the α-Al2O3 nanoparticles covalently linked with ubiquitin binding protein (Vx3) (denoted as α-Al2O3-Vx3) via a chemical linker. The functionalized α-Al2O3-Vx3 showed long-term stability and high efficiency for the enrichment of UPs from cancer cell lysates. Flow cytometry analysis results indicated dendritic cells (DCs) could more effectively phagocytize the covalently linked α-Al2O3-Vx3-UPs than the physical mixture of α-Al2O3 and Vx3-UPs (α-Al2O3/Vx3-UPs). Laser confocal microscopy images revealed that α-Al2O3-Vx3-UPs localized within the autophagosome of DCs, which then cross-presented α-Al2O3-Vx3-UPs to CD8+ T cells in an autophagosome-related cross-presentation pathway. Furthermore, α-Al2O3-Vx3-UPs enhanced more potent antitumor immune response and antitumor efficacy than α-Al2O3/cell lysate or α-Al2O3/Vx3-UPs. This work highlights the potential of using the Vx3 covalently linked α-Al2O3 as a simple and effective platform to enrich UPs from cancer cells for the development of highly efficient therapeutic cancer vaccines.

Airborne particulate concentration during laser hair removal: A comparison between cold sapphire with aqueous gel and cryogen skin cooling.

BACKGROUND: High concentrations of sub-micron nanoparticles have been shown to be released during laser hair removal (LHR) procedures. These emissions pose a potential biohazard to healthcare workers that have prolonged exposure to LHR plume. OBJECTIVE: We sought to demonstrate that cold sapphire skin cooling done in contact mode might suppress plume dispersion during LHR. METHODS: A total of 11 patients were recruited for laser hair removal. They were treated on the legs and axilla with a 755 or 1064 nm millisecond-domain laser equipped with either (i) cryogen spray (CSC); (ii) refrigerated air (RA); or (iii) contact cooling with sapphire (CC). Concentration of ultrafine nanoparticles <1 µm were measured just before and during LHR with the three respective cooling methods. RESULTS: For contact cooling (CC), counts remained at baseline levels, below 3,500 parts per cubic centimeter (ppc) for all treatments. In contrast, the CSC system produced large levels of plume, peaking at times to over 400,000 ppc. The CA cooled system produced intermediate levels of plume, about 35,000 ppc (or about 10× baseline). CONCLUSIONS: Cold Sapphire Skin cooling with gel suppresses plume during laser hair removal, potentially eliminating the need for smoke evacuators, custom ventilation systems, and respirators during LHR. Lasers Surg. Med. 50:280-283, 2018. © 2017 Wiley Periodicals, Inc.

Results of Total Elbow Arthroplasty with Cementless Implantation of an Alumina Ceramic Elbow Prosthesis for Patients with Rheumatoid Arthritis.

We investigated the long-term clinical results of total elbow arthroplasty (TEA) by cementless fixation of alumina ceramic unlinked elbow prostheses (J-alumina ceramic elbows: JACE) for the reconstruction of elbow joints with rheumatoid arthritis (RA). Seventeen elbows in 17 patients (aged 44-72 years, average 54.8) replaced by JACE TEA without bone cement were investigated. The average follow-up period was 10.7 (range, 1.0-19.3) years. Clinical conditions of each elbow before and after surgery were assessed according to the Mayo Elbow Performance Index (MEPI). Radiographic loosening was defined as a progressive radiolucent line of more than 1 mm that was completely circumferential around the intramedullary stem. The average MEPI significantly improved from 46.8 points preoperatively to 66.8 points at final follow-up (p=0.0226). However, aseptic loosening was noted in 10 of 17 elbows (58.8%) and revision surgery was required in 7 (41.2%). Most loosening was observed on the humeral side. With radiographic loosening and revision surgery defined as the end points, the likelihoods of prosthesis survival were 41.2% and 51.8%, respectively, up to 15 years by Kaplan-Meier analysis. The clinical results of JACE implantation without bone cement were disappointing, with high revision and loosening rates of the humeral component.

A randomised clinical in situ study to evaluate the effects of novel low abrasivity anti-sensitivity dentifrices on dentine wear.

OBJECTIVES: To compare the abrasive wear on human dentine in an in situ model associated with use of an experimental low abrasivity anti-sensitivity dentifrice containing 1% alumina and 5% sodium tripolyphosphate (STP) with an experimental ultra-low abrasivity non-alumina 5% STP dentifrice, a higher abrasivity daily-use whitening dentifrice, and water as controls. METHODS: This was a single-centre, single-blind, randomised, split-mouth, four-treatment, two-period, crossover in situ study in 29 healthy subjects. Subjects wore bilateral lower buccal appliances, each fitted with four dentine specimens. Study treatments were applied ex vivo (three times daily). Dentine loss was measured by non-contact profilometry after 5, 10 and 15days' treatment. RESULTS: All 29 subjects were included in the efficacy analysis. Significantly less dentine loss was associated with brushing with the low and ultra-low abrasivity dentifrices than with the higher abrasivity dentifrice at all timepoints (p<0.01). Brushing with ultra-low abrasivity dentifrice or water resulted in statistically significantly less dentine loss compared with brushing with the low abrasivity dentifrice at all timepoints (p<0.05). Dentine loss after brushing with ultra-low abrasivity dentifrice was not significantly different from brushing with water. CONCLUSIONS: The degree of dentine loss observed in this in situ model reflected the abrasivity of the study dentifrices. Brushing with low or ultra-low abrasivity STP-containing anti-sensitivity dentifrices resulted in significantly less dentine loss (equating to dentine wear) than with a higher abrasivity daily-use whitening dentifrice.

Aza-Michael Mono-addition Using Acidic Alumina under Solventless Conditions.

Aza-Michael reactions between primary aliphatic and aromatic amines and various Michael acceptors have been performed under environmentally-friendly solventless conditions using acidic alumina as a heterogeneous catalyst to selectively obtain the corresponding mono-adducts in high yields. Ethyl acrylate was the main acceptor used, although others such as acrylonitrile, methyl acrylate and acrylamide were also utilized successfully. Bi-functional amines also gave the mono-adducts in good to excellent yields. Such compounds can serve as intermediates for the synthesis of anti-cancer and antibiotic drugs.

Aluminum Oxide Sandblasting of Hexagonal Coping and Abutment: Influence on Retention and Marginal Leakage Using Temporary Cements.

PURPOSE: To compare the tensile strength and marginal leakage of prefabricated abutments/copings, with or without surface sandblasting with aluminum oxide, luted with a calcium hydroxide-based temporary cement (CH, Dycal; Dentsply, Petrópolis, RJ, Brazil) or a noneugenol zinc oxide cement (ZO, Temp Bond NE; Kerr, Orange, CA). MATERIALS AND METHODS: A total of 48 CeraOne abutment analogs and respective copings were divided into 6 groups (n = 8) according to the component that was sandblasted: the coping only, coping + abutment or no sandblasting and the temporary cement used: CH or ZO. After cementation, the samples underwent 500 thermal cycles (5°C ± 2°C and 55°C ± 2°C) and were subsequently immersed in an aqueous solution of 0.5% basic fuchsine dye for 24 hours. Next, the tensile test was performed, and microleakage was assessed qualitatively. Data were analyzed using Mann-Whitney, Kruskal-Wallis tests, followed by the Student-Newman-Keuls test (α = 0.05). RESULTS: CH cement showed a tensile strength (245.6 N) significantly higher than that of the ZO (18.1 N). Sandblasting both abutment and coping increased tensile strength by 1.7 times. Marginal leakage was not influenced by sandblasting; however, CH presented less microleakage. CONCLUSION: Aluminum oxide sandblasting of the coping and abutment favored the tensile strength of temporary cements and the CH showed a higher tensile strength and less microleakage than did the ZO cement.

Pit and Fissure Sealant Retention Following Air Abrasion Preparation with Bioactive Glass and Aluminum Oxide Particles.

PURPOSE: Alumina air abrasion is an alternative for acid-etch technique for tooth preparation before placement of a fissure sealant. The aim of this study was to compare the retention of sealants placed subsequent to air abrasion with alumina and bioactive glass (BAG) particles. METHODS: Sixty-two 6-12 year old children were included in this study. Using a halfmouth design, the fissures were prepared using air abrasion with alumina particles on randomly assigned permanent mandibular or/and maxillary first molars on one side of the mouth (Group 1) and air abrasion with BAG on the contralateral side of the mouth (Group 2). Sealants were applied on 180 teeth, and were scored as missing, partially retained, and completely retained after three, six, nine and 12 months. Data were analyzed using Friedman and Wilcoxon tests (α=0.05). RESULTS: Sealant retention rates in the alumina group were higher than those in the BAG group at all time periods (P<0.001). CONCLUSIONS: Sealant retention after air abrasion with alumina particles was higher than BAG over 12 months.

A Randomized Clinical Study Investigating the Stain-Removal Potential of Two Experimental Dentifrices.

OBJECTIVE: To evaluate the ability of two experimental desensitizing dentifrices, both containing a chemical cleaning agent, one with ultra-low abrasivity and one with low abrasivity, a standard fluoride dentifrice, and a daily-use whitening dentifrice to remove extrinsic tooth stain. METHODS: This was a single-center, examiner-blind, randomized, controlled, four-treatment, parallel-group study in healthy adults. Extrinsic stain was evaluated using the Macpherson modification of the Lobene Stain Index (MLSI). At baseline, eligible subjects with a total MLSI (area x intensity [A x I]) score of 15 for the facial surfaces of the 12 anterior teeth were stratified (based on total MLSI [A x I] score [< 45 = low; ≥ 45 = high] and smoking status) and randomized to treatment with one of four dentifrices: an experimental ultra-low abrasivity desensitizing dentifrice (relative dentin abrasion [RDA] -12); an experimental low abrasivity desensitizing dentifrice (RDA -40); a standard fluoride dentifrice with moderate abrasivity (RDA -80); and a whitening dentifrice with higher abrasivity (RDA -142). Both desensitizing dentifrices contained 5% potassium nitrate and 5% sodium tripolyphosphate (a chemical cleaning agent). Treatment effects were evaluated after four and eight weeks of twice-daily brushing. RESULTS: In total, 142 subjects were randomized and 133 subjects completed the study. All study dentifrices demonstrated statistically significant reductions in extrinsic tooth stain from baseline after four and eight weeks of twice-daily use (p < 0.01). There were no statistically significant between-treatment differences for the primary variable (mean MLSI [A x I] score across all assessed sites) at four or eight weeks, and no notable trends were observed. CONCLUSION: All study dentifrices reduced extrinsic tooth stain. The experimental ultra-low and low abrasivity desensitizing dentifrices containing 5% sodium tripolyphosphate performed similarly to both a moderate abrasivity standard fluoride dentifrice and a higher abrasivity whitening dentifrice.

Adaptação marginal em copings de dois sistemas cerâmicos livres de metal / Marginal fit in copings of two metal free ceramic systems

Este trabalhou avaliou a adaptação marginal de infraestruturas cerâmicas (copings em alumina) de dois sistemas cerâmicos livres de metal. Foram pesquisados os sistemas In-Ceram e Procera. Os valores de discrepância vertical presentes entre as margens de nove copings de cada sistema cerâmico e a margem de um modelo mestre metálico foram medidos com microscópio eletrônico de varredura em 5 pontos de cada infraestrutura. Esses valores foram medidos em micrômetros (pm). Os resultados foram analisados estatisticamente com o software SPSS (Statistical Package for the Social Sciences 11.0), através do teste t de Student, considerando-se significativos os valores de p<0(05. Os valores médios de discrepância marginal dos dois sistemas, medidos em microscópio eletrônico de varredura, mostraram diferença estatística entre si (p=0,001), sendo observadas desadaptações de 39±11pm (sistemas Procera) e 11 5±56pm (sistema In-Ceram). Conclui-se que os dois sistemas cerâmicos livres de metal avaliados apresentaram adaptação marginal dentro de limites aceitáveis clinicamente.

This work has evaluated the marginal fit of alumina copings of two metal free ceramic systems, namely Procera and In-Ceram systems. The marginal fit values of the margins in nine copings of each ceramic system and in a metal master model were assessed using electron- scanning microcopy in five points of the margin of each coping. Such values were measured in micrometers (pm). The results were analyzed statistically by the SPSS software (p<0.05). The marginal fit mean values for both systems have presented statistical difference (p=0.001), being of 39±11 pm and 115±56pm for the Procera and Inc-Ceram systems, respectively. Both systems have presented marginal fit according to the clinical acceptance.

Polyethylene wear and osteolysis after cementless total hip arthroplasty with alumina-on-highly cross-linked polyethylene bearings in patients younger than thirty years of age.

BACKGROUND: We asked whether cementless total hip arthroplasties that made use of alumina-on-highly cross-linked polyethylene bearings would improve hip score and functional activity and reduce the prevalence of polyethylene wear, osteolysis, and aseptic loosening. METHODS: Consecutive primary total hip arthroplasties were performed in fifty patients (a total of sixty hips among thirty-four men and sixteen women) who were younger than thirty years of age. The average age at the time of the index arthroplasty was 28.3 years (range, twenty-one to twenty-nine years). The average follow-up was 10.8 years (range, ten to twelve years). Osteolysis and polyethylene wear rates were evaluated with use of radiography and computed tomography. RESULTS: The mean Harris hip score, which was 38 points (range, 6 to 45 points) preoperatively, had improved to 95 points (range, 85 to 100 points) at a mean follow-up time of 10.8 years. The mean penetration (and standard error of the mean) of the polyethylene liner was 0.031 ± 0.004 mm per year. No hip had osteolysis or aseptic loosening. CONCLUSIONS: At a minimum of ten years and an average of 10.8 years postoperatively, the current generation of cementless acetabular and femoral components with alumina-on-highly cross-linked polyethylene bearings was functioning well and was not associated with the development of osteolysis in our group of patients younger than thirty years of age. While the long-term prevalence of polyethylene wear and osteolysis remains unknown, the midterm data are promising.

Morphological features of the maxillary incisors roots and relationship with neighbouring anatomical structures: possible implications in endodontic surgery.

The purpose of this study was to investigate the relationship between the root apex of the upper incisors and neighbouring anatomical structures as well as the morphology of the root-end foramen after apicoectomy. Fifty-seven patients requiring endodontic surgical treatment for a maxillary anterior root were enrolled. A preoperative diagnostic computed tomography (CT) scan was analysed to determine: the distance between the anterior wall of the nasopalatine duct and the central (CI-ND) incisor root 4mm from the apex; and the distance between the floor of the nasal cavity and the tip of either the central (CI-NF) or the lateral (LI-NF) incisor root. After apicoectomy, root-end foramen endoscopic pictures were taken in order to characterize their morphology. Fifty-nine central and 26 lateral incisors were evaluated. The average CI-ND was 4.71 ± 1.26 (SD) mm. The average CI-NF was 10.62 ± 2.25 mm. The average LI-NF was 13.05 ± 2.43 mm. The foramen shape after apicoectomy was ovoid to circular in about 90% of cases in both central and lateral incisors. A sound knowledge of the anatomical relationships at the surgical site is essential for the clinician to perform a safe endodontic surgical procedure.

[Large diameter femoral heads in primary alumina/alumina and XSPE/alumina total hip arthroplasty. A follow-up study of 50 hips after average 40 months and review of literature]. / Pierwotna calkowita bezcementowa endoprotezoplastyka stawów biodrowych--ceramika/ceramika i ceramika/polietylen XSPE z uzyciem glów o duzej srednicy. Ocena 50 bioder po okresie srednio 40 miesiecy i przeglad pismiennictwa.

INTRODUCTION: The aim of the study was a preliminary report of the use of large diameter alumina femoral heads in total hip arthroplasty. MATERIAL AND METHODS: In the years 2005-2008 50 THRs were implanted in 48 patients with the use of 36 mm alumina femoral heads. 5 women and 43 men in the age from 35 to 75 years (average 61 years) were operated on. Primary osteoarthritis was the cause of 41 arthroplasties, and AVN of femoral head of 9 surgeries. 18 alumina/alumina and 32 polyethylene/alumina THRs were implanted. The prospective study consisted of clinical examination with Harris Hip Score and X-ray evaluation. AP and lateral view X-rays were evaluated. The incidence of radiolucent lines around acetabular cups were noted with DeLee and Charnley zones and around stems with Gruen's zones. RESULTS: The follow up is from 24 to 58 months (average 40 months). There was an increase in Harris Hip Score from average 37 points (from 25 to 49 points) before operation to average 94 points (from 90 to 100 points) after the surgery. The incidence of postoperative dislocation have not been noted. Long-term postoperative X-ray examination have showed proper geometry of endoprostheses without radiolucent lines. Neither visible wear of bearing surfaces nor breakage of alumina components have been noted. CONCLUSIONS: 1) The use of 36 mm femoral heads in total hip arthroplasty decrease the risk of postoperative dislocation. 2) Innovative biomaterials: alumina ceramics and cross-linked polyethylene give chance for decrease the incidence of osteolysis.

Fechamento de diastema com coroas de alumina densamente sinterizadas / Diastema closure with densely sintered alumina crowns

O objetivo deste trabalho é apresentar um caso de fechamento de diastema com coroas de alumina densamente sinterizadas através da utilização do Sistema Procera®, mostrando as etapas de confecção e requisitos técnicos para o sucesso dos casos. O caso apresentado seguiu o seguinte protocolo clínico: enceramento diagnóstico, confecção de preparo comtérmino em chanfro e desgaste de 1,5mm nas paredes axiais e 2,0mm de desgaste incisal, confecção de restaurações provisórias, moldagem com técnica de duplo fio de afastamento, enceramento das subestruturas para duplo escaneamento, aplicação cerâmica e cimentação por meio de cimento resinoso. Os resultados obtidos foram julgados como bastante satisfatórios pela paciente e pelo profissional responsável sob os pontos de vista estéticos e biológicos.

Effect of guided tissue regeneration on the outcome of surgical endodontic treatment of through-and-through lesions: a retrospective study at 4-year follow-up.

PURPOSE: The main purpose of this retrospective cohort study was to evaluate the 4-year success rate of endodontic surgery in combination with a collagen resorbable membrane for the treatment of through-and-through periradicular lesions. MATERIALS AND METHODS: Patients with one or more teeth with a through-and-through periradicular lesion in need of endodontic surgery were treated. A clinical and radiographic evaluation was performed at 3, 6, 12, 24, 36, and 48 months. The outcome was categorized at 1 and 4-year follow-up as success, failure, and doubtful depending on clinical signs and symptoms and radiographic evaluation. Fisher's exact test was used to evaluate differences between successful and failed cases (P < 0.05). RESULTS: Forty-three teeth in 33 patients were radiographically and clinically evaluated after 4 years. Thirty-eight teeth were classified as success, 4 teeth as failure, and 1 tooth as doubtful. No statistically significant differences were found in results related to tooth type, tooth location, and presence of post. CONCLUSIONS: The association of endodontic surgery and guided tissue regeneration for the treatment of through-and-through periapical lesions leads to excellent outcomes up to 4 years. Standardized criteria are needed to determine the treatment outcome.

Effect of toothpaste containing d-limonene on natural extrinsic smoking stain: a 4-week clinical trial.

PURPOSE: To determine whether natural smoking stain could be removed/inhibited effectively by a toothpaste containing 5% d-limonene. For comparison and contrast, the effects of d-limonene on tea stain were also assessed. METHODS: The design was a randomized controlled double-blind trial with parallel groups. Toothpastes were: A: positive control with perlite whitening formulation; B: A+5% d-limonene; C: D + 5% d-limonene; D: negative control. The extrinsic stains were measured using Lobene Stain Index. Following baseline examination, all subjects were randomly assigned to one of the four toothpaste groups and instructed to brush with the assigned products twice daily. Subjects returned to the clinic after 4-week brushing for stain removal assessment, then all extrinsic stains, plaque and supragingival calculus were removed and use of assigned products was continued for another 4 weeks, and the stain scores were repeated for inhibition assessment. RESULTS: A total of 408 subjects, 201 with smoking stains and 207 with tea stains, participated in the trial. 5% d-limonene combined with Perlite whitening formulation significantly reduced stain scores both for smoking stain removal and inhibition (P < 0.05). Furthermore, 5% d-limonene alone (in negative formulation) exhibited an additional advantage for smoking stain inhibition (P < 0.05), but the advantage was not found for long-standing smoking stain removal (P > 0.05). The additional advantage of 5% d-limonene was shown neither for removal nor for inhibition in the tea stain study (P > 0.05). All test products were well tolerated over the study period.

Extremely high fracture rate of a modular acetabular component with a sandwich polyethylene ceramic insertion for THA: a preliminary report.

Improvements of ceramic components and design changes have reduced failure rates over the past 30 years in total hip arthroplasty. We present a series of n = 11 cases with ceramic failure out of n = 113 implantations, from which n = 66 were ceramic-on-ceramic (n = 50 with ceramic insert with sandwich in polyethylene and n = 16 with directly fixed ceramic inlay) and n = 47 ceramic on polyethylene bearings, between 1999 and 2001 after introduction of a new implantation system to the market. The overall fracture rate of ceramic for the whole series (n = 113) was 9.7%. For the combination ceramic head with UHMW-PE (n = 47) the fracture rate was 2.1%. For the combination ceramic with ceramic (n = 66) the fracture rate was 15.2%. For the combination ceramic with ceramic sandwich in PE (n = 50) the failure rate was 18%. Only three patients experienced a trauma. Demography of patients (age, gender, body weight and BMI) was not statistically different between patients with failed ceramics and the rest of the patients making patient-specific risk factors unlikely to be an explanation for the failures. Retrospective X-ray analysis of the cup positioning did not show significant difference between failed and non-failed implants in terms of mean cup inclination and version making also operation-specific factors unlikely to be the only reason of this high failure rate. Therefore, manufacturer-specific factors such as design features may have contributed to this high failure rate. Further analysis of the whole series with biomechanical testing of the retrieved material needs to be performed.