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Purpose: This study aimed to investigate the clinical outcome and estimated cumulative survival rate of feldspathic porcelain veneers in situ for up to 21 years while also accounting for clustered outcomes. Materials and Methods: Porcelain veneers(n = 499) placed in patients (n = 155) by a single prosthodontist between 1990 and 2010 were sequentially included, with 239 veneers (88 patients) placed before 2001 and 260 veneers (67 patients) placed thereafter. Nonvital teeth, molar teeth, or teeth with an unfavorable periodontal prognosis were excluded. Preparations had chamfer margins, incisal reduction, palatal overlap, and at least 80% enamel. Feldspathic veneers from refractory dies were etched (hydrofluoric acid), silanated, and bonded. Many patients received more than 1 veneer (mean: 5.8 ± 4.3). Clustered outcomes were accounted for by randomly selecting (random table) 1 veneer per patient for analysis. Clinical outcome (success, survival, unknown, dead, repair, failure) and Kaplan-Meier estimated cumulative survival were reported. Differences in survival were analyzed using the log-rank test. Results: For the random sample of veneers (n = 155), the estimated cumulative survival rates were 96% ± 2% (10 years) and 96% ± 2% (20 years). For the entire sample, the survival rates were 96% ± 1% (10 years) and 91% ± 2% (20 years). Survival did not statistically differ between these groups (P = .65). Seventeen veneers in 8 patients failed, 75 veneers in 30 patients were classified as unknown, and 407 veneers in 130 patients survived. Multiple veneers in the same mouth experienced the same outcome, clustering the results. Conclusions: Multiple dental prostheses in the same mouth are exposed to the same local and systemic factors, resulting in clustered outcomes. Clustered outcomes should be accounted for during analysis. When bonded to prepared enamel substrate, feldspathic porcelain veneers have excellent long-term survival with a low failure rate. The 21-year estimated cumulative survival for feldspathic porcelain veneers bonded to prepared enamel was 96% ± 2%. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review reports on the survival of feldspathic porcelain veneers.Materials and Methods: The Cochrane Library, MEDLINE (OVID), Embase, Web of Knowledge, selected journals, clinical trials registers, and conference proceedings were searched independently by two reviewers. Academic colleagues were also contacted to identify relevant research. Inclusion criteria were human cohort studies (prospective and retrospective) and controlled trials assessing outcomes of feldspathic porcelain veneers in more than 15 patients and with at least some of the veneers in situ for 5 years. Of 4,294 articles identified, 116 studies underwent full-text screenings and 69 were further reviewed for eligibility. Of these, 11 were included in the qualitative analysis and 6 (5 cohorts) were included in meta-analyses. Estimated cumulative survival and standard error for each study were assessed and used for meta-, sensitivity, and post hoc analyses. The I2 statistic and the Cochran Q test and its associated P value were used to evaluate statistical heterogeneity, with a random-effects meta-analysis used when the P value for heterogeneity was less than .1. Galbraith, forest, and funnel plots explored heterogeneity, publication patterns, and small study biases.Results: The estimated cumulative survival for feldspathic porcelain veneers was 95.7% (95% confidence interval [CI]: 92.9% to 98.4%) at 5 years and ranged from 64% to 95% at 10 years across three studies. A post hoc meta-analysis indicated that the 10-year best estimate may approach 95.6% (95% CI: 93.8% to 97.5%). High levels of statistical heterogeneity were found.Conclusions: When bonded to enamel substrate, feldspathic porcelain veneers have a very high 10-year survival rate that may approach 95%. Clinical heterogeneity is associated with differences in reported survival rates. Use of clinically relevant survival definitions and careful reporting of tooth characteristics, censorship, clustering, and precise results in future research would improve metaanalytic estimates and aid treatment decisions. [ABSTRACT FROM AUTHOR]

Introduction: Pyruvate kinase (PK) deficiency is a rare, under-recognised, hereditary condition that leads to chronic haemolytic anaemia and potentially serious secondary complications, such as iron overload, cholecystitis, pulmonary hypertension and extramedullary haematopoiesis. It is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the PKLR gene. Due to its rarity and clinical heterogeneity, information on the natural history and long-term clinical course of PK deficiency is limited, presenting major challenges to patient management, the development of new therapies and establishing disease-specific treatment recommendations. The Pyruvate Kinase Deficiency Global Longitudinal (Peak) Registry is an initiative to address the gaps in the knowledge of PK deficiency. This manuscript describes the objectives, study design and methodology for the Peak Registry., Methods and Analysis: The Peak Registry is an observational, longitudinal, global registry of adult and paediatric patients with a genetically confirmed diagnosis of PK deficiency. The Peak Steering Committee is composed of 11 clinicians and researchers with experience in the diagnosis and management of PK deficiency from 10 countries, a patient representative and representatives from the sponsor (Agios Pharmaceuticals). The registry objective is to foster an understanding of the longitudinal clinical implications of PK deficiency, including its natural history, treatments and outcomes, and variability in clinical care. The aim is to enrol up to 500 participants from approximately 60 study centres across 20 countries over 7 years, with between 2 and 9 years of follow-up. Data will include demographics, diagnosis history, genotyping, transfusion history, relevant clinical events, medications, emergency room visits and hospitalisations., Ethics and Dissemination: Registry protocol and informed consent forms are approved by institutional review boards/independent ethics committees at each study site. The study is being conducted in accordance with the Declaration of Helsinki. Registry data will be published in peer-reviewed journal articles and conference publications., Trial Registration Number: NCT03481738., Competing Interests: Competing interests: RFG receives research funding from Agios Pharmaceuticals, Novartis Pharmaceuticals and Sobi, and is a consultant for Agios Pharmaceuticals and Sanofi. EJvB is an advisory committee member for Agios Pharmaceuticals and receives research funding from Agios Pharmaceuticals, Novartis Pharmaceuticals, Pfizer and RR Mechatronics International B.V. BG is a consultant for Agios Pharmaceuticals. AG is a consultant for Agios Pharmaceuticals, bluebird bio, Bristol Myers Squibb, Novartis Pharmaceuticals, Novo Nordisk A/S and Pharmacosmos UK and receives research support from Agios Pharmaceuticals, Saniona, and Sanofi. KHMK is a consultant for Agios Pharmaceuticals, Alexion Pharmaceuticals, Apellis Pharmaceuticals, bluebird bio, Celgene Corporation, Novartis Pharmaceuticals and Pfizer, receives honoraria from Alexion Pharmaceuticals and Novartis Pharmaceuticals, is a member of the data safety monitoring board of Bioverativ and receives research funding from Agios Pharmaceuticals and Pfizer. CL receives payment as a patient representative on the Agios Pharmaceuticals PK Deficiency Patient Advocacy Advisory Council. DML is a consultant and advisory committee member for Agios Pharmaceuticals and Novartis Pharmaceuticals and is a member of the data safety monitoring board of Cerus Corporation. HK, J-LVC, DP and VV have no conflicts of interest to disclose. JL, ANB and YY are employees of Agios Pharmaceuticals and are shareholders in the company. CB is a former employee of Agios Pharmaceuticals. PB is a scientific advisor for Agios Pharmaceuticals., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with non-transfusion-dependent thalassaemia (NTDT), although they do not require regular blood transfusions for survival, can still accrue a heavy burden of comorbidities. No approved disease-modifying therapies exist for these patients. We aimed to investigate the safety and efficacy of mitapivat (Agios Pharmaceuticals, Cambridge, MA, USA), a pyruvate kinase activator, in adults with non-transfusion-dependent (NTD) α-thalassaemia or NTD β-thalassaemia., Methods: In this open-label, multicentre, phase 2 study, patients were recruited from four academic clinical study sites in Oakland, CA, and Boston, MA, USA; Toronto, ON, Canada; and London, UK. Patients were eligible if they were aged 18 years or older, with NTDT (including β-thalassaemia with or without α-globin gene mutations, haemoglobin E β-thalassaemia, or α-thalassaemia), and a baseline haemoglobin concentration of 10·0 g/dL or lower. During a 24-week core period, mitapivat was administered orally at 50 mg twice daily for the first 6 weeks followed by an escalation to 100 mg twice daily for 18 weeks thereafter. The primary endpoint was haemoglobin response (a ≥1·0 g/dL increase in haemoglobin concentration from baseline at one or more assessments between weeks 4 and 12). Efficacy and safety were assessed in the full analysis set (ie, all patients who received at least one dose of study drug). This study is registered with ClinicalTrials.gov, NCT03692052, and is closed to accrual., Findings: Between Dec 28, 2018, and Feb 6, 2020, 27 patients were screened, of whom 20 were enrolled (15 [75%] with β-thalassaemia and five [25%] with α-thalassaemia) and received mitapivat. The median age of patients was 44 years (IQR 35-56), 15 (75%) of 20 patients were female, five (25%) were male, and ten (50%) identified as Asian. 16 (80% [90% CI 60-93]) of 20 patients had a haemoglobin response (p<0·0001), five (100%) of five with α-thalassaemia and 11 (73%) of 15 with β-thalassaemia. 17 (85%) patients had a treatment-emergent adverse event, and 13 had a treatment-emergent event that was considered to be treatment related. One serious treatment-emergent adverse event occurred (grade 3 renal impairment), which was considered unrelated to study drug, resulting in discontinuation of treatment. The most commonly reported treatment-emergent adverse events were initial insomnia (ten [50%] patients), dizziness (six [30%]), and headache (five [25%]). No patients died during the 24-week core period., Interpretation: These efficacy and safety results support the continued investigation of mitapivat for the treatment of both α-thalassaemia and β-thalassaemia., Funding: Agios Pharmaceuticals., Competing Interests: Declaration of interests KHMK reports consultancy fees from Agios Pharmaceuticals, Alexion, Apellis, bluebird bio, Celgene, Forma, Pfizer, and Novartis; honoraria from Alexion and Novartis; membership on an advisory committee for Agios Pharmaceuticals and Bioverativ/Sanofi/Sangamo; and research funding from Pfizer. DML reports consultancy fees from Agios Pharmaceuticals and membership on the Board of Directors or advisory committee for Agios Pharmaceuticals and Cerus. AL reports research funding from bluebird bio, Celgene, Insight Magnetics, La Jolla Pharmaceutical Company, Novartis, Protagonist Therapeutics, Terumo Corporations, and Forma; consultancy fees from Agios Pharmaceuticals and Chiesi USA; and membership on the Board of Directors or advisory committee for Celgene and Protagonist Therapeutics. HA-S reports consultancy fees from Agios Pharmaceuticals, argenx, Dova/Sobi, Moderna, Novartis, Rigel, and Forma and research funding from Agios Pharmaceuticals, Amgen, and Dova. JB, PAK, BT, ML, and KU are employees and shareholders of Agios Pharmaceuticals. EPV reports consultancy fees and research funding from Agios Pharmaceuticals, bluebird bio, Global Blood Therapeutics, Novartis, and Pfizer., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: All SCD patients need extended RBC antigen typing (by serology or genotyping) for provision of extended RH, K matched blood and to guide RBC selection in those with complex transfusion requirements. Genotyping can also identify RH variants which can cause sensitisation even when extended RH phenotypically matched blood is provided and alloantibodies associated with RH variants can cause HTRs., Objectives: To review the use of RBC genotyping in SCD patients at two London trusts (ICHNT, LNWH) with a focus on RH variants., Methods: Retrospective review with data collected from clinical notes, local and national pathology reporting systems., Results: A 311/482 (64%) ICHNT patients and 181/346 (52%) LNWH patients had extended genotyping. Of genotyped patients, 68 (22%) ICHNT and 31 (17%) LNWH patients had RH variants. Eight ICHNT patients had RH variants and corresponding antibodies associated with RH variants; 4/8 received multiple transfusions with antigen positive RBCs but had no evidence of haemolysis. One LNWH patient had a RH variant with corresponding alloantibody but could not be investigated further for possible HTR., Conclusions: Most patients (59%) had genotyping and a significant number had RH variants (99, 20%). A small proportion (9, 9%) had antibodies associated with RH variants, but with no evidence of clinically significant HTRs despite transfusions in four of them with antigen positive RBCs. All SCD patients should have RBC genotyping including RH variants (preferentially over extended phenotyping) to guide better selection of RBC units. However, where antigen negative blood cannot be provided, the risk of alloimmunisation is not inevitable and subsequent HTRs from antibodies associated with RH variants might not always occur., (© 2021 British Blood Transfusion Society.)

Background: Pyruvate kinase deficiency is a rare, hereditary, chronic condition that is associated with hemolytic anemia. In a phase 2 study, mitapivat, an oral, first-in-class activator of erythrocyte pyruvate kinase, increased the hemoglobin level in patients with pyruvate kinase deficiency., Methods: In this global, phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency who were not receiving regular red-cell transfusions. The patients were assigned to receive either mitapivat (5 mg twice daily, with potential escalation to 20 or 50 mg twice daily) or placebo for 24 weeks. The primary end point was a hemoglobin response (an increase from baseline of ≥1.5 g per deciliter in the hemoglobin level) that was sustained at two or more scheduled assessments at weeks 16, 20, and 24. Secondary efficacy end points were the average change from baseline in the hemoglobin level, markers of hemolysis and hematopoiesis, and the change from baseline at week 24 in two pyruvate kinase deficiency-specific patient-reported outcome measures., Results: Sixteen of the 40 patients (40%) in the mitapivat group had a hemoglobin response, as compared with none of the 40 patients in the placebo group (adjusted difference, 39.3 percentage points; 95% confidence interval, 24.1 to 54.6; two-sided P<0.001). Patients who received mitapivat had a greater response than those who received placebo with respect to each secondary end point, including the average change from baseline in the hemoglobin level. The most common adverse events were nausea (in 7 patients [18%] in the mitapivat group and 9 patients [23%] in the placebo group) and headache (in 6 patients [15%] and 13 patients [33%], respectively). Adverse events of grade 3 or higher occurred in 10 patients (25%) who received mitapivat and 5 patients (13%) who received placebo., Conclusions: In patients with pyruvate kinase deficiency, mitapivat significantly increased the hemoglobin level, decreased hemolysis, and improved patient-reported outcomes. No new safety signals were identified in the patients who received mitapivat. (Funded by Agios Pharmaceuticals; ACTIVATE ClinicalTrials.gov number, NCT03548220.)., (Copyright © 2022 Massachusetts Medical Society.)

This study compared titanium (Ti), palladium (Pd), platinum (Pt), and gold (Au) ion release following induced accelerated tribocorrosion from three Au alloy abutment groups coupled with Ti implants over time; investigated contacting surface structural changes; and explored the effect of Au plating. Three abutment groups, G (n = 8, GoldAdapt, Nobel Biocare), N (n = 8, cast UCLA, Biomet3i), and P (n = 8, cast UCLA, Biomet3i, Au plated), coupled with implants (Nobel Biocare), immersed in 1% lactic acid, were cyclically loaded. Ions released (ppb) at T1, T2, and T3, simulating 3, 5, and 12 months of function, respectively, were quantified by inductively coupled plasma mass spectrometry (ICP-MS) and compared. Surface degradation and fretted particle composition after T3 were evaluated with scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM/EDX). ICP-MS data were nonparametric, expressed as medians and interquartile ranges. SEM/EDX showed pitting, crevice corrosion, and fretted particles on the components. Released ion concentrations in all groups across time significantly decreased for Pd (P < .001, median range: 1.70-0.09), Pt (P = .021, 0.55-0.00), and Au (P < .001, 1.01-0.00) and increased for Ti (P = .018, 2.49-5.84). Total Ti release was greater than other ions combined for G (P = .012, 9.86-2.30) and N (P < .001, 13.59-5.70) but not for P (P = .141, 8.21-3.53). Total Ti release did not differ between groups (P = .36) but was less variable across group P. On average, total ion release was 13.77 ppb (interquartile range 8.91-26.03 ppb) across the 12-month simulation. Tribocorrosion of Ti implants coupled with Au abutments in a simulated environment was evidenced by fretted particles, pitting, and crevice corrosion of the coupling surfaces and release of ions. More Ti was released compared with Pd, Pt, and Au and continued to increase with time. Abutment composition influenced ion release. Au-plated abutments appeared to subdue variation in and minimize high-concentration spikes of titanium.

Purpose: The impact of mediotrusive (MT) occlusal contacts has been a topic of controversy and confusion in both clinical practice and in the dental literature. The purpose of this Best Evidence Consensus Statement was to explore whether MT interferences are harmful in the natural or therapeutic occlusion directed by 4 focus questions relating to prevalence, jaw function, jaw dysfunction and biomechanical models., Materials and Methods: An electronic search in October 2020 sought evidence in MEDLINE (Ovid) using (mediotrus* OR nonworking side OR nonworking contact OR balancing side OR interfer* side OR premature contact) in the multipurpose (.mp) search field; and in Google Scholar using permutations of the above. Supplementary articles were sourced from the associated reference lists. There was no language restriction. The search yield was reviewed in duplicate., Results: The electronic search identified 420 articles. Following screening, 164 were selected for eligibility assessments. Of these, 47 were included in the current paper., Conclusions: Non-standardized nomenclature and methodology is used to identify MT interferences in patient populations, with resultant prevalence varying from 0% to 77%, (median = 16%). MT interferences may alter the biomechanics of mandibular function. Together with the presence of repeated high loads resultant strain can manifest as pathophysiology of the temporomandibular joint and associated muscle structures. MT interferences should be avoided in any therapeutic occlusal scheme to minimize pulpal, periodontal, structural and mechanical complications or exacerbation of temporomandibular disorders (TMDs). Naturally occurring molar MT interferences should be eliminated only if signs and symptoms of TMDs are present. Literature supports there being a biomechanical basis which can explain how MT interferences may affect temporomandibular joint morphology and jaw function., (© 2021 by the American College of Prosthodontists.)

Importance: Understanding the outcomes of interventions over time is essential for clinical decision making in surgical specialties., Background: Analysis of survival time (or time to event) is complicated when loss to follow up occurs. This article explores transparent data analysis methods where missing ("censored") data are present., Design: Manual search of the top 20 Ophthalmology journals from a recent year of the established literature (2014)., Samples: A total of 4565 articles were identified, of which 218 reported outcomes of treatment over time in humans., Methods: Pertinent details to assist the use of Kaplan-Meier and life table actuarial statistics are explained, and criteria that define whether each has high, acceptable or poor quality are explored. The quality of reporting from the literature sample is analysed., Main Outcome Measures: Reporting quality of survival curves and life tables from each sampled article is assessed according to the established criteria., Results: In total, 31.2% of samples (n = 68) presented survival curves, 53.2% (n = 116) presented life tables, 22% (n = 48) presented both, whilst 46.8% (n = 102) presented neither; 2% of survival curves and 13% of life tables were high quality, with quality of life tables significantly better than survival curves (P = .0042). 90.36% (n = 197) of articles reported time to event data which was classified as poor: due to poor analysis of survival curves (n = 50, 43.10%) poor analysis of life tables (n = 45, 66.18%); and complete omission of survival graphics (n = 102, 46.97%)., Conclusions and Relevance: Ophthalmology research that follows patient outcomes over time can be analysed with "time-to-event" statistics, and reported with transparency. This analysis showed that important contextural information was omitted from 90% of ophthalmic studies, and this could impact patient decision making., (© 2020 Royal Australian and New Zealand College of Ophthalmologists.)

With the developing COVID-19 pandemic, patients with inherited anaemias require specific advice regarding isolation and changes to usual treatment schedules. The National Haemoglobinopathy Panel (NHP) has issued guidance on the care of patients with sickle cell disease, thalassaemia, Diamond Blackfan anaemia (DBA), congenital dyserythropoietic anaemia (CDA), sideroblastic anaemia, pyruvate kinase deficiency and other red cell enzyme and membrane disorders. Cascading of accurate information for clinicians and patients is paramount to preventing adverse outcomes, such as patients who are at increased risk of fulminant bacterial infection due to their condition or its treatment erroneously self-isolating if their fever is mistakenly attributed to a viral cause, delaying potentially life-saving antibiotic therapy. Outpatient visits should be minimised for most patients, however some, such as first transcranial dopplers for children with sickle cell anaemia should not be delayed as known risk of stroke will outweigh the unknown risk from COVID-19 infection. Blood transfusion programmes should be continued, but specific changes to usual clinical pathways can be instituted to reduce risk of patient exposure to COVID-19, as well as contingency planning for possible reductions in blood available for transfusions. Bone marrow transplants for these disorders should be postponed until further notice. With the current lack of evidence on the risk and complications of COVID-19 infection in these patients, national data collection is ongoing to record outcomes and eventually to identify predictors of disease severity, particularly important if further waves of infection travel through the population., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Pyruvate kinase deficiency is caused by mutations in PKLR and leads to congenital hemolytic anemia. Mitapivat is an oral, small-molecule allosteric activator of pyruvate kinase in red cells., Methods: In this uncontrolled, phase 2 study, we evaluated the safety and efficacy of mitapivat in 52 adults with pyruvate kinase deficiency who were not receiving red-cell transfusions. The patients were randomly assigned to receive either 50 mg or 300 mg of mitapivat twice daily for a 24-week core period; eligible patients could continue treatment in an ongoing extension phase., Results: Common adverse events, including headache and insomnia, occurred at the time of drug initiation and were transient; 92% of the episodes of headache and 47% of the episodes of insomnia resolved within 7 days. The most common serious adverse events, hemolytic anemia and pharyngitis, each occurred in 2 patients (4%). A total of 26 patients (50%) had an increase of more than 1.0 g per deciliter in the hemoglobin level. Among these patients, the mean maximum increase was 3.4 g per deciliter (range, 1.1 to 5.8), and the median time until the first increase of more than 1.0 g per deciliter was 10 days (range, 7 to 187); 20 patients (77%) had an increase of more than 1.0 g per deciliter in the hemoglobin level at more than 50% of visits during the core study period, with improvement in markers of hemolysis. The response was sustained in all 19 patients remaining in the extension phase, with a median follow-up of 29 months (range, 22 to 35). Hemoglobin responses were observed only in patients who had at least one missense PKLR mutation and were associated with the red-cell pyruvate kinase protein level at baseline., Conclusions: The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with pyruvate kinase deficiency, with a sustained response during a median follow-up of 29 months during the extension phase. Adverse effects were mainly low-grade and transient. (Funded by Agios Pharmaceuticals; ClinicalTrials.gov number, NCT02476916.)., (Copyright © 2019 Massachusetts Medical Society.)

New treatments directly targeting polymerization of sickle hemoglobin (HbS), the proximate event in the pathophysiology of sickle cell disease (SCD), are needed to address the severe morbidity and early mortality associated with the disease. Voxelotor (GBT440) is a first-in-class oral therapy specifically developed to treat SCD by modulating the affinity of hemoglobin (Hb) for oxygen, thus inhibiting HbS polymerization and downstream adverse effects of hemolytic anemia and vaso-occlusion. GBT440-001 was a phase 1/2 randomized, double-blind, placebo-controlled, single and multiple ascending dose study of voxelotor in adult healthy volunteers and patients with SCD, followed by a single-arm, open-label extension study. This report describes results of voxelotor (500-1000 mg per day) in patients with sickle cell anemia. The study evaluated the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of voxelotor and established proof of concept by improving clinical measures of anemia, hemolysis, and sickling. Thirty-eight patients with SCD received 28 days of voxelotor 500, 700, or 1000 mg per day or placebo; 16 patients received 90 days of voxelotor 700 or 900 mg per day or placebo. Four patients from the 90-day cohort were subsequently enrolled in an extension study and treated with voxelotor 900 mg per day for 6 months. All patients who received multiple doses of voxelotor for ≥28 days experienced hematologic improvements including increased Hb and reduction in hemolysis and percentage of sickled red cells, supporting the potential of voxelotor to serve as a disease-modifying therapy for SCD. Voxelotor was well tolerated with no treatment-related serious adverse events and no evidence of tissue hypoxia. These trials were registered at www.clinicaltrials.gov as #NCT02285088 and #NCT03041909., (© 2019 by The American Society of Hematology.)

Objectives: To report the clinical outcomes for patients with implants treated for peri-implantitis who subsequently received supportive care (supportive peri-implant/periodontal therapy) for at least 3 years., Material and Methods: A systematic search of multiple electronic databases, grey literature and hand searching, without language restriction, to identify studies including ≥10 patients was constructed. Data and risk of bias were explored qualitatively. Estimated cumulative survival at the implant- and patient-level was pooled with random-effects meta-analysis and explored for publication bias (funnel plot) at different time intervals., Results: The search identified 5,761 studies. Of 83 records selected during screening, 65 were excluded through independent review (kappa = 0.94), with 18 retained for qualitative and 13 of those for quantitative assessments. On average, studies included 26 patients (median, IQR 21-32), with 36 implants (median, IQR 26-45). Study designs (case definitions of peri-implantitis, peri-implantitis treatment, supportive care) and population characteristics (patient, implant and prosthesis characteristics) varied markedly. Data extraction was affected by reduced reporting quality, but over 75% of studies had low risk of bias. Implant survival was 81.73%-100% at 3 years (seven studies), 74.09%-100% at 4 years (three studies), 76.03%-100% at 5 years (four studies) and 69.63%-98.72% at 7 years (two studies). Success and recurrence definitions were reported in five and two studies respectively, were heterogeneous, and those outcomes were unable to be explored quantitatively., Conclusion: Therapy of peri-implantitis followed by regular supportive care resulted in high patient- and implant-level survival in the medium to long term. Favourable results were reported, with clinical improvements and stable peri-implant bone levels in the majority of patients., (© 2018 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.)

Objectives: The aim of Working Group 4 was to address topics related to biologic risks and complications associated with implant dentistry. Focused questions on (a) diagnosis of peri-implantitis, (b) complications associated with implants in augmented sites, (c) outcomes following treatment of peri-implantitis, and (d) implant therapy in geriatric patients and/or patients with systemic diseases were addressed., Materials and Methods: Four systematic reviews formed the basis for discussion in Group 4. Participants developed statements and recommendations determined by group consensus based on the findings of the systematic reviews. These were then presented and accepted following further discussion and modifications as required by the plenary., Results: Bleeding on probing (BOP) alone is insufficient for the diagnosis of peri-implantitis. The positive predictive value of BOP alone for the diagnosis of peri-implantitis varies and is dependent on the prevalence of peri-implantitis within the population. For patients with implants in augmented sites, the prevalence of peri-implantitis and implant loss is low over the medium to long term. Peri-implantitis treatment protocols which include individualized supportive care result in high survival of implants after 5 years with about three-quarters of implants still present. Advanced age alone is not a contraindication for implant therapy. Implant placement in patients with cancer receiving high-dose antiresorptive therapy is contraindicated due to the associated high risk for complications., Conclusions: Diagnosis of peri-implantitis requires the presence of BOP as well as progressive bone loss. Prevalence of peri-implantitis for implants in augmented sites is low. Peri-implantitis treatment should be followed by individualized supportive care. Implant therapy for geriatric patients is not contraindicated; however, comorbidities and autonomy should be considered., (© 2018 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.)

Objectives: Evaluate intra- and inter-examiner agreement of radiographic marginal bone level (MBL) assessment around Brånemark single implants; and whether agreement related to radiograph brightness, discrimination level (accuracy), participant demographics or implant characteristics., Materials and Methods: Seventy-four participants assessed MBLs of 100 digital radiographs twice with normal brightness, and twice with increased brightness. Intra-examiner agreement with and without increased brightness to the same thread, and within one thread; and inter-examiner agreement as compared with the group (defined by the mode) for the first assessments with and without increased brightness, to the same thread, and within one thread were calculated with Cohen's Kappa. Relationships between agreement, thread discrimination level (accuracy), brightness, participant and implant characteristics were explored., Results: When assessing 100 "Normal" radiographs twice, a participant on average assessed 24% differently to themselves (poor intra-examiner agreement, median Kappa 0.58, range 0.21-0.82); and 28% differently to other participants (poor inter-examiner agreement, median Kappa 0.53, range 0.05-0.80). Agreement within examiners improved when radiographs were "Bright" (median Kappa 0.58 vs. 0.62, p < 0.001, accuracy to same thread; median Kappa 0.94 vs. 0.96, p < 0.001, accuracy within one thread). Agreement between examiners was neither better nor worse when radiographs were "Bright" (median Kappa 0.53 vs. 0.55, p = 0.64, accuracy to same thread; median Kappa 0.93 vs. 0.93, p = 0.23, accuracy within one thread). Intra- and inter-examiner agreements were lower when accuracy to the same thread was required (p < 0.001, p < 0.001). Neither intra- nor inter-examiner agreement related to age, time since graduation, specialty, viewing device, implant experience, external hex familiarity, periimplantitis treatment experience, implant location or width (p-values 0.05-0.999). Intra-examiner agreement increased across dental assistants (n = 11), general dentists (n = 16) and specialists (n = 47) ("Bright" assessments, p = 0.045, median Kappa's 0.55, 0.60, 0.65 respectively); and for females (n = 8, males = 58) ("Normal" assessments, p = 0.019, median 0.68 vs. 0.55), but female numbers were low., Conclusions: Agreement within and between examiners when assessing MBLs was poor. Disagreement occurred around 25% of the time, potentially affecting consistent disease assessments. No participant or implant characteristic clearly affected agreement. Brighter radiographs improved intra-examiner agreement. Overall, perceived MBL changes below 1 mm are likely due to human, not biological variation., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Implant placement requires precise planning and execution to avoid collision with critical anatomical structures. Technology advances may improve placement outcomes. The purpose of this study was to trial and measure in an in vitro environment the accuracy of placing a single dental implant in the planned position using a specific guided surgery technique compared with a freehand surgery technique. The dental model of a patient missing tooth 16 was printed 30 times (EnvisionTEC 3Dent). Each print was scanned (TRIOS color scanner) to create a 3D surface model, and radiographed (Gendex CB-500) to create cone beam computed tomography (CBCT) data. The surface data and CBCT data were merged (Implant Studio software), and a Straumann RC bone level Ø 4.1 × 8 mm implant placement was planned. A surgical guide was printed (Stratasys OrthoDesk) for each case (n = 30). Simulated cases were assigned to Group A (guided) or Group B (freehand, where the fabricated guide was discarded). Implants were placed, and the models rescanned (TRIOS). The new data was superimposed on the original data, and the surgical implant location compared with the planned position for each model (Convince software) by a researcher blinded to group allocation. Differences in angulation (degrees); shoulder, apex, and depth displacements (mm); and direction of displacement were assessed with Mann-Whitney U and Fisher exact tests. Data was expressed as medians bounded by interquartile ranges (IQRs). Implant angulation and apical displacement were significantly closer to the planned position in the guided group compared with the freehand group (3.91 degrees: IQR 2.45 to 5.38 degrees vs 8.82 degrees: IQR 4.84 to 9.84 degrees, P = 0.005; and 0.87 mm: IQR 0.53 to 1.11 mm vs 1.48 mm: IQR 1.14 to 1.72 mm, P < 0.001, respectively). Implant shoulder displacement, depth displacements, and direction of displacement did not differ between the groups. Within the in vitro environment, merged 3D surface scan data and 3D CBCT scan data can be used to plan and guide implant placement with greater accuracy than with the freehand technique.

Purpose: To assess patient satisfaction and patient-related outcomes across the domains of appearance, cleansibility, and costs; the perceived value and worth when single implant crowns (SICs) had been in situ up to 14 years; whether satisfaction differed between patients; and whether certain characteristics might affect the questionnaire response rate., Materials and Methods: Patients treated at a private prosthodontic practice between 2001 and 2014 (n = 207) who received a SIC (n = 256) were prospectively included. A previously validated patient satisfaction questionnaire (PSQ) exploring patient-centered outcomes was mailed to participants. Demographic (sex, age) and treatment data (number of SICs, time in situ, failure experience, complication experience) were collected. Visual analog scale (VAS) responses were converted to percentages. Differences between respondents and nonrespondents, differences in satisfaction between prosthesis placement and survey date, and differences with respect to demographic and treatment data were assessed. Averages were medians bounded by interquartile ranges. Statistical significance was set at P = .05., Results: Respondents (n = 128, 61.8%) and nonrespondents (n = 79, 38.2%) had similar demographic and treatment characteristics. Prostheses had been in situ for up to 14 years (median, 5 years; interquartile range [IQR], 24 to 96 months). Participants reported that treatment met their expectations (median, 93%; IQR, 85% to 100%); they reported high satisfaction with tooth color, tooth contour, peri-implant mucosa, appearance overall, and ease of cleaning (medians ranging from 90.5% to 95%, IQR ranging from 80% to 100%) and medium satisfaction with costs when prostheses were placed (median, 50%; IQR, 29% to 80%). Satisfaction with tooth contour, peri-implant tissues, overall appearance, and costs significantly improved over time (96%, 92.5%, 91.7%, and 75%, respectively; P < .001 to P = .049). Levels of satisfaction did not differ by sex, number of implants, survival, complications, number of complications, and time in situ. Younger patients were less satisfied with the overall appearance and costs than older patients (P = .004, P = .007, respectively). All patients would choose to undergo treatment again and would recommend it to a friend., Conclusion: Patients with SICs that were in situ up to 14 years who responded to the validated PSQ were highly satisfied with the appearance and cleansibility, noted improvements in peri-implant tissue contours, and found the treatment to be valuable and worthwhile. They reported that upfront costs were high, but this concern decreased when the SICs had been in the mouth for a period of time.

Clinicians and readers rely on accurate identification of articles to answer clinical questions and explore hypotheses. Commonly, these questions relate to the outcome and survival of dental treatments. Errors in indexing and inconsistencies in descriptions of these studies have meant that such articles are difficult to locate. To help address this problem, sensitive, precise and optimized electronic search strategies have been developed, and this article aims to explain how these new strategies can be used. These electronic search strategies have been shown to improve the identification of dental survival analyses.