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Infertility affects more than 14% of couples, 30% being caused by male factor infertility. This meta-analysis includes 28 studies, selected according to PRISMA guidelines. Data were extracted from these studies to collate cycles separating paternal age at 30, 35, 40, 45 and 50 years (±1 year). Primary outcomes of interest were clinical pregnancy, live birth and miscarriage rates. Secondary outcomes were the number of fertilized eggs, cleavage-stage embryos and blastocysts, and embryo quality per cycle. Fixed-effects and random-effects models giving pooled odds ratios (OR) were used to assess the effect of paternal age. This meta-analysis included a total 32,484 cycles from 16 autologous oocyte studies and 12 donor oocyte studies. In autologous cycles, a statistically significant effect of paternal age <40 years was noted in clinical pregnancy (OR 1.65, 95% confidence interval [CI] 1.27-2.15), live birth (OR 2.10, 95% CI 1.25-3.51) and miscarriage (OR 0.74, 95% CI 0.57-0.94) rates. Paternal age <50 years significantly reduced miscarriage rate (OR 0.68, 95% CI 0.54-0.86), and increased blastocyst rate (OR 1.61, 95% CI 1.08-2.38) and number of cleavage-stage embryos (OR 1.67, 95% CI 1.02-2.75) in donor oocyte cycles, where maternal age is controlled. This is an important public and societal health message highlighting the need to also consider paternal age alongside maternal age when planning a family., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: The aim of this study was to characterize left atrial (LA) pathology in explanted hearts with transthyretin amyloid cardiomyopathy (ATTR-CM); LA mechanics using echocardiographic speckle-tracking in a large cohort of patients with ATTR-CM; and to study the association with mortality., Background: The clinical significance of LA involvement in ATTR-CM is of great clinical interest., Methods: Congo red staining and immunohistochemistry was performed to assess the presence, type, and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle tracking was used to assess LA reservoir, conduit, contractile function, and stiffness in 906 patients with ATTR-CM (551 wild-type (wt)-ATTR-CM; 93 T60A-ATTR-CM; 241 V122I-ATTR-CM; 21 other)., Results: There was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, vessels remodeling, capillary disruption, and subendocardial fibrosis. Echo speckle tracking in 906 patients with ATTR-CM demonstrated increased atrial stiffness (median [25th-75th quartile] 1.83 [1.15-2.92]) that remained independently associated with prognosis after adjusting for known predictors (lnLA stiff: HR: 1.23; 95% CI: 1.03-1.49; P = 0.029). There was substantial impairment of the 3 phasic functional atrial components (reservoir 8.86% [5.94%-12.97%]; conduit 6.5% [4.53%-9.28%]; contraction function 4.0% [2.29%-6.56%]). Atrial contraction was absent in 22.1% of patients whose electrocardiograms showed sinus rhythm (SR) "atrial electromechanical dissociation" (AEMD). AEMD was associated with poorer prognosis compared with patients with SR and effective mechanical contraction (P = 0.0018). AEMD conferred a similar prognosis to patients in atrial fibrillation., Conclusions: The phenotype of ATTR-CM includes significant infiltration of the atrial walls, with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis., Competing Interests: Funding Support and Author Disclosures Dr Fontana is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/21/33447). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine the effect of patisiran on the cardiac amyloid load as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM)., Background: Administration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain., Methods: Patisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a "TTR-stabilizing" drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results., Results: Patisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed >80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: -6.2% [95% confidence interval [CI]: -9.5% to -3.0%]; p = 0.001) accompanied by a fall in N-terminal pro-B-type natriuretic peptide concentrations (adjusted mean difference between groups: -1,342 ng/l [95% CI: -2,364 to -322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%)., Conclusions: Reductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amyloid regression in a proportion of patients receiving patisiran., Competing Interests: Author Disclosures Dr. Fontana has done consultancy for Alnylam, Akcea, Eidos, Intellia, Pfizer, and Alexion; and is funded from the British heart foundation fellowship FS/18/21/33447. Drs. Fontana and Gillmore have a research grant from Pfizer. Dr. Hawkins is an expert Advisory board member for Alnylam. Dr. Gillmore is an expert Advisory board member for Alnylam, Akcea, Eidos, and Pfizer; and has a research grant from Alnylam., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness who had amyloid was suspected. We also aimed to further characterize the structural and functional changes associated with amyloid infiltration., Background: Cardiac amyloidosis (CA) is a serious but increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool., Methods: We studied 1,187 consecutive patients evaluated at 3 referral centers for CA and analyzed morphological, functional, and strain-derived echocardiogram parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified by using extracellular volume measurements at cardiac magnetic resonance., Results: A total of 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin CA. Concentric remodeling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E wave/e' wave ratio, longitudinal strain, and tricuspid annular plane systolic excursion had the greatest diagnostic performance in AL amyloidosis (area under the curve: 0.90; 95% confidence interval: 0.87 to 0.92), whereas the addition of septal apical-to-base ratio yielded the best diagnostic accuracy in the increased heart wall thickness group (area under the curve: 0.80; 95% confidence interval: 0.85 to 0.90)., Conclusions: Specific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances and enable the definition of 2 scores that are sensitive and specific tools with which diagnose or exclude CA., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: This study aimed to assess the diagnostic use of native T1 to detect cardiac amyloidosis (CA) in a large prospective cohort of patients referred for suspected systemic amyloidosis., Background: CA is a progressive and fatal underdiagnosed cause of heart failure. Cardiovascular magnetic resonance (CMR) has emerged as an extremely useful test for the non-invasive diagnosis of CA, but administration of contrast is still required to make a diagnosis., Methods: In this study, 868 patients with suspected CA referred between 2015 and 2017 underwent CMR with late gadolinium enhancement (LGE), T1 mapping, and an array of clinical investigations., Results: The final diagnosis was cardiac light-chain (AL) amyloidosis in 222, cardiac transthyretin (ATTR) amyloidosis in 214, and no cardiac involvement in 427 cases. T1 was significantly elevated in both types of CA and this was associated with high diagnostic accuracy in the overall population (area under the curve, 0.93). A native T1 <1,036 ms was associated with 98% negative predictive value for CA whereas a native T1 >1,164 ms was associated with 98% positive predictive value for CA. We propose the use of these cut-offs to exclude or confirm CA and to restrict the administration of contrast only to patients with intermediate probability (native T1 between 1,036 and 1,164 ms), 58% of patients in this population., Conclusions: Native myocardial T1 enables diagnosis of CA to be made without need for gadolinium contrast in a large proportion of patients with suspected systemic amyloidosis. We propose a diagnostic algorithm for non-contrast CMR applicable to patients with suspected amyloidosis., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Renal involvement causing progressive chronic kidney disease (CKD) is present in 70% of patients with systemic Ig light-chain (AL) amyloidosis at diagnosis. Chemotherapy that substantially suppresses free light chain production is associated with improved patient survival, but its benefit in delaying the onset of renal replacement therapy among patients who present with established advanced CKD has not been studied. To evaluate this, we studied 1000 patients enrolled in the prospective UK AL amyloidosis chemotherapy study (ALchemy). Of these, 84 patients had advanced amyloid-related CKD defined by an estimated glomerular filtration rate (eGFR) under 20 ml/min/1.73 m 2 . We determined outcomes among these 84 patients, who had a median eGFR of 10 ml/min/1.73 m 2 , in relation to response to chemotherapy evaluated at three, six, and 12 months from baseline. Patients who achieved suppression of 90% or more in their amyloidogenic free light chain (dFLC) within three months of baseline had significantly better overall survival, prolonged time to dialysis, and prolonged time to the composite endpoint of 'death or dialysis' compared to those who achieved lesser degrees of clonal response at the same time point. Even when this target of greater than 90% dFLC response was achieved but was delayed beyond 3 months, it was associated with worse outcomes. Cox regression analyses confirmed that a 90% or better dFLC response within 3 months was the only significant independent predictor of all three of these outcome measures. Thus, renal survival among patients with systemic immunologic light chain amyloidosis who present with advanced CKD is strongly dependent upon the magnitude and speed with which the underlying hematologic disorder is suppressed by chemotherapy., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Patient decision-making aids (PDAs) are instruments that facilitate shared decision making and enable patients to reach informed, individual decisions regarding health care. The objective of this study was to assess the efficacy of a PDA compared with traditional information provision for adolescent patients considering fixed appliance orthodontic treatment., Methods: Before treatment, orthodontic patients were randomly allocated into 2 groups: the intervention group received the PDA and standard information regarding fixed appliances, and the control group received the standard information only. Decisional conflict was measured using the Decisional Conflict Scale, and the levels of decisional conflict were compared between the 2 groups., Results: Seventy-two patients were recruited and randomized in a ratio of 1:1 to the PDA and control groups. Seventy-one patients completed the trial (control group, 36; PDA group, 35); this satisfied the sample size calculation. The median total Decisional Conflict Scale score in the PDA group was lower than in the control group (15.63 and 19.53, respectively). However, this difference was not statistically significant (difference between groups, 3.90; 95% confidence interval of the difference, -4.30 to 12.11). Sex, ethnicity, age, and the time point at which patients were recruited did not have significant effects on Decisional Conflict Scale scores. No harm was observed or reported for any participant in the study., Conclusions: The results of this study showed that the provision of a PDA to adolescents before they consented for fixed appliances did not significantly reduce decisional conflict. There may be a benefit in providing a PDA for some patients, but it is not yet possible to say how these patients could be identified., Registration: This trial was registered with the Harrow National Research Ethics Committee (reference 12/LO/0279)., Protocol: The protocol was not published before trial commencement., (Copyright © 2017. Published by Elsevier Inc.)

Introduction: Research has shown that orthodontic patients are more likely to retain information presented in an audiovisual format. However, there has been little research on the effectiveness of audiovisual information provided through different routes such as the Internet. This parallel-group randomized controlled trial assessed whether provision of audiovisual information on the YouTube (Google, San Bruno, Calif) Web site to orthodontic patients undergoing fixed appliance treatment results in improved patient knowledge when compared with conventional methods of information provision. The effects of sex and ethnicity were also investigated., Methods: Participants were recruited from the Department of Orthodontics of the Eastman Dental Hospital, University College London Hospitals NHS Foundation Trust, United Kingdom. The patients were 13 years of age and over, with no history of orthodontic treatment, and patient and parental (where appropriate) consent were obtained. The participants were randomized into control (n = 34) and intervention (n = 33) groups using a random number table; there was stratification based on age group, with permuted blocks of 10 patients. Both groups were given routine verbal and written patient information related to fixed appliances, and the participants in the intervention group were sent 3 e-mails over 6 weeks requesting that they view a 6-minute YouTube video containing similar information but in audiovisual format. Patient knowledge was measured using identical questionnaires answered on the day of recruitment (baseline) and again 6 to 8 weeks later. The researchers were unaware of group allocations when enrolling patients and scoring questionnaires., Results: Sixty participants (89.55%) completed the study. Those who completed the trial in the intervention group (n = 30) demonstrated significantly greater improvements in knowledge than did those in the control group (n = 30), scoring, on average, almost 1 point more (95% CI for the difference, 0.305-1.602; P = 0.005) on the final questionnaire. Ethnicity had a statistically significant effect on improvement in knowledge, but sex did not. No harm to any patient was noted during the trial., Conclusions: Presenting audiovisual information through the YouTube Web site to orthodontic patients resulted in a significant improvement in patient knowledge. Supplementation of verbal and written patient information with audiovisual information via the Internet is therefore worthy of consideration., Registration: National Research and Ethics Service (REC number 12/LO/0863), United Kingdom., Protocol: The protocol was not published before trial commencement., Funding: No funding or conflict of interest to be declared., (Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objective: This meta-analysis sought to investigate the association between carotid intima-media thickness (c-IMT), flow-mediated dilation (FMD) and periodontitis (PD) and to assess the effect of periodontal treatment on c-IMT and FMD., Methods: Electronic database searching, hand searching of bibliographic references of included papers, related reviews, and journals in relation to oral, cardiovascular and ultrasound imaging field was carried out. Random effects meta-analyses were performed to investigate the association of co-existence of increased c-IMT, impaired FMD and PD with potential changes in these variables following periodontal intervention., Results: 2009 citations and 101 full text articles were screened, with 35 meeting the review inclusion criteria of which 22 suitable for quantitative analysis. Meta-analysis demonstrated that the diagnosis of PD was associated with a mean increase in c-IMT of 0.08 mm (95% C.I. = 0.07-0.09) and a mean difference in FMD of 5.1% compared to controls (95% C.I. = 2.08-8.11%). A meta-analysis of the effects of periodontal treatment on FMD showed a mean improvement of 6.64% between test and control (95% C.I. = 2.83-10.44%)., Conclusions: This review demonstrated an association between increased c-IMT, impaired FMD and PD. Data from intervention studies suggested a beneficial effect of periodontal treatment on FMD indicating an improvement in endothelial function. The findings support investigation of periodontitis treatment on cardiovascular outcomes., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Despite the high prevalence of dental anxiety in children, there is little research examining anxiety before orthodontic procedures. This parallel-group randomized controlled trial assessed whether provision of additional multimedia information regarding the bond-up procedure affected anxiety in adolescent orthodontic patients. The effects of sex, ethnicity, and age were also investigated., Methods: Participants were recruited from the orthodontic department of the Eastman Dental Hospital, University College London Hospitals Foundation Trust, in the United Kingdom; all were 10 to 16 years of age, with no history of orthodontic treatment, and patient assent and parental consent were obtained. The participants were randomized into control (n = 45) and intervention (n = 45) groups using a random number table. Both groups were given verbal information regarding the bond-up procedure, and the intervention group was additionally given a DVD showing a bond-up. Anxiety was assessed in the department immediately before the bond-up using the State-Trait Anxiety Inventory for Children, with state anxiety as the primary outcome measure. The researchers were unaware of group allocations while enrolling patients, scoring questionnaires, and analyzing data., Results: A statistically significant difference was found between groups, with a difference in scores of 2 (95% confidence interval for the difference = 0.15 to 3.85). The median state anxiety was 32 in the control group (n = 42) and 30 in the intervention group (n = 43; P = 0.012). Sex, ethnicity, and age did not significantly affect anxiety. No harmful effects were noted., Conclusions: Additional information reduces anxiety levels, but other methods could be more cost-effective than the DVD. Sex, ethnicity, and age did not statistically affect the anxiety levels., (Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

Introduction: In this randomized clinical trial, we compared pain levels associated with 2 fixed appliance systems during initial orthodontic tooth movement., Methods: Sixty-six patients (36 female, 30 male) were randomly allocated to either a conventional twin bracket (Tru Straight, Ormco Europe, Amersfoort, The Netherlands) or a self-ligating bracket (Damon 3, Ormco). Both arches were bonded, and a 0.014-in superelastic copper-nickel-titanium archwire was ligated in position. Pain intensity levels were recorded twice a day, over 7 days, by using 10-cm visual analog scales. Patients also recorded whether analgesia was taken. Contact point displacements were measured on study models to calculate Little's irregularity index., Results: Fifty-two patients (78.8%) completed the trial (84.8% in the Tru Straight group and 72.7% in the Damon 3 group). Patients in the Damon 3 group reported lower mean maximum pain intensity (P = 0.053) and significantly lower mean pain intensity (P = 0.012) than did the Tru Straight patients. Patients who consumed analgesics reported significantly higher mean maximum pain intensity and mean pain intensity than those who did not take analgesia (P <0.001). The Damon 3 patients generally reported lower pain intensity than the Tru Straight patients., Conclusions: Although there were wide interindividual variations, in this study, the Damon 3 appliance resulted in lower pain intensity, on average, when compared with the Tru Straight appliance.

Introduction: This was a retrospective cephalometric study in patients undergoing mandibular advancement surgery. Our aim was to provide a more precise estimation of the postsurgical soft-tissue outcomes than can be achieved by using simple ratios of the hard and soft tissues., Methods: The lateral cephalograms of 64 patients undergoing mandibular advancement, from before and near the end of treatment, were scanned and digitized with a customized software program. Multivariable regression analyses were used to create prediction equations for soft-tissue changes at pogonion, inferior labial sulcus, labrale inferius, and stomion inferius (all in the horizontal plane)., Results and Conclusions: This method of using multiple explanatory variables appears to be useful in the prediction of soft-tissue changes. At least 96% of the variation of each dependent variable was explained by its relationship with the explanatory variables in the relevant multivariable regression equation, and the results appeared to be clinically useful.