External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion). OBJECTIVES: To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption. MAIN RESULTS: We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled. AUTHORS' CONCLUSIONS: Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.

Gestational hypertension and preeclampsia in living kidney donors.

BACKGROUND: Young women wishing to become living kidney donors frequently ask whether nephrectomy will affect their future pregnancies. METHODS: We conducted a retrospective cohort study of living kidney donors involving 85 women (131 pregnancies after cohort entry) who were matched in a 1:6 ratio with 510 healthy nondonors from the general population (788 pregnancies after cohort entry). Kidney donations occurred between 1992 and 2009 in Ontario, Canada, with follow-up through linked health care databases until March 2013. Donors and nondonors were matched with respect to age, year of cohort entry, residency (urban or rural), income, number of pregnancies before cohort entry, and the time to the first pregnancy after cohort entry. The primary outcome was a hospital diagnosis of gestational hypertension or preeclampsia. Secondary outcomes were each component of the primary outcome examined separately and other maternal and fetal outcomes. RESULTS: Gestational hypertension or preeclampsia was more common among living kidney donors than among nondonors (occurring in 15 of 131 pregnancies [11%] vs. 38 of 788 pregnancies [5%]; odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P=0.01). Each component of the primary outcome was also more common among donors (odds ratio, 2.5 for gestational hypertension and 2.4 for preeclampsia). There were no significant differences between donors and nondonors with respect to rates of preterm birth (8% and 7%, respectively) or low birth weight (6% and 4%, respectively). There were no reports of maternal death, stillbirth, or neonatal death among the donors. Most women had uncomplicated pregnancies after donation. CONCLUSIONS: Gestational hypertension or preeclampsia was more likely to be diagnosed in kidney donors than in matched nondonors with similar indicators of baseline health. (Funded by the Canadian Institutes of Health Research and others.).

Efficacy and safety of catheter ablation for atrial fibrillation in elderly patients: a systematic review and meta-analysis.

BACKGROUND: Catheter ablation (CA) is a well-established therapy for patients with atrial fibrillation (AF); however, there is paucity of data for elderly patients. We aimed to assess long-term efficacy and safety of CA for elderly patients with AF. METHODS: Medline, BVS, Cochrane, and Embase were searched through April 2023 to investigate comparative outcomes between elderly patients > 75 or 80 years, as per-study cutoff, and individuals ≤ 75/80 years, undergoing CA. Primary efficacy and safety endpoints (AF recurrence and procedure-related major complications) were pooled with the Comprehensive Meta-Analysis 3.0 software. Subgroup analyses were performed by age groups and type of procedure (radiofrequency vs. cryoballoon). RESULTS: Four thousand eight hundred twenty-nine titles were screened, and 27 studies were included, being 26 observational and 1 randomized trial, comprising 117,869 patients, being 8714 (7.4%) elderly > 75/80 years, with follow-up from 11.7 to 72.3 months. In comparative studies (N = 17 studies), elderly > 75/80 years had a higher risk of AF recurrence compared to those ≤ 75/80: relative risk (RR) 1.16 (95% CI 1.05-1.27, p = 0.002. However, funnel plot indicated publication bias, and after imputation of 5 studies, the groups were similar (RR 1.07 (95% CI 0.97-1.19)). The rates of major complications (N = 14 studies) were higher in elderly > 75/80 years (RR 1.30 (95% CI 1.10-1.54), I2 = 0, p = 0.002), but were similar in cryoablation studies (N = 7) (RR 1.10, 95% CI 0.94-1.29, p = 0.24, I2 = 0.0). Results were similar when individual study arms (N = 27 studies) were pooled. CONCLUSION: AF ablation is feasible in elderly patients > 75/80 years, with success rates compared to younger individuals. Complication rates, however, were higher.

Intra-thoracic fat volume is associated with myocardial infarction in patients with metabolic syndrome.

BACKGROUND: Visceral adiposity is increased in those with Metabolic Syndrome (MetS) and atherosclerotic disease burden. In this study we evaluate for associations between intra-thoracic fat volume (ITFV) and myocardial infarction (MI) in patients with MetS. METHODS: Ninety-four patients with MetS, MI or both were identified from a cardiovascular CMR clinical registry. MetS was defined in accordance to published guidelines; where-as MI was defined as the presence of subendocardial-based injury on late gadolinium enhancement imaging in a coronary vascular distribution. A healthy control group was also obtained from the same registry. Patients were selected into the following groups: MetS+/MI- (N = 32), MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification was performed using signal threshold analysis of sequential sagittal CMR datasets (HASTE) and indexed to body mass index. RESULTS: The mean age of the population was 59.8 ± 12.5 years. MetS+ patients (N=64) demonstrated a significantly higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a progressive elevation in the indexed ITFV (22.3 ± 10.6, 28.6 ± 12.6, 30.6 ± 12.3, and 35.2 ± 1.4 ml/kg/m(2), (p = 0.002)). Among MetS+ patients those with MI showed a significantly higher indexed ITFV compared to those without MI (p = 0.02). CONCLUSIONS: ITFV is elevated in patients with MetS and incrementally elevated among those with evidence of prior ischemic myocardial injury. Accordingly, the quantification of ITFV may be a valuable marker of myocardial infarction risk among patients with MetS and warrants further investigation.

Adolescent classroom education on knowledge and attitudes about deceased organ donation: a systematic review.

In many countries, adolescents can choose to register a deceased organ donation wish when they apply for a driver's license. They often receive education about deceased organ donation in order to make an informed choice. The objective of this review was to describe the effectiveness of school-based educational programs on deceased organ donation among adolescents. We reviewed any study of adolescent students receiving a school-based educational program on deceased organ donation. The outcomes were knowledge, attitudes, intent to register a preference toward deceased organ donation, and whether such education fostered family discussions about organ donation. Fifteen studies were summarized from nine countries, of which six were randomized controlled trials. Most educational programs consisted of one or two classroom sessions. The methods employed in five studies received a high-quality rating. Educational programs increased knowledge in 10 studies, and attitudes in five studies, with variable effects on intent to affirmative registration. Seven studies reported success in promoting family discussions. Adolescent classroom education is a promising strategy to improve knowledge about deceased organ donation and appears to increase public support for donation. Subjecting these programs to additional evaluation will clarify their impact on affirmative donor registration and realized donations.

Quality of Life and Hemodynamic Effects of Switching From Hemodialysis to Hemodiafiltration: A Canadian Controlled Cohort Study.

BACKGROUND: Recent randomized clinical trials have demonstrated beneficial effects of hemodiafiltration (HDF) compared with hemodialysis (HD) on mortality and hemodynamic stability. Data on quality of life in HDF compared with HD is limited. OBJECTIVE: This study aimed to determine whether patients receiving HD experience improvements in quality of life, hemodynamic and laboratory parameters after switching to HDF. DESIGN: Observational controlled cohort study. SETTING & PATIENTS: Adult patients receiving maintenance dialysis were followed for 3 months both before and after transfer to a new unit, where they received HDF. Prior to transfer, control patients were already treated by HDF. METHODS: Quality of life at baseline and follow-up was measured using the validated minutes to recovery (MR) question. Dialysis data were collected for 3 consecutive sessions monthly; laboratory values were collected monthly. Wilcoxon signed rank test and repeated measures analysis of covariance were used to evaluate pre/post transfer changes and quantile regression to identify predictors of change in recovery time. RESULTS: Of 227 patients, 82 died, were transplanted, were hospitalized or did not transfer, leaving 123 subjects and 22 controls for analysis. MR did not improve with switching to HDF, although patients with MR > 60 min before transfer experienced a significant decrease in their MR, compared with controls. There was no improvement in intradialytic hypotension with HDF. There were no differences in laboratory values before vs after switch. LIMITATIONS: Nonrandomized single-center study, including only small numbers of patients and covering a short follow-up period; hemodynamic values only evaluated over 1 week per month; residual kidney function not recorded. CONCLUSIONS: In this Canadian experience of HDF, patients remained stable with respect to several laboratory and dialysis related parameters. Switch to HDF was associated with substantially reduced recovery time in patients with MR > 60 minutes at baseline.

CONTEXTE: De récents essais cliniques randomisés ont démontré les effets bénéfiques de l'hémodiafiltration (HDF) comparativement à l'hémodialyse (HD) sur la mortalité et la stabilité hémodynamique. Les données sur la qualité de vie des patients traités par HDF plutôt que par HD sont toutefois limitées. OBJECTIF: Déterminer si des patients préalablement traités par HD bénéficient d'une amélioration de leur qualité de vie et de changements observables dans leurs paramètres hémodynamiques et de laboratoire en passant à l'HDF. TYPE D'ÉTUDE: Étude de cohorte observationnelle contrôlée. SUJETS: Des adultes recevant une dialyse d'entretien ont été suivis pendant trois mois avant et après le transfert à une nouvelle unité, où ils ont reçu l'HDF. Les patients témoins étaient traités par HDF avant le transfert. MÉTHODOLOGIE: La qualité de vie à l'inclusion et lors du suivi a été mesurée à l'aide d'une question validée sur le temps de récupération (TR). Les données de dialyse ont été recueillies pour trois séances consécutives par mois; les valeurs de laboratoire ont été recueillies mensuellement. Le test de rang de Wilcoxon et des mesures répétées ANCOVA ont servi à évaluer les changements pré/post-transfert, tandis que la régression par quantile a été employée pour déterminer les facteurs prédictifs d'un changement dans le TR. RÉSULTATS: Sur les 227 patients admissibles, 82 ont été exclus ­ soit parce qu'ils sont décédés, ont été transplantés, ont été hospitalisés ou n'ont pas été transférés ­ ce qui a laissé 123 sujets et 22 témoins pour l'analyse. Le passage à l'HDF n'a pas amélioré le TR, bien que les patients dont le TR était supérieur à 60 min avant le transfert aient observé une réduction significative de ce dernier par rapport aux témoins. L'hypotension intradialytique est demeurée inchangée avec l'HDF et aucune différence n'a été observée entre les valeurs de laboratoire mesurées avant et après le changement de modalité. LIMITES: Étude monocentrique non randomisée sur un faible échantillon et couvrant une courte période de suivi; valeurs hémodynamiques évaluées uniquement sur une semaine par mois; fonction rénale résiduelle non enregistrée. CONCLUSION: Dans cette expérience de passage à l'HDF qui s'est tenue au Canada, les paramètres de laboratoire et de dialyse des patients sont demeurés stables. Cependant, chez les patients dont le temps de récupération était supérieur à 60 minutes, le passage à l'HDF a été associé à une réduction considérable de celui-ci.

A Rapid Review on the Efficacy and Safety of Pharmacological Treatments for Chagas Disease.

Chagas disease remains a neglected tropical disease, causing significant burden in the Americas and countries that receive immigrants from endemic nations. Current pharmaceutical treatments are suboptimal, not only varying drastically in efficacy, depending on the stage of disease, but also presenting significant risk of adverse events. The objective of this review is to provide a timely update on the efficacy and safety of current trypanocidals. Eligible studies published from January 2015 to December 2020 were retrieved by one reviewer from six electronic databases. Ana-lysis was done with review management software and risk of bias was assessed using tools appropriate for the type of study (i.e., experimental or observational). Thirteen studies (10 observational and three RCTs) were included in the analysis. All 13 studies tested Benznidazole (BNZ) or Nifurtimox (NFX), and two studies also tested Posaconazole (POS) or E1224 (Ravucanazole). BNZ was found to be the most efficacious trypanocidal drug compared to Nifurtimox, POS, and E1224; it also resulted in the highest percentage of adverse effects (AEs) and treatment discontinuation due to its toxicity. Adults experienced higher frequency of neurological AEs while taking BNZ or NFX compared to children. Children had a higher frequency of general AEs compared to adults while taking BNZ. Overall, BNZ is still the most efficacious, but development of new, less toxic drugs is paramount for the quality of life of patients. Studies testing combination therapies and shorter regimens are needed, as is the devising of better clinical parameters and laboratory biomarkers to evaluate treatment efficacy. Considering the variability in methodology and reporting of the studies included in the present analysis, we offer some recommendations for the improvement and replicability of clinical studies investigating pharmacological treatment of Chagas disease. These include full disclosure of methodology, standardization of outcome measures, and always collecting and reporting data on both the efficacy of trypanocidals and on safety outcomes.

Pre-operative use of aspirin in patients undergoing coronary artery bypass grafting: a systematic review and updated meta-analysis.

Background: Aspirin therapy improves saphenous vein graft (SVG) patency in patients undergoing coronary artery bypass graft (CABG), however, its use in the pre-operative period remains controversial. Therefore, we conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) to update the evidence about risk and benefits of pre-operative aspirin therapy in patients undergoing CABG. Methods: Electronic databases (Medline, Embase, PubMed, Cochrane Library, and Scopus) were searched to identify RCTs evaluating the effect of aspirin versus placebo/control before CABG. Two investigators independently and in duplicate screened citations and extracted data and rated the risk of bias. The strength of evidence was appraised using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Meta-analysis was performed using a random-effects model. The main outcomes of interest were 30-day mortality, peri-operative myocardial infarction (MI), chest tube drainage and SVG occlusion. Results: A total of 13 RCTs involving 4,377 participants (2,266/2,111 pre-operative aspirin/control) met the inclusion criteria. Pre-operative aspirin reduced the risk of SVG occlusion [risk ratio (RR): 0.69, 95% confidence interval (CI): 0.49-0.97, P=0.03, I2=16%], but no differences in mortality (RR: 1.41, 95% Cl: 0.73-2.74, I2=0%) and MI (RR: 0.84, 95% CI: 0.69-1.03, I2=0%) were found. However, pre-operative aspirin increased chest tube drainage (MD: 100.40 mL, 95% CI: 24.32-176.47 mL, P=0.01, I2=84%) and surgical re-exploration (RR: 1.52, 95% CI: 1.02-2.27, P=0.04, I2=8%), with no significant difference in RBC transfusion (RR: 1.06, 95% CI: 0.90-1.25, I2=35%). Conclusions: Based on trials where the rated body of evidence was of low to very-low quality, pre-operative aspirin improves SVG patency but increases chest tube drainage and need for surgical re-exploration.

Erratum to pre-operative use of aspirin in patients undergoing coronary artery bypass grafting: a systematic review and updated meta-analysis.

[This corrects the article DOI: 10.21037/jtd.2018.05.187.].

Antithrombotic therapy in patients receiving saphenous vein coronary artery bypass grafts: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: The current evidence for the prevention of saphenous vein graft failure (SVGF) after coronary artery bypass graft (CABG) surgery consists of direct head-to-head comparison of treatments (including placebo) in randomised-controlled trials (RCTs) and observational studies. However, summarising the evidence using traditional pairwise meta-analyses does not allow the inclusion of data from treatments that have not been compared head to head. Exclusion of such comparisons could impact the precision of pooled estimates in a meta-analysis. Hence, to address the challenge of whether aspirin alone or in addition to another antithrombotic agent is a more effective regimen to improve SVG patency, a network meta-analysis (NMA) is necessary. The objectives of this study are to synthesise the available evidence on antithrombotic agents (or their combination) and estimate the treatment effects among direct and indirect treatment comparisons on SVGF and major adverse cardiovascular events, and to generate a treatment ranking according to their efficacy and safety outcomes. METHODS: We will perform a systematic review of RCTs evaluating antithrombotic agents in patients undergoing CABG. A comprehensive English literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles. Two individuals will independently and in duplicate screen potential studies, assess the eligibility of potential studies and extract data. Risk of bias and quality of evidence will also be evaluated independently and in duplicate. We will investigate the data to ensure its suitability for NMA, including adequacy of the outcome data and transitivity of treatment effects. We plan to estimate the pooled direct, indirect and the mixed effects for all antithrombotic agents using a NMA. ETHICS AND DISSEMINATION: Due to the nature of the study, there are no ethical concerns nor informed consent required. We anticipate that this NMA will be the first to simultaneously assess the relative effects of multiple antithrombotic agents in patients undergoing CABG. The results of this NMA will inform clinicians, patients and guideline developers the best available evidence on comparative effects benefits of antithrombotic agents after CABG while considering the side effect profile to support future clinical decision-making. We will disseminate the results of our systematic review and NMA through a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017065678.

Do biochemical measures change in living kidney donors? A systematic review.

BACKGROUND: Living kidney donation provides a unique opportunity to assess possible biochemical changes attributable to small decrements in glomerular filtration rate. We reviewed studies which followed 5 or more healthy donors, where changes in biochemical measures or anemia were assessed at least 4 months after nephrectomy. METHODS: We searched MEDLINE, EMBASE, and Science Citation databases, and reviewed reference lists from 1966 through June 2006. We abstracted data on study and donor characteristics and biochemical outcomes of interest. RESULTS: Eight studies examined at least one outcome of interest. The average time after donation ranged from 0.4 to 11 years, the postdonation creatinine clearance ranged from 73 to 99 ml/min, and the decrement after donation ranged from 11 to 38 ml/min. Nephrectomy did not change hemoglobin, erythropoietin, serum phosphate, calcium or C-reactive protein levels. The studies were inconsistent as to whether parathyroid hormone levels increased and 1,25-dihydroxyvitamin D levels decreased after nephrectomy. Uric acid levels increased variably post-donation. Plasma homocysteine increased in the single study included in this review. CONCLUSIONS: The mechanistic changes described above and their prognostic significance need clarification. Based on existing evidence, it is not necessary to routinely monitor living kidney donors for changes in these biochemical measures.

Erratum to: Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy?

[This corrects the article DOI: 10.1186/s13223-016-0110-8.].

Robot-assisted hysterectomy for endometrial and cervical cancers: a systematic review.

Total and radical hysterectomies are the most common treatment strategies for early-stage endometrial and cervical cancers, respectively. Surgical modalities include open surgery, laparoscopy, and more recently, minimally invasive robot-assisted surgery. We searched several electronic databases for randomized controlled trials and observational studies with a comparison group, published between 2009 and 2014. Our outcomes of interest included both perioperative and morbidity outcomes. We included 35 observational studies in this review. We did not find any randomized controlled trials. The quality of evidence for all reported outcomes was very low. For women with endometrial cancer, we found that there was a reduction in estimated blood loss between the robot-assisted surgery compared to both laparoscopy and open surgery. There was a reduction in length of hospital stay between robot-assisted surgery and open surgery but not laparoscopy. There was no difference in total lymph node removal between the three modalities. There was no difference in the rate of overall complications between the robot-assisted technique and laparoscopy. For women with cervical cancer, there were no differences in estimated blood loss or removal of lymph nodes between robot-assisted and laparoscopic procedure. Compared to laparotomy, robot-assisted hysterectomy for cervical cancer showed an overall reduction in estimated blood loss. Although robot-assisted hysterectomy is clinically effective for the treatment of both endometrial and cervical cancers, methodologically rigorous studies are lacking to draw definitive conclusions.

Contribution of mitral valve leaflet length and septal wall thickness to outflow tract obstruction in patients with hypertrophic cardiomyopathy.

We sought to examine whether elongation of the mitral valve leaflets in patients with hypertrophic cardiomyopathy (HCM) is synergistic to septal wall thickness (SWT) in the development of left ventricular outflow tract obstruction (LVOTO). HCM is a common genetic cardiac disease characterized by asymmetric septal hypertrophy and predisposition towards LVOTO. It has been reported that elongation of the mitral valve leaflets may be a primary phenotypic feature and contribute to LVOTO. However, the relative contribution of this finding versus SWT has not been studied. 152 patients (76 with HCM and 76 non-diseased age, race and BSA-matched controls) and 18 young, healthy volunteers were studied. SWT and the anterior mitral valve leaflet length (AMVLL) were measured using cine MRI. The combined contribution of these variables (SWT × AMVLL) was described as the Septal Anterior Leaflet Product (SALP). Peak LVOT pressure gradient was determined by Doppler interrogation and defined as "obstructive" if ≥ 30 mmHg. Patients with HCM were confirmed to have increased AMVLL compared with controls and volunteers (p < 0.01). Among HCM patients, both SWT and SALP were significantly higher in patients with LVOTO (N = 17) versus without. SALP showed modest improvement in predictive accuracy for LVOTO (AUC = 0.81) among the HCM population versus SWT alone (AUC = 0.77). However, in isolated patients this variable identified patients with LVOTO despite modest SWT. Elongation of the AMVLL is a primary phenotypic feature of HCM. While incremental contributions to LVOTO appear modest at a population level, specific patients may have dominant contribution to LVOTO. The combined marker of SALP allows for maintained identification of such patients despite modest increases in SWT.

Diagnostic accuracy of skin-prick testing for allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: Allergic rhinitis is the most common form of allergy worldwide. The accuracy of skin testing for allergic rhinitis is still debated. Our primary objective was to evaluate the diagnostic accuracy of skin-prick testing for allergic rhinitis using the nasal provocation as the reference standard. We also evaluated the diagnostic accuracy of intradermal testing as a secondary objective. METHODS: We searched EBM Reviews from 2005 to March 2015; Embase from 1980 to March 2015; and Ovid MEDLINE(R) from 1946 to until March 2015. We included any study with at least 10 subjects including children. We excluded non-English studies. We performed data extraction and quality assessment using the QUADAS-2 tool. RESULTS: We meta-analysed seven studies assessing the accuracy of skin-prick testing using the bivariate random-effects model, including a total of 430 patients. The pooled estimate for sensitivity and specificity for skin-prick testing was 85 and 77 % respectively. We did not pool results for intradermal testing due to few number of studies (n = 4), each with very small sample size. Of these, two evaluated the accuracy of intradermal testing in confirming skin-prick testing results, with sensitivity ranging from 27 to 50 % and specificity ranging from 60 to 100 %. The other two evaluated the accuracy of intradermal testing as a stand-alone test for diagnosing allergic rhinitis with sensitivity ranging from 60 to 79 % and specificity ranging from 68 to 69 %. CONCLUSIONS: Findings from this review suggest that skin-prick testing is accurate in discriminating subjects with or without allergic rhinitis.

Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy?

BACKGROUND: Food allergy is the most common cause of anaphylaxis in children. Intramuscular delivery of epinephrine auto-injectors (EAI) is the standard of care for the treatment of anaphylaxis. We examined if children and adolescents at risk of anaphylaxis weighing 15-30 kg and >30 kg would receive epinephrine into the intramuscular space with the currently available EAI in North America and Europe. METHODS: The distance from skin to muscle (STMD) and skin to bone (STBD) on the mid third anterolateral area of the right thigh was measured by ultrasound applying either high pressure (max) or slight pressure (min) in 102 children weighing 15-30 kg (group 1) and 100 children and adolescents, weighing more than 30 kg (group 2). RESULTS: Using a high pressure EAI (HPEAI), Epipen Jr(®) and Auvi-Q(®)/Allerject(®) 0.15 mg, 11/102 (11 %) children in group 1 and 38/102 (38 %) using another HPEAI, Jext(®), had a STMDmax that showed a risk of intraosseous injection. There was a 1 % risk of subcutaneous injection with these devices. There was no risk of intraosseous injection using a low pressure EAI (LPEAI), Emerade(®). In group 2, the risk of intraosseous injection using a HPEAI was 3 % and no risk using a LPEAI. However, the risk of subcutaneous injection using HPEAI was 9 % and using LPEAI was 2 %. CONCLUSION: There is a risk of intraosseous injection using HPEAI (Epipen(®)/Epipen Jr(®), Auvi-Q(®)/Allerject(®) and especially Jext(®)) in children at risk of anaphylaxis. There was also a risk of subcutaneous injection using the currently available HPEAI in children and adolescents.

Children under 15 kg with food allergy may be at risk of having epinephrine auto-injectors administered into bone.

BACKGROUND: The Epipen® Jr and Allerject® 0.15 mg are currently the most commonly prescribed epinephrine auto-injectors (EAIs) for the management of anaphylaxis in pediatric patients in North America and Canada. To ensure rapid absorption, it should be administered intramuscularly into the anterolateral aspect of the thigh. We examined whether the 12.7-mm needle length of the Epipen® Jr and Allerject® 0.15 mg is adequate for delivering epinephrine intramuscularly in pediatric patients who weighed <15 kg. METHODS: Consecutive pediatric patients with food allergy weighing <15 kg who required an EAI were included. Ultrasounds of the mid-anterolateral thigh were performed under minimal (min) and maximal (max) pressure. Skin-to-muscle depth (STMD) and skin-to-bone depth (STBD) measurements were completed. Baseline characteristics were compared between patients with a STBDmax <12.7 mm vs. ≥12.7 mm. Linear regression including variables such as age, sex, body mass index (BMI) and race was performed. The proportion of patients with a STBDmax <12.7 mm was compared in those weighing <10 kg vs. 10-14.9 kg. RESULTS: One hundred patients were included; 29 (29%) had STBDmax <12.7 mm. Height (p = 0.02) and weight (p = 0.0002) differed significantly between the two groups. Approximately 19% of those weighing 10-14.9 kg and 60% of those <10 kg had a STBDmax <12.7 mm. In the multivariable regression analysis, BMI was found to be a significant predictor of STBDmax. CONCLUSIONS: A large proportion of children <15 kg prescribed an EAI is at risk of having the auto-injector administered into bone. Since alternative EAIs with shorter needle lengths are not currently available, EAIs should be prescribed with appropriate counselling in this population.

Patients on subcutaneous allergen immunotherapy are at risk of intramuscular injections.

BACKGROUND: Allergen-specific subcutaneous immunotherapy is an effective treatment for certain allergic disorders. Ideally, it should be administered into the subcutaneous space in the mid-posterolateral upper arm. Injections are commonly given using a standard allergy syringe with a needle length of 13 mm. Therefore, there is a risk of intramuscular administration if patients have a skin-to-muscle depth <13 mm, which may increase the risk of anaphylaxis. The objective of this study was to determine whether the needle length of a standard allergy syringe is appropriate for patients receiving subcutaneous immunotherapy. METHODS: Ultrasounds of the left posterolateral arm were performed to measure skin-to-muscle depth in 200 adults receiving subcutaneous immunotherapy. The proportion of patients with a skin-to-muscle depth >13 mm vs. ≤13 mm was assessed and baseline characteristics of the two groups were compared. The proportion of patients with skin-to-muscle depths > 4 mm, 6 mm, 8 mm and 10 mm were also calculated. Multivariable logistic regression was performed to identify predictors of skin-to-muscle depth. RESULTS: Of the 200 patients included in the study, 80% had a skin-to-muscle depth ≤13 mm; the majority (91%) had a skin-to-muscle depth >4 mm. Body mass index was found to be a significant predictor of skin-to-muscle-depth. CONCLUSIONS: Most patients receiving subcutaneous immunotherapy have a skin-to-muscle depth less than the needle length of a standard allergy syringe (13 mm). These patients are at risk of receiving injections intramuscularly, which may increase the risk of anaphylaxis. Using a syringe with a needle length of 4 mm given at a 45° angle to the skin may decrease this risk.

Auto-injector needle length may be inadequate to deliver epinephrine intramuscularly in women with confirmed food allergy.

BACKGROUND: Epinephrine auto-injectors are the standard first aid treatment for anaphylaxis. Intramuscular delivery into the anterolateral aspect of the thigh is recommended for optimal onset of action of epinephrine. The most frequently prescribed auto-injector in North America and Canada is the EpiPen(®), which has a needle length of 15.2 mm. Currently, it is unknown whether this needle length is adequate for intramuscular delivery of epinephrine in adult patients at risk of anaphylaxis. METHODS: One hundred consecutive adult patients with confirmed food allergy requiring an epinephrine auto-injector were recruited. Skin to muscle depth (STMD) at the right mid-anterolateral thigh was measured using ultrasound under minimal (min) and maximum (max) pressure. The EpiPen(®) needle length was considered adequate if STMDmax was ≤15.2 mm. Baseline characteristics including age, gender, ethnicity, and body mass index (BMI) were compared in patients with STMDmax ≤15.2 mm vs. >15.2 mm. RESULTS: The EpiPen(®) needle length of 15.2 mm was inadequate for intramuscular delivery in 19 of the 100 enrolled patients (19%), all of whom were female; 28% of women had a STMDmax >15.2 mm. The mean STMDmax in the ≤15.2-mm and >15.2-mm groups were 9 ± 4 mm and 20 ± 4 mm, respectively (p = 0.0001). Linear regression analysis found BMI to be significantly associated with STMDmax after adjusting for age (p < 0.001). CONCLUSIONS: The needle length of the epinephrine auto-injectors may not be adequate for intramuscular delivery of epinephrine in a large proportion of women with food allergy; this may impact morbidity and mortality from anaphylaxis in this patient population.

Prevalence of myocardial fibrosis patterns in patients with systolic dysfunction: prognostic significance for the prediction of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy.

BACKGROUND: Late gadolinium enhancement-cardiac magnetic resonance is increasingly performed in patients with systolic dysfunction. Numerous patterns of fibrosis are commonly reported among this population. However, the relative prevalence and prognostic significance of these findings remains uncertain. METHODS AND RESULTS: Three hundred eighteen consecutive patients referred for late gadolinium enhancement-cardiac magnetic resonance and a left ventricular ejection fraction <55% were followed up for the primary end point of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy. Late gadolinium enhancement images were blindly interpreted for the presence of 6 distinct pattern(s) of myocardial fibrosis in addition to signal threshold-based quantification of total fibrosis volume. The mean age and left ventricular ejection fraction of participants were 62.0±12.9 years and 32.6±11.9%, respectively. Any pattern of myocardial fibrosis was seen in 248 patients (78%) with ≥2 patterns present in 25% of patients. During follow-up (median of 467 days), 49 patients (15%) had a primary outcome. After adjustment for left ventricular ejection fraction, cardiomyopathy pathogenesis, and total fibrosis volume, the presence of a midwall striae pattern of fibrosis was an independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy with a hazard ratio of 2.4 (95% confidence interval, 1.2-4.6; P=0.01); this finding is present in 30% of patients with nonischemic and 15% of patients with ischemic cardiomyopathy. Cumulative event rate was significantly higher among those with midwall striae, particularly among those with a left ventricular ejection fraction >35% (40% versus 6%; P=0.005). CONCLUSIONS: Patients with systolic dysfunction frequently demonstrate multiple patterns of myocardial fibrosis. Of these, a midwall striae pattern of fibrosis is the strongest independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy.