Minimally Invasive Treatments for Benign Prostatic Hyperplasia: Systematic Review and Network Meta-Analysis

PurposeTo review and to compare indirectly the outcomes of minimally invasive therapies for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.Materials and MethodsA literature search via Medline and Cochrane Central databases was completed for randomized control studies published between January 2000 to April 2020 for the following therapies: Rezum, Urolift, Aquablation, and prostatic artery embolization (PAE). Data on the following variables were included: International prostate symptom score (IPSS), maximum urinary flow rate, quality of life, and postvoid residual (PVR). Standard mean differences between treatments were compared through a meta-analysis using transurethral resection of the prostate (TURP) to assess differences in treatment effect.ResultsThere was no significant difference in outcomes between therapies for IPSS at the 3, 6, and 12-month follow ups. Although outcomes for Rezum were only available out to 3 months, there were no consistently significant differences in outcomes when comparing Aquablation versus PAE versus Rezum. TURP PVR was significantly better than Urolift at 3, 6, and 12 months. No significant differences in minor or major adverse events were noted.ConclusionAlthough significant differences in outcomes were limited, Aquablation and PAE were the most durable at 12 months. PAE has been well studied on multiple randomized control trials with minimal adverse events while Aquablation has limited high quality data and has been associated with bleeding-related complications.     

Atrial fibrillation after cardiac surgery: A systematic review and meta-analysis

ObjectiveNew-onset postoperative atrial fibrillation (POAF) after cardiac surgery is common, with rates up to 60%. POAF has been associated with early and late stroke, but its association with other cardiovascular outcomes is less known. The objective was to perform a meta-analysis of the studies reporting the association of POAF with perioperative and long-term outcomes in patients with cardiac surgery.MethodsWe performed a systematic review and a meta-analysis of studies that presented outcomes for cardiac surgery on the basis of the presence or absence of POAF. MEDLINE, EMBASE, and the Cochrane Library were assessed; 57 studies (246,340 patients) were selected. Perioperative mortality was the primary outcome. Inverse variance method and random model were performed. Leave-one-out analysis, subgroup analyses, and metaregression were conducted.ResultsPOAF was associated with perioperative mortality (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.58-2.33), perioperative stroke (OR, 2.17; 95% CI, 1.90-2.49), perioperative myocardial infarction (OR, 1.28; 95% CI, 1.06-1.54), perioperative acute renal failure (OR, 2.74; 95% CI, 2.42-3.11), hospital (standardized mean difference, 0.80; 95% CI, 0.53-1.07) and intensive care unit stay (standardized mean difference, 0.55; 95% CI, 0.24-0.86), long-term mortality (incidence rate ratio [IRR], 1.54; 95% CI, 1.40-1.69), long-term stroke (IRR, 1.33; 95% CI, 1.21-1.46), and longstanding persistent atrial fibrillation (IRR, 4.73; 95% CI, 3.36-6.66).ConclusionsThe results suggest that POAF after cardiac surgery is associated with an increased occurrence of most short- and long-term cardiovascular adverse events. However, the causality of this association remains to be established.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

Does Rest Time before Ultrasonography Imaging Affect Quadriceps Femoris Muscle Thickness,Cross-Sectional Area and Echo Intensity Measurements?

In the work described here, our aim was to determine, in an elderly population, changes in muscle thickness (MT), cross-sectional area (CSA) and echo intensity (EI) of the quadriceps muscles at four time points (0, 5, 10 and 15 min; i.e., T0, T5, T10 and T15, respectively) after changing from a standing to supine position. Twenty-one elderly participants (14 men: 68.1 ± 4.6 y; 8 women: 66.8 ± 4.1 y) were evaluated at four time points. Rectus femoris CSA (RF_CSA), MT and EI of the quadriceps femoris (QF) muscles were assessed. EI significantly increased from T0 to T5, T10 and T15 (p < 0.001), whereas no differences were observed between T5 and T15 in the rectus femoris (RF_EI), vastus intermedius (VI_EI) and quadriceps femoris (QF_EI). No differences were observed between any time points in the RF_CSA and MT of QF muscles. In summary, these results suggest that periods >5 min are not necessary to obtain consistent MT and EI measurements of quadriceps femoris muscles in the elderly population.     

On estimands arising from misspecified semiparametric rate-based analysis of recurrent episodic conditions

Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of the Nelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration.     

In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.