'Pain-free TRUS B': a phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasonography-guided prostate biopsy (ANZUP 1501).

OBJECTIVE: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. PATIENTS AND METHODS: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. RESULTS: The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. CONCLUSIONS: We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Experiences of Midwestern obstetric clinicians during the Coronavirus disease 2019 pandemic.

Background: The Coronavirus disease 2019 (COVID-19) pandemic led to healthcare system changes aimed at minimizing disease transmission that impacted experiences with obstetric healthcare. Objective: To explore experiences of clinicians providing obstetric care during the COVID-19 pandemic. Study Design: Qualitative, in-depth, semi-structured interviews were conducted with five nurse practitioners and 16 obstetrical physicians providing a mix of outpatient and inpatient obstetric care during the COVID-19 pandemic in a mid-sized, Midwestern city in the United States. Interviews elucidated challenges and facilitators of obstetric care provision and vaccination of pregnant patients against COVID-19 during the pandemic. Transcripts were coded inductively then deductively using the Health Equity Implementation Framework (HEIF), which integrates a disparities framework and implementation framework to highlight multilevel factors that influence obstetric care. Thematic analysis was conducted, and thematic saturation was reached. Results: We interviewed 21 clinicians. Clinicians recounted personal challenges such as social isolation and burnout that could be countered by social support. Challenges within the clinical encounter included implementation of infection mitigation efforts, vaccine counseling, and limitations of telehealth. However, when successfully implemented, telehealth facilitated care and circumvented barriers. Clinicians cited challenges at the healthcare system level such as rapidly evolving knowledge and recommendations, restrictive visitor policies, personnel shortage, and inadequate institutional resources to support pandemic-related stressors. However, interdisciplinary care and guidelines available for clinicians facilitated care. Clinicians reported that challenges at the societal level included financial strain, lack of childcare, medical mistrust, politicization of medicine, misinformation, and racism. Societal-level facilitators included insurance access, community outreach, positive policy changes, and fostering trust in medicine. Conclusion: The pandemic produced unique stressors and exacerbated existing challenges for clinicians providing obstetric care. Applying the HEIF to the findings emphasizes the influence of societal factors on all other levels. Identified facilitators can inform interventions to address stressors in obstetric care that have resulted from the changed sociopolitical landscape of the pandemic.

Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in men with benign prostatic hyperplasia (BPH) using systematic review and meta-analysis of clinical trials. SUBJECTS: Men treated with NSAIDs in comparison with placebo or other BPH medications. METHODS: All aspects of the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) statement were followed. Trials were eligible for inclusion provided they (i) randomized men with BPH to receive NSAIDs in comparison with placebo or other BPH medications, and (ii) included clinical outcomes such as urological symptom scales, symptoms or urodynamic measurements. Data analysis was performed using REVIEW MANAGER Version 5.0 software. Study weight was calculated by the inverse variances of the study effect estimates. RESULTS: In all, 183 men from three randomized, placebo-controlled trials (lasting 4-24 weeks) were assessed. NSAIDs improved urinary symptom scores and flow measures. The weighted mean difference for the International Prostate Symptom Score (IPSS) was -2.89 IPSS points (95% CI -3.84 to -1.95, P < 0.001, n = 3 studies). The weighted mean difference for peak urine flow was 0.89 mL/s (95% CI 0.21-1.58, P = 0.01, n = 3 studies) and for reported adverse effects was 1.51 (95% CI 0.66-3.43, P = 0.32, n = 3 studies,). All patients assigned to NSAIDs continued the treatment. There were no serious adverse effects and there were no withdrawals or losses to follow-up. CONCLUSION: The evidence suggests that NSAIDs improve urinary symptoms and flow measures. Their long-term effectiveness, safety and ability to prevent BPH complications are not known.

Which graphs are rigid in ℓ p d ?

We present three results which support the conjecture that a graph is minimally rigid in d-dimensional ℓ p -space, where p ∈ ( 1 , ∞ ) and p ≠ 2 , if and only if it is (d, d)-tight. Firstly, we introduce a graph bracing operation which preserves independence in the generic rigidity matroid when passing from ℓ p d to ℓ p d + 1 . We then prove that every (d, d)-sparse graph with minimum degree at most d + 1 and maximum degree at most d + 2 is independent in ℓ p d . Finally, we prove that every triangulation of the projective plane is minimally rigid in ℓ p 3 . A catalogue of rigidity preserving graph moves is also provided for the more general class of strictly convex and smooth normed spaces and we show that every triangulation of the sphere is independent for 3-dimensional spaces in this class.

Anchored boundary conditions for locally isostatic networks.

Finite pieces of locally isostatic networks have a large number of floppy modes because of missing constraints at the surface. Here we show that by imposing suitable boundary conditions at the surface the network can be rendered effectively isostatic. We refer to these as anchored boundary conditions. An important example is formed by a two-dimensional network of corner sharing triangles, which is the focus of this paper. Another way of rendering such networks isostatic is by adding an external wire along which all unpinned vertices can slide (sliding boundary conditions). This approach also allows for the incorporation of boundaries associated with internal holes and complex sample geometries, which are illustrated with examples. The recent synthesis of bilayers of vitreous silica has provided impetus for this work. Experimental results from the imaging of finite pieces at the atomic level need such boundary conditions, if the observed structure is to be computer refined so that the interior atoms have the perception of being in an infinite isostatic environment.