Rotational Stability of Toric Intraocular Lenses by Lens Model and Haptic Design: A Systematic Review and Single-Arm Meta-Analysis.

Rotational stability is key for optimizing postoperative visual outcomes as even a small degree of rotation of a toric intraocular lens (IOL) from its target axis can result in a significant reduction of astigmatic correction. This systematic review and meta-analysis evaluated the rotational stability of toric IOLs of different lens models and haptic designs. All published studies and clinical trials that investigate postoperative rotation of toric IOLs were searched and evaluated. Quality of studies was assessed using the Methodological Index for Nonrandomized Studies (MINORS) scale. A single-arm meta-analysis was performed in R4.3.1 software with subgroup analysis performed based on lens model and haptic design. Fifty-one published studies of 4863 eyes were included in the meta-analysis. The pooled mean absolute rotation of all toric IOLs was 2.36° (95% CI: 2.08-2.64). Postoperative rotation is dependent on many aspects of lens material and design. Modern commercially available toric IOLs exhibit exceptional rotational stability.

The pipeline starts in medical school: characterizing clinician-educator training programs for U.S. medical students.

In the past forty years, clinician-educators have become indispensable to academic medicine. Numerous clinician-educator-training programs exist within graduate medical education (GME) as clinician-educator tracks (CETs). However, there is a call for the clinician-educator pipeline to begin earlier. This work aims to identify and characterize clinician-educator track-like programs (CETLs) available in undergraduate medical education (UME). We developed an algorithm of 20 individual keyword queries to search the website of each U.S. allopathic medical school for CETLs. We performed the web search between March to April 2021 and repeated the search between July and September 2021. The search identified CETLs for 79 (51%) of the 155 U.S. allopathic medical schools. The identified CETLs commonly address the clinician-educator competency of educational theory (86%, 68/79), are formally organized as concentrations or analogous structures (52%, 41/79), and span all four years of medical school (37%, 29/79). The prevalence of CETLs varies with geography and medical school ranking. We provide an overview of the current state of CETLs as assessed from institutional websites. To create a future with a sustainable output of skilled clinician-educators, UME must continue to increase the number and quality of CETLs.

Multi-Institutional Study of Dorsal Onlay Urethroplasty of the Membranous Urethra after Endoscopic Prostate Procedures: Operative Results, Continence, Erectile Function and Patient Reported Outcomes.

(1) Background: To critically evaluate dorsal onlay buccal mucosal graft urethroplasty (DOBMGU) for posterior urethral stenosis repair following transurethral resection and other endoscopic prostate procedures. (2) Methods: A retrospective multi-institutional review of patients with membranous or bulbomembranous urethral stenosis for whom treatment with DOBMGU was conducted after receipt of prostate endoscopic procedures. Baseline data, peri-operative care, post-operative care and patient-reported outcomes were analyzed. The primary outcomes were procedural failure and development of de novo stress urinary incontinence (SUI). The secondary outcomes were changes in voiding, sexual function and patient satisfaction. (3) Results: A total of 107 men with a mean age of 69 ± 9.5 years and stenosis length of 3.5 ± 1.8 cm were included. Prior endoscopic procedures among participants were 47 patients (44%) with monopolar TURP, 33 (30.8%) with bipolar TURP, 16 (15%) with Greenlight laser, 9 (8.4%) with Holmium laser enucleation and 2 (1.9%) with bladder neck incision. At a mean follow-up time of 59.3 ± 45.1 months, stenosis recurred in 10 patients (9.35%). Multivariate analysis confirmed that postoperative complications (OR 12.5; p = 0.009), history of radiation (OR 8.3; p = 0.016) and ≥2 dilatations before urethroplasty (OR 8.3; p = 0.032) were independent predictors of recurrence. Only one patient (0.9%) developed de novo SUI. Patients experienced significant improvement in PVR (128 to 60 cc; p = 0.001), Uroflow (6.2 to 16.8 cc/s; p = 0.001), SHIM (11.5 to 11.7; p = 0.028), IPSS (20 to 7.7; p < 0.001) and QoL (4.4 to 1.7; p < 0.001), and 87 cases (81.3%) reported a GRA of + 2 or better. (4) Conclusions: DOBMGU is an effective and safe option for patients with posterior urethral stenosis following TURP and other prostate endoscopic procedures. This non-transecting approach minimizes external urinary sphincter manipulation, thus limiting postoperative risk of SUI or erectile dysfunction.

Overactive bladder phenotypes: development and preliminary data.

INTRODUCTION: The purpose of this study is to develop overactive bladder (OAB) phenotypes that can be used to develop diagnostic and treatment pathways and offer clues to the underlying etiologies of patients with OAB. MATERIALS AND METHODS: This is a retrospective, multicenter study of patients with lower urinary tract symptoms (LUTS). Evaluation included a 24-hour bladder diary (24HBD), the lower urinary tract symptoms score (LUTSS) questionnaire, uroflowmetry (Q), and post-void residual urine (PVR) measurement. Patients completed the 24HBD and LUTSS on a smartphone application or paper. Those with an OAB symptom sub-score (OABSS) ≥ 8 were included. An expert panel developed a phenotype classification system based on variables considered to be important for treatment. RESULTS: The following variables were selected for inclusion in the phenotype modeling: 24-hour voided volume (24HV), maximum voided volume (MVV), Qmax and PVR. Subjects were divided into three phenotypes based on the 24HV: polyuria (24HV > 2.5 L), normal (24 HV 1-2.5 L), and oliguria (24HV < 1 L). Each phenotype was subdivided based on MVV, Qmax & PVR, resulting in 18 sub-types. Five hundred thirty-three patients, 348 men and 185 women, completed the LUTSS and 24HBD. OAB was present in 399 (75%) - 261 men and 138 women. The prevalence of the primary phenotypes was polyuria (25%), normal (63%), and oliguria (11%). CONCLUSIONS: Classification of OAB variants into phenotypes based on 24HV, MVV, Qmax, and PVR provides the substrate for further research into the diagnosis, etiology, treatment outcomes and development of granular diagnostic and treatment algorithms.

A New Paradigm for Outpatient Diagnosis and Treatment of Lower Urinary Tract Symptoms Utilizing a Mobile App/Software Platform and Remote and In-Office Visits: A Feasibility Study.

INTRODUCTION: This pilot/feasibility study evaluated a new diagnostic and treatment paradigm for patients with lower urinary tract symptoms using a software platform comprised of a mobile app, validated patient reported outcome questionnaires, bladder diaries and remote patient monitoring. METHODS: New urology referrals for lower urinary tract symptoms completed validated lower urinary tract symptoms questionnaires and 24-hour bladder diaries on a mobile app. Patients were triaged based on symptom severity into an urgent or routine office visit or a remote visit. Outcome metrics assessed include acceptability, practicality, implementation and integration. RESULTS: Of 500 urology consults there were 226 (45%) patients with new lower urinary tract symptoms referrals of whom 201 (89%) had email addresses. In all there were 182 men and 19 women, aged 18 to 87 years (mean 59, SD 17), of whom 71/201 (35%) registered, 57/71 (80%) completed the app and 41/57 (72%) elected remote visits. Mean time from urology referral to initiation of a remote or in-office diagnostic and treatment plan was 7.4 days (SD 5.9) and 7.7 days (SD 7.6), respectively. CONCLUSIONS: Of patients who completed the app 72% were triaged to a remote visit. Time from urology referral to initiation of remote or in-office diagnostic and treatment plan averaged 1 week. This paradigm for management of lower urinary tract symptoms has potential to optimize the clinical workflow, improve health care outcomes and reduce costs.

Long term results of augmentation cystoplasty and urinary diversion in multiple sclerosis.

INTRODUCTION: There is a paucity of data about augmentation cystoplasty (AC) in multiple sclerosis (MS) patients with refractory lower urinary tract symptoms (LUTS). The aim of this study is to evaluate the long term outcomes and morbidity of these procedures in MS patients. MATERIALS AND METHODS: This is a retrospective observational study of consecutive patients (1984-2017) with MS and refractory LUTS who underwent AC with or without a continent/incontinent abdominal stoma or urinary diversion. Pre and postoperative evaluations included routine labs, videourodynamic studies (VUDS), cystoscopy, and upper tract imaging. Long term outcomes and complications were assessed by validated questionnaires and/or chart review. RESULTS: There were 17 patients (12 women, 5 men) ranging in age from 34-77 years. Thirteen patients were wheelchair-bound (10 quadriplegics, 3 paraplegics). Indications included neurogenic detrusor overactivity (NDO) in two, low bladder compliance (LBC) in 13 and both NDO and LBC in two. One patient committed suicide at 3 months, and one was lost to follow up. Of the remaining 15, median follow up was 13 years (range 4-22), and 11 were followed up until death. Overall, 14/15 (93%) had a successful outcome based on the Patient Global Impression of Improvement (PGI-I). With respect to incontinence, 14/15 (93%) had a successful outcome based on the Simplified Urinary Incontinence Score (SUIS). Median bladder capacity increased from 180 mL to 605 mL (p < 0.001). Median maximum detrusor pressure decreased from 63 cm H2 O to 18 cm H2O (p < 0.003). Two patients underwent stomal stenosis revisions, four patients had pyelonephritis, and two patients developed de novo bladder stones. CONCLUSIONS: AC is a major surgical procedure with high potential morbidity, but these data suggest that AC is efficacious in the long term with acceptable morbidity and mortality. We believe it is an underutilized procedure for refractory LUTS in MS patients.

Current guidelines and treatment paradigms for nocturnal polyuria: A "NEW" disease state for US physicians, patients and payers.

Nocturia is one of the most bothersome symptoms encountered in urology, and its prevalence rises with age. Causes include both urological and non-urological aetiologies, often in combination. The effects of nocturia on a patient's quality of life can be detrimental. The initial approach to managing this condition includes appropriately classifying nocturia based on the results of a 24-hour bladder diary. Broadly, the categories under which nocturia can be classified include: low nocturnal or global bladder capacity, nocturnal polyuria, global polyuria and mixed.Based on the type of nocturia and possible underlying causes, clinicians can appropriately discuss with patients the treatment plans that may include a combination of behavioural, pharmacologic, and invasive therapy. The available literature on the management of nocturia was reviewed. Findings were incorporated into a practice-based approach for its workup and treatment.

Two herpesviral noncoding PAN RNAs are functionally homologous but do not associate with common chromatin loci.

During lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear viral long noncoding RNA known as PAN RNA becomes the most abundant polyadenylated transcript in the cell. Knockout or knockdown of KSHV PAN RNA results in loss of late lytic viral gene expression and, consequently, reduction of progeny virion release from the cell. Here, we demonstrate that knockdown of PAN RNA from the related Rhesus macaque rhadinovirus (RRV) phenocopies that of KSHV PAN RNA. These two PAN RNA homologs, although lacking significant nucleotide sequence conservation, can functionally substitute for each other to rescue phenotypes associated with the absence of PAN RNA expression. Because PAN RNA is exclusively nuclear, previous studies suggested that it directly interacts with host and viral chromatin to modulate gene expression. We studied KSHV and RRV PAN RNA homologs using capture hybridization analysis of RNA targets (CHART) and observed their association with host chromatin, but the loci differ between PAN RNA homologs. Accordingly, we find that KSHV PAN RNA is undetectable in chromatin following cell fractionation. Thus, modulation of gene expression at specific chromatin loci appears not to be the primary, nor the pertinent function of this viral long noncoding RNA. PAN RNA represents a cautionary tale for the investigation of RNA association with chromatin whereby cross-linking of DNA spatially adjacent to an abundant nuclear RNA gives the appearance of specific interactions. Similarly, PAN RNA expression does not affect viral transcription factor complex expression or activity, which is required for generation of the late lytic viral mRNAs. Rather, we provide evidence for an alternative model of PAN RNA function whereby knockdown of KSHV or RRV PAN RNA results in compromised nuclear mRNA export thereby reducing the cytoplasmic levels of viral mRNAs available for production of late lytic viral proteins.

Knowledge-Based Methods To Train and Optimize Virtual Screening Ensembles.

Ensemble docking can be a successful virtual screening technique that addresses the innate conformational heterogeneity of macromolecular drug targets. Yet, lacking a method to identify a subset of conformational states that effectively segregates active and inactive small molecules, ensemble docking may result in the recommendation of a large number of false positives. Here, three knowledge-based methods that construct structural ensembles for virtual screening are presented. Each method selects ensembles by optimizing an objective function calculated using the receiver operating characteristic (ROC) curve: either the area under the ROC curve (AUC) or a ROC enrichment factor (EF). As the number of receptor conformations, N, becomes large, the methods differ in their asymptotic scaling. Given a set of small molecules with known activities and a collection of target conformations, the most resource intense method is guaranteed to find the optimal ensemble but scales as O(2(N)). A recursive approximation to the optimal solution scales as O(N(2)), and a more severe approximation leads to a faster method that scales linearly, O(N). The techniques are generally applicable to any system, and we demonstrate their effectiveness on the androgen nuclear hormone receptor (AR), cyclin-dependent kinase 2 (CDK2), and the peroxisome proliferator-activated receptor δ (PPAR-δ) drug targets. Conformations that consisted of a crystal structure and molecular dynamics simulation cluster centroids were used to form AR and CDK2 ensembles. Multiple available crystal structures were used to form PPAR-δ ensembles. For each target, we show that the three methods perform similarly to one another on both the training and test sets.