Urinary and Sexual Impact of Robotic Radical Prostatectomy: Reporting of Patient-reported Outcome Measures in the First Year after Radical Prostatectomy in a Contemporary Multicentre Cohort in the United Kingdom.

Background and objective: Radical prostatectomy (RP) is an established treatment for localised prostate cancer that can have a significant impact on urinary and sexual function, with recovery over time. Our aim was to describe functional recovery in the first year after RP, reporting descriptive outcomes alongside validated patient-reported outcome measure scores (Expanded Prostate Cancer Index Composite, EPIC-26). Methods: Men undergoing RP between September 2015 and November 2019 completed EPIC-26 at baseline and 1, 3, 6, and 12 mo. Key findings and limitations: Overall, 2030 men consented to participation, underwent RP, and completed EPIC-26. At baseline, 97% were pad-free (1928/1996; 95% confidence interval [CI] 96-97%) and 77% were leak-free and pad-free (1529/1996; 95% CI 75-78), with a median EPIC-26 incontinence domain score of 100 (interquartile range [IQR] 86-100). At 12 mo, 65% were pad-free (904/1388; 95% CI 63-68%) and 42% were leak-free and pad-free (583/1388; 95% CI 39-45%), with a median EPIC-26 score of 76 (IQR 61-100). While one in three men reported wearing a pad at 12 mo, fewer than one in ten men needed more than 1 pad/d. At baseline, 1.9% reported a "moderate or big problem" with urine leakage, which increased to 9.7% at 12 mo. At baseline, the median sexual domain score among 1880 men was 74 (IQR 43-92) and 52% had erections sufficient for intercourse without medication (975/1880; 95% CI 50-54%). Among these 975 men, 630 responded at 12 mo, of whom 17% reported sufficient erections for intercourse (105/630; 95% CI 14-20%), without medication in 6% (37/630; 95% CI 4-8%) and needing medication in 11% (68/630; 95% CI 9-13%); the median EPIC-26 domain score was 26 (IQR 13-57). Conclusions and clinical implications: Reporting of functional outcomes after RP in terms of easily understood concepts such as pad-free and leak-free status, and erections with and with medication, alongside the classical report using EPIC-26 domain scores, increases the understanding of RP recovery patterns over the first year. Patient summary: At 12 months after surgery for prostate cancer, one in ten men reported a moderate or big problem with urine leakage and one in five men reported sufficient erections.

Lung Herniation Associated With Crack Cocaine Use: An Uncommon Cause of Chest Pain.

Lung herniation is an uncommon clinical entity characterized by protrusion of pulmonary tissue through an area of weakness in the chest wall. We present the case of a 56-year-old man with a history of chronic obstructive pulmonary disease (COPD) and crack-cocaine use who presented to the emergency department due to left-sided lateral chest pain, as well as a two-week history of cough, shortness of breath, and wheezing. Chest imaging revealed a contusion on the left flank and intercostal widening with a left-sided pulmonary herniation between ribs 8 and 9. Cardiothoracic surgery was consulted for assessment of pulmonary herniation and recommended conservative management. His pain was managed with multimodal analgesia and the patient was deemed stable for discharge. At outpatient follow-up two weeks later, his pain was well-controlled. To our knowledge, this is the first reported case of pulmonary herniation in which crack cocaine use is implicated as a contributing cause. The outcome achieved in our case supports the use of conservative management with analgesia as a valid strategy for select patients with lung herniation.

Assessment of a patient-reported outcome measure in men with prostate cancer who had radical surgery: a Rasch analysis.

OBJECTIVES: To evaluate the psychometric properties (and identify specific anomalies to be resolved) of urinary and sexual function scales of the Symptom Tracking and Reporting (STAR) instrument for use in clinical practice with individual men using Rasch analysis. DESIGN: Prospective cohort study. SETTING: 9 UK surgery centres in secondary care. PARTICIPANTS: 403 men diagnosed with prostate cancer and completed at least one questionnaire immediately before and at 1 or 3 months after radical prostatectomy. PRIMARY AND SECONDARY OUTCOMES: STAR instrument before surgery and 1 and 3 months afterwards. RESULTS: Neither scale fitted the Rasch model (both scales p<0.001). Both urinary (seven items) and sexual function (six items) had disordered thresholds, suggesting response categories are not working as intended. Both scales (three urinary items; five sexual function items) showed problems with item fit (large fit residuals, significant χ2, an inspection of item characteristic curves). Both scales showed items that were unstable over time (differential item functioning (DIF) by time). Both scales (four pairs of items in each scale) showed local response dependency (residual correlations >0.2 above the average). Internal consistency was acceptable at the group level for both scales. Targeting was poor for both scales, indicating an inadequate match between the location of items and the distribution of the patients, suggesting that the underlying constructs that the scales purport to measure are not clear. CONCLUSION: Using Rasch analysis as a diagnostic tool, we identified that both the urinary and the sexual function scales have issues that need to be resolved before STAR can be used with confidence in clinical practice. The sexual function scale, in particular, is unlikely to provide precise estimates for the outcomes experienced by men after radical prostatectomy. These results demonstrate the need to evaluate the suitability of any patient-reported outcome measure before implementation in routine clinical practice, preferably using modern psychometric methods.

Patient-reported outcome (PRO) questionnaires for men who have radical surgery for prostate cancer: a conceptual review of existing instruments.

To critically review conceptual frameworks for available patient-reported outcome (PRO) questionnaires in men having radical prostatectomy (RP), psychometrically evaluate each questionnaire, and identify whether each is appropriate for use at the level of the individual patient. We searched PubMed, the Reports and Publications database of the University of Oxford Patient-Reported Outcomes Measurement Group and the website of the International Consortium for Health Outcomes Measurement (ICHOM) for psychometric reviews of prostate cancer-specific PRO questionnaires. From these we identified relevant questionnaires and critically appraised the conceptual content, guided by the Wilson and Cleary framework and psychometric properties, using well established criteria. The searches found four reviews and one recommendation paper. We identified seven prostate cancer-specific PROs: the Expanded Prostate Cancer Index Composite-26 (EPIC-26), Expanded Prostate Cancer Index Composite-50 (EPIC-50), University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), Functional Assessment of Cancer Therapy - Prostate Cancer Subscale (FACT-P PCS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - prostate specific 25-item (EORTC QLQ-PR25), Prostate Cancer - Quality of Life (PC-QoL), and Symptom Tracking and Reporting (STAR). Six out of seven measures purported to measure health-related quality of life (HRQL), but items focused strongly on urinary and sexual symptoms/functioning. The remaining questionnaire (STAR) claimed to assess functional recovery after RP. The psychometric evidence for these questionnaires was incomplete and variable in quality; none had evidence that they were appropriate for use with individual patients. Several questionnaires provide the basis of measures of urinary and/or sexual symptoms/functioning. Further work should explore other aspects of HRQL that are important for men having RP. Further psychometric work is also needed to determine whether they can be used at the individual level.

Adeno-associated virus Rep represses the human integration site promoter by two pathways that are similar to those required for the regulation of the viral p5 promoter.

UNLABELLED: Adeno-associated virus serotype 2 (AAV2) can efficiently replicate in cells that have been infected with helper viruses, such as adenovirus or herpesvirus. However, in the absence of helper virus infection, AAV2 establishes latency by integrating its genome site specifically into PPP1R12C, a gene located on chromosome 19. This integration target site falls into one of the most gene-dense regions of the human genome, thus inviting the question as to whether the virus has evolved mechanisms to control this complex transcriptional environment in order to facilitate integration, maintain an apparently innocuous latency, and/or establish conditions that are conducive to the rescue of the integrated viral genome. The viral replication (Rep) proteins control and direct every known aspect of the viral life cycle and have been shown to tightly control all AAV2 promoters. In addition, a number of heterologous promoters are repressed by the AAV2 Rep proteins. Here, we demonstrate that Rep proteins efficiently repress expression from the target site PPP1R12C promoter. We find evidence that this repression employs mechanisms similar to those described for Rep-mediated AAV2 p5 promoter regulation. Furthermore, we show that the repression of the cellular target site promoter is based on two distinct mechanisms, one relying on the presence of a functional Rep binding motif within the 5' untranslated region (UTR) of PPP1R12C, whereas the second pathway requires only an intact nucleoside triphosphate (NTP) binding site within the Rep proteins, indicating the possible reliance of this pathway on interactions of the Rep proteins with cellular proteins that mediate or regulate cellular transcription. IMPORTANCE: The observation that repression of transcription from the adeno-associated virus serotype 2 (AAV2) p5 and integration target site promoters is mediated by shared mechanisms highlights the possible coevolution of virus and host and could lead to the identification of host factors that the virus exploits to navigate its life cycle.