Association of Patient and Visit Characteristics With Rate and Timing of Urologic Procedures for Patients Discharged From the Emergency Department With Renal Colic

Importance: Little is known about the timing of urologic interventions in patients with renal colic discharged from the emergency department. Understanding patients\u27 likelihood of a subsequent urologic intervention could inform decision-making in this population. Objectives: To examine the rate and timing of urologic procedures performed after an emergency department visit for renal colic and the factors associated with receipt of an intervention. Design, Setting, and Participants: This retrospective cohort study used the Massachusetts All Payers Claims Database to identify patients 18 to 64 years of age who were seen in a Massachusetts emergency department for renal colic from January 1, 2011, to October 31, 2014, Patients were identified via International Classification of Diseases, Ninth Revision codes, and all medical care was linked, enabling identification of subsequent health care use. Data analysis was performed from January 1, 2017, to December 31, 2018. Main Outcomes and Measures: The main outcome was receipt of urologic procedure within 60 days. Secondary outcomes included rates of return emergency department visit and urologic and primary care follow-up. Results: A total of 66218 unique index visits by 55314 patients (mean [SD] age, 42.6 [12.4] years; 33 590 [50.7%] female; 25 411 [38.4%] Medicaid insured) were included in the study. A total of 5851 patients (8.8%) had visits resulting in admission at the index encounter, and 1774 (2.7%) had visits resulting in a urologic procedure during that admission. Of the 60367 patient visits resulting in discharge from the emergency department, 3018 (5.0%) led to a urologic procedure within 7 days, 4407 (7.3%) within 14 days, 5916 (9.8%) within 28 days, and 7667 (12.7%) within 60 days. A total of 3226 visits (5.3%) led to a subsequent emergency department visit within 7 days and 6792 (11.3%) within 60 days. For the entire cohort (admitted and discharged patients), 39 189 (59.2%) had contact with a urologist or primary care practitioner within 60 days. Having Medicaid-only insurance was associated with lower rates of urologic procedures (odds ratio, 0.70; 95% CI, 0.66-0.74) and urologic follow-up (5.6% vs 8.8%; P \u3c .001) and higher rates of primary care follow-up (59.2% vs 47.2%; P \u3c .001) compared with patients with all other insurance types. Conclusions and Relevance: In this cohort study, most adult patients younger than 65 years who were discharged from the emergency department with a diagnosis of renal colic did not undergo a procedure or see a urologist within 60 days. This finding has implications for both the emergency department and outpatient treatment of these patients

Quality of life impact and recovery after ureteroscopy and stent insertion: Insights from daily surveys in STENTS

BACKGROUND: Our objective was to describe day-to-day evolution and variations in patient-reported stent-associated symptoms (SAS) in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS), a prospective multicenter observational cohort study, using multiple instruments with conceptual overlap in various domains. METHODS: In a nested cohort of the STENTS study, the initial 40 participants having unilateral ureteroscopy (URS) and stent placement underwent daily assessment of self-reported measures using the Brief Pain Inventory short form, Patient-Reported Outcome Measurement Information System measures for pain severity and pain interference, the Urinary Score of the Ureteral Stent Symptom Questionnaire, and Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index. Pain intensity, pain interference, urinary symptoms, and bother were obtained preoperatively, daily until stent removal, and at postoperative day (POD) 30. RESULTS: The median age was 44 years (IQR 29,58), and 53% were female. The size of the dominant stone was 7.5 mm (IQR 5,11), and 50% were located in the kidney. There was consistency among instruments assessing similar concepts. Pain intensity and urinary symptoms increased from baseline to POD 1 with apparent peaks in the first 2 days, remained elevated with stent in situ, and varied widely among individuals. Interference due to pain, and bother due to urinary symptoms, likewise demonstrated high individual variability. CONCLUSIONS: This first study investigating daily SAS allows for a more in-depth look at the lived experience after URS and the impact on quality of life. Different instruments measuring pain intensity, pain interference, and urinary symptoms produced consistent assessments of patients\u27 experiences. The overall daily stability of pain and urinary symptoms after URS was also marked by high patient-level variation, suggesting an opportunity to identify characteristics associated with severe SAS after URS

A Multifaceted Intervention to Implement Guidelines and Improve Admission Paediatric Care in Kenyan District Hospitals: A Cluster Randomised Trial

Philip Ayieko and colleagues report the outcomes of a cluster-randomized trial carried out in eight Kenyan district hospitals evaluating the effects of a complex intervention involving improved training and supervision for clinicians. They found a higher performance of hospitals assigned to the complex intervention on a variety of process of care measures, as compared to those receiving the control intervention

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Role of systematic reviews and meta-analysis in evidence-based clinical practice

Introduction: Systematic reviews and meta-analyses of well-designed and executed randomized controlled trials have the potential to provide the highest levels of evidence to support diagnostic and therapeutic interventions in urology. Materials and Methods: The role of systematic reviews in the urological literature is described. A three-step appraisal of the validity, magnitude and applicability of results will permit an evidence-based approach to incorporating findings of systematic reviews and meta-analyses into practice. Results: The validity of systematic reviews depends on a focused clinical question that generates specific inclusion and exclusion criteria for identifying studies through an exhaustive literature search. The primary studies must be of high methodological quality and assessments should be reproducible. Informed consumers of the urological literature should be aware of the consistency of results between trials in a review, as well as the magnitude and precision of the best estimate of the treatment effects. When making decisions about implementing the results, urologists should consider all patient-important outcomes, the overall quality of the evidence and the balance between benefits, potential harms and costs. Conclusion: This framework will lead to a more evidence-based application of systematic reviews within the urological literature. Ideally, utilization of an evidence-based approach to systematic reviews will improve the quality of urological patient care

How to appraise the effectiveness of treatment

Introduction: Advances in treatment and disease prevention occur frequently in urology. Urologists must identify a framework within which to evaluate these therapeutic innovations. Materials and Methods: The evidence-based approach to critical appraisal is described using an example from the urological literature. A three-part assessment of the trial validity, treatment effect, and applicability of results will permit the urologist to critically incorporate medical and surgical advances into practice. Results: Validity of clinical trials hinges upon balancing patient prognosis at the initiation, execution, and conclusion of the trial. Readers should be aware of not only the magnitude of the estimated treatment effect, but also its precision. Finally, urologists should consider all patient-important outcomes as well as the balance of potential benefits, harms, and costs, and patient values and preferences when making treatment decisions. Conclusion: Use of this framework for critical appraisal will lead to a more evidence-based application of new therapies for patients. Incorporation of a more evidence-based practice within urology will lead to an increase in the quality of patient care

Interpreting Statistics in the Urological Literature

Purpose: Knowledge of statistical terminology and the ability to critically interpret research findings are critical skills in the practice of evidence based medicine. Materials and Methods: We provide a series of nontechnical explanations of basic statistical concepts commonly encountered in the urological literature. In addition, we provide examples of common statistical pitfalls to increase awareness of limitations to consider when applying research findings to practice. Results: Statistical goals encountered in the urological literature can be broadly categorized as summarizing outcome variables, comparing 2 or more groups, measuring association among variables or predicting 1 variable from another. Errors frequently include the use of an inappropriate test for the data type of interest or using statistical testing in a manner that increases the likelihood of false-positive results. Such errors pose a threat to the validity of research findings and they may undermine study conclusions. Conclusions: Editors and reviewers alike should strive for high standards of statistical analysis and reporting, and promote the publication of high quality evidence in the urological literature. The understanding of basic statistical concepts and the principles of the hypothesis testing framework is essential to the critical appraisal process and, therefore, important to all urologists. Statistical literacy should be fostered through educational materials and courses in the urological community. Key Words: urology, statistics, evidence-based medicine K nowledge of statistical terminology and methods has a pivotal role in the conduct of clinical research and it is an essential tool for the urologist critically appraising the literature. 5 Curricular trends in undergraduate and graduate medical education now emphasize a basic knowledge of clinical research and statistical methods as part of a broader preparation for evidence based patient care. 6 -8 Despite these efforts recent evidence suggests that statistical literacy and a knowledge of clinical research methods among urologists may be suboptimal, as among other physicians. Studies in the urological literature and other subspecialties frequently contain statistical errors or they are underpowered. 9 -12 These errors threaten to undermine the validity of published studies and flawed investigations may influence medical practice in undesirable ways. RESULTS Outcome Measures Three types of outcome measures or variables are common in biomedical research, including continuous, categorical and time to event. 15 Continuous variables have values, such that the distance between the values 3 and 5, for example, is the same as the distance between 20 and 22 or the distance between 66 and 68. Examples of continuous measures are age in years, tumor size in cm and length of hospital stay in days. Categorical variables, of which dichotomous and ordinal are special cases, are measures that have 2 or more categories with no intrinsic numerical value, eg renal cell carcinoma histology (clear cell, papillary and other). Dichotomous (binary) variables have only 2 categories, eg side right/left or stone recurrence yes/no. Many specialized statistical procedures, such as logistic regression, are used for the analysis of dichotomous data. Ordinal variables are categorical variables in which the categories can be ordered. Examples in the urology literature are Gleason score and the visual analog pain scale. Time-to-event data are frequently found in oncological studies of mortality or disease recurrence. Examples are time to death or biochemical failure as well as time to stone passage and time to urethral stricture recurrence. 16,17 Summarizing Continuous Data The first question that should arise in the analysis of a continuous outcome variable is whether the data have a normal (also called Gaussian) distribution. Since normal distributions have a bell-shaped symmetry, an approximate assessment of normality can be made by making a histo- In contrast, SEM measures variability in the distribution of sample means from the population mean. Summarizing Nonnormal Continuous Data and Ordinal Data For nonnormal continuous data or ordinal data the median and IQR are often the preferred descriptive statistics. In these cases the median is preferred over the mean because the mean may be affected by outliers or a skewed distribution. For example, let us consider a simple case of 5 men with prostate cancer who have PSA 3.5, 3.5, 4.0, 4.5 and 4.5 ng/ml, respectively. In this case the mean and median are identical (4.0 ng/ml). However, if instead we have a group of men with PSA 3.5, 3.5, 4.0, 4.5 and 15.0 ng/ml, respectively, the mean becomes 6.1, while the median remains unchanged (4.0 ng/ml). In this case when an outlier is present, the median is less affected than the mean. IQR is the range of values from the 25th to the 75th percentile of the group of subjects and it gives the reader a sense of the variability in the data. Although SD characterizes the variance of distribution even for nonnormal distributions, it cannot be interpreted in the same way. SD values are easily interpretable only if the distribution is normal.