Bladder cancer with pioglitazone: A case-control study.

BACKGROUND: Varied reports suggest a contentious relationship of bladder malignancy with pioglitazone in patients with type 2 diabetes. AIM: To study an association (prevalence and predictors) of bladder malignancy with pioglitazone therapy in Asian-Indian type 2 diabetes patients. METHOD: In this observational multicenter study, type 2 diabetic patients attending out-patient diabetes-clinic were evaluated. A detailed history of anti-diabetic medication, dose, duration, pioglitazone usage, time since initiation of pioglitazone, physical examination, biochemical tests and details pertaining to prevalent neuropathy, retinopathy and nephropathy were recorded. Details of bladder cancer or any malignancy (if present), time since diagnosis, risk factors for bladder cancer and histopathology records were noted. The study cohort was divided into two groups-pioglitazone ever users (Group A) and never users (Group B). RESULTS: A total of 8000 patients were screened out of which 1560 were excluded. Among 6440 included patients, 1056 (16.3%) patients were in group A and 5384 (83.6%) group B. Patients on pioglitazone were older (59.1 vs 57.7 years, p < 0.001), had longer duration of diabetes (12.7 vs 10.6 years, p < 0.001) with poor glycemic control (HbA1c 8.5 vs 8.3%, p < 0.01). A total of 74 patients had prevalent bladder cancer [16 (1.5%) in Group A and 58 in Group B (1.0%)]. Prevalent bladder cancer was not significantly greater in ever-users (odds ratio OR = 1.29, 95% confidence interval CI, 0.83-2.00) compared to never-users (odds ratio OR = 0.94, 95% confidence interval CI, 0.834-1.061) of pioglitazone (p = 0.207). However, history of hematuria in pioglitazone-users; while older age (>58 year), history of smoking and hematuria in the whole cohort were significant associated with bladder cancer. In the entire study cohort, 254 patients; 3.5% of males (128 out of 3575) and 4.6% of females (126 out of 2713) developed any malignancy. Age was significantly associated with prevalent malignancy in people with diabetes (odds ratio OR 1.036, 95% confidence interval CI: 1.022-1.051, p = 0.00) on multivariate forward regression. CONCLUSION: Pioglitazone use in Asian-Indians is not associated with an increased bladder cancer risk. However, pioglitazone should be restricted in individuals with history of hematuria. Age more than 58 years is a significant risk factor for development of any malignancy, particularly bladder cancer.

Integrity of clinical information in computerized order requisitions for diagnostic imaging.

Objective: Assess information integrity (concordance and completeness of documented exam indications from the electronic health record [EHR] imaging order requisition, compared to EHR provider notes), and assess potential impact of indication inaccuracies on exam planning and interpretation. Methods: This retrospective study, approved by the Institutional Review Board, was conducted at a tertiary academic medical center. There were 139 MRI lumbar spine (LS-MRI) and 176 CT abdomen/pelvis orders performed 4/1/2016-5/31/2016 randomly selected and reviewed by 4 radiologists for concordance and completeness of relevant exam indications in order requisitions compared to provider notes, and potential impact of indication inaccuracies on exam planning and interpretation. Forty each LS-MRI and CT abdomen/pelvis were re-reviewed to assess kappa agreement. Results: Requisition indications were more likely to be incomplete (256/315, 81%) than discordant (133/315, 42%) compared to provider notes (p < 0.0001). Potential impact of discrepancy between clinical information in requisitions and provider notes was higher for radiologist's interpretation than for exam planning (135/315, 43%, vs 25/315, 8%, p < 0.0001). Agreement among radiologists for concordance, completeness, and potential impact was moderate to strong (Kappa 0.66-0.89). Indications in EHR order requisitions are frequently incomplete or discordant compared to physician notes, potentially impacting imaging exam planning, interpretation and accurate diagnosis. Such inaccuracies could also diminish the relevance of clinical decision support alerts if based on information in order requisitions. Conclusions: Improved availability of relevant documented clinical information within EHR imaging requisition is necessary for optimal exam planning and interpretation.

Medicare Imaging Demonstration: Assessing Attributes of Appropriate Use Criteria and Their Influence on Ordering Behavior.

OBJECTIVE: Persistent concern exists about the variable and possibly inappropriate utilization of high-cost imaging tests. The purpose of this study is to assess the influence of appropriate use criteria attributes on altering ambulatory imaging orders deemed inappropriate. MATERIALS AND METHODS: This secondary analysis included Medicare Imaging Demonstration data collected from three health care systems in 2011-2013 via the use of clinical decision support (CDS) during ambulatory imaging order entry. The CDS system captured whether orders were inappropriate per the appropriate use criteria of professional societies and provided advice during the intervention period. For orders deemed inappropriate, we assessed the impact of the availability of alternative test recommendations, conflicts with local best practices, and the strength of evidence for appropriate use criteria on the primary outcome of cancellation or modification of inappropriate orders. Expert review determined conflicts with local best practices for 250 recommendations for abdominal and thoracic CT orders. Strength of evidence was assessed for the 15 most commonly triggered recommendations that were deemed inappropriate. A chi-square test was used for univariate analysis. RESULTS: A total of 1691 of 63,222 imaging test orders (2.7%) were deemed inappropriate during the intervention period; this amount decreased from 364 of 11,675 test orders (3.1%) in the baseline period (p < 0.00001). Of 270 inappropriate recommendations with alternative test recommendations, 28 (10.4%) were modified, compared with four of 1024 inappropriate recommendations without alternatives (0.4%) (p < 0.0001). Seventy-eight of 250 recommendations (31%) conflicted with local best practices, but only six of 69 inappropriate recommendations (9%) conflicted (p < 0.001). No inappropriate recommendations that conflicted with local best practices were modified. All 15 commonly triggered recommendations had an Oxford Centre for Evidence-Based Medicine level of evidence of 5 (i.e., expert opinion). CONCLUSION: Orders for imaging tests that were deemed inappropriate were modified infrequently, more often with alternative recommendations present and only for appropriate use criteria consistent with local best practices.

JOURNAL CLUB: Predictors of Provider Response to Clinical Decision Support: Lessons Learned From the Medicare Imaging Demonstration.

OBJECTIVE: The efficacy of imaging clinical decision support (CDS) varies. Our objective was to identify CDS factors contributing to imaging order cancellation or modification. SUBJECTS AND METHODS: This pre-post study was performed across four institutions participating in the Medicare Imaging Demonstration. The intervention was CDS at order entry for selected outpatient imaging procedures. On the basis of the information entered, computerized alerts indicated to providers whether orders were not covered by guidelines, appropriate, of uncertain appropriateness, or inappropriate according to professional society guidelines. Ordering providers could override or accept CDS. We considered actionable alerts to be those that could generate an immediate order behavior change in the ordering physician (i.e., cancellation of inappropriate orders or modification of orders of uncertain appropriateness that had a recommended alternative). Chi-square and logistic regression identified predictors of order cancellation or modification after an alert. RESULTS: A total of 98,894 radiology orders were entered (83,114 after the intervention). Providers ignored 98.9%, modified 1.1%, and cancelled 0.03% of orders in response to alerts. Actionable alerts had a 10 fold higher rate of modification (8.1% vs 0.7%; p < 0.0001) or cancellation (0.2% vs 0.02%; p < 0.0001) orders compared with nonactionable alerts. Orders from institutions with preexisting imaging CDS had a sevenfold lower rate of cancellation or modification than was seen at sites with newly implemented CDS (1.4% vs 0.2%; p < 0.0001). In multivariate analysis, actionable alerts were 12 times more likely to result in order cancellation or modification. Orders at sites with preexisting CDS were 7.7 times less likely to be cancelled or modified (p < 0.0001). CONCLUSION: Using results from the Medicare Imaging Demonstration project, we identified potential factors that were associated with CDS effect on provider imaging ordering; these findings may have implications for future design of such computerized systems.

A tri-marker proliferation index predicts biochemical recurrence after surgery for prostate cancer.

Prostate cancer exhibits tremendous variability in clinical behavior, ranging from indolent to lethal disease. Better prognostic markers are needed to stratify patients for appropriately aggressive therapy. By expression profiling, we can identify a proliferation signature variably expressed in prostate cancers. Here, we asked whether one or more tissue biomarkers might capture that information, and provide prognostic utility. We assayed three proliferation signature genes: MKI67 (Ki-67; also a classic proliferation biomarker), TOP2A (DNA topoisomerase II, alpha), and E2F1 (E2F transcription factor 1). Immunohistochemical staining was evaluable on 139 radical prostatectomy cases (in tissue microarray format), with a median clinical follow-up of eight years. Each of the three proliferation markers was by itself prognostic. Notably, combining the three markers together as a "proliferation index" (0 or 1, vs. 2 or 3 positive markers) provided superior prognostic performance (hazard ratio = 2.6 (95% CI: 1.4-4.9); P = 0.001). In a multivariate analysis that included preoperative serum prostate specific antigen (PSA) levels, Gleason grade and pathologic tumor stage, the composite proliferation index remained a significant predictor (P = 0.005). Analysis of receiver-operating characteristic (ROC) curves confirmed the improved prognostication afforded by incorporating the proliferation index (compared to the clinicopathologic data alone). Our findings highlight the potential value of a multi-gene signature-based diagnostic, and define a tri-marker proliferation index with possible utility for improved prognostication and treatment stratification in prostate cancer.

Is lymphadenectomy indicated in patients with T1 moderately differentiated penile cancer?

OBJECTIVE: In patients with penile squamous cell carcinomas (SCCs), lymphadenectomy can be curative and should be considered in cases deemed high risk for metastatic spread to regional lymph nodes. Management of patients without palpable lymphadenopathy remains controversial. Current guidelines for T1 penile SCCs based on previous studies have suggested that moderately differentiated tumors are at low risk for metastatic disease; however given our experience with such patients we sought to examine whether such tumors were truly observable or should be treated more aggressively. MATERIALS AND METHODS: A retrospective chart review of penile cancer cases at three institutions was performed. All slides of patients diagnosed with T1 lesions were rereviewed by our reference pathologists to confirm the original diagnosis and stage. These patients were also reviewed regarding lymphadenectomy results and clinical outcomes. RESULTS: Between 1988 and 2004, a total of 34 cases of SCC of the penis were identified, of which 10 were stage T1. Of these 10 cases, seven had moderately differentiated carcinoma without vascular invasion on pathological evaluation. Metastatic disease was present in one patient at the time of diagnosis and subsequently developed in three of the remaining six patients during follow up. Thus a total of 4 (57%) of the patients developed metastatic disease. CONCLUSIONS: Current management protocols place moderately differentiated T1 penile squamous carcinoma without vascular invasion in a low risk category for metastatic disease. As such, expectant management is currently offered as a primary option for these patients. Our experience suggests that patients in this category are in fact at higher risk for metastatic disease, and may be offered early groin dissection in place of expectant management.

Clinical presentation and urachal remnant pathology: implications for treatment.

PURPOSE: Symptomatic pediatric urachal remnants are frequently excised but to our knowledge it is unknown whether incidentally identified urachal remnants require removal. Urachal remnant excision in childhood is advocated to avoid future malignancy. Urachal anomalies that contain fibrostromal tissue without epithelium may have lower malignant potential and not require excision. In contrast, lesions with epithelium may have increased potential to undergo malignant transformation. We examined whether incidentally identified urachal remnants would be less likely to contain epithelial elements and not require removal. MATERIALS AND METHODS: At our institution 29 patients underwent surgical excision of a urachal anomaly from 1999 to 2008. We retrospectively investigated the presentation mode, radiographic findings, associated genitourinary abnormalities, operative approach, tissue pathology, complications and followup in each patient. RESULTS: The male-to-female ratio was 1.2:1. Patient presentation was incidental (5) or symptomatic (24). Symptomatic presentations included umbilical discharge without omphalitis in 13 cases, umbilical discharge with omphalitis in 7, omphalitis without umbilical discharge in 3 and urinary tract infection in 1. The epithelial types identified were transitional, gastrointestinal, squamous, metaplastic and mixed. Epithelium was present on pathological analysis in 3 of 5 patients who presented incidentally and in 17 of 24 who presented symptomatically. Statistical analysis showed no association between presentation mode and pathology (p = 0.63). Five patients 4 weeks to 2.5 months old had vesicoureteral reflux on voiding cystourethrogram for urachal remnant evaluation. CONCLUSIONS: Analysis of 29 patients with urachal anomalies showed no association between incidental presentation and fibrostromal pathology. Patients presenting without symptoms were as likely to have epithelial elements in the urachal remnant as those presenting with symptoms. We could not define treatment recommendations for incidentally identified urachal remnants based on predicting the histopathological composition.

hCAP-D3 expression marks a prostate cancer subtype with favorable clinical behavior and androgen signaling signature.

Growing evidence suggests that only a fraction of prostate cancers detected clinically are potentially lethal. An important clinical issue is identifying men with indolent cancer who might be spared aggressive therapies with associated morbidities. Previously, using microarray analysis we defined 3 molecular subtypes of prostate cancer with different gene-expression patterns. One, subtype-1, displayed features consistent with more indolent behavior, where an immunohistochemical marker (AZGP1) for subtype-1 predicted favorable outcome after radical prostatectomy. Here we characterize a second candidate tissue biomarker, hCAP-D3, expressed in subtype-1 prostate tumors. hCAP-D3 expression, assayed by RNA in situ hybridization on a tissue microarray comprising 225 cases, was associated with decreased tumor recurrence after radical prostatectomy (P=0.004), independent of pathologic tumor stage, Gleason grade, and preoperative prostate-specific antigen levels. Simultaneous assessment of hCAP-D3 and AZGP1 expression in this tumor set improved outcome prediction. We have previously demonstrated that hCAP-D3 is induced by androgen in prostate cells. Extending this finding, Gene Set Enrichment Analysis revealed enrichment of androgen-responsive genes in subtype-1 tumors (P=0.019). Our findings identify hCAP-D3 as a new biomarker for subtype-1 tumors that improves prognostication, and reveal androgen signaling as an important biologic feature of this potentially clinically favorable molecular subtype.

Workflow modeling in critical care: piecing together your own puzzle.

The intensive care unit (ICU) is an instance of a very dynamic health care setting where critically ill patients are being managed. To provide good care, an extensive and coordinated communication amongst the role players, use of numerous information systems and operation of devices for monitoring and treatment purposes are required. The purpose of this research is to study error evolution and management within this environment. The focus is on representing the workflow of critical care environment, which emphasizes the importance such a representation may play in strategizing the management of medical errors. We used ethnographic observation and interview data to build individual pieces of the workflow, dependent on the individual and the activity concerned. Key personnel were intensively followed during their respective patient care activities and the related actions. All interactions were recorded for analysis. These clinicians and nurses were interviewed to complement the observation data and to delineate their individual workflows. These pieces of the ICU workflow were used to develop a generalize-able cognitive model to represent the intricate workflow applicable to other health care settings. The proposed model can be used to identify and characterize medical errors and for error prediction in practice.

Designing the design phase of critical care devices: a cognitive approach.

In this study, we show how medical devices used for patient care can be made safer if various cognitive factors involved in patient management are taken into consideration during the design phase. The objective of this paper is to describe a methodology for obtaining insights into patient safety features--derived from investigations of institutional decision making--that could be incorporated into medical devices by their designers. The design cycle of a product, be it a medical device, software, or any kind of equipment, is similar in concept, and course. Through a series of steps we obtained information related to medical errors and patient safety. These were then utilized to customize the generic device design cycle in ways that would improve the production of critical care devices. First, we provided individuals with different levels of expertise in the clinical, administrative, and engineering domains of a large hospital setting with hypothetical clinical scenarios, each of which described a medical error event involving health professionals and medical devices. Then, we asked our subjects to "think-aloud" as they read through each scenario. Using a set of questions as probes, we then asked our subjects to identify key errors and attribute them to various players. We recorded and transcribed the responses and conducted a cognitive task analysis of each scenario to identify different entities as "constant," "partially modifiable," or "modifiable." We compared our subjects' responses to the results of the task analysis and then mapped them to the modifiable entities. Lastly, we coded the relationships of these entities to the errors in medical devices. We propose that the incorporation of these modifiable entities into the device design cycle could improve the device end product for better patient safety management.

Workflow modeling in critical care: piecing your own puzzle.

The intensive care unit (ICU) is an instance of a very dynamic health care setting where critically ill patients are being managed. It comprises of an extensive amount of communication amongst the role players, use of numerous information systems and operation of devices for monitoring and treatment purposes. The purpose of this research is to study error evolution and management within this environment. Ethnographic observation and semi-structured interview data were used to build individual pieces of the workflow dependent on the individual and the activity concerned. These pieces of the ICU workflow were used to develop a generalizable cognitive model to represent the intricate workflow in health care settings. The proposed model can be used to identify and characterize medical errors and also used for error prediction in practice.

Vascular invasion predicts recurrence after radical prostatectomy: stratification of risk based on pathologic variables.

OBJECTIVES: To determine whether vascular invasion (VI) is an independent predictor of prostate cancer recurrence and/or survival and to stratify risk of recurrence in patients with VI. METHODS: Vascular invasion status was documented in 620 radical prostatectomy specimens with an average of 7.5 years of follow-up. The relationship between VI and other clinical and pathologic features was tested. Vascular invasion as an independent predictor of recurrence was investigated by logistic regression analysis. Survival analyses and stratification of VI patients was developed with Kaplan-Meier survival curves. RESULTS: Vascular invasion was identified in 110 patients (18%) and correlated significantly (P <0.0001) with high Gleason grade, extracapsular extension (EPE), seminal vesicle invasion, increasing cancer volumes, positive margins, and elevated preoperative prostate-specific antigen (PSA) levels. Logistic regression analysis demonstrated that VI was a strong and independent predictor for disease recurrence, when considered with grade, EPE, seminal vesicle invasion, lymph node involvement, cancer volume, preoperative PSA levels, and positive margins. At 12 years after radical prostatectomy, patients with VI demonstrated significantly lower disease-specific survival (P = 0.0005). Among patients with VI, stratification of grade, EPE, and the number of VI foci identified three significantly different prognostic groups. CONCLUSIONS: In long-term follow-up, VI was a significant predictor of prostate cancer recurrence and death after radical prostatectomy. In patients with VI, high Gleason grade, EPE, and more than five foci of VI are associated with poor prognosis.

Urinary tract infections in children: treatment.

Urinary tract infection is a frequent diagnosis in children who are referred to the urologist. Infections vary in scope and severity, warranting thoughtful consideration of appropriate therapy. Infections of the genitourinary system may include bacterial,viral, fungal, or parasitic microorganisms. Adequate therapy requires rapid detection and control of these conditions to prevent pyelonephritic renal scarring and its sequelae.

Management of sternal wounds with bilateral pectoralis major myocutaneous advancement flaps in 114 consecutively treated patients: refinements in technique and outcomes analysis.

Because life-threatening sternal wound complications can occur following sternotomy, the optimal management of sternal wound infections remains an important topic. To decrease morbidity following operative treatment of these patients, the authors made a number of refinements in their treatment protocol over the past several years, particularly with regard to the extent of débridement, method of flap apposition, and management of drains. The purpose of this study was to obtain specific outcomes data by reviewing a large series of patients treated by a single surgeon. In this series of 114 consecutive sternal wounds treated by the senior author (Ascherman), patients were managed almost exclusively with débridement and immediate closure with bilateral pectoralis major myocutaneous advancement flaps. There were no intraoperative deaths. The 30-day perioperative mortality rate was 7.9 percent, with only one death directly related to sternal infection. Nineteen patients (16.7 percent) experienced postoperative morbidity, including partial wound dehiscences (5 percent), skin edge necrosis (5 percent), and seromas (3.5 percent). The authors advocate single-stage management of complicated sternal wounds with immediate débridement and bilateral pectoralis major myocutaneous advancement flaps. The procedure is rapid and effective. Refinements in technique have significantly lowered morbidity.