Primary care physician PSA screening practices before and after the final U.S. Preventive Services Task Force recommendation

ObjectivesIn May 2012, United States Preventive Services Task Force (USPSTF) finalized its recommendation against prostate-specific antigen (PSA) screening in all men. We aimed to assess trends in PSA screening frequency amongst primary care physicians (PCPs) surrounding the May 2012 USPSTF recommendation.Methods and materialsThe electronic data warehouse was used to identify men aged between 40 and 79 years with no history of prostate cancer or urology visit who were evaluated by an internal medicine or family practice physician between 2007 and 2012. Analyses were directed toward PSA testing within 6-month time period from June to November, with particular focus on the 2011 (pre-USPSTF recommendation) and 2012 (post-USPSTF recommendation) cohorts. The primary outcome measure was proportion of men with at least 1 PSA test during the 6-month pre- and post-USPSTF recommendation periods.ResultsA total of 112,221 men met inclusion criteria. There was a significant decrease in screening frequency between the 2011 and 2012 cohorts (8.6% vs. 7.6%, P = 0.0001; adjusted odds ratio 0.89, 95% confidence interval 0.83–0.95). This decrease was most evident amongst patients aged 40 to 49 years (5.6% vs. 4.6%, P = 0.004) and 70 to 79 years (7.9% vs. 6.2%, P = 0.01). A significant decrease was also observed in patients with highest previous PSA value<1.0 (P<0.0001) and 1.0 to 2.49 ng/ml (P = 0.0074).ConclusionsSince the USPSTF recommendation was finalized, there is evidence of continuing decreases in PSA testing by PCPs. PCPs may be shifting toward more selective screening practices, as decreases in screening are most pronounced in the youngest and oldest patients and in those with history of PSA values<2.5 ng/ml.     

Roadmap for the development of the University of North Carolina at Chapel Hill Genitourinary OncoLogy Database—UNC GOLD

BackgroundThe management of genitourinary malignancies requires a multidisciplinary care team composed of urologists, medical oncologists, and radiation oncologists. A genitourinary (GU) oncology clinical database is an invaluable resource for patient care and research. Although electronic medical records provide a single web-based record used for clinical care, billing, and scheduling, information is typically stored in a discipline-specific manner and data extraction is often not applicable to a research setting. A GU oncology database may be used for the development of multidisciplinary treatment plans, analysis of disease-specific practice patterns, and identification of patients for research studies. Despite the potential utility, there are many important considerations that must be addressed when developing and implementing a discipline-specific database.Methods and materialsThe creation of the GU oncology database including prostate, bladder, and kidney cancers with the identification of necessary variables was facilitated by meetings of stakeholders in medical oncology, urology, and radiation oncology at the University of North Carolina (UNC) at Chapel Hill with a template data dictionary provided by the Department of Urologic Surgery at Vanderbilt University Medical Center. Utilizing Research Electronic Data Capture (REDCap, version 4.14.5), the UNC Genitourinary OncoLogy Database (UNC GOLD) was designed and implemented.ResultsThe process of designing and implementing a discipline-specific clinical database requires many important considerations. The primary consideration is determining the relationship between the database and the Institutional Review Board (IRB) given the potential applications for both clinical and research uses. Several other necessary steps include ensuring information technology security and federal regulation compliance; determination of a core complete dataset; creation of standard operating procedures; standardizing entry of free text fields; use of data exports, queries, and de-identification strategies; inclusion of individual investigators' data; and strategies for prioritizing specific projects and data entry.ConclusionsA discipline-specific database requires a buy-in from all stakeholders, meticulous development, and data entry resources to generate a unique platform for housing information that may be used for clinical care and research with IRB approval. The steps and issues identified in the development of UNC GOLD provide a process map for others interested in developing a GU oncology database.     

Persistence of urothelial carcinoma of the bladder risk among former smokers: Results from a contemporary,prospective cohort study

ObjectivesCigarette smoking is a known risk factor for urothelial carcinoma (UC) of the bladder. However, the persistence of an increased risk for UC following smoking cessation is not well established. We assessed the risk of UC among former smokers using a recent, prospective cohort with a high proportion of former smokers.Materials and methodsStudy participants were members of the VITamins And Lifestyle cohort (VITAL), a group of 77,719 men and women between the ages of 50 and 76 years from western Washington State. Smoking history and other risk factors were obtained at the time of recruitment. The primary outcome was a new diagnosis of UC (n =385), as determined through linkage to a population-based cancer registry.Results and limitationsThe cohort included 8% current and 44% former smokers, and among the UC cases, 15% were current and 60% former smokers. Both the current and former smoker had an increased risk of UC compared with never smokers (hazard ratio [HRs]: 3.81; 95% confidence intervals [CI] 2.71–5.35 and 2.0; 95% CI 1.55–2.58, respectively). Among former smokers, the risk of UC increased with the pack-years smoked and decreased with the years since quitting. When both the measures of smoking were considered together, the risk of UC was similar for long-term quitters and recent quitters for a given level of pack-years. For example, for those with pack-years of 22.5–37.5, the HR of UC was 1.91 (95% CI 1.17–3.11) for the distant quitters (≥23.5 y before baseline) and HR = 1.92 (95% CI 1.26–2.94) among the recent quitters. Limitations include the small number of cases at the extremes of smoking history and errors in self-reported smoking history.ConclusionsThe risk of bladder cancer in former smokers remains elevated>32 years after quitting, even among those with moderate smoking histories. This argues that a history of smoking confers a lifelong increased risk of UC.     

Surgical Treatment for Women with Breast Cancer in Relation to Socioeconomic and Insurance Status

Based on the National Breast Cancer Audit of the Royal Australasian College of Surgeons an association between patient age and type of breast cancer surgery received has already been demonstrated. The aim of this study is to assess the patterns of surgical treatment for women with early breast cancer in relation to socioeconomic and insurance status. Data on patient demographics, diagnostic, and surgical procedures and cancer characteristics in 115,872 episodes of early breast cancer reported to the National Breast Cancer Audit between 1998 and 2012 is used for this study. Tumor size, histologic grade, number of tumors, lymph node positivity, and lymphovascular invasion are the major prognostic factors adjusted for. Reconstruction following mastectomy is the most likely surgical procedure for the higher socioeconomic and privately insured patients. Mastectomy alone is the most likely surgical procedure for the lower socioeconomic and for public patients. No surgery is the most likely surgical outcome for the lower socioeconomic and the least likely for the higher socioeconomic population. Open biopsy is the most likely diagnostic procedure for the lower socioeconomic and fine needle aspiration for the higher socioeconomic population. Socioeconomic and insurance status, are both independently associated with the types of treatment and diagnostic procedure for women with breast cancer. Opportunities present to investigate an association of these factors with morbidity and survival outcomes.     

Clinical Features of Bacterial Conjunctivitis in Children

Objectives
Conjunctivitis is a common cause of primary care and emergency department (ED) visits. There is a paucity of data in recent literature on the prevalence of pediatric bacterial conjunctivitis, and there are no evidence-based clinical guidelines for empirical treatment. The study objective was to describe clinical features most predictive of bacterial conjunctivitis.
Methods
This was a prospective study in a children's hospital ED. Conjunctival swabs for bacterial culture were obtained from patients aged 1 month to 18 years presenting with red or pink eye and/or the diagnosis of conjunctivitis.
Results
A total of 111 patients were enrolled over one year. Patients had a mean (±SD) age of 33.2 (±37.5) months, and 55% were male. Eighty-seven patients (78%) had positive bacterial cultures. Nontypeable Haemophilus influenzae accounted for 82% (71/87), Streptococcus pneumoniae for 16% (14/87), and Staphylococcus aureus for 2.2% (2/87). Five clinical variables were significantly associated with a positive bacterial culture. Regression analysis revealed that the combination of a history of gluey or sticky eyelids and the physical finding of mucoid or purulent discharge had a posttest probability of 96% (95% confidence interval = 90% to 99%). Subjective scoring by physicians for a positive culture was 50.6%.
Conclusions
Conjunctivitis in children is predominantly bacterial, with nontypeable H. influenzae being the most common organism. A history of gluey or sticky eyelids and physical findings of mucoid or purulent discharge are highly predictive of bacterial infection. Based on the above data, empirical ophthalmic antibiotic therapy may be appropriate in children presenting with conjunctivitis.     

Global Analysis Reveals the Complexity of the Human Glomerular Extracellular Matrix

The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the cellular components have helped to build understanding of glomerular disease; however, the full composition and regulation of glomerular ECM remains poorly understood. We used mass spectrometry-based proteomics of enriched ECM extracts for a global analysis of human glomerular ECM in vivo and identified a tissue-specific proteome of 144 structural and regulatory ECM proteins. This catalog includes all previously identified glomerular components plus many new and abundant components. Relative protein quantification showed a dominance of collagen IV, collagen I, and laminin isoforms in the glomerular ECM together with abundant collagen VI and TINAGL1. Protein network analysis enabled the creation of a glomerular ECM interactome, which revealed a core of highly connected structural components. More than one half of the glomerular ECM proteome was validated using colocalization studies and data from the Human Protein Atlas. This study yields the greatest number of ECM proteins relative to previous investigations of whole glomerular extracts, highlighting the importance of sample enrichment. It also shows that the composition of glomerular ECM is far more complex than previously appreciated and suggests that many more ECM components may contribute to glomerular development and disease processes. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000456.The glomerulus is a sophisticated organelle comprising unique cellular and extracellular matrix (ECM) components. Fenestrated capillary endothelial cells and overlying podocytes are separated by a specialized glomerular basement membrane (GBM), and these three components together form the filtration barrier. Mesangial cells and their associated ECM, the mesangial matrix, exist between adjacent capillary loops and maintain the three-dimensional organization of the capillary bundle. In turn, the parietal epithelial cells and ECM of Bowman’s capsule enclose this network of capillaries. Cells adhere to ECM proteins by adhesion receptors, and these interactions are required to maintain intact barrier function of the glomerulus.^1,2In addition to operating as a signaling platform, ECM provides a structural scaffold for adjacent cells and has a tissue-specific molecular composition.^3,4 Candidate-based investigations of glomerular ECM have focused on the GBM and shown that it resembles the typical basal lamina found in multicellular organisms, containing a core of glycoproteins (collagen IV, laminins, and nidogens) and heparan sulfate proteoglycans (agrin, perlecan, and collagen XVIII).⁵ Mesangial and parietal cell ECMs have been less well investigated; nonetheless, they are also thought to contain similar core components in addition to other glycoproteins, including fibronectin.^6,7 Thus, the glomerulus consists of a combination of condensed ECM within the GBM and Bowman’s capsule and loose ECM supporting the mesangial cells.The ECM compartments in the glomerulus are thought to be distinct and exhibit different functional roles. The GBM is integral to the capillary wall and therefore, functionally linked to glomerular filtration.⁵ Mutations of tissue-restricted isoforms of collagen IV (COL4A3, COL4A4, and COL4A5) and laminin (LAMB2), which are found in the GBM, cause significant barrier dysfunction and ultimately, renal failure.^8,9 Less is understood about the functions of mesangial and parietal cell ECMs, although expansion of the mesangial compartment is a histologic pattern seen across the spectrum of glomerular disease.¹⁰Compositional investigation of the distinct glomerular ECM compartments is limited by the technical difficulties of separation. Early investigations of GBM constituents used the relative insolubility of ECM proteins to facilitate separation from cellular proteins in the glomerulus but did not separate the GBM from mesangial and parietal cells ECMs.^11,12 Recently, studies incorporating laser microdissection of glomerular sections have been coupled with proteomic analyses.^13,14 These studies report both cellular and ECM components and typically require pooled material from glomerular sections to improve protein identification. The ability of laser microdissection to separate glomerular ECM compartments has not yet been tested; however, this approach will be limited by the amount of protein that is possible to retrieve. To achieve good coverage of ECM proteins within a tissue, proteomic studies need to combine a reduction in sample complexity with maximal protein quantity. Currently, the inability to separate glomerular ECM compartments in sufficient quantity is a limitation that prohibits proteomic studies of these structures; however, for other tissues, proteomic analysis of ECM has been achieved by enrichment of ECM combined with sample fractionation.¹⁵Although the composition of the ECM in other tissues has been addressed using proteomic approaches,¹⁵ studies of glomerular ECM to date have used candidate-based technologies. These studies have identified key molecular changes during development and disease and highlighted the compositional and organizational dynamics of glomerular ECM. Nonetheless, the extracellular environment within the glomerulus is the setting for a complex series of interactions between both structural ECM proteins and ECM-associated proteins, such as growth factors^16–18 and proteases,¹⁹ which together provide a specialized niche to support glomerular cell function. Therefore, to interrogate this complexity effectively, a systems-level understanding of glomerular ECM is required. To address the need for a global analysis of the extracellular environment within the glomerulus, we used mass spectrometry (MS)-based proteomics of glomerular ECM fractions to define the human glomerular ECM proteome.