eScholarship@UMMS

Syndicate content
Recent documents in eScholarship@UMMS
Updated: 55 min 47 sec ago

Use of Indwelling Urinary Catheters in Nursing Homes: Implications for Quality Improvement Efforts

Sun, 05/28/2017 - 6:08pm

OBJECTIVES: To describe the epidemiology of indwelling urinary catheter use in nursing homes (NHs). DESIGN: Observational cohort study. SETTING: A purposeful sampling strategy was used to identify a diverse sample of 28 Connecticut NHs, defined in terms of ownership, quality ratings, and bed size.

PARTICIPANTS: Long-stay (>100 days) residents of study NHs with an indwelling urinary catheter present at any time over a 1-year period.

MEASUREMENTS: Duration of catheter use was determined, and indications for catheter placement were documented. Indications considered appropriate included urinary retention or outlet obstruction, pressure ulcer (Stage 3 or 4 with risk of contamination by urine), hospice care, and need for accurate measurement of input and output. During quarterly follow-up assessments, whether the catheter was still in place or had been removed for any reason other than routine maintenance was determined.

RESULTS: The overall rate of any urinary catheter use per 100 resident-beds over a 1-year period was 4.8 (range 1.0-9.9, median 5.1). Of the 228 residents meeting eligibility criteria, a documented indication for the catheter was present in the NH record for 195 (86%). Of those with a documented indication, 99% (n = 193) had one or more indications deemed appropriate, including urinary retention (83%), pressure ulcer (21%), hospice care (10%), and need for accurate measurement of input and output (6%). The urinary catheter was removed at some point during the period of observation in 49% (n = 111) of participants; those with a shorter duration of catheter use before study enrollment were more likely to have the catheter removed during the follow-up period. Of the 111 residents who had the catheter removed, 58 (52.3%) had it reinserted at some point during follow-up.

CONCLUSION: These findings suggest that indwelling urinary catheter use in long-stay NH residents is uncommon and generally appropriate and that efforts to improve catheter care and outcomes should extend beyond a singular focus on reducing use.

The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury

Sun, 05/28/2017 - 6:08pm

Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents. Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Our results suggest that AIM2 may be a new therapeutic target for ionizing radiation exposure.

Racial and Ethnic Disparities in Contraceptive Use in Young Women

Fri, 05/26/2017 - 11:50am

Background: Young women have the highest rates of unintended pregnancies among reproductive­ aged women. Black and Latina women are at highest risk. Few studies have examined reasons for these differences. In this study, we examined disparities in contraceptive use and contraceptive counseling by race and ethnicity among young women.

Methods: Using the 2011-2013 National Survey of Family Growth (NSFG), a cross-sectional, nationally representative database, our analysis included women aged 15-24 years who had sexual intercourse within the past year, and were not pregnant or seeking pregnancy. The primary outcomes were contraceptive use and receipt of contraceptive services within the past 12 months.

Results: Young women who identify as Hispanic (H) or Non-Hispanic Black (NHB) are less likely to report current contraceptive use than their non-Hispanic White (NHW) or Non-Hispanic Other (NHO) counterparts. This finding remains statistically significant among NHB women after controlling for confounders (H: adjusted OR=0.57±0.17, 95% CI [0.32, 1.02]; NHB: adjusted OR=0.51±0.13, 95% CI [0.31-0.82;] NHO: OR=1.91±0.67, 95% CI [0.96, 3.81]). There were no differences in birth control counseling received by race/ethnicity. However, NHW and NHO were more likely to have been issued contraception within the last 12 months (H: 49.6%, NHB: 49.0%, NHW: 60.1%, NHO: 64.8; p=0.047).

Conclusions/Implications: Young Black and Latina women are less likely to use contraception than other racial and ethnic groups; this difference persists among young black women after controlling for sociodemographic differences. Future studies should explore reasons for the decreased contraceptive usage rate among young black women.

Changes in Physician Decision Making after CT: A Prospective Multicenter Study in Primary Care Settings

Fri, 05/26/2017 - 11:50am

Purpose: To determine the effect of computed tomography (CT) results on physician decision making in three common clinical scenarios in primary care.

Materials and Methods: This research was approved by the institutional review board (IRB) and was HIPAA compliant. All physicians consented to participate with an opt-in or opt-out mechanism; patient consent was waived with IRB approval. In this prospective multicenter observational study, outpatients referred by primary care providers (PCPs) for CT evaluation of abdominal pain, hematuria, or weight loss were identified. Prior to CT, PCPs were surveyed to elicit their leading diagnosis, confidence in that diagnosis (confidence range, 0%-100%), a rule-out diagnosis, and a management plan if CT were not available. Surveys were repeated after CT. Study measures were the proportion of patients in whom leading diagnoses and management changed (PCP management vs specialist referral vs emergency department transfer), median changes in diagnostic confidence, and the proportion of patients in whom CT addressed rule-out diagnoses. Regression analyses were used to identify associations between study measures and site and participant characteristics. Specifically, logistic regression analysis was used for binary study measures (change in leading diagnosis, change in management), and linear regression analysis was used for the continuous study measure (change in diagnostic confidence). Accrual began on September 5, 2012, and ended on June 28, 2014.

Results: In total, 91 PCPs completed pre- and post-CT surveys in 373 patients. In patients with abdominal pain, hematuria, or weight loss, leading diagnoses changed after CT in 53% (131 of 246), 49% (36 of 73), and 57% (27 of 47) of patients, respectively. Management changed in 35% (86 of 248), 27% (20 of 74), and 54% (26 of 48) of patients, respectively. Median absolute changes in diagnostic confidence were substantial and significant (+20%, +20%, and +19%, respectively; P≤ .001 for all); median confidence after CT was high (90%, 88%, and 80%, respectively). PCPs reported CT was helpful in confirming or excluding rule-out diagnoses in 98% (184 of 187), 97% (59 of 61), and 97% (33 of 34) of patients, respectively. Significant associations between primary measures and site and participant characteristics were not identified.

Conclusion: Changes in PCP leading diagnoses and management after CT were common, and diagnostic confidence increased substantially.

Role of CT in the Diagnosis of Nonspecific Abdominal Pain: A Multicenter Analysis

Fri, 05/26/2017 - 11:50am

OBJECTIVE: The objective of our study was to determine whether specific patient and physician factors-known before CT-are associated with a diagnosis of nonspecific abdominal pain (NSAP) after CT in the emergency department (ED).

MATERIALS AND METHODS: We analyzed data originally collected in a prospective multicenter study. In the parent study, we identified ED patients referred to CT for evaluation of abdominal pain. We surveyed their physicians before and after CT to identify changes in leading diagnoses, diagnostic confidence, and admission decisions. In the current study, we conducted a multiple regression analysis to identify whether the following were associated with a post-CT diagnosis of NSAP: patient age; patient sex; physicians' years of experience; physicians' pre-CT diagnostic confidence; and physicians' pre-CT admission decision if CT had not been available. We analyzed patients with and those without a pre-CT diagnosis of NSAP separately. For the sensitivity analysis, we excluded patients with different physicians before and after CT.

RESULTS: In total, 544 patients were included: 10% (52/544) with a pre-CT diagnosis of NSAP and 90% (492/544) with a pre-CT diagnosis other than NSAP. The leading diagnoses changed after CT in a large proportion of patients with a pre-CT diagnosis of NSAP (38%, 20/52). In regression analysis, we found that physicians' pre-CT diagnostic confidence was inversely associated with a post-CT diagnosis of NSAP in patients with a pre-CT diagnosis other than NSAP (p = 0.0001). No other associations were significant in both primary and sensitivity analyses.

CONCLUSION: With the exception of physicians' pre-CT diagnostic confidence, the factors evaluated were not associated with a post-CT diagnosis of NSAP.

An Old Idea Revisited: Reflections on the Role of Aesthetic Surgery in Behavioral and Social Change

Fri, 05/26/2017 - 11:49am

Although the notion that an individual’s morality can be changed from bad to good solely with a procedure that improves physical appearance is controversial, the relationship between appearance and behavior is complex and pertinent to an individual’s psychology and quality of life. Where plastic surgery comes into play, as either treatment or adjuvant therapy, remains to be determined.

Antibiotic-associated diarrhoea in emergency department observation unit patients

Fri, 05/26/2017 - 11:49am

Clostridium difficile diarrhoea is an urgent threat to patients, but little is known about the role of antibiotic administration that starts in emergency department observation units (EDOUs). We studied risk factors for antibiotic-associated diarrhoea (AAD) and C. difficile infection (CDI) in EDOU patients. This prospective cohort study enrolled adult patients discharged after EDOU antibiotic treatment between January 2013 and 2014. We obtained medical histories, EDOU treatment and occurrence of AAD and CDI over 28 days after discharge. We enrolled and followed 275 patients treated with antibiotics in the EDOU. We found that 52 (18.6%) developed AAD and four (1.5%) had CDI. Patients treated with vancomycin [relative risk (RR) 0.52, 95% confidence interval (CI) 0.3-0.9] were less likely to develop AAD. History of developing diarrhoea with antibiotics (RR 3.11, 95% CI 1.92-5.03) and currently failing antibiotics (RR 1.90, 95% CI 1.14-3.16) were also predictors of AAD. Patients with CDI were likely to be treated with clindamycin. In conclusion, AAD occurred in almost 20% of EDOU patients with risk factors including a previous history of diarrhoea with antibiotics and prior antibiotic therapy, while the risk of AAD was lower in patients receiving treatment regimens utilizing intravenous vancomycin.

External Volume Expansion in Irradiated Tissue: Effects on the Recipient Site

Fri, 05/26/2017 - 11:49am

BACKGROUND: External volume expansion prepares recipient sites to improve outcomes of fat grafting. For patients receiving radiotherapy after mastectomy, results with external volume expansion vary, and the relationship between radiotherapy and expansion remains unexplored. Thus, the authors developed a new translational model to investigate the effects in chronic skin fibrosis after radiation exposure.

METHODS: Twenty-four SKH1-E mice received 50 Gy of beta-radiation to each flank and were monitored until fibrosis developed (8 weeks). External volume expansion was then applied at -25 mmHg to one side for 6 hours for 5 days. The opposite side served as the control. Perfusion changes were assessed with hyperspectral imaging. Mice were euthanized at 5 (n = 12) and 15 days (n = 12) after the last expansion application. Tissue samples were analyzed with immunohistochemistry for CD31 and Ki67, Masson trichrome for skin thickness, and picrosirius red to analyze collagen composition.

RESULTS: All animals developed skin fibrosis 8 weeks after radiotherapy and became hypoperfused based on hyperspectral imaging. Expansion induced edema on treated sides after stimulation. Perfusion was decreased by 13 percent on the expansion side (p < 0.001) compared with the control side for 5 days after stimulation. Perfusion returned to control-side levels by day 15. Dermal vasculature increased 38 percent by day 15 (p < 0.01) in expansion versus control. No difference was found in collagen composition.

CONCLUSIONS: External volume expansion temporarily reduces perfusion, likely because of transient ischemia or edema. Together with mechanotransduction, these effects encourage a proangiogenic and proliferative environment in fibrotic tissue after radiotherapy in the authors' mouse model. Further studies are needed to assess these changes in fat graft retention.

The use of in-situ simulation to improve safety in the plastic surgery office: a feasibility study

Fri, 05/26/2017 - 11:49am

OBJECTIVE: Simulation-based interventions and education can potentially contribute to safer and more effective systems of care. We utilized in-situ simulation to highlight safety issues, regulatory requirements, and assess perceptions of safety processes by the plastic surgery office staff.

METHODS: A high-fidelity human patient simulator was brought to an office-based plastic surgery setting to enact a half-day full-scale, multidisciplinary medical emergency. Facilitated group debriefings were conducted after each scenario with special consideration of the principles of team training, communication, crisis management, and adherence to evidence-based protocols and regulatory standards. Abbreviated AHRQ Medical Office Safety Culture Survey was completed by the participants before and after the session.

RESULTS: The in-situ simulations had a high degree of acceptance and face validity according to the participants. Areas highlighted by the simulation sessions included rapid communication, delegation of tasks, location of emergency materials, scope of practice, and logistics of transport. The participant survey indicated greater awareness of patient safety issues following participation in simulation and debriefing exercises in 3 areas (P < 0.05): the need to change processes if there is a recognized patient safety issue (100% vs 75%), openness to ideas about improving office processes (100% vs 88%), and the need to discuss ways to prevent errors from recurring (88% vs 62%).

CONCLUSIONS: Issues of safety and regulatory compliance can be assessed in an office-based setting through the short-term (half-day) use of in-situ simulation with facilitated debriefing and the review of audiovisual recordings by trained facilities inspectors.

Decreased Thromboembolic Stroke but not Atherosclerosis or Vascular Remodeling in Mice with ROCK2-deficient Platelets

Wed, 05/24/2017 - 4:34pm

Aims: Rho-associated coiled-coil containing kinase (ROCK)-2 is an important mediator of the actin cytoskeleton. Because changes in the actin cytoskeleton are critical for platelet function, we hypothesized that ROCK2 in platelets will play important role in thrombosis and can be potentially a target for therapeutic intervention in thromboembolic stroke.

Methods and Results: We generated platelet-specific ROCK2-deficient mice (ROCK2 Plt-/- ) from conditional ROCK2 fl degrees x/fl degrees x and platelet factor (PF)-4-Cre transgenic mice. Platelets from ROCK2 Plt-/- mice were less responsive to thrombin stimulation in terms of pseudopodia formation, collagen adhesion, and in the formation of homotypic and heterotypic aggregates. This corresponded to prolonged bleeding time and delayed vascular occlusion following vessel injury. To determine whether these changes in platelet function could affect thrombotic disease, we utilized a clot-embolic model of ischemic stroke. When pre-formed clots from ROCK2 Plt-/- mice were injected into the middle cerebral artery of control mice, cerebral blood flow recovery occurred more rapidly, leading to decreased cerebral injury and neurological deficits, compared to pre-formed clots from control mice. Interestingly, pre-formed clots from control mice produced similar degree of cerebral injury when injected into control or ROCK2 Plt-/- mice, suggesting that platelet ROCK2 deficiency affects clot formation but not propagation. Indeed, in a non-thrombotic intra-filament MCA occlusion model of stroke, platelet ROCK2 deletion was not protective. Furthermore, ROCK2 Plt-/- mice exhibit similar atherosclerosis severity and vascular remodeling as control mice.

Conclusion: These findings indicate that platelet ROCK2 plays important role in platelet function and thrombosis, but does not contribute to the pathogenesis of atherosclerosis and vascular remodeling.

RUNX1 and breast cancer

Wed, 05/24/2017 - 4:34pm

News on: Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition, by Hong et al. Oncotarget. 2017; 8:17610-27. doi: 10.18632/oncotarget.15381.

Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics

Wed, 05/24/2017 - 4:34pm

The human microbiota greatly affects physiology and disease; however, the contribution of bacteria to the response to chemotherapeutic drugs remains poorly understood. Caenorhabditis elegans and its bacterial diet provide a powerful system to study host-bacteria interactions. Here, we use this system to study how bacteria affect the C. elegans response to chemotherapeutics. We find that different bacterial species can increase the response to one drug yet decrease the effect of another. We perform genetic screens in two bacterial species using three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FUDR), and camptothecin (CPT). We find numerous bacterial nucleotide metabolism genes that affect drug efficacy in C. elegans. Surprisingly, we find that 5-FU and FUDR act through bacterial ribonucleotide metabolism to elicit their cytotoxic effects in C. elegans rather than by thymineless death or DNA damage. Our study provides a blueprint for characterizing the role of bacteria in the host response to chemotherapeutics.

Unravelling the pleiotropic role of the MceG ATPase in Mycobacterium smegmatis

Wed, 05/24/2017 - 4:34pm

The Mce systems are complex ABC transporters that are encoded by different numbers of homologous operons in Actinobacteria. While the four Mce systems of Mycobacterium tuberculosis are all energized by a single ATPase, MceG, each system appears to import different fatty acids or sterols. To explore if this behaviour can be extended to saprophytic mycobacteria, whose more complex genomes encode more Mce systems, we have identified and characterized the MceG orthologue of Mycobacterium smegmatis. This bacterium relies on MceG to energize its six Mce systems that contribute to a variety of cellular functions including sterol uptake and cell envelope maintenance. In the absence of MceG, M. smegmatis was not able to utilize cholesterol or phytosterols as carbon sources implying that this ATPase is necessary to energize the Mce4-sterol transport system. Other phenotypic alterations observed in the DeltaMceG mutant, such as cell envelope modifications, suggest a pleiotropic functionality of the Mce systems that are particularly important for stress responses. Several DeltaMceG phenotypes were recapitulated in a strain lacking only the unique C-terminal region of MceG, suggesting an important functional or regulatory function for this domain.

The Complex Roles of Mechanistic Target of Rapamycin in Adipocytes and Beyond

Wed, 05/24/2017 - 4:34pm

Having healthy adipose tissue is essential for metabolic fitness. This is clear from the obesity epidemic, which is unveiling a myriad of comorbidities associated with excess adipose tissue including type 2 diabetes, cardiovascular disease, and cancer. Lipodystrophy also causes insulin resistance, emphasizing the importance of having a balanced amount of fat. In cells, the mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2, respectively) link nutrient and hormonal signaling with metabolism, and recent studies are shedding new light on their in vivo roles in adipocytes. In this review, we discuss how recent advances in adipose tissue and mTOR biology are converging to reveal new mechanisms that maintain healthy adipose tissue, and discuss ongoing mysteries of mTOR signaling, particularly for the less understood complex mTORC2.

The Vitiligo Working Group recommendations for narrowband ultraviolet B light phototherapy treatment of vitiligo

Wed, 05/24/2017 - 4:34pm

BACKGROUND: Treatment of vitiligo with narrowband ultraviolet B light (NBUVB) is an important component of the current standard of care. However, there are no consistent guidelines regarding the dosing and administration of NBUVB in vitiligo, reflected by varied treatment practices around the world.

OBJECTIVE: To create phototherapy recommendations to facilitate clinical management and identify areas requiring future research.

METHODS: The Vitiligo Working Group (VWG) Phototherapy Committee addressed 19 questions regarding the administration of phototherapy over 3 conference calls. Members of the Photomedicine Society and a group of phototherapy experts were surveyed regarding their phototherapy practices.

RESULTS: Based on comparison and analysis of survey results, expert opinion, and discussion held during conference calls, expert recommendations for the administration of NBUVB phototherapy in vitiligo were created.

LIMITATIONS: There were several areas that required further research before final recommendations could be made. In addition, no standardized methodology was used during literature review and to assess the strength of evidence during the development of these recommendations.

CONCLUSION: This set of expert recommendations by the VWG is based on the prescribing practices of phototherapy experts from around the world to create a unified, broadly applicable set of recommendations on the use of NBUVB in vitiligo.

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity

Wed, 05/24/2017 - 4:34pm

BACKGROUND: Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies.

OBJECTIVE: To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects.

METHODS: Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups.

RESULTS: In screening and validation, CD8+ T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3.

LIMITATIONS: A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response.

CONCLUSION: Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.

The role of RNA uptake in platelet heterogeneity

Wed, 05/24/2017 - 4:34pm

The role of platelets in regulating vascular homeostasis has expanded beyond mediation of haemostasis and thrombosis. The discovery of platelet RNA and the presence of subpopulations of platelets containing varying amounts of RNA suggest a role for platelet transcripts in vascular function. As the RNA in anucleated platelets is biologically functional and may transfer to other vascular cells, we hypothesised that platelet RNA diminishes over the lifespan of the platelet with diminishing platelet size due to horizontal cellular transfer. The purpose of this study is to determine if platelet RNA variance is the result of horizontal cellular transfer between platelets and other vascular cells. Utilising platelet sorting and RNA sequencing, we found that smaller platelets contained a more diverse set of transcripts than larger platelets. Further investigation using fluorescence imaging, gene expression analyses and in vitro and in vivo modelling revealed that platelets take up RNA from other vascular cells in a complex manner, revealing a dynamic role for platelets in modulating vascular homeostasis through bidirectional RNA transfer. The resultant RNA profile heterogeneity suggests unique functional roles for platelets dependent on size and complexity. This study expands our basic understanding of platelet function and heterogeneity and is the first to evaluate endogenous vascular RNA uptake and its relation to platelet processes. Our findings describe a novel endogenous phenomenon that can help elucidate the platelet's role in these non-thrombotic and haemostatic fields, as well as present potential for diagnostic and therapeutic development.

Integrating the UPRmt into the mitochondrial maintenance network

Wed, 05/24/2017 - 4:34pm

Mitochondrial function is central to many different processes in the cell, from oxidative phosphorylation to the synthesis of iron-sulfur clusters. Therefore, mitochondrial dysfunction underlies a diverse array of diseases, from neurodegenerative diseases to cancer. Stress can be communicated to the cytosol and nucleus from the mitochondria through many different signals, and in response the cell can effect everything from transcriptional to post-transcriptional responses to protect the mitochondrial network. How these responses are coordinated have only recently begun to be understood. In this review, we explore how the cell maintains mitochondrial function, focusing on the mitochondrial unfolded protein response (UPRmt), a transcriptional response that can activate a wide array of programs to repair and restore mitochondrial function.

Purposeful Pathway: Strategic Plan 2016-2020

Wed, 05/24/2017 - 3:19pm

Introduction: The Lamar Soutter Library (LSL) is a Purposeful Library. A purposeful library is one that engages its users and aligns its mission and goals to the larger institution. The LSL will fulfill its missions of service, education, and research by capitalizing on the strengths of its staff and collections. It will demonstrate leadership in its commitment to interdisciplinary activities that serve all its users and provide them the resources they need when they need it. LSL’s commitment to service is a programmatic approach using a purposeful plan of action that is both strategic and nimble enough to adapt to the rapidly changing health sciences, technology, and information environment. Having a purpose that is clear, meaningful, and intentional, while at the same time flexible, helps position LSL as the core knowledge and cultural base of UMMS. Preparing students for a career in the health professions, assisting faculty with their research and classroom activities, and providing evidence based information in support of patient care have always been important dimensions of LSL’s work. But in today’s world, these goals need to be achieved with greater focus and effectiveness. We believe this “Purposeful Pathway” gives meaning and relevance to LSL as we embark on our information pathway of the 21st century.