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Rankings versus reality in pancreatic cancer surgery: a real-world comparison

Tue, 11/24/2015 - 1:41pm

BACKGROUND: Patients are increasingly confronted with systems for rating hospitals. However, the correlations between publicized ratings and actual outcomes after pancreatectomy are unknown.

METHODS: The Massachusetts Division of Health Care Finance and Policy Hospital Inpatient Discharge Database was queried to identify pancreatic cancer resections carried out during 2005-2009. Hospitals performing fewer than 10 pancreatic resections in the 5-year period were excluded. Primary outcomes included mortality, complications, median length of stay (LoS) and a composite outcomes score (COS) combining primary outcomes. Ranks were determined and compared for: (i) volume, and (ii) ratings identified from consumer-directed hospital ratings including the US News and World Report (USN), Consumer Reports, Healthgrades and Hospital Compare. An inter-rater reliability analysis was performed and correlation coefficients (r) between outcomes and ratings, and between rating systems were calculated.

RESULTS: Eleven hospitals in which a total of 804 pancreatectomies were conducted were identified. Surgical volume correlated with overall outcome, but was not the strongest indicator. The highest correlation referred to that between USN rank and overall outcome. Mortality was most strongly correlated with Healthgrades ratings (r = 0.50); however, Healthgrades ratings demonstrated poorer correlations with all other outcomes. Consumer Reports ratings showed inverse correlations.

CONCLUSIONS: The plethora of publicly available hospital ratings systems demonstrates heterogeneity. Volume remains a good but imperfect indicator of surgical outcomes. Further systematic investigation into which measures predict quality outcomes in pancreatic cancer surgery will benefit both patients and providers.

Distinct cellular origin and genetic requirement of Hedgehog-Gli in postnatal rhabdomyosarcoma genesis

Tue, 11/24/2015 - 1:41pm

Dysregulation of the Hedgehog (Hh)-Gli signaling pathway is implicated in a variety of human cancers, including basal cell carcinoma (BCC), medulloblastoma (MB) and embryonal rhabdhomyosarcoma (eRMS), three principle tumors associated with human Gorlin syndrome. However, the cells of origin of these tumors, including eRMS, remain poorly understood. In this study, we explore the cell populations that give rise to Hh-related tumors by specifically activating Smoothened (Smo) in both Hh-producing and -responsive cell lineages in postnatal mice. Interestingly, we find that unlike BCC and MB, eRMS originates from the stem/progenitor populations that do not normally receive active Hh signaling. Furthermore, we find that the myogenic lineage in postnatal mice is largely Hh quiescent and that Pax7-expressing muscle satellite cells are not able to give rise to eRMS upon Smo or Gli1/2 overactivation in vivo, suggesting that Hh-induced skeletal muscle eRMS arises from Hh/Gli quiescent non-myogenic cells. In addition, using the Gli1 null allele and a Gli3 repressor allele, we reveal a specific genetic requirement for Gli proteins in Hh-induced eRMS formation and provide molecular evidence for the involvement of Sox4/11 in eRMS cell survival and differentiation.

Antitussives and substance abuse

Tue, 11/24/2015 - 1:41pm

Abuse of antitussive preparations is a continuing problem in the United States and throughout the world. Illicit, exploratory, or recreational use of dextromethorphan and codeine/promethazine cough syrups is widely described. This review describes the pharmacology, clinical effects, and management of toxicity from commonly abused antitussive formulations.

Fever in the pediatric patient

Tue, 11/24/2015 - 1:41pm

Fever is the most common reason that children and infants are brought to emergency departments. Emergency physicians face the challenge of quickly distinguishing benign from life-threatening conditions. The management of fever in children is guided by the patient's age, immunization status, and immune status as well as the results of a careful physical examination and appropriate laboratory tests and radiographic views. In this article, the evaluation and treatment of children with fevers of known and unknown origin are described. Causes of common and dangerous conditions that include fever in their manifestation are also discussed.

DNA immunization

Tue, 11/24/2015 - 1:41pm

DNA immunization was discovered in early 1990s, and its use has been expanded from vaccine studies to a broader range of biomedical research areas, such as the generation of high-quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation, and gene gun. In addition, several common considerations related to DNA immunization are discussed.

UMCCTS Newsletter, November 2015

Tue, 11/24/2015 - 10:06am

This is the November 2015 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.

Care that Matters: Quality Measurement and Health Care

Tue, 11/24/2015 - 9:04am

Barry Saver and colleagues caution against the use of process and performance metrics as health care quality measures in the United States.

Perceiving one's heart condition to be cured following hospitalization for acute coronary syndromes: Implications for patient-provider communication

Fri, 11/20/2015 - 2:26pm

OBJECTIVE: We examined the proportion of patients perceiving their heart condition to be cured following hospitalization for ACS and identified characteristics associated with these perceptions.

METHODS: We conducted a prospective cohort study of adults hospitalized with ACS (N=396). Patient interviews during hospitalization and one week post-discharge provided demographic and psychosocial characteristics. Medical records provided clinical characteristics. At one week, patients who rated "My heart condition is cured" as "definitely true" or "mostly true" were considered to perceive their heart condition cured.

RESULTS: Participants were aged 60.7 (SD:11.0) years, 26.5% female, and 89.0% non-Hispanic white; 16.7% had unstable angina, 59.6% NSTEMI, and 23.7% STEMI. One week post-discharge, 30.3% perceived their heart condition to be cured. Characteristics associated with cure perceptions were older age (OR=2.2; 95% CI: 1.2-4.0 for > /=65 years vs < 55 years), male sex (OR=2.4; 95%CI: 1.3-4.2), history of hypertension (OR=1.8; 95%CI: 1.1-3.1), history of stroke (OR=4.2; 95%CI: 1.1-16.7), no history of CHD (OR=2.8; 95%CI: 1.6-4.9), and receipt of CABG during hospitalization (OR=4.8, 95%CI: 1.9-12.0 vs medical management).

CONCLUSION: One week post-discharge, 3 in 10 patients perceived their heart condition to be cured.

PRACTICE IMPLICATIONS: Conversations with patients should frame ACS as a chronic disease and dispel cure perceptions.

A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute EBV Infection

Fri, 11/20/2015 - 2:26pm

Virus-specific CD8(+) T cells expand dramatically during acute EBV infection, and their persistence is important for lifelong control of EBV-related disease. To better define the generation and maintenance of these effective CD8(+) T cell responses, we used microarrays to characterize gene expression in total and EBV-specific CD8(+) T cells isolated from the peripheral blood of 10 individuals followed from acute infectious mononucleosis (AIM) into convalescence (CONV). In total CD8(+) T cells, differential expression of genes in AIM and CONV was most pronounced among those encoding proteins important in T cell activation/differentiation, cell division/metabolism, chemokines/cytokines and receptors, signaling and transcription factors (TF), immune effector functions, and negative regulators. Within these categories, we identified 28 genes that correlated with CD8(+) T cell expansion in response to an acute EBV infection. In EBV-specific CD8(+) T cells, we identified 33 genes that were differentially expressed in AIM and CONV. Two important TF, T-bet and eomesodermin, were upregulated and maintained at similar levels in both AIM and CONV; in contrast, protein expression declined from AIM to CONV. Expression of these TF varied among cells with different epitope specificities. Collectively, gene and protein expression patterns suggest that a large proportion, if not a majority of CD8(+) T cells in AIM are virus specific, activated, dividing, and primed to exert effector activities. High expression of T-bet and eomesodermin may help to maintain effector mechanisms in activated cells and to enable proliferation and transition to earlier differentiation states in CONV.

Modeling Epidemics Spreading on Social Contact Networks

Fri, 11/20/2015 - 9:09am

Social contact networks and the way people interact with each other are the key factors that impact on epidemics spreading. However, it is challenging to model the behavior of epidemics based on social contact networks due to their high dynamics. Traditional models such as susceptible-infected-recovered (SIR) model ignore the crowding or protection effect and thus has some unrealistic assumption. In this paper, we consider the crowding or protection effect and develop a novel model called improved SIR model. Then, we use both deterministic and stochastic models to characterize the dynamics of epidemics on social contact networks. The results from both simulations and real data set conclude that the epidemics are more likely to outbreak on social contact networks with higher average degree. We also present some potential immunization strategies, such as random set immunization, dominating set immunization, and high degree set immunization to further prove the conclusion.

Specialization and utilization after hepatectomy in academic medical centers

Thu, 11/19/2015 - 2:16pm

BACKGROUND: Specialized procedures such as hepatectomy are performed by a variety of specialties in surgery. We aimed to determine whether variation exists among utilization of resources, cost, and patient outcomes by specialty, surgeon case volume, and center case volume for hepatectomy.

METHODS: We queried centers (n = 50) in the University Health Consortium database from 2007-2010 for patients who underwent elective hepatectomy in which specialty was designated general surgeon (n = 2685; 30%) or specialist surgeon (n = 6277; 70%), surgeon volume was designated high volume ( > 38 cases annually) and center volume was designated high volume ( > 100 cases annually). We then stratified our cohort by primary diagnosis, defined as primary tumor (n = 2241; 25%), secondary tumor (n = 5466; 61%), and benign (n = 1255; 14%).

RESULTS: Specialist surgeons performed more cases for primary malignancy (primary 26% versus 15%) while general surgeons operated more for secondary malignancies (67% versus 61%) and benign disease (18% versus 13%). Specialists were associated with a shorter total length of stay (LOS) (5 d versus 6 d; P < 0.01) and lower in-hospital morbidity (7% versus 11%; P < 0.01). Patients treated by high volume surgeons or at high volume centers were less likely to die than those treated by low volume surgeons or at low volume centers, (OR 0.55; 95% CI 0.33-0.89) and (OR 0.44; 95% CI 0.13-0.56).

CONCLUSIONS: Surgical specialization, surgeon volume and center volume may be important metrics for quality and utilization in complex procedures like hepatectomy. Further studies are necessary to link direct factors related to hospital performance in the changing healthcare environment.

Epidemiology and outcomes of community-acquired Clostridium difficile infections in Medicare beneficiaries

Thu, 11/19/2015 - 2:16pm

BACKGROUND: The incidence of community-acquired Clostridium difficile (CACD) is increasing in the United States. Many CACD infections occur in the elderly, who are predisposed to poor outcomes. We aimed to describe the epidemiology and outcomes of CACD in a nationally representative sample of Medicare beneficiaries.

STUDY DESIGN: We queried a 5% random sample of Medicare beneficiaries (2009-2011 Part A inpatient and Part D prescription drug claims; n = 864,604) for any hospital admission with a primary ICD-9 diagnosis code for C difficile (008.45). We examined patient sociodemographic and clinical characteristics, preadmission exposure to oral antibiotics, earlier treatment with oral vancomycin or metronidazole, inpatient outcomes (eg, colectomy, ICU stay, length of stay, mortality), and subsequent admissions for C difficile.

RESULTS: A total of 1,566 (0.18%) patients were admitted with CACD. Of these, 889 (56.8%) received oral antibiotics within 90 days of admission. Few were being treated with oral metronidazole (n = 123 [7.8%]) or vancomycin (n = 13 [0.8%]) at the time of admission. Although 223 (14%) patients required ICU admission, few (n = 15 [1%]) underwent colectomy. Hospital mortality was 9%. Median length of stay among survivors was 5 days (interquartile range 3 to 8 days). One fifth of survivors were readmitted with C difficile, with a median follow-up time of 393 days (interquartile range 129 to 769 days).

CONCLUSIONS: Nearly half of the Medicare beneficiaries admitted with CACD have no recent antibiotic exposure. High mortality and readmission rates suggest that the burden of C difficile on patients and the health care system will increase as the US population ages. Additional efforts at primary prevention and eradication might be warranted.

Planning and implementing a statewide soccer HIV awareness and health promotion intervention for African-born men living in the United States

Thu, 11/19/2015 - 2:16pm

The increasing number of African-born individuals newly diagnosed with HIV in Massachusetts led to a grassroots effort to advocate for needed resources, policies, and programs. This article describes the African Health Cup (AHC), one of the major innovative programs developed by Africans For Improved Access (AFIA) in collaboration with community members.

Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth

Thu, 11/19/2015 - 2:16pm

OBJECTIVES: We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.

METHODS: Ninety subjects 4 to < 25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.

RESULTS: At entry, 26 (29%) subjects had pH1N1 protective HAI titers ( > /=1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p /=1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI < 1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNgamma, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNgamma responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.

CONCLUSIONS: HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI>/=1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00992836.

Meeting Report: 2015 Scientific Meeting of the Pan Arab Interventional Radiology Society

Thu, 11/19/2015 - 10:15am

The second Annual Scientific Meeting of the Pan Arab Interventional Radiology Society (PAIRS), held March 12-14, 2015, was a step above the inaugural edition, and opened new concepts for development.

Imaging in the Khmer’s Land: Cambodia Country Report

Thu, 11/19/2015 - 10:15am

Cambodia is located in Southeast Asia on the Indochina Peninsula and borders Vietnam, Laos, Thailand and the Gulf of Thailand (Figure 1). With a total area of 69,898 square miles and population of 15,458,332, Cambodia’s population density has steadily increased since 1980. The country’s annual rate of urbanization is 2.65 %. As of 2014, 20.5% of the population lives in an urban setting. The estimated population growth rate is 1.63% (1).

The capital of Cambodia is Phnom Penh, which is located in the southern part of the country. Other major cities include Battambang and Siem Reap, both of which have populations over 150,000. There are officially 24 provinces and one municipality (Phnom Penh). However, many consider Phnom Penh to be its own province. As a result, some research puts the number of Cambodian provinces at 25.

The climate is tropical with two seasons: monsoon season (May to November) and dry season (December to April). Temperatures range from approximately 70 to 95°F. Cambodia’s economy largely depends on the garment industry, tourism, construction, real estate and agriculture.

Cambodia gained independence from France in 1953 and was first ruled by a constitutional monarchy under King Norodom Sihanouk. After a five-year struggle starting in 1970, the Khmer Rouge captured Phnom Penh in 1975. Pol Pot, the leader of the Khmer Rouge, oversaw a brutal regime that, through executions and forced labor, was responsible for the deaths of at least 1.5 million Cambodians. The Vietnamese drove out the Khmer Rouge in 1979. After years of Vietnamese occupation, the 1991 Paris Peace Accords established a ceasefire and a democratic framework for the country. By 1993 elections established a new coalition government; yet, political instability and violence persisted throughout the 1990s. Cambodia most recently held elections in 2013, as a multiparty democracy under a constitutional monarchy.

The devastation caused by the Khmer Rouge has had long-lasting negative effects on Cambodia’s political and economic systems, as well as to its infrastructure, and public health. Despite this, Cambodia has made measurable improvements. At the end of Khmer Rouge rule in 1980, life expectancy was 30 years (1). Political stabilization, economic improvement and a growing healthcare system improved the life expectancy to 63.78 years by 2015 (2). The physician density remains low, at 0.17 physicians per 1,000 people (2). As of 2012, there were eight national hospitals and three levels of referral hospitals in the public sector. Referral hospitals are categorized by three levels of Complementary Package of Activity (CPA): 1) CPA-1 hospitals do not perform surgery; 2) CPA-2 hospitals perform surgeries but with more limited specialized services; and 3) CPA-3 hospitals perform surgery with more specialized services. There are 26 CPA-3 hospitals in Cambodia (3). As of 2011 there were 2,391 doctors, 8,433 nurses and 3,748 midwives (3). There are also NGOs that run hospitals throughout Cambodia, as well as private sector health care facilities.

Systems and Psychosocial Advances Research Center Annual Report to the Massachusetts Department of Mental Health 2014-2015

Wed, 11/18/2015 - 3:13pm

We are grateful to the Massachusetts Department of Mental Health (DMH) for its continued support of the University of Massachusetts Medical School’s (UMMS) DMH Research Center of Excellence, the Systems and Psychosocial Advances Research Center (SPARC). We continue to leverage the DMH investment to support innovative, recovery-oriented, state-of-the-art psychosocial and systems research. Highlights of Fiscal Year 2015 include another increase in research dollars awarded through new grants and contracts, and the end of our three-year Strategic Plan to guide our growth and trajectory over the coming years.

The Systems and Psychosocial Advances Research Center conducts research to enhance services, improve the quality of life, and promote recovery for people with behavioral health conditions. Our research informs and advises individuals with lived experience and their families, providers, administrators and policy-makers navigating the behavioral health landscape in the Commonwealth and beyond. SPARC was created in 1993 when it was designated a Center of Excellence for Psychosocial and Systems Research by the Massachusetts DMH. Our mission mirrors the DMH commitment to collaborating with other state agencies, consumers, families, advocates, providers, and communities. DMH and SPARC are aligned in their vision of promoting mental health through early intervention, treatment, education, policy, and regulation to provide opportunities for citizens of the Commonwealth to live full and productive lives.

Single-Molecule Imaging Reveals that Argonaute Reshapes the Binding Properties of Its Nucleic Acid Guides

Wed, 11/18/2015 - 2:24pm

Argonaute proteins repress gene expression and defend against foreign nucleic acids using short RNAs or DNAs to specify the correct target RNA or DNA sequence. We have developed single-molecule methods to analyze target binding and cleavage mediated by the Argonaute:guide complex, RISC. We find that both eukaryotic and prokaryotic Argonaute proteins reshape the fundamental properties of RNA:RNA, RNA:DNA, and DNA:DNA hybridization—a small RNA or DNA bound to Argonaute as a guide no longer follows the well-established rules by which oligonucleotides find, bind, and dissociate from complementary nucleic acid sequences. Argonautes distinguish substrates from targets with similar complementarity. Mouse AGO2, for example, binds tighter to miRNA targets than its RNAi cleavage product, even though the cleaved product contains more base pairs. By re-writing the rules for nucleic acid hybridization, Argonautes allow oligonucleotides to serve as specificity determinants with thermodynamic and kinetic properties more typical of RNA-binding proteins than of RNA or DNA.

Does Thinking Itch?

Wed, 11/18/2015 - 8:57am