A universal stress protein upregulated by hypoxia has a role in Burkholderia cenocepacia intramacrophage survival: Implications for chronic infection in cystic fibrosis.

Universal stress proteins (USPs) are ubiquitously expressed in bacteria, archaea, and eukaryotes and play a lead role in adaptation to environmental conditions. They enable adaptation of bacterial pathogens to the conditions encountered in the human niche, including hypoxia, oxidative stress, osmotic stress, nutrient deficiency, or acid stress, thereby facilitating colonization. We previously reported that all six USP proteins encoded within a low-oxygen activated (lxa) locus in Burkholderia cenocepacia showed increased abundance during chronic colonization of the cystic fibrosis (CF) lung. However, the role of USPs in chronic cystic fibrosis infection is not well understood. Structural modeling identified surface arginines on one lxa-encoded USP, USP76, which suggested it mediated interactions with heparan sulfate. Using mutants derived from the B. cenocepacia strain, K56-2, we show that USP76 is involved in host cell attachment. Pretreatment of lung epithelial cells with heparanase reduced the binding of the wild-type and complement strains but not the Δusp76 mutant strain, indicating that USP76 is directly or indirectly involved in receptor recognition on the surface of epithelial cells. We also show that USP76 is required for growth and survival in many conditions associated with the CF lung, including acidic conditions and oxidative stress. Moreover, USP76 also has a role in survival in macrophages isolated from people with CF. Overall, while further elucidation of the exact mechanism(s) is required, we can conclude that USP76, which is upregulated during chronic infection, is involved in bacterial survival within CF macrophages, a hallmark of Burkholderia infection.

Scholarly Activity and Research Training in Urology Residency Programs: Assessment of Current Practice and Barriers.

OBJECTIVE: To identify factors associated with effective scholarly activity and identify barriers to research during urology residency. METHODS: An online survey was sent to 134 urology residency program directors in the United States. The survey assessed program characteristics, available support, and barriers for scholarly activity. Logistic regression analysis was used to identify characteristics of programs in the top quintile for success in scholarly activity. RESULTS: There was a 40% response rate (n = 40). The majority of programs (86%) were university affiliated. Nearly all programs (98%) require participation in scholarly activity as a requirement for graduation. There were 3 primary outcomes evaluated: participation in original research, published scholarly activity and presentation of scholarly activity. Factors significantly associated with participation in original research were required research time (P = 0.06), lack of experienced faculty (P = 0.006), statistical and IRB support (P = 0.03, P = 0.01), funding (P = 0.02), and research curriculum (P = 0.006). Factors significantly associated with publication in peer reviewed journals were lack of funding and experienced faculty (P = 0.07, P = 0.01). Factors significantly associated with presentation of scholarly activity included research director (P = 0.05), chairman support (P = 0.02), research training (P = 0.03), protected time for faculty (P = 0.07), and faculty /resident attitudes toward conducting scholarly activity (P = 0.08, P = 0.02) and resident promotion linked to scholarly activity (P = 0.01). CONCLUSION: Training urology residents in research is essential. Current methods and available resources are variable. Programs should identify resources and barriers that have the greatest impact on resident success in scholarly activity, and may implement changes to improve productivity within their program.

Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors.

Pseudomonas aeruginosa is a dominant pathogen in people with cystic fibrosis (CF) contributing to morbidity and mortality. Its tremendous ability to adapt greatly facilitates its capacity to cause chronic infections. The adaptability and flexibility of the pathogen are afforded by the extensive number of virulence factors it has at its disposal, providing P. aeruginosa with the facility to tailor its response against the different stressors in the environment. A deep understanding of these virulence mechanisms is crucial for the design of therapeutic strategies and vaccines against this multi-resistant pathogen. Therefore, this review describes the main virulence factors of P. aeruginosa and the adaptations it undergoes to persist in hostile environments such as the CF respiratory tract. The very large P. aeruginosa genome (5 to 7 MB) contributes considerably to its adaptive capacity; consequently, genomic studies have provided significant insights into elucidating P. aeruginosa evolution and its interactions with the host throughout the course of infection.

Understanding Pseudomonas aeruginosa-Host Interactions: The Ongoing Quest for an Efficacious Vaccine.

Pseudomonas aeruginosa is a leading cause of chronic respiratory infections in people with cystic fibrosis (CF), bronchiectasis or chronic obstructive pulmonary disease (COPD), and acute infections in immunocompromised individuals. The adaptability of this opportunistic pathogen has hampered the development of antimicrobial therapies, and consequently, it remains a major threat to public health. Due to its antimicrobial resistance, vaccines represent an alternative strategy to tackle the pathogen, yet despite over 50 years of research on anti-Pseudomonas vaccines, no vaccine has been licensed. Nevertheless, there have been many advances in this field, including a better understanding of the host immune response and the biology of P. aeruginosa. Multiple antigens and adjuvants have been investigated with varying results. Although the most effective protective response remains to be established, it is clear that a polarised Th2 response is sub-optimal, and a mixed Th1/Th2 or Th1/Th17 response appears beneficial. This comprehensive review collates the current understanding of the complexities of P. aeruginosa-host interactions and its implication in vaccine design, with a view to understanding the current state of Pseudomonal vaccine development and the direction of future efforts. It highlights the importance of the incorporation of appropriate adjuvants to the protective antigen to yield optimal protection.

Candida duobushaemulonii: An Old But Unreported Pathogen.

Candidiasis caused by species of the Candida haemulonii complex (Candida haemulonii and Candida duobushaemulonii) and closely related species, Candida auris and Candida pseudohaemulonii are increasing. These species often show reduced susceptibility to antifungal drugs, such as azoles and amphotericin B or, less frequently, echinocandins. However, conventional phenotypic identification methods are unable to accurately differentiate these species and, therefore, their prevalence may have been underestimated. In this study, 150 isolates that were probably misidentified were reanalyzed using two novel PCR approaches. We found that one isolate previously identified in 1996 as Candida intermedia was C. duobushaemulonii, being one of the oldest isolates of this species described to date. We also found that this isolate had reduced susceptibility to fluconazole, itraconazole, and amphotericin B.

Utility of two PCR-RFLP-based techniques for identification of Candida parapsilosis complex blood isolates.

BACKGROUND: Candida parapsilosis is the second or third most frequently isolated Candida species related to nosocomial infections, even overtaking Candida albicans in some hospitals. C. parapsilosis constitutes a complex of closely related species: Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. Accurate detection of these species is of importance, as the incidence of C. orthopsilosis has been reported to surpass that of Candida krusei. OBJECTIVE: To evaluate the diagnostic utility of two PCR-RFLP methods targeting the SADH and FKS1 genes and to determine the prevalence of cryptic species in 96 bloodstream isolates of C. parapsilosis from 93 patients. METHODS: Restriction patterns of the SADH and FKS1 genes were analysed, and sequencing of the D1/D2 regions of the ribosomal RNA was used to evaluate the reliability of both PCR-RFLP methods. RESULTS: In our study, 77 C. parapsilosis sensu stricto, 13 C. orthopsilosis and five C. metapsilosis were identified by sequencing. Both PCR-RFLP methods demonstrated strong agreement with D1/D2 sequencing in the identification of C. parapsilosis and C. orthopsilosis, while both methods were unable to identify the C. metapsilosis isolates. Moreover, unexpected restriction patterns were observed for two isolates on SADH PCR-RFLP and for four isolates on FKS1 PCR-RFLP. Mixed bloodstream infections of C. parapsilosis sensu stricto and C. orthopsilosis were detected for three patients, for which differential growth characteristics were observed. CONCLUSION: The molecular method chosen for identification could have an impact on determination of the real prevalence of C. metapsilosis in candidaemia, and mixed fungaemias can remain undetected.

Predictors and Barriers to Faculty Scholarly Activity in United States Urology Residency Programs.

OBJECTIVE: To determine factors and barriers associated with scholarly activity among faculty members at urology residency programs in the United States. METHODS: An online survey was sent to all 134 urology residency program directors. The survey assessed program characteristics including size, location and definition of scholarly activity. It assessed available support for and barriers to resident scholarly activity, faculty participation in scholarly activity and mentorship of residents. Linear regression analysis was used. RESULTS: We had a 40% response rate (N = 40). Faculty attitudes toward conducting scholarly activity (P < .001) and lack of a research curriculum (P = .05) were barriers to the outcome 'participation in scholarly activity'. Faculty attitudes toward conducting scholarly activity was also a barrier to the outcomes 'mentorship of residents' (P = .004) and 'publication of at least 1 paper' (P = .004). Available statistician was positively associated with the outcomes 'publications' (P = .062) and 'presentations' (P = .032). A minimum requirement of a local presentation (P=0.04) and chairman support (P = .015) were positively associated with the outcome 'presentation at a conference.' CONCLUSION: Training residents in research matters for the resident, the institution and future generations of surgeon scientists. Higher levels of faculty scholarly activity were associated with a minimum requirement for residents to submit a manuscript for publication, strong chairman support for resident research, and the availability of a statistician. A common barrier to faculty scholarly activity, publications, and resident mentorship was faculty attitudes toward resident scholarly activity. Urology residency programs seeking to prioritize scholarly activity among faculty should consider these factors.

A Novel Intervention for High-Need, High-Cost Medicaid Patients: a Study of ECHO Care.

BACKGROUND: A small number of high-need patients account for a disproportionate amount of Medicaid spending, yet typically engage little in outpatient care and have poor outcomes. OBJECTIVE: To address this issue, we developed ECHO (Extension for Community Health Outcomes) Care™, a complex care intervention in which outpatient intensivist teams (OITs) provided care to high-need high-cost (HNHC) Medicaid patients. Teams were supported using the ECHO model™, a continuing medical education approach that connects specialists with primary care providers for case-based mentoring to treat complex diseases. DESIGN: Using an interrupted time series analysis of Medicaid claims data, we measured healthcare utilization and expenditures before and after ECHO Care. PARTICIPANTS: ECHO Care served 770 patients in New Mexico between September 2013 and June 2016. Nearly all had a chronic mental illness, and over three-quarters had a chronic substance use disorder. INTERVENTION: ECHO Care patients received care from an OIT, which typically included a nurse practitioner or physician assistant, a registered nurse, a licensed mental health provider, and at least one community health worker. Teams focused on addressing patients' physical, behavioral, and social issues. MAIN MEASURES: We assessed the effect of ECHO Care on Medicaid costs and utilization (inpatient admissions, emergency department (ED) visits, other outpatient visits, and dispensed prescriptions. KEY RESULTS: ECHO Care was associated with significant changes in patients' use of the healthcare system. At 12 months post-enrollment, the odds of a patient having an inpatient admission and an ED visit were each reduced by approximately 50%, while outpatient visits and prescriptions increased by 23% and 8%, respectively. We found no significant change in overall Medicaid costs associated with ECHO Care. CONCLUSIONS: ECHO Care shifts healthcare utilization from inpatient to outpatient settings, which suggests decreased patient suffering and greater access to care, including more effective prevention and early intervention for chronic conditions.

ECHO Care: Providing Multidisciplinary Specialty Expertise to Support the Care of Complex Patients.

BACKGROUND: Programs for high-need, high-cost (HNHC) patients can improve care and reduce costs. However, it may be challenging to implement these programs in rural and underserved areas, in part due to limited access to specialty consultation. AIM: Evaluate the feasibility of using the Extension for Community Health Outcomes (ECHO) model to provide specialist input to outpatient intensivist teams (OITs) dedicated to caring for HNHC patients. SETTING: Weekly group videoconferencing sessions that connect multidisciplinary specialists with OITs. PARTICIPANTS: Six OITs across New Mexico, typically consisting of a nurse practitioner or physician assistant, a registered nurse, a counselor or social worker, and at least one community health worker. PROGRAM DESCRIPTION: OITs and specialists participated in weekly teleECHO sessions focused on providing the OITs with case-based mentoring and support. PROGRAM EVALUATION: OITs and specialists discussed 427 highly complex patient cases, many of which had social or behavioral health components to address. In 70% of presented cases, the teams changed their care plan for the patient, and 87% reported that they applied what they learned in hearing case presentations to other HNHC patients. DISCUSSION: Pairing the ECHO model with intensive outpatient care is a feasible strategy to support OITs to provide high-quality care for HNHC patients.

Contingent engagement: What we learn from patients with complex health problems and low socioeconomic status.

OBJECTIVE: Elicit patients' perceptions of factors that facilitate their engagement in care METHODS: In-depth interviews with 20 adult Medicaid patients who had complex health problems, frequent hospitalizations/emergency department use, and who were enrolled in an intensive, team-based care program designed to address medical, behavioral, and social needs. RESULTS: Prior to engaging in the program, participants described weak relationships with primary care providers, frequent hospitalizations and emergency visits, poor adherence to medications and severe social barriers to care. After participating in the program, participants identified key factors that enabled them to develop trust and engage with care including: availability for extended intensive interactions, a non-judgmental approach, addressing patients' material needs, and providing social contact for isolated patients. After developing relationships with their care team, participants described changes such as sustained interactions with their primary care team and incremental improvements in health behaviors. CONCLUSION: These findings illuminate factors promoting "contingent engagement" for low socio-economic status patients with complex health problems, which allow them to become proactive in ways commensurate with their circumstances, and offers insights for designing interventions to improve patient outcomes. PRACTICE IMPLICATIONS: For these patients, engagement is contingent on healthcare providers' efforts to develop trust and address patients' material needs.

Causas de sufrimiento en enfermos oncológicos al final de la vida / No disponible

Objetivo: conocer y analizar el grado de malestar y las principales causas de sufrimiento de los enfermos oncológicos en situación avanzada desde la perspectiva de los pacientes. Método: en una muestra de 132 pacientes atendidos en la Fundación Cudeca, se valoró, mediante la escala del paso subjetivo del tiempo, el grado de sufrimiento y su atribución. Los datos fueron analizados mediante SPSS.11. Resultados: la mayoría de los pacientes relacionan su percepción subjetiva del paso del tiempo principalmente con el control sintomático, seguido de la capacidad para realizar actividades distractoras y su estado de ánimo. Para los niveles de sufrimiento más elevados, las causas del sufrimiento se relacionan con la sintomatología física y el aburrimiento. Que "la vida trascurre con normalidad", es destacado en un 14% de los pacientes y asociado a la percepción de que el tiempo ni se alarga ni se acorta respecto al cronológico. Conclusiones: los pacientes no se refieren a la muerte próxima como su principal amenaza sino a los factores cambiantes. El aburrimiento se relaciona con la sensación de vacío, tanto en lo que se refiere a carencia de actividades como a su significado. La capacidad de distracción, descubrimiento de nuevas actividades y sensación de utilidad facilitan la adaptación y reducen el malestar. Conocer lo que preocupa al paciente permite al profesional orientar su intervención hacia la causa del sufrimiento (AU)

Objective: to know and analyze the discomfort level and main causes of suffering in advanced cancer patients from a patient's perspective. Method: in a sample of 132 patients cared for at Cudeca Foundation suffering and its causes were evaluated using a subjective perception scale. Data were analyzed using the SPSS 11. Results: most patients associate time perception with symptom control, their capacity for distraction, and mood. In the highest levels of suffering, the main causes are physical symptoms and boredom. For 14% of patients life time is normal and associated with the perception that its passing is neither slow or fast. Conclusions: patients do not report death proximity perception as their main threat. Their main threats are changing factors. Boredom is related with a feeling of void, both for lack of activities and the meaning adscribed to life. The capacity of enjoying, discovering new capacities and a useful feeling could enhance adaptation and reduce discomfort. Knowing the patient's main threat will allow the professional to help the patient directly about his/her worries (AU)

Dolor y sufrimiento en enfermos oncológicos al final de la vida: el papel del conocimiento de la enfermedad / No disponible

Objetivo: contrastar el papel que tienen el conocimiento de la enfermedad y el estado emocional, en la experiencia de dolor y sufrimiento en una muestra de enfermos oncológicos en fase terminal. Material y método: en una muestra de 89 pacientes oncológicos en fase avanzada-terminal se valoró, mediante una entrevista semi-estructurada de 5 minutos, el estado general, el conocimiento de la enfermedad, el grado de sufrimiento y su atribución, la intensidad de la tristeza y ansiedad y el dolor. Se realizó el estudio mediante modelos de ecuaciones estructurales (LISREL 8.30). Resultados: a menor grado de conocimiento de la enfermedad se produce un mayor grado de ansiedad y tristeza (gamma = -0,27 para la ansiedad; gamma = -0,19 para la tristeza). La ansiedad hace aumentar el dolor(beta = 0,30) y este aumenta la tristeza (beta = 0,10). Por último, el dolor ejerce un efecto positivo sobre el sufrimiento (beta = 0,15) que a su vez se ve influido por el estado general del paciente (beta = 0, 24). Conclusiones: el punto de unión entre dolor y sufrimiento podría situarse en los aspectos emocionales que a su vez son fruto del significado atribuido al dolor. Una explicación adecuada a las necesidades del enfermo sobre su enfermedad reducirá la ansiedad asociada al desconocimiento y consecuentemente, se lograría un mejor control del dolor (AU)

Objective: to examine the role played by disease awareness and emotions in the pain and suffering experience in a sample of patients with advanced cancer. Material and method: the sample consisted of 89 patients with advanced or terminal cancer. A semistructured interview was administered to assess their general condition, disease awareness, suffering, sadness, anxiety, and pain severity. This study was analyzed using structural equation modeling (LISREL 8.30). Results: the final model showed that disease awareness was determinant for anxiety (gamma = -0.27) and depression (gamma = -0.19). Anxiety had a significant effect on pain intensity (beta = 0.30), and pain intensity was determinant for sadness (beta = 0.10). Patient suffering was influenced by pain severity (beta = 0.15) and general condition (beta =0.24). Conclusions: emotional reactions to pain are crucial to explain the relationship between pain and suffering. A suitable explanation about the diagnosis and prognosis will contribute to reduce the anxiety associated with pain, and to a better control of pain (AU)

Experiencia asistencial del programa de Cuidados Paliativos de la Fundación CUDECA / No disponible

Introducción/Objetivos: la Fundación CUDECA esta formada por un equipo asistencial multidisciplinar formado por médicos, enfermeros-as, trabajadora social, psicóloga y voluntarios cualificados, que atiende al paciente paliativo tanto en el Centro CUDECA, como en el propio domicilio del enfermo, consiguiendo así que se puedan cumplir los deseos de las personas en esta situación, enfermos y familiares, de permanecer en su propio hogar. Se analizan, en este estudio, los datos de 3.400 pacientes atendidos en el Programa Asistencial de Cuidados Paliativos de la Fundación CUDECA. Material y métodos: se procesaron los datos de 3.400 pacientes, incluidos en programa desde 1992 hasta 2005, mediante el programa estadístico SPSS 11.0, se realizó un estudio descriptivo de las siguientes características de los pacientes: sexo, edad de los pacientes, edad del cuidador, tiempo de permanencia en programa, tipo de tumor más frecuente y lugar de defunción de los pacientes, que figuraba codificado de la siguiente manera: domicilio, hospital, UCP (Unidad de Cuidados Paliativos), residencia y otros. Resultados: la media de edad es de 67 años. Acorde con la mayor prevalencia de tumores en pacientes mayores y también en relación con el mayor envejecimiento de la población. Predominan los varones: 59,4%. En relación a la mayor incidencia de tumores, destaca el de pulmón en varones, que es el tumor más prevalente en nuestra población. La media de estancia en programa es de 76 días. La mediana es de 36 días. Destaca el tumor de pulmón como el más frecuente con un 24%. Seguido del colorrectal con un 14%, cabeza y cuello y cáncer de mama con un 10%. La mayoría de nuestros pacientes, el 76,8%, fallecen en el domicilio. Conclusiones: la mayoría de nuestros pacientes, el 76,8% fallecen en el domicilio. Es un dato muy importante de calidad de asistencia en Cuidados Paliativos, ya que se consigue que los pacientes mueran en su ambiente familiar. Supone un importantísimo ahorro al Sistema Nacional de Salud y compañías privadas, ya que se evitan estancias prolongadas en hospital, con el ahorro que supone de coste cama/día. Los datos de alta frecuencia de cáncer de pulmón coinciden con los descritos en la literatura, ya que se trata del tumor más prevalente. En nuestra población destaca la alta frecuencia de tumores de cabeza y cuello, en posible relación al tabaco y al consumo de alcohol. La media de estancia en programa es corta, estos datos demuestran la sospecha inicial de que los pacientes son derivados a las Unidades de Cuidados Paliativos por los Servicios de Oncología en situación muy avanzada de su enfermedad, es necesario, por tanto, mejorar la coordinación entre las Unidades de Cuidados Paliativos y los Servicios de Oncología de Procedencia (AU)

Objectives: CUDECA Foundation is formed by a multidisciplinary team of doctors, nurses, social workers, psychologists, and qualified volunteers who care for patients at CUDECA's center and in their homes, so that patients can stay with their families in their own houses. We analyzed the data of 3,400 patients who entered the palliative care program of CUDECA Foundation. The main objectives of CUDECA are: to offer «specialised palliative care» to patients suffering from terminal cancer, and also to support their families during illness and the bereavement process. To constitute a study, training, investigation, and awareness program regarding palliative care. Our care is offered completely free of charge to those patients and families who need it and who live in Malaga province, Spain. Methods: We analyzed the data of 3400 patients who entered the palliative program of CUDECA Foundation using the statistical program SPSS 11.0. A descriptive study was performed of the following patient characteristics: sex, median age, median age of caregiver, time in the program, and place of death, which was coded with the following variables -nursing home, hospital, palliative care unit (PCU), home, other. Results: The majority of our patients, 76.8%, died in their homes. Median age of patients: 67 years. Median age of caregiver: 55 years. Males predominated (59.4%) in the prevalence of tumours, especially of the lungs. Mean time in the program: 76 days. Lung cancer was the most frequent malignancy (24%), followed by colorectal cancer (14%), and head and neck tumours (10%). Conclusions: Mean age of patients was high due to the greater prevalence of tumours in older patients and also in relation to population ageing. Mean time in the program was not very long (76 days); as patients are sent to palliative care units by oncology departments when disease is advanced, coordination between palliative care units and oncology departments. The high frequency of lung cancer is consistent with the data described in the literature, as this is the tumour with the highest prevalence. A majority of our patients, 76.8 %, died in their homes. This is avery important quality-of-life issue in palliative care, as we allowed patients to die with their families and in their homes according to their own wishes (AU)