Pragmatic Approach to In Situ Simulation to Identify Latent Safety Threats Before Moving to a Newly Built ICU.

OBJECTIVES: Transitions to new care environments may have unexpected consequences that threaten patient safety. We undertook a quality improvement project using in situ simulation to learn the new patient care environment and expose latent safety threats before transitioning patients to a newly built adult ICU. DESIGN: Descriptive review of a patient safety initiative. SETTING: A newly built 24-bed neurocritical care unit at a tertiary care academic medical center. SUBJECTS: Care providers working in neurocritical care unit. INTERVENTIONS: We implemented a pragmatic three-stage in situ simulation program to learn a new patient care environment, transitioning patients from an open bay unit to a newly built private room-based ICU. The project tested the safety and efficiency of new workflows created by new patient- and family-centric features of the unit. We used standardized patients and high-fidelity mannequins to simulate patient scenarios, with "test" patients created through all electronic databases. Relevant personnel from clinical and nonclinical services participated in simulations and/or observed scenarios. We held a debriefing after each stage and scenario to identify safety threats and other concerns. Additional feedback was obtained via a written survey sent to all participants. We prospectively surveyed for missed latent safety threats for 2 years following the simulation and fixed issues as they arose. MEASUREMENTS AND MAIN RESULTS: We identified and addressed 70 latent safety threats, including issues concerning physical environment, infection prevention, patient workflow, and informatics before the move into the new unit. We also developed an orientation manual that highlighted new physical and functional features of the ICU and best practices gleaned from the simulations. All participants agreed or strongly agreed that simulations were beneficial. Two-year follow-up revealed only two missed latent safety threats. CONCLUSIONS: In situ simulation effectively identifies latent safety threats surrounding the transition to new ICUs and should be considered before moving into new units.

A Quality Improvement Initiative Is Associated With Reduced Time to Administer Biologics and Small Molecules and Emergency Room Visits in Inflammatory Bowel Disease.

BACKGROUND: Delays in biologic or small molecule medication administration are associated with increased adverse events, hospitalization, and surgery in inflammatory bowel disease (IBD). We evaluated the impact of a quality improvement (QI) intervention on the time to administration of biologics or small molecules (TABS) in IBD. METHODS: Data were retrospectively extracted for IBD patients prescribed biologics or small molecules from a convenience sample of providers participating in an accredited QI educational intervention (baseline cohort). Subsequent to the intervention, data were prospectively collected from patients prescribed these medications (postintervention cohort). Dates related to steps between a treatment decision to medication administration were collected. The primary outcome compared TABS in baseline and postintervention cohorts. RESULTS: Eighteen physicians provided survey and patient data for 200 patients in each cohort (n=400). The median time to medication administration (TABS) decreased from baseline to postintervention cohorts (30 vs. 26 d, P=0.04). Emergency room visits before medication administration also decreased (25.5% vs. 12.5%, P=0.001). Similar numerical TABS reductions were observed in subgroups limited to physicians providing patients to both cohorts and for individual medications prescribed. Primary contributors to delays included filling prescriptions subsequent to insurance approval and dispensation subsequent to this. CONCLUSIONS: A QI intervention successfully reduced medication administration times (TABS) by accelerating provider-dependent steps. This intervention was associated with reduced emergency room visits. We propose TABS as a quality metric to assess the effective delivery of therapies in IBD. Further evaluation of QI interventions, patient education on prescription drug insurance, and quality metrics are warranted.

Outcomes for Hand Burns Treated With Autologous Skin Cell Suspension in 20% TBSA and Smaller Injuries.

In order to address the confounder of TBSA on burn outcomes, we sought to analyze our experience with the use of autologous skin cell suspensions (ASCS) in a cohort of subjects with hand burns whose TBSA totaled 20% or less. We hypothesized that the use of ASCS in conjunction with 2:1 meshed autograft for the treatment of hand burn injuries would provide comparable outcomes to hand burns treated with sheet or minimally meshed autograft alone. A retrospective review was conducted for all deep partial and full-thickness hand burns treated with split-thickness autograft (STAG) at our urban verified burn center between April 2018 and September 2020. The exclusion criterion was a TBSA greater than 20%. The cohorts were those subjects treated with ASCS in combination with STAG (ASCS(+)) vs those treated with STAG alone (ASCS(-)). All ASCS(+) subjects were treated with 2:1 meshed STAG and ASCS overspray while all ASCS(-) subjects had 1:1, piecrust, or unmeshed sheet graft alone. Outcomes measured included demographics, time to wound closure, proportion returning to work (RTW), and length of time to RTW. Mann-Whitney U test was used for comparisons of continuous variables and Fisher's exact test for categorical variables. Values are reported as medians and 25th and 75th interquartile ranges. Fifty-one subjects fit the study criteria (ASCS(+) n = 31, ASCS(-) n = 20). The ASCS(+) group was significantly older than the ASCS(-) cohort (44 [32-54] vs 32 years [27.5-37], P = .009) with larger %TBSA burns (15% [9.5-17] vs 2% [1-4], P < .0001) and larger size hand burns (190 [120-349.5] vs 126 cm2 [73.5-182], P = .015). Comparable results were seen between ASCS(+) and ASCS(-), respectively, for time to wound closure (9 [7-13] vs 11.5 days [6.75-14], P = .63), proportion RTW (61% vs 70%, P = .56), and days for RTW among those returning (35 [28.5-57] vs 33 [20.25-59], P = .52). The ASCS(+) group had two graft infections with no reoperations, while ASCS(-) had one infection with one reoperation. No subjects in either group had a dermal substitute placed. Despite being significantly older, having larger hand wounds, and larger overall wounds within the parameters of the study criteria, patients with 20% TBSA burns or smaller whose hand burns were treated with 2:1 mesh and ASCS overspray had comparable time to wound closure, proportion of RTW, and time to return to work as subjects treated with 1:1 or piecrust meshed STAG. Our group plans to follow this work with scar assessments for a more granular picture of pliability and reconstructive needs.

Re-Accessing Mental Health Care After Age 18: A Longitudinal Cohort Study of Youth Involved with Community-based Child and Youth Mental Health Agencies in Ontario.

OBJECTIVE: About 20-26% of children and youth with a mental health disorder (depending on age and respondent) report receiving services from a community-based Child and Youth Mental Health (CYMH) agency. However, because agencies have an upper age limit of 18-years old, youth requiring ongoing mental health services must "transition" to adult-oriented care. General healthcare providers (e.g., family physicians) likely provide this care. The objective of this study was to compare the likelihood of receiving physician-based mental health services after age 18 between youth who had received community-based mental health services and a matched population sample. METHOD: A longitudinal matched cohort study was conducted in Ontario, Canada. A CYMH cohort that received mental health care at one of five CYMH agencies, aged 7-14 years at their first visit (N=2,822), was compared to age, sex, region-matched controls (N=8,466). RESULTS: CYMH youth were twice as likely as the comparison sample to have a physician-based mental health visit (i.e., by a family physician, pediatrician, psychiatrists) after age 18; median time to first visit was 3.3 years. Having a physician mental health visit before age 18 was associated with a greater likelihood of experiencing the outcome than community-based CYMH services alone. CONCLUSION: Most youth involved in community-based CYMH agencies will re-access services from physicians as adults. Youth receiving mental health services only within community agencies, and not from physicians, may be less likely to receive physician-based mental health services as adults. Collaboration between CYMH agencies and family physicians may be important for youth who require ongoing care into adulthood.

OBJECTIF: Environ 20 à 26 % des enfants et des adolescents souffrant d'un trouble de santé mentale (dépendant de l'âge et du répondant) déclarent recevoir des services d'un organisme communautaire de santé mentale pour enfants et adolescents (SMEA) Toutefois, puisque les organismes ont une limite d'âge supérieur de 18 ans, les jeunes nécessitant des services de santé mentale doivent faire la « transition ¼ aux soins pour adultes. Les prestataires de soins de santé généraux (p. ex., les médecins de famille) dispensent probablement ces services. La présente étude visait à comparer la probabilité de recevoir des services de santé mentale par un médecin après l'âge de 18 ans entre un jeune qui avait reçu des services de santé mentale et un échantillon apparié dans la population. MÉTHODE: Une étude de cohorte longitudinale appariée a été menée en Ontario, Canada. Une cohorte SMEA qui recevait des soins de santé mentale à l'un des cinq organismes SMEA, âgés entre 7 et 14 ans à leur première visite (N = 2,822), a été comparée pour l'âge, le sexe, les contrôles appariés par région (N = 8,466). RÉSULTATS: Les jeunes des SMEA étaient deux fois plus susceptibles que l'échantillon de comparaison d'avoir une visite de santé mentale par un médecin (c.-à-d. par un pédiatre médecin de famille, des psychiatres) après l'âge de 18 ans le temps moyen avant une première visite était 3,3 ans. Avoir une visite de santé mentale avec un médecin avant l'âge de 18 ans était associé à une plus grande probabilité de connaître le résultat que par les services SMEA communautaires à eux seuls. CONCLUSION: La plupart des jeunes impliqués dans les organismes communautaires SMEA accéderont de nouveau aux services de médecins en tant qu'adulte. Les jeunes recevant des services de santé mentale uniquement d'organismes communautaires et non de médecins peuvent être moins susceptibles de recevoir des services de santé mentale par un médecin en tant qu'adultes. La collaboration entre les organismes SMEA et les médecins de famille peut être importante pour les jeunes qui nécessitent des soins constants à l'âge adulte.

Association of a Surgical Task During Training With Team Skill Acquisition Among Surgical Residents: The Missing Piece in Multidisciplinary Team Training.

IMPORTANCE: The human patient simulators that are currently used in multidisciplinary operating room team training scenarios cannot simulate surgical tasks because they lack a realistic surgical anatomy. Thus, they eliminate the surgeon's primary task in the operating room. The surgical trainee is presented with a significant barrier when he or she attempts to suspend disbelief and engage in the scenario. OBJECTIVE: To develop and test a simulation-based operating room team training strategy that challenges the communication abilities and teamwork competencies of surgeons while they are engaged in realistic operative maneuvers. DESIGN, SETTING, AND PARTICIPANTS: This pre-post educational intervention pilot study compared the gains in teamwork skills for midlevel surgical residents at Wake Forest Baptist Medical Center after they participated in a standardized multidisciplinary team training scenario with 3 possible levels of surgical realism: (1) SimMan (Laerdal) (control group, no surgical anatomy); (2) "synthetic anatomy for surgical tasks" mannequin (medium-fidelity anatomy), and (3) a patient simulated by a deceased donor (high-fidelity anatomy). INTERVENTIONS: Participation in the simulation scenario and the subsequent debriefing. MAIN OUTCOMES AND MEASURES: Teamwork competency was assessed using several instruments with extensive validity evidence, including the Nontechnical Skills assessment, the Trauma Management Skills scoring system, the Crisis Resource Management checklist, and a self-efficacy survey instrument. Participant satisfaction was assessed with a Likert-scale questionnaire. RESULTS: Scenario participants included midlevel surgical residents, anesthesia providers, scrub nurses, and circulating nurses. Statistical models showed that surgical residents exposed to medium-fidelity simulation (synthetic anatomy for surgical tasks) team training scenarios demonstrated greater gains in teamwork skills compared with control groups (SimMan) (Nontechnical Skills video score: 95% CI, 1.06-16.41; Trauma Management Skills video score: 95% CI, 0.61-2.90) and equivalent gains in teamwork skills compared with high-fidelity simulations (deceased donor) (Nontechnical Skills video score: 95% CI, -8.51 to 6.71; Trauma Management Skills video score: 95% CI, -1.70 to 0.49). CONCLUSIONS AND RELEVANCE: Including a surgical task in operating room team training significantly enhanced the acquisition of teamwork skills among midlevel surgical residents. Incorporating relatively inexpensive, medium-fidelity synthetic anatomy in human patient simulators was as effective as using high-fidelity anatomies from deceased donors for promoting teamwork skills in this learning group.

Integrated Knowledge Translation: illustrated with outcome research in mental health.

Through this article the authors present a case summary of the early phases of research conducted with an Integrated Knowledge Translation (iKT) approach utilizing four factors: research question, research approach, feasibility, and outcome. iKT refers to an approach for conducting research in which community partners, referred to as knowledge users, are engaged in the entire research process. In this collaborative approach, knowledge users and researchers jointly devise the entire research agenda beginning with the development of the research question(s), determination of a feasible research design and feasible methods, interpretation of the results, dissemination of the findings, and the translation of knowledge into practice or policy decisions. Engaging clinical or community partners in the research enterprise can enhance the utility of the research results and facilitate its uptake. This collaboration can be a complex arrangement and flexibility may be required to accommodate the various configurations that the collaboration can take. For example, the research question can be jointly determined and refined; however, one person must take the responsibility for orchestrating the project, including preparing the proposal and application to the Research Ethics Board. This collaborative effort also requires the simultaneous navigation of barriers and facilitators to the research enterprise. Navigating these elements becomes part of the conduct of research with the potential for rewarding results, including an enriched work experience for clinical partners and investigators. One practice implication is that iKT may be considered of great utility to service providers due to its field friendly nature.

Referral patterns in pediatric burn patients.

Though multiple studies have demonstrated superior outcomes amongst adult burn patients at verified burn centers (VBCs) relative to nondedicated burn centers (NBCs), roughly half of such patients meeting American Burn Association (ABA) referral guidelines are not sent to these centers. We sought examine referral patterns amongst pediatric burn patients. Retrospective review of a statewide patient database identified pediatric burn patients from 2000 to 2007 using International Classification of Disease (ICD-9) discharge codes. These injuries were crossreferenced with ABA referral criteria to determine compliance with the ABA guidelines. 1831 children sustained burns requiring hospitalization during the study period, of which 1274 (70%) met ABA referral criteria. Of 557 treated at NBCs, 306 (55%) met criteria for transfer. Neither age, gender, nor payer status demonstrated significant association with treatment center. VBCs treated more severely injured patients, but there was no difference in survival or rate of discharge home from NBCs versus VBCs. Studies to evaluate differences in functional outcomes between pediatric burn patients treated at VBCs versus NBCs would be beneficial to ensure optimization of outcomes in this population.

Non-suicidal self-injury and suicidal behaviour in children and adolescents accessing residential or intensive home-based mental health services.

OBJECTIVE: There is a dearth of Canadian research with clinical samples of youth who self-harm, and no studies could be located on self-harm in children and youth accessing residential or intensive home-based treatment. The purposes of this report were to explore the proportion and characteristics of children and youth identified as self-harming at admission by clinicians compared to youth not identified as self-harming, compare self-harming children to adolescents, and to compare caregiver ratings of self-harm at intake to clinician ratings at admission. METHOD: This report was developed from a larger longitudinal, observational study involving 210 children and youth accessing residential and home-based treatment and their caregivers in partnership with five mental health treatment centres in southwestern Ontario. Agency data were gleaned from files, and caregivers reported on symptom severity at 12 to 18 months and 36 to 40 months post-discharge. RESULTS: Fifty-seven (34%) children and youth were identified as self-harming at admission. The mean age was 11.57 (SD 2.75). There were statistically significant differences on symptom severity at intake between those identified as self-harming and those not so identified; most of these differences were no longer present at follow up. Children were reported to have higher severity of conduct disorder symptoms than adolescents at intake, and there was some consistency between caregiver-rated and clinician-rated self-harm. Children were reported to engage in a wide range of self-harming behaviours. CONCLUSION: These findings suggest that youth who were identified as self-harming at admission have elevated scores of symptom severity, self-harm can occur in young children and while many improve, there remains a concern for several children and youth who did not improve by the end of service. Children engage in some of the same types of self-harm behaviours as adolescents, and they also engage in behaviours unique to children.

Rapid histochemistry using slow off-rate modified aptamers with anionic competition.

Immunohistochemistry is used in both research and clinical settings to identify proteins in tissue samples. Despite the power and versatility of immunohistochemistry, limitations are imposed by the slow diffusion of antibodies through tissue and the need for secondary staining or signal amplification. Aptamers can circumvent these limitations, but their application has been hindered by nonspecific binding to cellular components, particularly in the nucleus. Here we describe unique slow off-rate modified aptamers that facilitate rapid and selective binding to target proteins in tissue. Specifically, we have developed a fluorescent aptamer that binds to the human epidermal growth factor receptor 2 (HER2) in breast carcinomas quickly and specifically, and we have shown that the slow off-rate of the aptamer from the HER2 protein contributes to its selectivity. These findings open the door to aptamer histochemistry applications in both research and clinical settings, including intraoperative diagnostics in which speed and accuracy are paramount.

Aptamer-based multiplexed proteomic technology for biomarker discovery.

BACKGROUND: The interrogation of proteomes ("proteomics") in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine. METHODOLOGY/PRINCIPAL FINDINGS: We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (~100 fM-1 µM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states. CONCLUSIONS/SIGNIFICANCE: We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine.

Expanding the chemistry of DNA for in vitro selection.

Six new 5-position modified dUTP derivatives connected by a unique amide linkage were synthesized and tested for compatibility with the enzymatic steps of in vitro selection. Six commercially available DNA polymerases were tested for their ability to efficiently incorporate each of these dUTP derivatives during PCR. It was not possible to perform PCR under standard conditions using any of the modified dUTP derivatives studied. In contrast, primer extension reactions of random templates, as well as defined sequence templates, were successful. KOD XL and D. Vent DNA polymerases were found to be the most efficient at synthesizing full-length primer extension product, with all of the dUTP derivatives tested giving yields similar to those obtained with TTP. Several of these modified dUTPs were then used in an in vitro selection experiment comparing the use of modified dUTP derivatives with TTP for selecting aptamers to a protein target (necrosis factor receptor superfamily member 9, TNFRSF9) that had previously been found to be refractory to in vitro selection using DNA. Remarkably, selections employing modified DNA libraries resulted in the first successful isolation of DNA aptamers able to bind TNFRSF9 with high affinity.

Selective inducible microsomal prostaglandin E(2) synthase-1 (mPGES-1) inhibitors derived from an oxicam template.

Here we describe the SAR of a series of potent and selective mPGES-1 inhibitors based on an oxicam template. Compound 13j demonstrated low nanomolar mPGES-1 inhibition in an enzyme assay. In addition, it displayed PGE(2) inhibition in a cell-based assay (0.42microM) and had over 238-fold selectivity for mPGES-1 over COX-2 and over 200-fold selectivity for mPGES-1 over 6-keto PGF(1alpha).

Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor.

Inflammation-induced microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme that synthesizes prostaglandin E(2) (PGE(2)) downstream of cyclooxygenase-2 (COX-2). The efficacy of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors in the treatment of the signs and symptoms of osteoarthritis, rheumatoid arthritis and inflammatory pain, largely attributed to the inhibition of PGE(2) synthesis, provides a rationale for exploring mPGES-1 inhibition as a potential novel therapy for these diseases. Toward this aim, we identified PF-9184 as a novel mPGES-1 inhibitor. PF-9184 potently inhibited recombinant human (rh) mPGES-1 (IC(50)=16.5+/-3.8nM), and had no effect against rhCOX-1 and rhCOX-2 (>6500-fold selectivity). In inflammation and clinically relevant biological systems, mPGES-1 expression, like COX-2 expression was induced in cell context- and time-dependent manner, consistent with the kinetics of PGE(2) synthesis. In rationally designed cell systems ideal for determining direct effects of the inhibitors on mPGES-1 function, but not its expression, PF-9184 inhibited PGE(2) synthesis (IC(50) in the range of 0.5-5 microM in serum-free cell and human whole blood cultures, respectively) while sparing the synthesis of 6-keto-PGF(1alpha) (PGF(1alpha)) and PGF(2alpha). In contrast, as expected, the selective COX-2 inhibitor, SC-236, inhibited PGE(2), PGF(1alpha) and PGF(2alpha) synthesis. This profile of mPGES-1 inhibition, distinct from COX-2 inhibition in cells, validates mPGES-1 as an attractive target for therapeutic intervention.

Sympathetic innervation of the spleen in male Brown Norway rats: a longitudinal aging study.

Aging leads to reduced cellular immunity with consequent increased rates of infectious disease, cancer, and autoimmunity in the elderly. The sympathetic nervous system (SNS) modulates innate and adaptive immunity via innervation of lymphoid organs. In aged Fischer 344 (F344) rats, noradrenergic (NA) nerve density in secondary lymphoid organs declines, which may contribute to immunosenescence with aging. These studies suggest there is SNS involvement in age-induced immune dysregulation. The purpose of this study was to longitudinally characterize age-related change in sympathetic innervation of the spleen and sympathetic activity/tone in male Brown Norway (BN) rats, which live longer and have a strikingly different immune profile than F344 rats, the traditional animal model for aging research. Splenic sympathetic neurotransmission was evaluated between 8 and 32 months of age by assessing (1) NA nerve fiber density, (2) splenic norepinephrine (NE) concentration, and (3) circulating catecholamine levels after decapitation. We report a decline in NA nerve density in splenic white pulp (45%) at 15 months of age compared with 8-month-old (M) rats, which is followed by a much slower rate of decline between 24 and 32 months. Lower splenic NE concentrations between 15 and 32 months of age compared with 8M rats were consistent with morphometric findings. Circulating catecholamine levels after decapitation stress generally dropped with increasing age. These findings suggest there is a sympathetic-to-immune system dysregulation beginning at middle age. Given the unique T-helper-2 bias in BN rats, altered sympathetic-immune communication may be important for understanding the age-related rise in asthma and autoimmunity.

Sympathetic nervous system and lymphocyte proliferation in the Fischer 344 rat spleen: a longitudinal study.

UNLABELLED: Aging is associated with reduced cellular immunity, which leads to increased rates of infectious disease, cancer and autoimmunity in the elderly. Previous findings from our laboratory revealed an age-related decline in sympathetic innervation of immune organs that affects immunity. These studies suggested potential sympathetic nervous system involvement in age-induced immune dysregulation. OBJECTIVES: The purpose of this study was to longitudinally characterize the effects of age on sympathetic neurotransmission in the spleen and net sympathetic activity/tone in male Fischer 344 rats. METHODS: Splenic sympathetic neurotransmission was evaluated between 8 and 24 months of age by (1) splenic norepinephrine (NE) concentration and turnover, (2) beta-adrenergic receptor (beta-AR) expression and (3) beta-AR-stimulated splenocyte cAMP production. Measures of sympathetic neurotransmission were correlated with age-related changes in Concanavalin A (Con A)-stimulated splenocyte proliferation. RESULTS: Splenic NE turnover increased during middle age, then subsequently declined by 18 months of age compared with 8-month-old controls (young). Splenic NE concentration increased at 10 months and decreased at 18-24 months, compared with young rats; however, plasma NE levels were not affected by age. Plasma epinephrine levels were decreased at 24 months. NE synthesis blockade increased and decreased the rate of plasma catecholamine depletion in middle and old age, respectively. beta-AR-stimulated cAMP production increased in splenocytes by 15 months. An age-related decrease in Con A-induced splenocyte proliferation was apparent by 10 months and persisted through 24 months. The decline in Con A-induced splenocyte proliferation correlated with the age-related increase in cAMP production. CONCLUSIONS: Aging alters sympathetic nervous system metabolism in the spleen to affect beta-AR signaling to splenocytes, suggesting that altered sympathetic-immune modulation changes are evident by early middle age.

A consensus rating method for small virus-retentive filters. I. Method development.

Virus filters are membrane-based devices that remove large viruses (e.g., retroviruses) and/or small viruses (e.g., parvoviruses) from products by a size exclusion mechanism. In 2002, the Parenteral Drug Association (PDA) organized the PDA Virus Filter Task Force to develop a common nomenclature and a standardized test method for classifying and identifying viral-retentive filters. One goal of the task force was to develop a test method for small virus-retentive filters. Because small virus-retentive filters present unique technical challenges, the test method development process was guided by laboratory studies to determine critical variables such as choice of bacteriophage challenge, choice of model protein, filtration operating parameters, target log10 reduction value, and filtration endpoint definition. Based on filtration, DLS, electrospray differential mobility analysis, and polymerase chain reaction studies, a final rating based on retention of bacteriophage PP7 was chosen by the PDA Virus Filter Task Force. The detailed final consensus filter method was published in the 2008 update of PDA Technical Report 41. Virus Filtration.

A consensus rating method for small virus-retentive filters. II. Method evaluation.

Virus filters are membrane-based devices that remove large viruses (e.g., retroviruses) and/or small viruses (e.g., parvoviruses) from products by a size exclusion mechanism. In 2002, the Parenteral Drug Association (PDA) organized the PDA Virus Filter Task Force to develop a common nomenclature and a standardized test method for classifying and identifying viral-retentive filters. A test method based on bacteriophage PP7 retention was chosen based on developmental studies. The detailed final consensus filter method is published in the 2008 update of PDA Technical Report 41: Virus Filtration. Here, we evaluate the method and find it to be acceptable for testing scaled-down models of small virus-retentive filters from four manufacturers. Three consecutive lots of five filter types were tested (Pegasus SV4, Viresolve NFP, Planova 20N and 15N, Virosart CPV). Each passed the criteria specified in the test method (i.e., >4 log10 PP7 retention, >90% intravenous immunoglobulin passage, and passing integrity/installation testing) and was classified as PP7-LRV4.

Nanostructured polymers with embedded self-assembled reactive gel networks.

Generating polymers in the presence of a self-assembling gelator with terminal double bonds yields polymeric materials with embedded reactive nano-skeletons-subsequent washing gives nanoscale imprinted materials with fibrillar architectures.

Failure at the transition of care: challenges in the discharge of the vulnerable elderly patient.

The case of an elderly patient with mild dementia and severe depression is reviewed including analysis of the barriers to successful transition that led to readmission. Situations likely to result in failed transitions include poor social support, discharge during times when ancillary services are unavailable, uncertain medication reconciliation, depression, and patients' cognitive limitations. Evidence suggests deficits in communication by hospital physicians to primary care providers occur commonly but this is only one of many systems barriers to successful discharge. Review of the literature reveals interventions such as involvement of advance practice nurses or family members in the transition may overcome some of the difficulties inherent in discharge of the vulnerable geriatric patient. Weekend discharges present unique challenges and potential solutions are explored. This case offers the opportunity to review the elements necessary for success and insight into the systems limitations which underlie failed transitions.

Sympathetic modulation of immunity: relevance to disease.

Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far has focused on neural-immune modulation in secondary lymphoid organs, has revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease- or injury-induced 'fight' responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks.