bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular automata simulation of topological effects on the dynamics of feed-forward motifs
Authors: Apte Advait A , Cain John W , Bonchev Danail G , Fong Stephen S
Published: February 2008

Background

Feed-forward motifs are important functional modules in biological and other complex networks. The functionality of feed-forward motifs and other network motifs is largely dictated by the connectivity of the individual network components. While studies on the dynamics of motifs and networks are usually devoted to the temporal or spatial description of processes, this study focuses on the relationship between the specific architecture and the overall rate of the processes of the feed-forward family of motifs, including double and triple feed-forward loops. The search for the most efficient network architecture could be of particular interest for regulatory or signaling pathways in biology, as well as in computational and communication systems.

Results

Feed-forward motif dynamics were studied using cellular automata and compared with differential equation modeling. The number of cellular automata iterations needed for a 100% conversion of a substrate into a target product was used as an inverse measure of the transformation rate. Several basic topological patterns were identified that order the specific feed-forward constructions according to the rate of dynamics they enable. At the same number of network nodes and constant other parameters, the bi-parallel and tri-parallel motifs provide higher network efficacy than single feed-forward motifs. Additionally, a topological property of isodynamicity was identified for feed-forward motifs where different network architectures resulted in the same overall rate of the target production.

Conclusion

It was shown for classes of structural motifs with feed-forward architecture that network topology affects the overall rate of a process in a quantitatively predictable manner. These fundamental results can be used as a basis for simulating larger networks as combinations of smaller network modules with implications on studying synthetic gene circuits, small regulatory systems, and eventually dynamic whole-cell models.
What do we know about communicating risk? A brief review and suggestion for contextualising serious, but rare, risk, and the example of cox-2 selective and non-selective NSAIDs
Authors: Moore R Andrew , Derry Sheena , McQuay Henry J , Paling John
Published: February 2008

Background

Communicating risk is difficult. Although different methods have been proposed – using numbers, words, pictures or combinations – none has been extensively tested. We used electronic and bibliographic searches to review evidence concerning risk perception and presentation. People tend to underestimate common risk and overestimate rare risk; they respond to risks primarily on the basis of emotion rather than facts, seem to be risk averse when faced with medical interventions, and want information on even the rarest of adverse events.

Methods

We identified observational studies (primarily in the form of meta-analyses) with information on individual non-steroidal anti-inflammatory drug (NSAID) or selective cyclooxygenase-2 inhibitor (coxib) use and relative risk of gastrointestinal bleed or cardiovascular event, the background rate of events in the absence of NSAID or coxib, and the likelihood of death from an event. Using this information we present the outcome of additional risk of death from gastrointestinal bleed and cardiovascular event for individual NSAIDs and coxibs alongside information about death from other causes in a series of perspective scales.

Results

The literature on communicating risk to patients is limited. There are problems with literacy, numeracy and the human tendency to overestimate rare risk and underestimate common risk. There is inconsistency in how people translate between numbers and words. We present a method of communicating information about serious risks using the common outcome of death, using pictures, numbers and words, and contextualising the information. The use of this method for gastrointestinal and cardiovascular harm with NSAIDs and coxibs shows differences between individual NSAIDs and coxibs.

Conclusion

Although contextualised risk information can be provided on two possible adverse events, many other possible adverse events with potential serious consequences were omitted. Patients and professionals want much information about risks of medical interventions but we do not know how best to meet expectations. The impact of contextualised information remains to be tested.
Critical care management and outcome of severe Pneumocystis pneumonia in patients with and without HIV infection
Authors: Monnet Xavier , Vidal-Petiot Emmanuelle , Osman David , Hamzaoui Olfa , Durrbach Antoine , Goujard Cécile , Miceli Corinne , Bourée Patrice , Richard Christian
Published: February 2008

Background

Little is known about the most severe forms of Pneumocystis jiroveci pneumonia (PCP) in HIV-negative as compared with HIV-positive patients. Improved knowledge about the differential characteristics and management modalities could guide treatment based on HIV status.

Methods

We retrospectively compared 72 patients (73 cases, 46 HIV-positive) admitted for PCP from 1993 to 2006 in the intensive care unit (ICU) of a university hospital.

Results

The yearly incidence of ICU admissions for PCP in HIV-negative patients increased from 1993 (0%) to 2006 (6.5%). At admission, all but one non-HIV patient were receiving corticosteroids. Twenty-three (85%) HIV-negative patients were receiving an additional immunosuppressive treatment. At admission, HIV-negative patients were significantly older than HIV-positive patients (64 [18 to 82] versus 37 [28 to 56] years old) and had a significantly higher Simplified Acute Physiology Score (SAPS) II (38 [13 to 90] versus 27 [11 to 112]) but had a similar PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio (160 [61 to 322] versus 183 [38 to 380] mm Hg). Ventilatory support was required in a similar proportion of HIV-negative and HIV-positive cases (78% versus 61%), with a similar proportion of first-line non-invasive ventilation (NIV) (67% versus 54%). NIV failed in 71% of HIV-negative and in 13% of HIV-positive patients (p < 0.01). Mortality was significantly higher in HIV-negative than HIV-positive cases (48% versus 17%). The HIV-negative status (odds ratio 3.73, 95% confidence interval 1.10 to 12.60) and SAPS II (odds ratio 1.07, 95% confidence interval 1.02 to 1.12) were independently associated with mortality at multivariate analysis.

Conclusion

The yearly incidence of ICU admissions for PCP in HIV-negative patients in our unit increased from 1993 to 2006. The course of the disease and the outcome were worse in HIV-negative patients. NIV often failed in HIV-negative cases, suggesting that NIV must be watched closely in this population.
Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus
Authors: Yamaguchi Hiroshi , Takagi Junichi , Miyamae Takako , Yokota Shumpei , Fujimoto Takashi , Nakamura Shinobu , Ohshima Shiro , Naka Tetsuji , Nagata Shigekazu
Published: February 2008

Mouse milk fat globule epidermal growth factor 8 (MFG-E8), which is secreted by a subset of activated macrophages, binds to apoptotic cells by recognizing phosphatidylserine and promotes their engulfment. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in MFG-E8−/− mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus (hSLE). Here, we report that hMFG-E8 bound to phosphatidylserine and an integrin αvβ3 complex. Increasing concentrations of MFG-E8 generated a bell-shaped response curve for the efficiency of phagocytosis. That is, in NIH3T3 and MFG-E8−/− thioglycollate-elicited peritoneal macrophages that do not express MFG-E8, hMFG-E8 enhanced engulfment at low concentrations but inhibited it at high concentrations. On the other hand, hMFG-E8 dose-dependently inhibited the engulfment of apoptotic cells by MFG-E8+/+ thioglycollate-elicited peritoneal macrophages, indicating that an excess of MFG-E8 has an inverse effect on the engulfment of apoptotic cells. To investigate the role of MFG-E8 in human disease, we generated two mAb against MFG-E8 and screened human blood samples for MFG-E8 using an ELISA. We found that some childhood-onset and adult SLE patients carried a significant level of MFG-E8 in their blood samples. These results suggested that the aberrant expression of MFG-E8 is involved in the pathoetiology of some cases of hSLE.
Prediction of Biot’s coefficient from rock-physical modeling of North Sea chalk
Authors: Olsen Casper , Hedegaard Kathrine , Fabricius Ida L. , Prasad Manika
Published: February 2008

We predict Biot’s coefficient for North Sea chalk based on density and P-wave velocity for water-saturated chalk. We compare three effective medium models: Berryman’s self-consistent model, the isoframe model, and the bounding-average method (BAM). The self-consistent model is used with two combinations of aspect ratios. In one combination, the aspect ratio is equal for pores and grains. In the other combination, the aspect ratio for grains is kept constant close to 1 and the aspect ratio for pores varies. All the models include one free parameter that determines the stiffness of the rock for a fixed porosity. This free parameter is compared with Biot’s coefficient to discuss whether the free parameter is related to pore-space compressibility for North Sea chalk. We also discuss how consistent the models are between P-wave modulus and shear modulus for dry and water-saturated chalk. The acoustic velocity and the density data for dry and water-saturated chalk are all laboratory data. The isoframe model and the BAM model predict Biot’s coefficient with a smaller error than the self-consistent model does. The free parameter in the isoframe model and the BAM model is related to Biot’s coefficient. The free parameter in the self-consistent model is related only to Biot’s coefficient for water-saturated chalk when the aspect ratios for pores and grains are equal. The isoframe and the BAM model are generally more consistent for chalk than the self-consistent model is.
Regulation of Fat-Stimulated Neurotensin Secretion in Healthy Subjects
Authors: Drewe Juergen , Mihailovic Svetlana , D'Amato Massimo , Beglinger Christoph
Published: February 2008

Context: Cholecystokinin (CCK) and neurotensin are stimulated during meal intake by the presence of fat in the small intestine. The sequence of events suggests that fat hydrolysis is crucial for triggering the release.

Objective: The aim of this study was to investigate whether CCK mediated the effect of intraduodenal (ID) fat on neurotensin secretion via CCK-1 receptors.

Setting: This was a single center study; 34 male volunteers were studied in consecutive, randomized, double-blind, cross-over studies.

Subjects and Methods: CCK and neurotensin release were quantified in: 1) 12 subjects receiving an ID fat infusion with or without 60 mg orlistat, an irreversible inhibitor of gastrointestinal lipases, in comparison to vehicle; 2) 12 subjects receiving ID long chain fatty acids (C18s), ID medium chain fatty acids, or ID vehicle; and 3) 10 subjects receiving ID C18 with and without the CCK-1 receptor antagonist dexloxiglumide or ID vehicle plus iv saline (placebo). Hormone concentrations were measured by specific RIA systems.

Results: ID fat induced a significant increase in CCK and neurotensin concentrations (P < 0.001–0.002). Inhibition of fat hydrolysis by orlistat abolished both effects. C18 stimulated CCK and neurotensin release (P < 0.001, respectively), whereas medium chain fatty acid was ineffective. Dexloxiglumide administration partially blocked the effect of C18 on neurotensin; the effect was only present in the first phase of neurotensin secretion.

Conclusions: Generation of C18 through hydrolysis of fat is a critical step for fat-induced stimulation of neurotensin in humans; the signal is in part mediated via CCK release and CCK-1 receptors.
Increased Plasma Osteoprotegerin Concentrations Are Associated with Indices of Bone Strength of the Hip
Authors: Samelson Elizabeth J. , Broe Kerry E. , Demissie Serkalem , Beck Thomas J. , Karasik David , Kathiresan Sekar , Kiel Douglas P.
Published: February 2008

Objective: Osteoprotegerin (OPG) is an important regulator of bone turnover through its effects on osteoclastogenesis, yet findings from previous studies of circulating OPG and commonly measured bone indices in humans have been conflicting. We conducted a cross-sectional study to evaluate the association between plasma OPG and femoral neck (FN) bone density (BMD) and geometry in a large cohort of women and men.

Design: Participants included 1379 postmenopausal women and 1165 men, aged 50–89 yr (mean, 64 yr), in the Framingham Offspring Study. Dual x-ray absorptiometry was used to evaluate FN BMD and geometry (bone width, section modulus, and cross-sectional area at the narrow neck region). Plasma OPG concentrations were measured by ELISA. Sex-specific analysis of covariance was used to calculate means and assess linear trend in BMD and geometry values across OPG quartiles, adjusted for confounders.

Results: OPG concentrations were greater in women than men, increased with age, and were greater in smokers and those with diabetes and heart disease. Multivariable-adjusted mean FN BMD in women increased from the lowest to the highest OPG quartile (trend, P < 0.01). However, no linear trend between FN BMD and OPG was observed in men (trend, P = 0.34). Section modulus and bone width increased with OPG in men (trend, P < 0.01), whereas no association between hip geometry indices and OPG was observed in women.

Conclusion: Higher OPG concentration may indicate greater skeletal strength in women and men, possibly through reducing bone loss in women and increasing periosteal apposition in men.
IKAP localizes to membrane ruffles with filamin A and regulates actin cytoskeleton organization and cell migration
Authors: Johansen Lars Dan , Naumanen Tiina , Knudsen Astrid , Westerlund Nina , Gromova Irina , Junttila Melissa , Nielsen Christina , Bøttzauw Trine , Tolkovsky Aviva , Westermarck Jukka , Coffey Eleanor T. , Jäättelä Marja , Kallunki Tuula
Published: February 2008

Loss-of-function mutations in the IKBKAP gene, which encodes IKAP (ELP1), cause familial dysautonomia (FD), with defective neuronal development and maintenance. Molecular mechanisms leading to FD are poorly understood. We demonstrate that various RNA-interference-based depletions of IKAP lead to defective adhesion and migration in several cell types, including rat primary neurons. The defects could be rescued by reintroduction of wild-type IKAP but not by FD-IKAP, a truncated form of IKAP constructed according to the mutation found in the majority of FD patients. Cytosolic IKAP co-purified with proteins involved in cell migration, including filamin A, which is also involved in neuronal migration. Immunostaining of IKAP and filamin A revealed a distinct co-localization of these two proteins in membrane ruffles. Depletion of IKAP resulted in a significant decrease in filamin A localization in membrane ruffles and defective actin cytoskeleton organization, which both could be rescued by the expression of wild-type IKAP but not by FD-IKAP. No downregulation in the protein levels of paxillin or beclin 1, which were recently described as specific transcriptional targets of IKAP, was detected. These results provide evidence for the role of the cytosolic interactions of IKAP in cell adhesion and migration, and support the notion that cell-motility deficiencies could contribute to FD.
Quantitative live-cell analysis of microtubule-uncoupled cargo-protein sorting in the ER
Authors: Dukhovny Anna , Papadopulos Andreas , Hirschberg Koret
Published: February 2008

The sorting and concentration of cargo proteins within ER exit sites (ERESs) is a fundamental function of the secretory machinery. The mechanism by which peripheral coat complexes and their small GTPase effectors mediate this function with export membrane domains is only partially understood. The secretory-machinery-mediated sorting to ERESs is a process that counters the entropy-driven even distribution of membrane proteins within organellar membranes. Here, for the first time, we quantified the dynamic properties of GFP-VSVG sorting to ERESs in living cells by uncoupling it from later translocation steps using microtubule depolymerization. The dynamics of the ER to ERES redistribution of cargo proteins was quantified in single cells by measuring changes in fluorescence-intensity variance after shift to the permissive temperature. Cargo concentration within ERESs continued in cells overexpressing the GTP-locked ARF1Q71L or in the presence of brefeldin A. In the absence of COPI and microtubules, ERESs transformed from tubulovesicular to spherical membranes that actively accumulated secretory cargo and excluded ER-membrane markers. We found sorting to ERESs to be a slow and diffusion-unlimited process. Our findings exclude COPI, and identify the COPII protein complex to be directly involved in the secretory cargo sorting and redistribution functions of ERESs.
Chemical genetic analysis of the regulatory role of Cdc2p in theS. pombeseptation initiation network
Authors: Dischinger Sandra , Krapp Andrea , Xie Linfeng , Paulson James R. , Simanis Viesturs
Published: February 2008

The protein kinase Cdc2p is the master regulator of cell cycle progression in the fission yeast Schizosaccharomyces pombe. It is required both for entry into mitosis and for onset of DNA replication. Cdc2p must be inactivated to permit exit from mitosis, licensing of replication origins and cytokinesis. To study the role of Cdc2p in greater detail, we generated a cdc2 allele that is sensitive to an inhibitory ATP analogue. We show that the inhibitor-induced cell cycle arrest is reversible and examine the effect of inhibiting Cdc2p on the regulation of the septation initiation network (SIN), which controls the initiation of cytokinesis in S. pombe. We found that specific inactivation of Cdc2p in a mitotically arrested cell promotes the asymmetrical recruitment of SIN proteins to the spindle poles and the recruitment of the most downstream SIN components and β-(1,3) glucan synthase to the contractile ring. Thus, we conclude that inactivation of Cdc2p is sufficient to activate the SIN and promote cytokinesis.
Mechanism of PHERES1 imprinting in Arabidopsis
Authors: Makarevich Grigory , Villar Corina B. R. , Erilova Aleksandra , Köhler Claudia
Published: February 2008

Genomic imprinting is a phenomenon where only one of the two alleles of a gene is expressed – either the maternally or the paternally inherited allele. Imprinting of the plant gene PHERES1 requires the function of the FERTILIZATION INDEPENDENT SEED (FIS) Polycomb group (PcG) complex for repression of the maternal PHERES1 allele. In this study we investigated the mechanism of PHERES1 imprinting and found that PcG silencing is necessary but not sufficient for imprinting establishment of PHERES1. We provide evidence that silencing of the maternal PHERES1 allele depends on a distantly located region downstream of the PHERES1 locus. This region needs to be methylated to ensure PHERES1 expression but must not be methylated for PHERES1 repression. This mechanism is analogous to the regulation of several imprinted genes in mammals, suggesting the employment of similar evolutionary mechanisms for the regulation of imprinted genes in mammals and flowering plants.
Fabrication of a Shear Force-based Ion-selective Capillary Probe for Scanning Electrochemical Microscopy
Authors: Yamada Hiroshi , Ikuta Yuuya , Koike Tohru , Matsue Tomokazu
Published: February 2008

A shear force-based ion-selective probe for scanning electrochemical microscopy was fabricated for the imaging of localized potassium ions. A solution of dibenzo-18-crown-6/1,2-dichloroethane was added to a pulled capillary which was contact with a tuning fork attached to a piezoelectric buzzer. 10 μm of a Nafion island on glass was imaged, and the topography and current image originating from localized potassium ion concentration were obtained.
Organizational learning and patient safety in the NHS: an exploration of the organizational learning that occurs following a coroner's report under Rule 43
Authors: Claridge Tanya , Cook Gary , Hale Richard
Published: February 2008

Patient safety is enhanced by harnessing multiple sources of data, including sources external to the organization – such as the coroner. Following an inquest, the coroner can make a report under the Coroner's Rule 43 to any statutory body or organization when it is identified at inquest that similar fatalities could be prevented if lessons are learnt from the findings of the inquest. An exploratory study was undertaken, using qualitative methodology to investigate the characteristics of organizational learning following recommendations of the coroner under Rule 43 in one district health economy. The role of the coroner was not clear even to the most senior interviewees. There was little evidence of organizational learning generated or shared in the organizations involved in this study from the recommendation of the coroner after a comiogenic (iatrogenic) death. There was evidence of a lack of clarity in both structure and function in the handling of and learning from coroner's recommendations both within and between the organizations involved in this study. The role of Rule 43 reports should be explored at national level and standardized tools developed in order to facilitate learning within and between NHS organizations.
Intraoperative cell salvage in obstetrics
Authors: Catling Sue
Published: February 2008

Cell salvage is widely used in many surgical specialties to reduce the use of allogeneic blood, which is associated with well-recognized significant complications such as incorrect transfusion, acute and delayed immunological transfusion reactions and transfusion-transmitted infection. Theoretical concerns over the use of cell salvage in obstetrics have focused on the risk of Rhesus immunization and the risk of contamination of the cell-saved blood with traces of amniotic fluid. This article examines the in vitro and in vivo evidence for the safety of the technique, presents current usage figures from Wales and the entire UK, and discusses the current perception of amniotic fluid embolus as an anaphylactoid reaction. It suggests that patients will have to choose between the risks of allogeneic or cell-saved blood, and concludes that the balance of evidence is now in favour of cell salvage in obstetrics.
Implementing a Balanced Scorecard as a Strategic Management Tool in a Long-Term Care Organization
Authors: Schalm Corinne
Published: February 2008

Background

The Capital Care Group, the largest public sector continuing care organization in Canada, had no ready access to information on its own performance and therefore was limited in its pursuit of evidence-informed decisionmaking. To remedy this, it was decided to introduce a balanced scorecard.

Assessment of problem

A literature review was conducted together with interviews with 10 other health care organizations which had implemented balanced scorecards. With this information, a workshop was held that resulted in a framework and about 120 potential indicators. Subsequently the number of indicators was reduced to 29, using pre-determined criteria.

Results

Development of a corporate balanced scorecard facilitated executive strategic thinking and clarified the organization's strategic direction. In parallel, scorecards were developed at the level of care centres. These had a common core of indicators, plus some site-specific ones. Development of the corporate scorecard took three years and an additional six months for the care centre scorecards.

Strategies for change

A formal implementation plan has been accepted by the executive team. Key to this is communicating to staff the role of scorecards for strategic management and not just performance measurement. Traditional thinking needs to change from a short-term operational focus to long-term strategy. In addition, champions need to be identified in each care centre and they need to be networked together. Finally, the scorecard is being integrated into existing operational management as a routine component together with resources to support its use.

Lessons and messages

The balanced scorecard has focused on its role as a strategic management tool. The indicators and dimensions need to be customized to the organization. Senior management must be seen to be driving its introduction. It is worth spending sufficient time developing and implementing a scorecard rather than trying to rush its introduction. The scorecard needs to be integrated with existing management processes and sufficient resources must be assigned. However, success will ultimately depend on the culture of the organization being appropriate and receptive.
Bridging the Gap between Primary and Secondary Care: Use of a Clinical Pathway for the Investigation and Management of Deep Vein Thrombosis
Authors: Campbell Samuel , Macdonald Michael , Carr Brendan , Anderson David , Mackinley Robert , Cairns Susan
Published: February 2008

Background

Clinical processes that span the boundary between primary and secondary care often suffer from poor standardization of practice and lines of communication. One example is the clinical management of suspected deep vein thrombosis (DVT). Making or excluding the diagnosis can be complex. Tools to investigate DVT were not available to family physicians so patients had to be referred to the hospital emergency department and endure a long wait which could exacerbate the condition. In addition, urgent referrals to the ultrasound department disrupted the scheduled list of patients.

Assessment of problem

A team of stakeholders including all relevant specialties and professions from primary and secondary care was established. After reviewing the literature and interviewing those involved in delivering care, an evidence-based scoring system to calculate the clinical probability of a DVT was adopted and introduced as part of a clinical pathway from primary to secondary care. Its introduction was based on the Plan, Do, Study, Act (PDSA) cycle.

Results

In the first year after the introduction of the clinical pathway, 70% of family physicians had used it and were very satisfied. Patients found it efficient (75%) with 96% very satisfied or satisfied. The waiting time in the emergency department fell from a mean of 379 minutes to 285 minutes. Although the incidence of initial investigations (D-Dimer tests) increased by 42%, the proportion of patients undergoing a subsequent ultrasound test found to have a DVT was unchanged (14%). This suggested the level of suspicion of a DVT in the community had risen. Referrals to the hospital's DVT clinic increased by 14% overall, driven partly by a large increase in those who had come from the new clinical pathway from primary care.

Lessons and messages

Key lessons include the importance of including all relevant stakeholders and the benefits of using PDSA to make rapid changes during implementation. We are now seeking to extend the use of the clinical pathway to other hospitals and more family physicians. In addition, the clinical pathway approach will be applied to other conditions and interventions. We have demonstrated how a multidisciplinary group of stakeholders in a clinical care process can develop and introduce a clinical pathway that allows smooth transit of patients over the barriers between different sectors of the health care system and between independent disciplines. We have also demonstrated the use of untapped non-physician potential in the system to safely facilitate patient care.
Moving to a Culture of Safety in Community Home Health Care
Authors: Stevenson Lynn , McRae Cora , Mughal Waqar
Published: February 2008

Objective

Community home health care workers and their clients are faced with a mixture of occupational health and safety challenges that are not typically experienced by health care providers or patients in the acute care sector. The aim of this project was to explore the concept of safety in community home health in one health care authority in British Columbia.

Methods

A participatory action research approach was employed to explore staff and client safety risks in this environment. In the first phase, three focus groups were held with staff (n 5 39) and the data analysed to identify themes. These were validated by additional focus groups. In the second phase, interviews were held with staff followed by chart reviews. Finally, in phase three, an interdisciplinary working group developed a risk identification tool for staff which was subsequently piloted. The exploration focused on answering the following questions: What constitutes safety in community home health care? What are the priority areas for action in relation to safety? What type of risk identification would be most helpful to community health workers to prepare them adequately to meet their clients’ and their own safety needs?

Results

Risk themes identified included: poor communication, acute care staff not understanding the needs of community staff, working alone, mobility, medication concerns, lack of pre-screening of clients’ homes, and community health workers accepting a high degree of risk.

Conclusions

Findings suggest that typical notions of safety and risk in acute care are not easily translated into the community sector, that staff and clients’ safety concerns are intertwined, and staff require better and more timely information from acute care staff when patients are discharged home.
Advancing Employee Engagement Through a Healthy Workplace Strategy
Authors: Seymour Andrea , Dupré Kathryne
Published: February 2008

Background

In recent years, there has been increased focus on improving the quality of the working lives of staff in health care organizations. Research shows that improvements can be achieved through a comprehensive organizational approach to workplace health. Improved worker engagement is a realizable outcome of such an approach, provided that it is based on reliable and relevant data and is tailored to the specific environment in which it is being implemented.

Assessment of problem

An intervention project was designed to develop an organization-wide approach to employee workplace health. A comprehensive health risk assessment was undertaken, along with a staff survey on workplace culture, individual health practice and environmental effects on physical health.

Results

In general, the findings present a positive picture of the culture and factors that influence psychological wellbeing. However, improvement is needed in some areas: satisfaction is only marginally outweighing stress, and musculoskeletal disorders account for much absenteeism. Employee health needs include weight management, improving fitness and nutrition, and decreasing coronary risk.

Strategies for change

Results have prompted this organization to pursue the development of a Healthy Workplace Policy that will be used as a filter for all other policies relating to workplace culture, environment and practice, and have provided the impetus and focus to review the organization of employee health services.

Lessons learned

Three major administrative activities are necessary to move from planning to sustained action: ensure adherence of all staff to any policy derived from a health risk assessment; ensure staff feel proposed changes are relevant and important; and create a road map to guide the development of a strategic and an implementation plan. The findings outlined in this report can be addressed by organizations that are willing to commit to a comprehensive approach to workplace health.
Is Public Health Ready for a Professional Practice Framework?
Authors: Cava Maureen
Published: February 2008

Objective

To develop a framework for professional practice for a large urban public health unit in Canada.

Methods

The project involved a literature search, key informant interviews, an environmental scan and focus groups.

Results

Analysis and synthesis led to recommendations for the development of discipline-specific Professional Practice Leaders (PPL) and an Interprofessional Practice Leaders Network. The latter meets to discuss cross-cutting practice issues and is chaired by the chief executive officer of the health unit, the Medical Officer of Health. The one-year evaluation has demonstrated that this initiative has worked well in practice. It is a flexible framework which provides new leadership opportunities and gives staff valuable input into decisionmaking on practice issues. It is also a more efficient use of staff resources, including a comprehensive approach to solving problems and in breaking down silos between programs. Communication and collaboration between disciplines has increased.

Conclusion

The initiative was evaluated successfully after the pilot year. In going forward areas to review include the time allotment for the PPL, communication between the PPL, the respective Program Director and the entire department, and expanding professional development opportunities for the PPL.
Accuracy of a Provincial Prescription Database for Assessing Medication Adherence in Heart Failure Patients
Authors: Dahri Karen , Shalansky Stephen J , Jang Linda , Jung Leon , Ignaszewski Andrew P , Clark Catherine
Published: February 2008

Background:

British Columbia's central prescription database, PharmaNet, is often used for both clinical and research applications. However, PharmaNet details prescription transactions, not actual medication consumption, resulting in many potential sources of inaccuracy when the information is assumed to reflect population or individual drug utilization.

Objective:

To assess the accuracy of PharmaNet for adherence assessment in patients with heart failure who are taking β-blockers.

Methods:

A 6-month prospective, longitudinal assessment of adherence to the prescribed β-blocker regimen was carried out using both PharmaNet data and the Medication Event Monitoring System (MEMS) for each patient enrolled. The limit of agreement between the 2 adherence assessment methods was assessed using the Bland-Altman approach.

Results:

Fifteen of 58 patients initially enrolled in the study were excluded, most due to misuse of MEMS or failure to return the MEMS vial despite thorough follow-up. For the 43 patients included in the final analysis, mean ± SD adherence was 97.8 ± 11.8% when assessed by PharmaNet and 97.1 ± 7.3% when MEMS was used. However, the limit of agreement, reported as the mean of the differences ± 2SD, was 6.8 ± 18.5%, indicating a moderate-to-high level of agreement between the 2 methods when the confidence interval is taken into consideration.

Conclusions:

These results suggest that PharmaNet data accurately reflect medication adherence for most patients. The MEMS system proved unreliable in several cases, illustrating the difficulty of identifying a gold standard for adherence assessment.
Reduced Argatroban Doses After Coronary Artery Bypass Graft Surgery
Authors: Hoffman William D , Czyz Yvonne , McCollum David A , Hursting Marcie J
Published: February 2008

Background:

The Food and Drug Administration–approved argatroban dose for heparin-induced thrombocytopenia (HIT) is 2 μg/kg/min (0.5 μg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) 1.5–3 times baseline. Recent data suggest that reduced doses are required after cardiovascular surgery.

Objective:

To characterize dosing requirements, aPTTs, factors affecting dosage, and clinical outcomes in patients administered argatroban after coronary artery bypass graft (CABG) surgery.

Methods:

Charts of 39 patients who underwent CABG surgery and were administered argatroban postoperatively for laboratory-confirmed HIT (n = 25), antibody-negative suspected HIT (n = 10), or previous HIT requiring anticoagulation (n = 4) were retrospectively reviewed. Patient characteristics, argatroban dosing information, aPTTs (target range 45–90 sec), and outcomes were summarized. Regression analyses explored potential effectors of dosage.

Results:

Patient features, argatroban dosing patterns, and aPTTs were similar among groups. Many patients had laboratory evidence of some hepatic and/or renal dysfunction (median [range] bilirubin 1.0 [0.3–8.0] mg/dL, creatinine clearance 47 [18–287] mL/min). Overall, median argatroban doses were 0.5 μg/kg/min initially and 0.6 μg/kg/min during therapy (median duration 5.3 days). After argatroban initiation, aPTTs were greater than 90 seconds at first assessment in 4 patients (3 with abnormal hepatic function test results) initially administered 0.5, 1, 2, and 2 μg/kg/min, respectively. Within approximately 16 hours of therapy, 33 (85%) patients achieved consecutive therapeutic aPTTs. No association was detected between mean dose during therapy and preoperative ejection fraction, routine hepatic or renal function test results (other than blood urea nitrogen [BUN]), or surgery type. A clinically insignificant association existed between dose and BUN: there was an approximately 0.15 μg/kg/min dose decrease for each 10 mg/dL BUN increase. One patient developed thrombosis, 1 underwent finger amputation, 7 died (5 after argatroban cessation), and 4 had significant bleeding.

Conclusions:

These findings suggest that reduced initial argatroban doses (eg, 0.5 μg/kg/min), adjusted to achieve therapeutic aPTTs, provide rapid, adequate anticoagulation in postoperative CABG patients with presumed or previous HIT. Prospective study of reduced initial dosing in this setting is warranted.
Impact of Treatment Guidelines on Clinical and Economic Outcomes of Acute Decompensated Heart Failure
Authors: DiDomenico Robert J , Perez Alexandra , Schumann Heather M , Fontana Dee R , Kondos George T , Schumock Glen T
Published: February 2008

Background:

No data exist that demonstrate the impact of comprehensive acute decompensated heart failure (ADHF) treatment guidelines on clinical and economic outcomes in hospitalized patients with this condition.

Objectives:

To compare clinical and economic outcomes before and after implementation of treatment guidelines for ADHF.

Methods:

A single-center, retrospective, chart review study was conducted in a university hospital. ADHF treatment guidelines were developed and implemented on January 1, 2004. Patients hospitalized for ADHF between January 2003 and November 2004 were identified using the Acute Decompensated Heart Failure Registry. Study periods were 12 months prior to and the 11 months following guideline implementation.

Results:

This cohort was comprised of 683 ADHF hospitalizations (357 preguideline, 326 postguideline); several patients were admitted more than once. There was a trend toward increased use of intravenous vasoactive drugs (VADs) following guideline implementation (19.9% vs 24.2%; p = 0.05). The duration of intravenous VAD use decreased by more than 40% following guideline implementation, but this was not statistically significant after risk adjustment (p = 0.22). The need for intensive care unit monitoring decreased from 45.1% before guideline implementation to 25.3% following guideline implementation (p < 0.02) in patients treated with intravenous VADs. The need for mechanical ventilation was reduced by nearly 80% (p = 0.04) following guideline implementation. Significantly more patients of the postguideline cohort were prescribed β-blockers at discharge (54.9% vs 75.2%; p = 0.0001). Costs were not significantly different between the groups.

Conclusions:

Implementation of ADHF treatment guidelines was associated with reduced need for mechanical ventilation, improved utilization of β-blockers at discharge, and trends toward increased use of intravenous VADs, while not significantly changing total costs. More rigorous studies need to be conducted to estimate the true effect of treatment guidelines on ADHF care and outcomes.
Abacavir Hypersensitivity Reaction: an Update
Authors: Hughes Christine A , Foisy Michelle M , Dewhurst Norman , Higgins Niamh , Robinson Linda , Kelly Deborah V , Lechelt Kelly E
Published: February 2008

Objective:

To review the clinical features, risk factors, diagnosis, and management of abacavir hypersensitivity reaction (HSR).

Data Sources:

A MEDLINE (1950–October 2007) and EMBASE (1980–October 2007) search using key words abacavir, HIV, human immunodeficiency virus, hypersensitivity reaction, HLA-B*5701, and patch tests was conducted. Conference abstracts and article bibliographies were reviewed to identify relevant studies.

Study Selection and Data Extraction:

Studies that investigated the clinical and immunogenetic risk factors for abacavir hypersensitivity and the benefit of genetic screening, as well as articles that focused on the clinical presentation, assessment, and management of abacavir HSR, were considered for this review.

Data Synthesis:

Abacavir hypersensitivity is an immune-mediated reaction that typically occurs within the first 6 weeks of therapy. Signs and symptoms of abacavir HSR are nonspecific, which makes the diagnosis challenging, particularly in medically complex patients. Patch testing may improve the diagnosis and confirmation of abacavir HSR, but it remains experimental. Clinical management is aimed at supportive therapy and discontinuation of abacavir. Rechallenge with abacavir is contraindicated due to the risk of precipitating a life-threatening reaction. Appropriate patient education and a clear communication plan are essential for the safe use of this medication. Identification of patients at risk of developing abacavir hypersensitivity through routine genetic screening for human leukocyte antigen (HLA) HLA-B*5701 represents a significant advance in the field of pharmacogenomics, with an apparent 100% negative predictive value when used to screen for abacavir HSR. Preliminary data suggest that pharmacogenetic testing for HLA-B*5701 is cost effective. However, until routine testing is available, pharmacovigilance is necessary for the safe and effective use of abacavir.

Conclusions:

Serious adverse events associated with the use of abacavir can be avoided by appropriate recognition and management of the HSR. Screening patients for HLA-B*5701 prior to initiation of abacavir represents a tool to further decrease the risk of HSRs as well as unnecessary discontinuation of this drug.
Use of Intravenous Valproic Acid for Acute Migraine
Authors: Frazee Lawrence A , Foraker Kimberly C
Published: February 2008

Objective:

To review the literature regarding the use of intravenous valproic acid in aborting an acute migraine attack.

Data Sources:

A MEDLINE (1967–June 2007) and bibliographic search of the English-language literature was conducted using the search terms valproic acid and migraine disorders.

Study Selection and Data Extraction:

All articles indentified through the search were included.

Data Synthesis:

Divalproex sodium is approved by the Food and Drug Administration for the prevention of migraine headaches. The use of intravenous valproic acid has been studied as a possible treatment for acute migraine. Available studies are small, mostly open-label and non–placebo-controlled, and used variable doses. Valproic acid has not been shown to be superior to comparator drugs and was inferior to prochlorperazine in one trial.

Conclusions:

Intravenous valproic acid has not been proven effective for acute migraine treatment. Future trials should be larger, placebo-controlled, and use a standardized dose and outcome measures.
Memantine-Induced Myoclonus and Delirium Exacerbated by Trimethoprim
Authors: Moellentin Dan , Picone Claudia , Leadbetter Emma
Published: February 2008

Objective:

To report a case of myoclonus and delirium seen in a patient taking a combination of memantine and trimethoprim.

Case Summary:

A 78-year-old woman was admitted to the medical center in October 2007 with rapid deterioration of Alzheimer's dementia and progressive myoclonus. In 2003, donepezil 5 mg/day had been initiated and her disease slowly progressed. In 2006, memantine 10 mg twice daily was added. Myoclonic activity and delirium were noted in 2007 when a urinary tract infection (UTI) was treated with double-strength trimethoprim/sulfamethoxazole (TMP/SMX 160 mg/800 mg). After discontinuation of TMP/SMX, the patient's condition returned to baseline level. Several weeks later, trimethoprim 100 mg daily was added for UTI prophylaxis. Within weeks, spontaneous generalized myoclonic activity resumed to the extent that the patient was unable to walk. She became increasingly delirious. A week before admission, levodopa/carbidopa 250 mg/100 mg was added for presumptive restless legs syndrome and the patient became extremely delirious and combative, requiring hospitalization. Because of the striking similarity of dose-related toxicities reported with amantadine, a slightly different aminoadamantane, memantine was withheld. Trimethoprim was discontinued due to a likely interaction with memantine. Donepezil and famotidine were withheld due to questions of therapeutic necessity. After 3 days, the myoclonus had completely resolved and the patient was no longer agitated or combative during the remainder of her hospitalization. She was cooperative and ambulatory and was discharged.

Discussion:

Memantine is cleared primarily through the kidneys and should be renally dosed. Drugs that interfere with elimination—that is, other drugs utilizing the organic cation transporter-2 in the tubule, such as trimethoprim, metformin, or imipramine—may lead to drug accumulation. Our patient, who had impaired renal function, developed severe myoclonus and delirium after trimethoprim was added to therapy with memantine. As there were no reports of myoclonus and delirium with this drug combination and because of the structural, pharmacologic, and pharmacokinetic similarities between the aminoadamantanes memantine and amantadine, we researched similar dual adverse effects reported with amantadine. Amantadine has led to the same adverse effects noted in our patient, not only in patients with renal impairment, but also in one patient when trimethoprim was added to a stable dose of amantadine.

Conclusions:

This is the first reported case of a drug interaction between memantine and trimethoprim, which resulted in clinically significant myoclonus and delirium. Clinicians should be aware of this potential interaction, since there have been reports of this adverse effect with the use of amantadine. Because memantine chemically and pharmacologically resembles amantadine, it is quite possible that their toxicities are similar.
When does national identification lead to the rejection of immigrants? Cross‐sectional and longitudinal evidence for the role of essentialist in‐group definitions
Authors: Pehrson Samuel , Brown Rupert , Zagefka Hanna
Published: February 2008

Two studies were carried out in England to investigate the role of essentialist national group definitions in determining the effect of national identification on prejudice towards immigrants, and asylum seekers in particular. It was expected that the relationship between national identification and prejudice would depend on the degree to which participants endorse an essentialist (‘ethnic’) definition of their nationality. Consistent with this, Study 1 (N=154) found that national identification is associated with negativity towards asylum seekers only among individuals who endorse an essentialist conception of the group, and shows no significant association with prejudice among those who reject such a conception. Study 2 (N=219) used a longitudinal design conducted over 6 weeks, allowing cross‐lagged analysis of causality between essentialism, identification, and behavioural intentions towards asylum seekers. A causal effect of essentialism on willingness to support a group acting against asylum seekers was observed, with no significant causal effect in the reverse direction. The reverse causal direction was observed in the case of support for a group seeking to support asylum seekers, with intended behaviours determining essentialism. The results are discussed in terms of the importance of group definitions in the study of in‐group affiliations and prejudice.