Geriatric hip fracture clinical pathway: the Hong Kong experience

Geriatric hip fracture is one of the commonest fractures in orthopaedic trauma. There is a trend of further increase in its incidence in the coming decades. Besides the development of techniques and implants to overcome the difficulties in fixation of osteoporosis bone, the general management of the hip fracture is also very challenging in terms of the preparation of the generally poorer pre-morbid state and complicate social problems associated with this group of patients. In order to cope with the increasing demand, our hospital started a geriatric hip fracture clinical pathway in 2007. The aim of this pathway is to provide better care for this group of patients through multidisciplinary approach. From year 2007 to 2009, we had managed 964 hip fracture patients. After the implementation of the pathway, the pre-operative and the total length of stay in acute hospital were shortened by over 5 days. Other clinical outcomes including surgical site infection, 30 days mortality and also incidence of pressure sore improved when compared to the data before the pathway. The rate of surgical site infection was 0.98%, and the 30 days mortality was 1.67% in 2009. The active participation of physiotherapists, occupational therapists as well as medical social workers also helped to formulate the discharge plan as early as the patient is admitted. In conclusion, a well-planned and executed clinical pathway for hip fracture can improve the clinical outcomes of the geriatric hip fractures

A Gammaherpesvirus Cooperates with Interferon-alpha/beta-Induced IRF2 to Halt Viral Replication, Control Reactivation, and Minimize Host Lethality

The gammaherpesviruses, including Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), establish latency in memory B lymphocytes and promote lymphoproliferative disease in immunocompromised individuals. The precise immune mechanisms that prevent gammaherpesvirus reactivation and tumorigenesis are poorly defined. Murine gammaherpesvirus 68 (MHV68) is closely related to EBV and KSHV, and type I (alpha/beta) interferons (IFNαβ) regulate MHV68 reactivation from both B cells and macrophages by unknown mechanisms. Here we demonstrate that IFNβ is highly upregulated during latent infection, in the absence of detectable MHV68 replication. We identify an interferon-stimulated response element (ISRE) in the MHV68 M2 gene promoter that is bound by the IFNαβ-induced transcriptional repressor IRF2 during latency in vivo. The M2 protein regulates B cell signaling to promote establishment of latency and reactivation. Virus lacking the M2 ISRE (ISREΔ) overexpresses M2 mRNA and displays uncontrolled acute replication in vivo, higher latent viral load, and aberrantly high reactivation from latency. These phenotypes of the ISREΔ mutant are B-cell-specific, require IRF2, and correlate with a significant increase in virulence in a model of acute viral pneumonia. We therefore identify a mechanism by which a gammaherpesvirus subverts host IFNαβ signaling in a surprisingly cooperative manner, to directly repress viral replication and reactivation and enforce latency, thereby minimizing acute host disease. Since we find ISREs 5′ to the major lymphocyte latency genes of multiple rodent, primate, and human gammaherpesviruses, we propose that cooperative subversion of IFNαβ-induced IRFs to promote latent infection is an ancient strategy that ensures a stable, minimally-pathogenic virus-host relationship

Nutritional care of medical inpatients: a health technology assessment

BACKGROUND: The inspiration for the present assessment of the nutritional care of medical patients is puzzlement about the divide that exists between the theoretical knowledge about the importance of the diet for ill persons, and the common failure to incorporate nutritional aspects in the treatment and care of the patients. The purpose is to clarify existing problems in the nutritional care of Danish medical inpatients, to elucidate how the nutritional care for these inpatients can be improved, and to analyse the costs of this improvement. METHODS: Qualitative and quantitative methods are deployed to outline how nutritional care of medical inpatients is performed at three Danish hospitals. The practices observed are compared with official recommendations for nutritional care of inpatients. Factors extraneous and counterproductive to optimal nutritional care are identified from the perspectives of patients and professional staff. A review of the literature illustrates the potential for optimal nutritional care. A health economic analysis is performed to elucidate the savings potential of improved nutritional care. RESULTS: The prospects for improvements in nutritional care are ameliorated if hospital management clearly identifies nutritional care as a priority area, and enjoys access to management tools for quality assurance. The prospects are also improved if a committed professional at the ward has the necessary time resources to perform nutritional care in practice, and if the care staff can requisition patient meals rich in nutrients 24 hours a day. At the kitchen production level prospects benefit from a facilitator contact between care and kitchen staff, and if the kitchen staff controls the whole food path from the kitchen to the patient. At the patient level, prospects are improved if patients receive information about the choice of food and drink, and have a better nutrition dialogue with the care staff. Better nutritional care of medical patients in Denmark is estimated to hold a cost savings potential reaching approximately USD 22 million. CONCLUSION: Every hospital and every bed ward has its strengths and weaknesses, but none of the participating bed wards fully satisfy nutritional care success criteria. All organisational levels have a significant potential for improvements of nutritional care of medical inpatients

Sentinel node biopsy in early vulvar cancer

Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1–T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node as positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer. © 2000 Cancer Research Campaig

Evolution of Assortative Mating in a Population Expressing Dominance

In this article, we study the influence of dominance on the evolution of assortative mating. We perform a population-genetic analysis of a two-locus two-allele model. We consider a quantitative trait that is under a mixture of frequency-independent stabilizing selection and density- and frequency-dependent selection caused by intraspecific competition for a continuum of resources. The trait is determined by a single (ecological) locus and expresses intermediate dominance. The second (modifier) locus determines the degree of assortative mating, which is expressed in females only. Assortative mating is based on similarities in the quantitative trait (‘magic trait’ model). Analytical conditions for the invasion of assortment modifiers are derived in the limit of weak selection and weak assortment. For the full model, extensive numerical iterations are performed to study the global dynamics. This allows us to gain a better understanding of the interaction of the different selective forces. Remarkably, depending on the size of modifier effects, dominance can have different effects on the evolution of assortment. We show that dominance hinders the evolution of assortment if modifier effects are small, but promotes it if modifier effects are large. These findings differ from those in previous work based on adaptive dynamics

High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing

We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system

Physical activity and depression in adolescents: cross-sectional findings from the ALSPAC cohort

Purpose: Few studies have examined the association between physical activity (PA), measured objectively, and adolescent depressive symptoms. The aim of this study was to determine whether there is an association between objective measures of PA (total PA and time spent in moderate and vigorous PA (MVPA)) and adolescent depressive symptoms. Methods: Data on 2,951 adolescents participating in ALSPAC were used. Depressive symptoms were measured using the self-report Mood and Feelings Questionnaire (MFQ) (short version). Measures of PA were based on accelerometry. The association between PA and MFQ scores was modelled using ordinal regression. Results: Adolescents who were more physically active (total PA or minutes of MVPA) had a reduced odds of depressive symptoms [ORadj total PA (tertiles): medium 0.82 (95% CI: 0.69, 0.97); high 0.69 (95% CI: 0.57, 0.83)]; ORadj per 15 min MVPA: 0.92 (95% CI: 0.86, 0.98). In a multivariable model including both total PA and the percentage of time spent in MVPA, total PA was associated with depressive symptoms (ORadj total PA (tertiles): medium 0.82 (95% CI: 0.70, 0.98); high 0.70 (95% CI: 0.58, 0.85) but the percentage of time spent in MVPA was not independently associated with depressive symptoms [ORadj MVPA (tertiles) medium 1.05 (95% CI: 0.88, 1.24), high 0.91 (95% CI: 0.77, 1.09)]. Conclusions: The total amount of PA undertaken was associated with adolescent depressive symptoms, but the amount of time spent in MVPA, once total PA was accounted for, was not. If confirmed in longitudinal studies and randomised controlled trials, this would have important implications for public health messages.Nicola J. Wiles, Anne M. Haase, Debbie A. Lawlor, Andy Ness, Glyn Lewi

Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre - Rio Grande do Sul, Brazil