Guideline chaos: conflicting recommendations for preoperative cardiac assessment

The American College of Cardiology/American Heart Association (ACC/AHA) and the American College of Physicians (ACP) have disseminated guidelines to assess preoperative cardiac risks before noncardiac surgery. The objectives of this study were to determine if these guidelines differ in preoperative recommendations for a group of patients, and whether these recommendations differ from actual provider recommendations. In this retrospective cohort study, patient characteristics and physician recommendations were abstracted from electronic medical records of consecutive patients attending a Veteran Affairs medical preoperative evaluation clinic from January 1 to April 1, 1998. Patient characteristics were used to determine what preoperative cardiac testing should have been ordered if each guideline was followed. Possible recommendations included operation without testing (OWT), noninvasive stress testing (NST), cardiac catheterization (CC), or cancel or delay surgery (OTHER). Recommendations were compared using statistical tests for agreement. Of the 138 patients identified, most underwent moderate-risk surgeries. Recommendations for preoperative testing were discordant between guidelines for 17% of patients (kappa = 0.38). Guidelines never agreed on the need for NST. Extreme differences in recommendations (i.e., one recommends OWT, the other CC) occurred in 9 patients (7%). Physicians ordered NST more often (n = 27) than either guideline. In this subgroup of patients where providers ordered a NST, the 2 guidelines significantly differed (kappa = 0.26). When applied to real patients being evaluated for surgery, ACC/AHA and ACP guidelines significantly differed in recommendations for preoperative cardiac testing. Results have implications for implementation, management, and practitioner adherence to published guidelines.     

Provision of hepatitis B vaccination for primary care dental staff in Scotland

OBJECTIVES: All dental surgeons should be protected from hepatitis B virus (HBV) infection by immunisation, ideally administered and monitored via occupational health services (OHS). This study examined relevant OHS systems in place for dental primary care healthcare workers (DHCW) across all Health Board Areas (HBAs) in Scotland. It also explored the DHCWs' knowledge of, and access to, these systems in three HBAs. METHODS: Data from senior staff in all Scottish Health Boards and Primary Care Trusts were collected by self-completing questionnaires. Information from DHCWs was collected via telephone interviews with General Dental Practitioners (GDPs) and Community Dental Officers (CDOs) in each of Ayrshire and Arran, Highland and Lothian Health Boards. RESULTS: Thirteen of the 15 HBAs had robust HBV vaccination and monitoring systems. However, only 7/15 (47%) of these covered all DHCWs. Seven HBAs provided vaccination and monitoring for CDOs only, leaving GDPs to undertake these responsibilities for themselves. Of the 105 DHCWs approached, 82 gave an interview. These interviews highlighted major differences between HBAs in relation to access of DHCWs to OHS and indicated that CDOs had greater access than GDPs to OHS. Overall, 31% of DHCWs were not satisfied with the OHS available. CONCLUSION: In order to safeguard both staff and patients, significant further work is required to ensure that all DHCWs have access to appropriate OHS support for provision and monitoring of immunisation procedures and related functions such as management of sharps injuries.     

Immortalization and characterization of human cell lines with mast cell and monocytic properties

Summary. We have previously derived a cell strain which had both mast cell and monocytic properties from the bone marrow of a child with diffuse cutaneous mastocytosis. This cell strain, termed HBM-M, consisted of two cell populations both of which possessed certain ultrastructural, cytochemi-cal and surface phenotypic features of degranulated mast cells. The cells also displayed cytochemical and surface phenotypic features of monocytes. These cells may represent a common bone marrow derived mast cell/monocyte precursor. Studies of human mast cells have been hindered by the fact that it is difficult to establish such cells in long-term culture. Thus, we sought to immortalize HBM-M cells by introducing Simian virus 40 large T-antigen. Following transfection by the strontium phosphate technique, transformed cells were selected, expanded and passaged until the cells entered a non-proliferative phase termed crisis. Certain clones passed through crisis 3 months later and by this means two immortal cell lines, HBM-MI-1 and HBM-MI-2, were obtained. The criterion for immortality was growth for greater than 100 population doublings. The immortal cell lines retained some, but not all. of the mast cell and monocytic properties of the original HBM-M cell strain. The immortalization of the cell strain HBM-M provides an opportunity to investigate the mast cell and monocytic properties of these cells, and the apparent relationship between mast cells and monocytes.     

Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium

Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.     

Biological evaluation of intervertebral disc cells in different formulations of gellan gum‐based hydrogels

Gellan gum (GG)‐based hydrogels are advantageous in tissue engineering not only due to their ability to retain large quantities of water and provide a similar environment to that of natural extracellular matrix (ECM), but also because they can gelify in situ in seconds. Their mechanical properties can be fine‐tuned to mimic natural tissues such as the nucleus pulposus (NP). This study produced different formulations of GG hydrogels by mixing varying amounts of methacrylated (GG‐MA) and high‐acyl gellan gums (HA‐GG) for applications as acellular and cellular NP substitutes. The hydrogels were physicochemically characterized by dynamic mechanical analysis. Degradation and swelling abilities were assessed by soaking in a phosphate buffered saline solution for up to 170 h. Results showed that as HA‐GG content increased, the modulus of the hydrogels decreased. Moreover, increases in HA‐GG content induced greater weight loss in the GG‐MA/HA‐GG formulation compared to GG‐MA hydrogel. Potential cytotoxicity of the hydrogel was assessed by culturing rabbit NP cells up to 7 days. An MTS assay was performed by seeding rabbit NP cells onto the surface of 3D hydrogel disc formulations. Viability of rabbit NP cells encapsulated within the different hydrogel formulations was also evaluated by Calcein‐AM and ATP assays. Results showed that tunable GG‐MA/HA‐GG hydrogels were non‐cytotoxic and supported viability of rabbit NP cells. Copyright © 2012 John Wiley & Sons, Ltd.     

IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2^V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34⁺ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2^V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.     

Bilateral vestibular loss in cats leads to active destabilization of balance during pitch and roll rotations of the support surface

Although the balance difficulties accompanying vestibular loss are well known, the underlying cause remains unclear. We examined the role of vestibular inputs in the automatic postural response (APR) to pitch and roll rotations of the support surface in freely standing cats before and in the first week after bilateral labyrinthectomy. Support surface rotations accelerate the body center of mass toward the downhill side. The normal APR consists of inhibition in the extensors of the uphill limbs and excitation in the downhill limbs to decelerate the body and maintain the alignment of the limbs with respect to earth-vertical. After vestibular lesion, cats were unstable during rotation perturbations and actively pushed themselves downhill rather than uphill, using a postural response that was opposite to that seen in the control trials. The extensors of the uphill rather than downhill limbs were activated, whereas those of the downhill limbs were inhibited rather than being excited. We propose that vestibular inputs provide an important reference to earth-vertical, which is critical to computing the appropriate postural response during active orientation to the vertical. In the absence of this vestibular information, subjects orient to the support surface using proprioceptive inputs, which drives the body downhill resulting in instability and falling. This is consistent with current models of sensory integration for computation of body posture and orientation.     

Invitation to grief in the family context

Grief is a family affair, yet it is commonly viewed as an individual phenomenon. As an international, interdisciplinary team, we explore grief within a family context across theoretical, research, practice, and educational domains. Families are complex and working with this complexity is challenging but necessary for a holistic view of grief. We therefore encourage an increased focus on theorizing, researching, practicing, and educating using innovative approaches to address the complexities of grief within the context of families. Learnings from within each domain will affirm and enhance the development of family-level thinking and approaches.     

Economic evaluation of fluoride varnish application of daily supervision versus daily supervision and additional six-monthly intervals in Scotland (Protecting Teeth @ 3): a randomised controlled trial

BackgroundEconomic evaluations of public health interventions aid decision makers in efficient resource allocation. Our aim was to do an economic evaluation of a subintake of the Protecting Teeth @ 3 Study ([email protected]), a Scottish, 2 year, parallel group, randomised controlled trial, which explored the additional preventive value of fluoride varnish application at six-monthly intervals in nursery settings over and above daily supervised toothbrushing in nursery settings (treatment as usual).MethodsFrom Nov 21, 2012 to Aug 31, 2017, eligible children were randomly assigned to receive either fluoride varnish plus treatment as usual (fluoride varnish group) or treatment as usual in a 1:1 ratio. The economic evaluation was a within-trial, cost-utility analysis comparing the fluoride varnish group with the treatment as usual group. Cost-utility analysis was done from a National Health Service perspective. Within-trial costs included intervention and health-care resource use costs. Health outcomes were expressed in quality-adjusted life-years (QALYs) accrued over the 2 year period. The Child Health Utility 9 Dimensions questionnaire was used to obtain utility scores. Staff travel and labour costs were collected using a staff costs form. Information on other costs was requested from the trial coordinators. National reference costs were used, a discount rate of 1·5% for public health investments was adopted, multiple imputation methods for missing data were employed, sensitivity analyses done, and incremental cost-effectiveness ratios calculated. Ethical approval was from the West of Scotland Research Ethics Service. This trial is registered with EudraCT, 2012-002287-26.FindingsThe data for 534 participants from the 2014–15 intake were used in the analyses. Of these, 265 were assigned to fluoride varnish and assigned to 269 treatment as usual. The mean difference in costs between the fluoride varnish and treatment as usual group was GBP£36·64 (95% CI –48·51 to 111·47; p=0·64). The mean difference in QALYs was –0·0044 (95% CI –0·0168 to 0·0065; p=0·64). The fluoride varnish intervention had higher costs and resulted in less QALYs than that of the treatment as usual. The probability that the fluoride varnish intervention was cost-effective at the £30 000 threshold was 18·5%.InterpretationOur results indicate that there was no substantial difference in costs and QALYs between the two groups. Applying fluoride varnish in nursery settings in addition to daily supervised nursery toothbrushing seems not to be good value for money. We recommended that the funds could be used better on other more cost-effective oral health interventions.Funding[email protected] was funded by the Scottish Government.