The impact of point-of-care testing for influenza A and B on patient flow and management in a medical assessment unit of a general hospital.

OBJECTIVES: Timely implementation of influenza infection control and treatment can significantly reduce the impact on Hospital resources and patient management when demand is at peak. Turnaround times of Laboratory based screening tests for the diagnosis of influenza may have an impact on the implementation of infection control measures and treatment. In this study the objectives included determining the correlation between the Abbott ID NOW point-of-care testing (POCT) instrument using the Influenza A&B2 test and the laboratory based GeneXpert Flu+RSV kit. In addition the impact of the POCT instrument on the prescription of antivirals and antibiotics was evaluated by comparing with practice when the instrument was not in place. RESULTS: The results of the correlation study with a cohort of 54 patients revealed the Abbott ID NOW POCT has 92% sensitivity for the detection of Influenza A, while specificity was 100% for both Influenza A and B. The impact of the POCT instrument on the frequency of prescription of antivirals and amount of antibiotics consumed (33% reduction in antibiotic consumption in a cohort of 65 (2017) and 61 (2018)) was significant. In addition the average patient length of Hospital stay was significantly reduced from 5.26 days to 3.73 days.

Balancing training and outcomes in total knee replacement: A ten-year review.

INTRODUCTION: 10-year study examining differences in total knee arthroplasty (TKA) functional outcomes and survivorship in patients operated on by consultant and trainee orthopaedic surgeons. METHOD: Data was prospectively collected from all elective TKAs performed at our three linked institutions. Patient demographics, surgeon grade, and length of hospital stay were recorded. Outcomes pre-operatively and at 1, 3, 5, 7 and 10 years included mortality, need for revision surgery and function as documented by the patients' Knee Society Score. RESULTS: 686 patients were included in the study. 450 (65.5%) patients were operated by consultant surgeons and 236 (34.4%) by trainees. On multivariate analysis no significant differences were observed between groups in length of hospital stay (p = 0.695), implant survival (p = 0.422), and function (p = 0.507) at 10 years. On Cox regression analysis no significant difference was observed in mortality (p = 0.209) at 10 years. 4 patients over this time period were lost to formal follow up. CONCLUSION: No significant difference was observed in the TKA outcomes between consultants and trainees 10 years post-operatively.

Do trainee surgeons have an adverse effect on the outcome after total hip arthroplasty?: a ten-year review.

AIMS: The long-term functional outcome of total hip arthroplasty (THA) performed by trainees is not known. A multicentre retrospective study of 879 THAs was undertaken to investigate any differences in outcome between those performed by trainee surgeons and consultants. PATIENTS AND METHODS: A total of 879 patients with a mean age of 69.5 years (37 to 94) were included in the study; 584 THAs (66.4%) were undertaken by consultants, 138 (15.7%) by junior trainees and 148 (16.8%) by senior trainees. Patients were scored using the Harris Hip Score (HHS) pre-operatively and at one, three, five, seven and ten years post-operatively. Surgical outcome, complications and survival were compared between groups. The effect of supervision was determined by comparing supervised and unsupervised trainees. A primary univariate analysis was used to select variables for inclusion in multivariate analysis. RESULTS: There was no evidence that the grade of the surgeon had a significant effect on the survival of the patients or the rate of revision (p = 0.987 and 0.405, respectively) up to 12 years post-operatively. There was no significant difference in post-operative functional HHS or total HHS among consultants, junior and seniors up to ten years post-operatively (p = 0.401 and 0.331), respectively. There was no significant difference in hospital stay (p = 0.855) between different grades of surgeons. There was no evidence that the level of supervision had an effect on the survival of the patients or the rate of revision (p = 0.837 and 0.203, respectively) up to 12 years post-operatively. There was no significant difference between supervised and unsupervised trainee groups in post-operative functional HHS or total HHS up to ten years post-operatively (p = 0.213 and 0.322, respectively). There was no significant difference in the mean hospital stay between supervised and unsupervised trainees (p = 0.908). TAKE HOME MESSAGE: This study suggests that when trainees are appropriately supervised, they can obtain results comparable with those of their consultant colleagues when performing THA.

Targeting the Pim kinases in multiple myeloma.

Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and/or with novel drugs targeting other survival pathways in MM.

Corticosteroid injection of the arthritic hip: what is the indication?

Forty-four patients who had image-guided corticosteroid injection of the hip were reviewed as part of a service improvement project to ascertain the medium term benefit of the procedure. Injections were indicated for treatment of hip pain or as part of a diagnostic work up to differentiate hip from back pain. At 42-month review, 39 patients fulfilled the criteria for the study. Of those having therapeutic injections, 70% had gone on to hip replacement, while only 20% of those having diagnostic injections had done so. These results suggest that, for patients who are fit for surgery, hip replacement should be the intervention of choice as corticosteroid injection does not substantially delay the need for surgery. Where there is doubt about the source of pain, there seems to be a clear role for diagnostic injection.

Causative organisms in revision total hip & knee arthroplasty for infection: Increasing multi-antibiotic resistance in coagulase-negative Staphylococcus and the implications for antibiotic prophylaxis.

BACKGROUND AND PURPOSE: Increasing resistance among post-operative Coagulase-negative Staphylococci (CNS) infections have been reported. We present our experience changing resistance patterns. METHODS: We examined microbiological results from hip and knee revisions from 2001 to 2010 and compared resistance to all Staphylococcus aureus (SA) and CNS cultured from regional pan-speciality sources, in order to examine the patterns of antibiotic resistance. MAIN FINDINGS: 72 revisions in 67 patients were included. The most common organisms were SA (36%) and CNS (35%). Resistance to methicillin was 72% for CNS versus 20% for SA and resistance to gentamicin was 40% for CNS versus 4% for SA. Among all regional (background pan-speciality) cultures SA resistance to methicillin fell from 32% to 16% from 2006 to 10 with no change in gentamicin resistance at 3%. During the same period resistance of CNS to methicillin and gentamicin increased from 63% to 70% and 32%-47% respectively. CONCLUSIONS: Resistance of CNS to both methicillin and gentamicin is higher than with SA and appears to be increasing. At least 32% of CNS and 4% of SA from infected TKRs/THRs were resistant to our current prophylaxis regime. These changing patterns of resistance may have implications for future antibiotic prophylaxis regimes.

Are we missing post-thrombotic syndrome syndrome? An orthopaedic perspective in lower limb arthroplasty.

2-5% of patients undergoing hip or knee arthroplasty develop a symptomatic DVT; there is evidence to suggest that without prophylaxis 40-60% of patients have a subclinical DVT. This can be reduced by around half with appropriate thromboprophylaxis; there still remains a significant incidence of subclinical DVT. Therefore, it is important to know, as orthopaedic surgeons, if our patients undergoing large joint arthroplasty are being adversely affected. Post-thrombotic syndrome (PTS) is usually associated with symptomatic DVT, and the purpose of this paper is to address if asymptomatic DVT is also associated with an increased risk of PTS. The majority of evidence gathered does not support a link; therefore, there is no evidence to warrant a change in practice to warn patients of a potential risk or to routinely screen asymptomatic patients.

Sphingosine 1-phosphate: a regulator of arterial lesions.

Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid that is critical in the development of blood vessels, and in the adult regulates vascular functions including vascular tone, endothelial integrity, and angiogenesis. Further, S1P may regulate arterial lesions in disease and after injury by controlling leukocyte recruitment and smooth muscle cell functions.

Apoptosis of dedifferentiated hepatoma cells is independent of NF-kappaB activation in response to LPS.

Dedifferentiated hepatoma cells, in contrast to most other cell types including hepatoma cells, undergo apoptosis when treated with lipopolysaccharide (LPS) plus the protein synthesis inhibitor cycloheximide (CHx). We recently reported that the dedifferentiated hepatoma cells also exhibit a strong and prolonged NF-kappaB induction phenotype upon exposure to LPS, suggesting that NF-kappaB signaling may play a pro-survival role, as reported in several other cell systems. To test the role of NF-kappaB in preventing LPS-mediated apoptosis, we examined the dedifferentiated cell line M38. Results show that antioxidants strongly inhibited LPS + CHx-mediated cell death in the M38 cells, yet only modestly inhibited NF-kappaB induction. In addition, inhibition of NF-kappaB translocation by infection of the M38 cells with an adenoviral vector expressing an IkappaBalpha super-repressor did not result in LPS-mediated cell death. These results suggest that unlike TNFalpha induction, the cell survival pathway activated in response to LPS is independent of NF-kappaB translocation in the dedifferentiated cells. Addition of inhibitors of JNK, p38 and ERK pathways also failed to elicit LPS-mediated apoptosis similar to that observed when protein synthesis is prevented. Thus, cell survival pathways other than those involving NF-kappaB inducible gene expression or other well-known pathways appear to be involved in protecting the dedifferentiated hepatoma variant cells from LPS-mediated apoptosis. Importantly, this pro-apoptotic function of LPS appears to be a function of loss of hepatic gene expression, as the parental hepatoma cells resist LPS-mediated apoptosis in the presence of protein synthesis inhibitors.

Portal hypertension and granulomatous liver disease in a lung transplant recipient due to disseminated atypical mycobacterial infection.

The incidence of atypical mycobacterial infection among solid organ transplant recipients is increasing. While lung transplant recipients in particular are at greater risk of atypical mycobacterial infection than other solid organ transplant recipients, it is typically confined to the lung and disseminated infection remains quite rare. We describe a case of disseminated Mycobacterium avium-complex (MAC) in a lung transplant recipient presenting as granulomatous liver disease with signs of portal hypertension. After identification of the infection and institution of proper therapy, the patient had significant improvement in both clinical signs of portal hypertension and liver function tests. Current literature suggests a favorable prognosis in most cases of MAC infection in lung transplant recipients with appropriate treatment. This case highlights the need to maintain an elevated index of suspicion for atypical pathogens with unusual clinical presentations among the lung transplant population.

Clinical comparison of microporous biocompatible composite of PMMA, PHEMA and calcium hydroxide grafts and expanded polytetrafluoroethylene barrier membranes in human mandibular molar Class II furcations. A case series.

BACKGROUND: Class II furcations present difficult treatment problems. Several treatment approaches to obtain furcation fill have been used with varying success. METHODS: The response of mandibular Class II furcations to treatment with either a microporous biocompatible composite of PMMA (poly-methyl-methacrylate), PHEMA (poly-hydroxyl-ethyl methacrylate) and calcium hydroxide graft synthetic bone (HTR) replacement graft material; ePTFE barrier membrane; or a combination of the two was evaluated in trios of mandibular molars with Class II furcations in 8 patients with moderate to advanced periodontitis. Following initial preparation, full-thickness flaps were raised in the areas being treated, the bone and furcation defects debrided of granulomatous tissue, and the involved root surfaces mechanically prepared and chemically conditioned. By random allocation, HTR, ePTFE, or a combination of both was placed into and/or fitted over the furcations, packed and/or secured in place, and the host flap replaced or coronally positioned with sutures. Postsurgical deplaquing was performed every 10 days leading up to ePTFE removal at approximately 6 weeks. Continuing periodontal maintenance therapy was provided until surgical reentry at 6 months for documentation and any further necessary treatment. RESULTS: Direct clinical measurements demonstrated essentially similar clinical results with all 3 treatments for bone and soft tissue changes. There were no statistically or clinically significant differences except for better horizontal amount and percent defect fill with HTR alone. Four of 8 furcations became Class I clinically with HTR alone, 5 of 8 became Class I with ePTFE alone, and 5 of 8 with combination treatment. The only complete furcation closure occurred with HTR. CONCLUSION: The findings of this study suggest essentially equal clinical results with HTR bone replacement graft material alone, ePTFE barrier alone, and a combination of the two in mandibular molar Class II furcations. However, a real difference may not have been detected based on the small number of subjects in the study.

Modulation of smooth muscle proliferation in rat carotid artery by platelet-derived mediators and fibroblast growth factor-2.

Endothelial denuding injury to the rat carotid artery stimulates smooth muscle cell proliferation in the tunica media. Fibroblast growth factor-2 (FGF2) is responsible for a significant portion of this proliferation but other factors may contribute, particularly those released from adherent platelets. We therefore tested the effects of a range of platelet-derived factors. After filament injury, which minimises FGF2 release, the proliferation rate in thrombocytopaenic rats was decreased by 74% (P < 0.02). After balloon injury, antibody neutralisation of platelet-derived growth factor (PDGF) caused a 27% decrease in proliferation (P < 0.05), while inhibition of histamine H(1) receptors caused a 53% increase (P < 0.05). When filament injury was performed 1 h after FGF2 injection, the proliferation rate increased from 2.3+/-0.7 to 32.8+/-2.7% (P < 0.001), while filament injury alone caused a proliferation rate of only 18.3+/-2.9% (P < 0.01 versus filament plus FGF2). These data suggest that platelet-derived factors interact with FGF2 that is adsorbed to the vessel wall in the control of smooth muscle cell proliferation, and that the net effect of platelets is to stimulate smooth muscle cell proliferation. PDGF, but no other platelet agonist tested, contributes to that stimulation.

Clinical evaluation of acellular allograft dermis for the treatment of human gingival recession.

BACKGROUND: Periodontal root coverage procedures to treat recession areas are indicated for unesthetic, exposed, and/or painful root surfaces. Many methods, most using autogenous soft tissue grafts, have been utilized, but with associated morbidity at the donor sites. An alternative donor material would reduce the morbidity and provide for sufficient available donor tissue. METHODS: An acellular allogeneic dermal connective tissue matrix (AD) and autogenous palatal connective tissue (CT) were compared as subepithelial grafts for the treatment of gingival recession. Twenty-two patients with similar isolated gingival recession of > or = 2 mm on 2 separate teeth were treated with the subepithelial graft technique. Exposed roots were hand root planed only and, by random allocation, either a fitted AD or fitted CT graft was secured in place and covered by coronally positioned flaps. RESULTS: Mann Whitney U test analysis found the following changes at 6 months for AD and CT, respectively, compared to presurgical conditions: root coverage of 1.7 +/- 1.2 (65.9%) and 2.2 +/- 1.1 mm (74.1%) (both P<0.01), increase in keratinized tissue (KT) of 1.2 +/- 1.3 and 1.6 +/- 1.9 (both P<0.01), and an increase in gingival thickness with both; 83.2% of expected root coverage was obtained with AD and 88.6% with CT (P= 0.43). There were no significant differences between treatments for any parameter. Global assessments by clinicians and patients suggested a more esthetic clinical result with AD. CONCLUSIONS: These results suggest that acellular allogeneic dermal matrix may be a useful substitute for autogenous connective tissue grafts in root coverage procedures.

Clinical comparison of bioactive glass bone replacement graft material and expanded polytetrafluoroethylene barrier membrane in treating human mandibular molar class II furcations.

BACKGROUND: Class II furcations present difficult treatment problems and historically several treatment approaches to obtain furcation fill have been used. METHODS: The response of mandibular Class II facial furcations to treatment with either bioactive glass (PG) bone replacement graft material or expanded polytetrafluoroethylene (ePTFE) barrier membrane was evaluated in 27 pairs of mandibular molars in 27 patients with moderate to advanced periodontitis. Following initial preparation, full thickness flaps were raised in the area being treated, the bone and furcation defects debrided of granulomatous tissue, and the involved root surfaces mechanically prepared and chemically conditioned. By random allocation, PG or ePTFE was placed into or fitted over the furcations, packed or secured in place, and the host flap replaced or coronally positioned with sutures. Postsurgical deplaquing was performed every 10 days leading up to ePTFE removal at about 6 weeks. Continuing periodontal maintenance therapy was provided until surgical reentry at 6 months for documentation and any further necessary treatment. RESULTS: Direct clinical measurements demonstrated essentially similar clinical results with both treatments for bone and soft tissue changes. There were no statistically or clinically significant differences (e.g., mean horizontal furcation fill 1.4 mm PG, 1.3 mm ePTFE; mean percent horizontal furcation fill 31.6% PG, 31.1% ePTFE, both P>0.85). Seventeen of the PG treated and 18 of the ePTFE furcations became Class I clinically and 1 furcation completely closed clinically with each treatment. Intrapatient comparisons showed similar horizontal furcation responses with both treatments. CONCLUSION: The findings of this study suggest essentially equal clinical results with PG bone replacement graft material and e-PTFE barriers in mandibular molar Class II furcations. PG use was associated with simpler application and required no additional material removal procedures.

Telephone support group intervention for persons with hemophilia and HIV/AIDS and family caregivers.

The purpose of this pilot project was to test the feasibility of a telephone support group intervention for persons with hemophilia and HIV/AIDS and for their family caregivers. Their support needs were unique because they did not identify with predominant groups of persons with AIDS and were geographically dispersed from peers. The 12 week intervention involved separate telephone support groups for hemophiliacs and for family caregivers. The two groups, comprised of a predetermined maximum of six people, were co-led by a professional and a peer. The support group for family caregivers involved six people and the group for men with hemophilia included five people, including one peer facilitator and one professional facilitator in each group. The telephone support group discussions were taped, transcribed, and analyzed for prevalent themes. The peer and professional facilitators maintained weekly field notes. All participants reported that the telephone groups had a positive impact on meeting their support needs. They believed that they had benefitted from sharing information and that the support groups had decreased their feelings of isolation and loneliness. Participants, however, contended that the intervention should be longer than 12 weeks.

An economic evaluation of a chlorhexidine chip for treating chronic periodontitis: the CHIP (chlorhexidine in periodontitis) study.

BACKGROUND: The authors previously suggested that an adjunctive, controlled-release chlorhexidine, or CHX, chip may reduce periodontal surgical needs at little additional cost. This article presents an economic analysis of the CHX chip in general dental practice. METHODS: In a one-year prospective clinical trial, 484 chronic periodontitis patients in 52 general practices across the United States were treated with either scaling and root planing, or SRP, plus any therapy prescribed by treating, unblinded dentists; or SRP plus other therapy as above but including the CHX chip. Economic data were collected from bills, case report forms and 12-month treatment recommendations from blinded periodontist evaluators. RESULTS: Total dental charges were higher for SRP + CHX chip patients vs. SRP patients when CHX chip costs were included (P = .027) but lower when CHX chip costs were excluded (P = .012). About one-half of the CHX chip acquisition cost was offset by savings in other charges. SRP + CHX chip patients were about 50 percent less likely to undergo surgical procedures than were SRP patients (P = .021). At the end of the trial, periodontist evaluators recommended similar additional procedures for both groups: SRP, about 46 percent; maintenance, about 37 percent; surgery, 56 percent for SRP alone and 63 percent for SRP + CHX chip. CONCLUSIONS: Adjunctive CHX chip use for general-practice patients with periodontitis increased costs but reduced surgeries over one year. At study's end, periodontists recommended similar additional surgical treatment for both groups. CLINICAL IMPLICATIONS: In general practice, routine use of the CHX chip suggests that costs will be partially offset by reduced surgery over at least one year.

Mitogen-activated protein kinases mediate matrix metalloproteinase-9 expression in vascular smooth muscle cells.

Expression of matrix metalloproteinase (MMP)-9 has been linked to the progression of plaque rupture and intimal formation in arterial lesions. In this study, we determined which factors and signaling pathways are involved in regulating the MMP-9 gene. Rat carotid arterial smooth muscle cells treated with tumor necrosis factor (TNF)-alpha showed a marked increase in MMP-9 activity and mRNA level, whereas platelet-derived growth factor (PDGF) showed a slight induction of the MMP-9 mRNA level. TNF-alpha treatment caused an increase in c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and extracellular signal-regulated kinase (ERK) activities, whereas PDGF treatment caused an increase in ERKs and p38 MAPK activities without any effect on JNK activity. Treatment with either SB203580 (inhibitor of p38 MAPK) or U0126 (inhibitor of the ERK pathway) downregulated the TNF-alpha-induced MMP-9 expression in a dose-dependent manner. Treatment of cells with TNF-alpha and PDGF together stimulated the MMP-9 expression at a level higher than that observed with either factor alone, suggesting that TNF-alpha and PDGF have a synergistic effect on MMP-9 expression in arterial smooth muscle cells. Furthermore, suboptimal inhibitory concentrations of SB203580 and U0126 together almost completely inhibited the MMP-9 expression. These results suggest that p38 MAPK and ERK pathways contribute to the transcriptional regulation of MMP-9 in arterial smooth muscle cells.

Phosphatidylinositol 3-kinase signaling is important for smooth muscle cell replication after arterial injury.

The phosphoinositide 3-kinase [PI(3)K] pathway is a key signaling pathway important for replication of mammalian cells. In this study, we examined the role of PI(3)K in smooth muscle cell (SMC) replication after balloon catheter injury of rat carotid arteries. Protein kinase B (PKB), a downstream target of PI(3)K, was phosphorylated at 30 and 60 minutes after injury and to a lesser degree after 6 hours and 1 and 2 days but not after 7 days. Wortmannin (10 microgram per rat), a PI(3)K inhibitor, given to rats 60 and 5 minutes before and 11 hours after balloon injury, reduced the levels of phosphorylated PKB. SMC replication quantified between 24 to 48 hours was significantly reduced compared with control replication, as were the levels of cyclin D(1). Wortmannin was also administered to rats between days 7 and 8 and between days 7 and 9 after balloon catheter injury. A reduction in levels of phosphorylated PKB was detected, but no decrease in the replication of intimal SMCs was observed in either experiment. These data demonstrate that the PI(3)K signal transduction pathway plays an important role in medial but not intimal SMC replication.