Ultrasound-guided infraclavicular axillary vein cannulation: a useful alternative to the internal jugular vein.

BACKGROUND: Ultrasound (US) guidance reduces complications and increases accuracy during internal jugular vein (IJV) cannulation. The subclavian vein (SCV) is popular but is less amenable to US guidance. The axillary vein (AxV), a direct continuation of the SCV, is an alternative, but to date, experience with US is limited to small case series. METHODS: Retrospective procedural data were collected on 2586 sequential patients referred for insertion of tunnelled central venous access at a UK tertiary centre from 2004 to 2011. RESULTS: A total of 99.8% of patients tolerated the procedure with local anaesthesia ± sedation; six patients had general anaesthesia. Twenty-six (1%) patients had uncorrected coagulopathy or thrombocytopenia. A total of 2572 (99.5%) of patients were cannulated successfully: right AxV 1644 cases, left AxV 279, right IJV 547, left IJV 89, other techniques 13, and 14 (0.5%) cases failed. The initial site chosen was successful in 96%. In patients who previously underwent long-term cannulation, 93.3% of lines were sited easily. Forty-eight (1.9%) procedural complications occurred. CONCLUSIONS: In this large analysis of US-guided central venous access in a complex patient group, the majority of patients were cannulated successfully and safely. The subset of patients undergoing AxV cannulation demonstrated a low rate of complications. The AxV route of access appears to be a safe and effective alternative to the IJV.

The impact of frailty in major trauma in older patients.

As our population ages and increasing numbers of older patients experience major trauma it is important to understand factors that influence outcomes in this patient cohort. The aim of this study is to assess the impact of frailty in older patients who experience major trauma (Injury Severity Score (ISS) greater than 15). A retrospective cohort review using the national trauma registry data (Trauma Audit and Research Network) and an institutional database was carried out on all patients aged 60 years or older with an ISS> 15 who were treated at the regional Major Trauma Centre from 2014 to 2017 following major trauma. Frailty was assessed using the modified frailty index (mFI). Outcomes assessed included mortality, complications, hospital stay, functional outcome and discharge destination. 819 patients were included in the study. The most common mechanism of injury was fall from a height less than 2m (57.4%). 412 (51.3%) patients had a low frailty score, 280 (35%) had an intermediate frailty score and 110 (14%) had high frailty score. Increased frailty was associated with increased mortality at discharge (18.7%, 14.6% and 26.4% for low, intermediate and high frailty groups) and at one year (26.2%, 35.2% and 51%, respectively). Other predictors of mortality included male sex, age >90 years and the occurrence of a serious complication. Increasing frailty was also associated with an increased risk of serious complications including unplanned intubation, infection and progressive renal failure, and discharge to a destination other than home. This is the first study that has delineated the impact of frailty in older patients who experience major trauma and provides important information for patients, their families and healthcare providers. Future studies should focus on identifying care pathways that counteract the impact of frailty in this setting.

Management of invasive candidiasis and candidaemia in critically ill adults: expert opinion of the European Society of Anaesthesia Intensive Care Scientific Subcommittee.

OBJECTIVE: The global burden of invasive fungal disease is increasing. Candida albicans remains the leading cause of fungal bloodstream infections, although non-albicans candidal infections are emerging. Areas of controversy regarding diagnosis and management are hampering our ability to respond effectively to this evolving threat. The purpose of this narrative review is to address current controversies and provide recommendations to supplement guidelines. DIAGNOSIS OF INVASIVE CANDIDIASIS: Diagnosis of invasive candidiasis requires a combination of diagnostic tests and patient risk factors. Beta-D glucan and Candida albicans germ tube antibody are both used as biomarkers as adjuncts to diagnosis, although direct culture remains the gold standard. Scoring systems are available to help distinguish between colonization and invasive disease. TREATMENT OF INVASIVE CANDIDIASIS: Echinocandins are recommended as first-line therapy in candidaemia, with de-escalation to fluconazole when clinical stability is achieved. Empirical therapy is highly recommended in high-risk patients, but a more targeted pre-emptive approach is now being favoured. The evidence for prophylactic therapy remains weak. SUMMARY: Mortality attributable to invasive candidiasis may be as high as 70%. Prompt diagnosis and treatment, in conjunction with source control, are the key to improving outcomes.

Cost implications for the NHS of using the Alere™ i Influenza A & B near patient test with nasal swabs.

BACKGROUND: Influenza is an acute viral infection of the respiratory tract. A rapid confirmatory diagnosis of influenza is important, since it is highly transmissible and outbreaks of influenza within the hospital setting increase morbidity and mortality. The objective of this study was to evaluate the cost implications, from the perspective of the UK NHS, of using on-label nasal swabs with the Alere™ i Influenza A & B test in a near patient setting. METHODS: A cost consequence model was developed. The time horizon of the model was from hospital admission on suspicion of influenza until the end of treatment (following a diagnosis of influenza or discharge from hospital). Data on the prevalence of influenza and the sensitivity and specificity of the Alere™ i Influenza A & B test came from two prospective observational diagnostic accuracy studies. Costs were obtained from published resources. Uncertainties in the model data were investigated using deterministic, one-way sensitivity analyses. RESULTS: Using the Alere™ i Influenza A & B point of care test with nasal swabs (on label) in NHS medical assessment units and emergency departments could save approximately £242,730 per 1000 adults presenting with influenza-like symptoms. The main cause for this was reduced times to availability of the result compared with the laboratory RT-PCR test. Other key drivers of savings were the cost of isolation, the prevalence of influenza, the specificity of the test, and the availability of isolation resources. CONCLUSIONS: The Alere™ i Influenza A & B point of care test would have greatest impact in hospitals that have extensive delays in the time to receive a result. Sensitivity analyses identified the model parameters which would have greatest effect on the result and confirmed that assumptions were conservative, i.e. did not change key results.

Multiple intra-hospital transports during relocation to a new critical care unit.

OBJECTIVE: Intra-hospital transport (IHT) of critically ill patients is associated with morbidity and mortality. Mass transfer of patients, as happens with unit relocation, is poorly described. We outline the process and adverse events associated with the relocation of a critical care unit. DESIGN: Extensive planning of the relocation targeted patient and equipment transfer, reduction in clinical pressure prior to the event and patient care during the relocation phase. SETTING: The setting was a 30-bed, tertiary referral, combined medical and surgical critical care unit, located in a 570-bed hospital that serves as the national referral centre for cardiothoracic surgery and spinal injuries. PARTICIPANTS: All stakeholders relevant to the critical care unit relocation were involved, including nursing and medical staff, porters, information technology services, laboratory staff, project development managers, pharmacy staff and building contractors. MAIN OUTCOME MEASURES: Mortality at discharge from critical care unit and discharge from hospital were the main outcome measures. A wide range of adverse events were prospectively recorded, as were transfer times. RESULTS: Twenty-one patients underwent IHT, with a median transfer time of 10 min. Two transfers were complicated by equipment failure and three patients experienced an episode of hypotension requiring intervention. There were no cases of central venous or arterial catheter or endotracheal tube dislodgement, and hospital mortality at 30 days was 14%. CONCLUSION: Although IHT is associated with morbidity and mortality, careful logistical planning allows for efficient transfer with low complication rates.

Diagnostic accuracy and cost analysis of the Alere™ i Influenza A&B near-patient test using throat swabs.

BACKGROUND: Clinical diagnostic sensitivity alone is inadequate in the diagnosis of influenza. Polymerase chain reaction (PCR) testing is sensitive but the inherent delays in result availability potentially prolong time to isolation and treatment. Until recently no near-patient test (NPT) has demonstrated adequate sensitivity for routine clinical use. AIM: To evaluate diagnostic accuracy, time to result availability, clinical impact, and cost consequences of Alere™ i Influenza A&B NPT (Alere Inc., Waltham, MA, USA) using off-label throat swabs. METHODS: Prospective, multi-centre [four UK National Health Service (NHS) hospitals], diagnostic accuracy cohort study with cost modelling. Throat swab samples from suspected influenza patients were tested for influenza using the reference standard of PCR; a second throat swab was tested using NPT. FINDINGS: A total of 827 participants were recruited; 589 were suitable for analysis: sensitivity was 75.8% [95% confidence interval (CI): 67.0-84.6]; specificity was 96.8% (95% CI: 95.2-98.3). Sensitivity varied between Sheffield (Northern General Hospital: 82.1%; Royal Hallamshire Hospital: 83.3%) and other sites (Doncaster Royal Infirmary: 71.4%; Newcastle's Royal Victoria Infirmary: 50.0%) whereas specificity was high (92-100%). Positive predictive value (PPV) was 81.2% (95% CI: 72.9-89.5) with negative predictive value 95.6% (95% CI: 93.9-97.4) with observed prevalence of 15.4%. Median time to result for PCR was 1.1 days (on-site laboratories) and 5.2 days (remote laboratories). Isolation findings: 75% influenza positive not isolated; 69% of isolated participants did not have influenza. For a cohort of 1000 participants, annual estimated non-diagnostic cost savings with NPT are £215,040. CONCLUSION: This first prospective study of the Alere i NPT using throat swabs demonstrates high specificity, high PPV during seasonal epidemics, and rapid result availability which could lead to substantial cost savings.

Cardiotrophin-1 can protect cardiac myocytes from injury when added both prior to simulated ischaemia and at reoxygenation.

OBJECTIVE: The cytokine cardiotrophin-1 (CT-1) has previously been shown to protect cultured cardiocytes from cell death induced by serum removal or hypoxia when administered prior to the damaging stimulus. We wished to test whether a similar protective effect could be observed if CT-1 was added after the ischaemic period and to investigate the signalling pathways involved in the protective effect when CT-1 is given prior to or after ischaemia. METHODS: We therefore examined the protective effect of CT-1 in cultured rat cardiocytes exposed to simulated ischaemia followed by reoxygenation when CT-1 was administered either prior to simulated ischaemia or at reoxygenation. RESULTS: We show that CT-1 can exert a protective effect against the damaging effects of simulated ischaemia/reoxygenation both when added after the simulated ischaemia at reoxygenation (P<0.05 in trypan blue, TUNEL and annexin V assays) or when added prior to the simulated ischaemia (P<0.05). In both cases, these protective effects are blocked by an inhibitor of the p42/p44 MAPK pathway (P<0.05 in all assays). CONCLUSION: CT-1 can protect cardiac cells when added either prior to simulated ischaemia or at the time of reoxygenation following simulated ischaemia and these effects are dependent upon its ability to activate the p42/p44 MAPK pathway. Hence CT-1 may have therapeutic potential when added at the time of reperfusion following ischaemic damage.

A study of a synaptosomal thyrotropin releasing hormone-inactivating pyroglutamate aminopeptidase from bovine brain.

Pyroglutamate aminopeptidase type II is a highly specific membrane-bound neuropeptidase that has the ability to remove N-terminal pyroglutamate (Glp) from Thyrotropin Releasing Hormone (Glp-His-Pro-NH2) or very closely related tripeptides or tripeptide amides. In this paper we report on the purification and characterisation of a pyroglutamate aminopeptidase activity from the synaptosomal membranes of bovine brain. The Triton X-100 solubilised enzyme was purified nearly 600-fold by a combination of conventional column chromatography steps with a recovery/yield of 17.0%. Phase-partitioning experiments with Triton X-114 showed the activity to be an integral membrane protein. This detergent-solubilised pyroglutamate aminopeptidase activity was found to have a relative molecular mass of 240 kDa on a calibrated S-200 column. HPLC analysis on a C18 reverse-phase column showed that the purified activity displayed a very narrow substrate specificity cleaving only Thyrotropin Releasing Hormone (TRH) or the very closely related acid-TRH, LHRH (1-3) and the TRH-analogue (methyl-His)-TRH and had a Km of 100 microM for the fluorimetric substrate Glp-His-Pro-methyl-coumarin. The enzyme was inactivated by the metalchelator 1,10-ortho-phenanthroline but showed less sensitivity to EDTA. It also showed some inhibition by thiol protease inhibitors such as iodoacetate and n-ethyl-maleimide. In summary, we have purified a pyroglutamate aminopeptidase from the synaptosomal membrane of bovine brain. This enzyme displays characteristics consistent with it being classified as a PAP type II neuropeptidase with only minor differences from other proteases in this group.

Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain.

Prolyl endopeptidase has been predominantly described as a cytosolic activity capable of cleaving a number of important neuropeptides (including TRH, LHRH, Bradykinin, Angiotensin, Substance P, Neurotensin, Oxytocin and Vasopressin) on the carboxy side of proline. In this paper, we report, for the first time, on the complete purification and characterization of a membrane-bound form of prolyl endopeptidase. This novel activity has been isolated from the synaptosomal (plasma membranes) membranes of bovine brain. Following gel filtration, hydroxylapatite and hydrophobic interaction chromatographies, the prolyl endopeptidase activity was purified 1400-fold with a 23% recovery of activity. The enzyme was shown to have a relative molecular mass of 87 kDa and a Km of 60 microM for its specific fluorimetric substrate, Z-GlyProMCA. The purified enzyme demonstrated a relatively broad substrate specificity and a relatively high affinity for proline-containing neuropeptides. It was shown to be inhibited by certain thiol-protease inhibitors and by the metal chelator, 1,10-phenanthroline, thus possibly classifying it as a 'thimet' activity. The purified particular form of proyl endopeptidase displayed a similar substrate specificity to the previously reported cytosolic forms of the enzyme. However, there were differences between the two forms in term of their sensitivity to inhibitors, their affinities for the peptide substrates and their relative molecular masses. The different subcellular location (i.e. the synaptosomal membrane) of the particulate prolyl endopeptidase is also of potential physiological significance given that here it is more likely to come in contact with the vesicle-bound neuropeptides than is its cytosolic counterpart.

A three-dimensional in-vitro model for the study of peritoneal tumour metastasis.

Peritoneal metastasis is a frequent complication of gastrointestinal malignancy. We have developed a three-dimensional model of the human peritoneum that simulates the metastatic process in vitro. Peritoneal fibroblasts were incorporated into collagen lattices, allowed to contract, then overlaid with mesothelial cells. Scanning and transmission electron microscopy showed the model to have similar physical properties to human peritoneum. Mesothelial expression of the beta1 integrin family, the basement membrane proteins fibronectin, laminin, collagen types III and IV, and the cell adhesion molecules ICAM-1, VCAM-1 and PECAM were assessed and showed similar results to in vivo tissue. Gastrointestinal tumour cells seeded onto the model exhibited mesothelial adhesion, cell spreading and vesicle formation, and invasion of the mesothelial monolayer on scanning electron microscopy. Two distinct patterns of tumour cell growth were observed using light microscopy: a superficial spreading layer, and discrete invasive deposits. Invasion was accompanied by disruption of the mesothelial monolayer, degradation and re-orientation of the matrix, and rudimentary tumour cell differentiation. We believe the use of this in vitro peritoneal model will facilitate the study of the molecular mechanisms involved in the metastatic process.

Agreement between preoperative core needle biopsy and postoperative invasive breast cancer histopathology is not dependent on the amount of clinical material obtained.

AIMS: To establish the relation between the amount of breast core needle biopsy (CNB) material examined and agreement between preoperative and postoperative histopathology parameters in invasive breast cancer. METHODS: The CNB and surgical specimen histopathology reports of 113 patients with invasive breast carcinoma were reviewed and the total amount of CNB material examined for each case was determined. Agreement was calculated for tumour type, grade, mitoses, nuclear pleomorphism, and tubule formation. Associations between the amount of CNB material and histopathology agreement before and after surgery were explored using binary logistic regression. RESULTS: Tumour type and grade agreed in 65.4% and 61.6% of cases, respectively. The components used to calculate grade--nuclear pleomorphism (57.4%), mitoses (59.4%), and tubule formation (55.6%)--agreed slightly less frequently. The proportion of cases with preoperative and postoperative assessments that agreed did not depend on the number of cores collected or the total amount of material examined. CONCLUSION: Neither tumour type and grade, nor the individual components used to calculate grade agreed consistently between the CNB and surgical specimen. The number of cores collected and the total amount of material reviewed by the pathologist does not influence the likelihood of agreement between preoperative and postoperative histopathology reports.

A novel in vitro dermal wound-healing model incorporating a response to mechanical wounding and repopulation of a fibrin provisional matrix.

Previously our laboratory, and others, described an in vitro model for the study of fibroblast wound repopulation. The so-called punch-wounded, fibroblast-populated collagen lattice has been used extensively in tissue repair research. We now identify certain shortcomings with this model, which have led to its enhancement by the introduction of a provisional matrix fabricated in situ from fibrinogen and alpha-thrombin. In the previous model, fibroblasts repopulate the wound defect (WD) as a monolayer of cells and on reaching confluence, a process reminiscent of fibroplasia fills the wound space. The enhanced model, with fibrin acting as a provisional matrix, allowed fibroblasts to repopulate the WD as a three-dimensional network of cells that were morphologically different from cells migrating over the collagen substratum of the previous model. Fibroblast repopulation of the fibrin matrix was typically around double the rate of repopulation of the empty wound space. We propose this model as an enhanced, yet sufficiently reproducible, model for the study of fibroblast responses to tissue damage. It can be further enhanced by the addition of other cell types and matrix components.

Curative radiotherapy for anterior commissure laryngeal carcinoma.

There is continuing controversy surrounding the most effective treatment of glottic carcinoma involving the anterior commissure (AC). Surgery has been the preferred method of treatment, since studies previously indicated early tumor invasion of the thyroid cartilage at the AC, thereby assuming less curability by radiotherapy (RT). Subsequent laryngeal anatomic studies and refinement of RT techniques have brought into question the ineffectiveness of curative irradiation. A retrospective review of 174 patients with early-stage glottic carcinoma treated with standard fractionation curative RT revealed 34 patients with T1 and T2 lesions involving the AC. Allowing for a follow-up of at least 3 years, we observed only a 12% (4 of 34 patients) local recurrence rate after RT alone, with excellent voice quality and no major complications related to the irradiation. The 4 local recurrences were controlled by total laryngectomy, although 2 patients developed distant metastatic disease. Radiotherapy represents an effective method of treating T1 squamous cell carcinoma of the glottis with AC involvement. The small number of T2 glottic carcinomas in this study prevents a meaningful conclusion concerning treatment of these lesions.

Investigation into the effects of modification of the passive phase for improved manufacture of 1-3 connectivity piezocomposite transducers.

The 1-3 connectivity composite transducers comprise active piezoceramic pillars within a passive polymer matrix. The first stage in manufacturing the 1-3 material is to produce a bristle block (comprising a solid stock of active material with protruding pillars) by injection moulding or by dicing a piece of ceramic using precision sawing equipment. The bristle block is filled with a reactive polymer liquid that produces the passive polymer phase, and the filled block is machined to the desired dimensions. For optimum performance, the polymer phase should have complementary interaction with the ceramic phase as well as imparting dimensional stability. Epoxy-based polymers are the most usual passive materials because of their low viscosity in the uncured state and solvent resistance, coupled with their excellent adhesive, mechanical, and electrical properties. However, the curing of epoxy resins results in shrinkage of the polymer matrix and internal stress within the passive phase. This can lead to prestressing of the active ceramic material, distortion of pillars, reduction in the parallelism between the sides of pillars, acid, in certain circumstances, warpage of transducers. This is particularly evident when the solid stock in the bristle block is relatively thin. This paper reports the in situ modification of epoxy in the bristle block by UV-based low temperature polymerization of acrylate monomers within the epoxy matrix prior to polymerization of the epoxy resin. Internal stress measurements are presented to quantify the influence of this modification via a reduction of internal stress within the polymer matrix. Results from finite element analysis emphasise the conclusions of the experimental work, and examples of manufactured devices are presented. Composite transducer performance is assessed by laser measurement of surface displacement profiles, and a 50% improvement in surface displacement magnitude was observed for the modified devices.

Thermographic evaluation of the autonomic effects of nerve blocks in the foot.

The authors evaluated regional skin temperatures of the foot following the administration of a variety of local anesthetic nerve blocks with either Xylocaine (lidocaine hydrochloride) or Sensorcaine (bupivacaine hydrochloride). The study was carried out on ten randomized parallel groups of five subjects, each group being tested with one drug and one regional nerve block. The results indicated that both Xylocaine and Sensorcaine, when administered as a posterior tibial block, result in a significantly increased blood flow to the foot. Nerve blockade of the remaining nerves of the foot did not significantly increase the sympatholytic effect obtained by posterior tibial nerve block alone.

Use of pilot plant facilities to aid validation programs.

According to the FDA guidelines (1), pilot plant facilities may be used to generate material to support process validation studies. The guidelines also state that process modifications are an inevitable part of process development and scale-up. However, if such modifications are made, there is a need to demonstrate that the products from both the old and new processes are comparable (2). Both of these guidelines were combined and applied during a recent development of a product at Genentech. In order to implement the process modifications and demonstrate product comparability, the pilot plant facilities were used for these production runs. As the process had changed and the product was being prepared for BLA submission, in process samples from the new manufacturing process were also required to support the process validation studies. By using pilot plant facilities to implement the process modifications, test product comparability, and produce material for process validation, we were able to minimize the impact of such work on the large-scale manufacturing facility.

Magnetic resonance imaging of the foot and ankle.

Magnetic resonance imaging enhances the inherent differences in the density of tissues to allow the diagnosis of pedal disorders not readily observed by other diagnostic means. The technique is particularly useful for the evaluation of the nature and extent of soft tissue pathology. In addition, certain osseous and joint disorders, such as osteomyelitis and Sudeck's atrophy, may be detected in their incipient stages.

Politics in health--the American experience.

By examining various trends of the hospital industry in the context of the American political and social system. Mr O'Leary comments on the expanding role of government in planning, financing and regulating health services in the US. As government has taken on a more powerful central role in American Health care, the hospital industry has become more active in the legislative and political arena. By activating physicians, boards, employees and the patient community to become more involved in the political process, hospitals have been able to have a stronger hand in shaping decisions which will affect the future health care delivery system in the States.

Forging a future for nursing. A system's nurse executives collaborate to create a strategic plan.

In early 1991 the Nurse Executives' Council (NEC) of the Seattle-based Sisters of Providence Health System completed a survey assessing the effectiveness of patient care delivery processes and gauging the extent to which nurses participate in planning programs and services. Later that spring the NEC reviewed the survey and made a preliminary identification of nursing strategic issues. To complement this internal survey, in fall 1991 the council was given an overview of the external environment as it relates to nursing. The council also formed three committees--Strategic Planning/Bylaws, Human Resources, and Productivity--to address concerns that surfaced in the internal assessment survey process and to help design a document outlining the council's strategic plan for system nurses. After working with the NEC liaison, the Strategic Planning/Bylaws Committee drafted a plan for review by NEC members before submitting it for approval by appropriate bodies within the organization. The final plan, unveiled at the fall 1992 NEC meeting, identifies four key strategic issues for nursing, including the need to: Develop nursing leadership; Maximize human resources; Coordinate client and patient care over a continuum of healthcare services; Demonstrate fiscal stewardship.