An evaluation of a collaborative pharmacist prescribing model compared to the usual medical prescribing model in the emergency department.

BACKGROUND: Workforce reform has placed a significant focus on the role of non-medical prescribers in the healthcare system. Pharmacists are trained in pharmacology and therapeutics, and therefore well placed to act as non-medical prescribers. OBJECTIVES: To assess the safety and accuracy of inpatient medication charts within a pharmacist collaborative prescribing model (intervention), compared to the usual medical model (control) in the emergency department (ED). Another objective compared venous thromboembolism (VTE) risk assessment and prescribing, between intervention and control groups. METHODS: Adult patients in ED referred for hospital admission were randomised into control or intervention by a block randomisation method, until the required sample size was reached. Medication charts were audited retrospectively by an independent auditor, using validated audit forms. RESULTS: Intervention group medication charts contained significantly fewer prescribing errors, omissions and discrepancies compared to the control group, and improved documentation of adverse drug reactions. VTE risk assessment and prescribing had higher guideline concordance in the intervention group compared to the control group. CONCLUSIONS: This collaborative prescribing trial showed excellent results in safety and accuracy of pharmacist prescribing when compared to the usual medical model of prescribing. The admitting medical practitioner and extended scope pharmacist prescriber worked as a collaborative team in emergency, which improved Australian national prescribing safety indicators.

Fifty-four emergent cricothyroidotomies: are surgeons reluctant teachers?

BACKGROUND: Emergent cricothyroidotomy remains an uncommon, but life-saving, core procedural training requirement for emergency medicine (EM) physician training. We hypothesized that, although most cricothyroidotomies occur in the emergency department (ED), they are rarely performed by EM physicians. METHODS: We conducted a retrospective analysis of all emergent cricothyroidotomies performed at two large level one trauma centers over 10 years. Operators and assistants for all procedures were identified, as well as mechanism of injury and patient demographics were examined. RESULTS: Fifty-four cricothyroidotomies were performed. Patients were: mean age of 50, 80% male and 90% blunt trauma. The most common primary operator was a surgeon (n = 47, 87%), followed by an Emergency Medical Services (EMS) provider (n = 6, 11%) and a EM physician (n = 1, 2%). In all cases, except those performed by EMS, the operator or assistant was an attending surgeon. All EMS procedures resulted in serious complications compared to in-hospital procedures (p < 0.0001). CONCLUSIONS: 1. Pre-hospital cricothyroidotomy results in serious complications. 2. Despite the ubiquitous presence of emergency medicine physicians in the ED, all crico-thyroidotomies were performed by a surgeon, which may represent a serious emergency medicine training deficiency.

Heterosexual men and women with HIV test positive at a later stage of infection than homo- or bisexual men.

The current strategy of offering HIV testing to individuals with known risk has had no impact on the reduction in the number of patients diagnosed with immune suppression of infection. A prospective observational study to compare the baseline CD4+ T-cell counts in HIV-infected homosexual/bisexual men, intravenous drug users, heterosexual men and women diagnosed in GUM/RIDU and that of patients diagnosed during routine maternal screening for HIV between December 1999 and January 2003 was carried out at the Departments of Genitourinary Medicine (GUM), Regional Infectious Disease Unit (RIDU) and Obstetrics in Edinburgh. Late presentation was defined as positive HIV test with baseline CD4+ T-cell count of less than 200 cells/mL. During the study period, 189 patients tested in GUM/RIDU setting and 13 screened women were diagnosed with HIV infection. Thirty-four percent of the former and 38% of the latter group had CD4+ T-cell count of less than 200 cells/mL by the time of diagnosis. Heterosexual individuals contributed to 78% of HIV tests in the GUM/RIDU setting. Amongst the 78 HIV-infected heterosexual individuals diagnosed in GUM/RIDU 45% were late presenters. Significantly fewer homosexual men were late presenters. There was no difference between the proportion of late presenters amongst women screened at the antenatal (5/13) compared to heterosexual patients diagnosed in GUM/RIDU (35/78). A significant number of HIV infected heterosexual patients are late presenters in the HIV testing at GUM/RIDU. HIV screening programmes for heterosexual individuals in any medical encounter may reduce the number of late presenters.

Herpes simplex virus type 1 remains the principal cause of initial anogenital herpes in Edinburgh, Scotland.

GOAL: The goal of this study was to investigate the trends in the prevalence of anogenital herpes caused by herpes simplex virus (HSV) type-1 and HSV-2 among patients attending a sexually transmitted infections clinic. METHODS: We conducted a retrospective study of virologically proven first-episode genital herpes diagnosed in the Department of Genitourinary Medicine in Edinburgh between 1989 and 2002. RESULTS: First-episode anogenital herpes was associated with HSV-1 in 659 (62%) women and 294 (42%) men (P <0.0002). HSV-1 was recovered more often from women younger than 25 years than from older women (P <0.0005). For both HSV-1 and HSV-2 infections, the median ages of heterosexual men (26.0 and 28.0 years, respectively) were significantly higher than those of women (23.0 and 25.0 years, respectively)(P <0.05). The median age of men who have sex with men with HSV-1 (29.0 years) was significantly higher than that of heterosexual men (26.0 years)(P <0.01). CONCLUSION: HSV-1 remains the most common cause of symptomatic first-episode anogenital herpes, especially among young women in our clinic population.

Best Practice No 175. Guidelines for virological and non-viral serological examination of specimens in routine diagnostic microbiological laboratories.

Viral examination is routinely carried out in most routine diagnostic microbiology laboratories. Most often, this comprises the detection of viral antigens and antibodies, and less commonly the isolation of viruses and the detection of viral nucleic acids. However, there are no standards or guidelines available for processing these specimens in routine diagnostic laboratories or for referral to specialist virology centres or units. Clinical Pathology Accreditation (CPA) has defined standards for assessing the quality of service provided by laboratories, but these do not include the scientific and technical aspects of provision of service. The Association of Medical Microbiologists has recently published Standards for Laboratory practice in medical microbiology, which covers scientific and technical aspects of provision of microbiology service, mainly bacteriological examination of specimens in routine diagnostic microbiology laboratories. These guidelines are complementary to the CPA guidelines and aim to ensure a consistent and high quality service. This article presents guidelines for the examination of specimens for the diagnosis of viral infections.

Guidelines for laboratory monitoring of treatment of persistent virus infections.

A growing number of antiviral agents are available for treatment of persistent viral infections. This has increased the requirement for virology laboratories to undertake sophisticated assays for monitoring the efficacy of treatment and identifying drug failure at an early stage. The consensus guidelines within this article address the laboratory requirements for monitoring treatment of the herpes viruses, HIV-1, Hepatitis B and Hepatitis C.

Molecular techniques should not now replace cell culture in diagnostic virology laboratories.

The value of molecular techniques for virology is not in dispute; the issue debated here is whether or not to abandon virus isolation altogether. Modern clinical virology relies on rapid virus detection for timely infection control and antiviral therapy. The role of virus isolation, inevitably a slower process as it involves replication in cell cultures, is most significant in providing epidemiological data, in the diagnosis of new or unexpected infection, and in yielding infectious virus for further study. Examples include identification of enterovirus serotypes in outbreaks, diagnosis of atypical virus infections, and provision of virus isolates for phenotypic antiviral susceptibility assays. Many viruses can be detected after overnight culture using the centrifugation-enhanced (shell vial) technique. In contrast to this established track record, the commercial development of molecular assays has been concentrated on blood-borne viruses, and standardisation of procedures for other viruses is lacking. Accreditation of molecular techniques is just beginning, and few external quality assurance schemes are available yet. In my view, it is premature to abandon routine virus isolation, although as molecular diagnosis expands, the facilities for cell culture and isolation work may become more centralised to retain expertise and to provide the range and quality of service required.

Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts.

Erythropoietin (Epo) is required for the production of mature red blood cells. The requirement for Epo and its receptor (EpoR) for normal heart development and the response of vascular endothelium and cells of neural origin to Epo provide evidence that the function of Epo as a growth factor or cytokine to protect cells from apoptosis extends beyond the hematopoietic lineage. We now report that the EpoR is expressed on myoblasts and can mediate a biological response of these cells to treatment with Epo. Primary murine satellite cells and myoblast C2C12 cells, both of which express endogenous EpoR, exhibit a proliferative response to Epo and a marked decrease in terminal differentiation to form myotubes. We also observed that Epo stimulation activates Jak2/Stat5 signal transduction and increases cytoplasmic calcium, which is dependent on tyrosine phosphorylation. In erythroid progenitor cells, Epo stimulates induction of transcription factor GATA-1 and EpoR; in C2C12 cells, GATA-3 and EpoR expression are induced. The decrease in differentiation of C2C12 cells is concomitant with an increase in Myf-5 and MyoD expression and inhibition of myogenin induction during differentiation, altering the pattern of expression of the MyoD family of transcription factors during muscle differentiation. These data suggest that, rather than acting in an instructive or specific mode for differentiation, Epo can stimulate proliferation of myoblasts to expand the progenitor population during differentiation and may have a potential role in muscle development or repair.

Infection with respiratory syncytial virus and water-soluble components of cigarette smoke alter production of tumour necrosis factor alpha and nitric oxide by human blood monocytes.

Cigarette smoke and virus infections contribute to the pathogenesis and exacerbation of chronic obstructive pulmonary disease and asthma. The objective of this study was to examine the effects of a water-soluble cigarette smoke extract (CSE) and/or respiratory syncytial virus (RSV) infection on release from monocytes of the blood from donors of tumour necrosis factor alpha (TNF-alpha) and nitric oxide (NO). Both RSV infection and CSE stimulated TNF-alpha release from monocytes and there was an additive effect if both the agents were present. There was a decrease in NO release, but the effect was significant only with CSE or a combination of CSE and RSV infection. Interferon gamma significantly increased TNF-alpha release and cotinine significantly increased NO release. Nicotine decreased both TNF-alpha and NO responses. The general pattern observed for individual donors was increased TNF-alpha and decreased NO. The proportion of extreme responses with very high TNF-alpha and very low NO in the presence of both RSV and CSE increased to 20% compared with 5% observed with CSE or RSV alone. The results show that RSV infection and components of cigarette smoke elicit inflammatory responses that could contribute to damage to the respiratory tract and these individual factors could be more harmful in combination.

Binding of bacteria to HEp-2 cells infected with influenza A virus.

Epidemiological studies indicate influenza virus infection increases susceptibility to bacterial respiratory pathogens and to meningococcal disease. Because density of colonisation is an important factor in the development of bacterial disease, the objectives of the study were to use flow cytometry methods for assessment of bacterial binding and detection of cell surface antigens to determine: (1) if HEp-2 cells infected with human influenza A virus bind greater numbers of bacteria than uninfected cells; (2) if influenza infection alters expression of cell surface antigens which act as receptors for bacterial binding; (3) if neuraminidase affects binding of bacteria to HEp-2 cells. There was significantly increased binding of all isolates tested regardless of surface antigen characteristics. There were no significant differences between virus-infected and -uninfected Hep-2 cells in binding of monoclonal antibodies to Lewisb, Lewisx or H type 2. There were significant increases in binding of monoclonal antibodies to CD14 (P < 0.05) and CD18 (P < 0.01). Treatment of cells with monoclonal antibodies significantly reduced binding of Neisseria meningitidis strain C:2b:P1.2, CD14 (P < 0.001) and CD18 (P < 0.001). No reduction in binding of a strain of Streptococcus pneumoniae (12F) was observed in these experiments. Neuraminidase treatment of HEp-2 cells increased binding of monoclonal antibodies to CD14 (P < 0.01) and CD18 (P < 0.01). In three experiments, the increase in binding of meningococcal strain C:2b:P1.2 to neuraminidase-treated cells was not significant, but binding of Staphylococcus aureus strain NCTC 10655 was significant (P < 0.05).

Infection with respiratory syncytial virus enhances expression of native receptors for non-pilate Neisseria meningitidis on HEp-2 cells.

Respiratory virus infections have been suggested to be predisposing factors for meningococcal disease. Respiratory syncytial virus (RSV) affects young children in the age range at greatest risk of disease caused by Neisseria meningitidis. It has been previously shown that glycoprotein G expressed on the surface of RSV-infected HEp-2 cells (a human epithelial cell line) contributed to higher levels of binding of meningococci compared with uninfected cells. The aim of the present study was to examine the effect of RSV infection on expression of surface molecules native to HEp-2 cells and their role in bacterial binding. Flow cytometry and fluorescence microscopy were used to assess bacterial binding and expression of host cell antigens. Some molecules analysed in this study have not been reported previously on epithelial cells. RSV infection significantly enhanced the expression of CD15 (P < 0.05), CD14 (P < 0.001) and CD18 (P < 0.01), and the latter two contributed to increased binding of meningococci to cells but not the Gram-positive Streptococcus pneumoniae.

The effect of cigarette smoke on adherence of respiratory pathogens to buccal epithelial cells.

Smoking is associated with an increased risk of respiratory tract infection in adults. In children, exposure to cigarette smoke is a risk factor for respiratory tract infection and bacterial meningitis: Active smoking and passive exposure to cigarette smoke is also associated with carriage of some potentially pathogenic species of bacteria in both adults and children. The aims of the study were to determine the effect of active smoking on: (1) bacterial binding to epithelial cells; (2) expression of host cell antigens that act as receptors for some species; and (3) the effects of passive exposure to water-soluble components of cigarette smoke on bacterial binding. Flow cytometry was used to assess binding to buccal epithelial cells of the following species labelled with fluorescein isothiocyanate: Neisseria meningitidis, Neisseria lactamica, Streptococcus pneumoniae, Bordetella pertussis, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus. Flow cytometry was also used to assess expression of host cell antigens which have been identified as bacterial receptors. For each species, binding to cells of smokers was significantly higher than to cells of non-smokers; however, expression of host cell antigens was similar on epithelial cells of both groups. Non-dilute cigarette smoke extract reduced binding of bacteria to epithelial cells, but dilutions between 1 in 10 and 1 in 320 enhanced binding. We conclude that smokers might be more densely colonised by a variety of potentially pathogenic bacteria. The enhanced bacterial binding to epithelial cells of smokers is not related to enhanced expression of host cell antigens that can act as receptors for some species, but possibly to components in the smoke that alter charge or other properties of the epithelial cell surface. Passive coating of mucosal surfaces with components of cigarette smoke might enhance binding of potentially pathogenic bacteria.

Antiviral prophylaxis and treatment in chickenpox. A review prepared for the UK Advisory Group on Chickenpox on behalf of the British Society for the Study of Infection.

Prophylactic intervention with varicella-zoster immunoglobulin early in the incubation period can prevent or attenuate the disease manifestations of varicella in susceptible contacts at high risk from this infection. Detailed guidelines are issued in the UK Department of Health publication on Immunization against Infectious Disease. Sensitive immunoassays are available for investigation of antibody status and subclinical seroconversion. Live attenuated varicella vaccine, which has been used successfully post-exposure as well as electively elsewhere, is at present not generally available in the UK. Effective protocols for prophylaxis against varicella with the antiviral agent aciclovir are not yet established. The nucleoside analogue aciclovir (syn: acyclovir, Zovirax) is effective in inhibiting replication of VZV when given at a dosage higher than that required for treatment of HSV, and is currently the only available and approved treatment for varicella in the U.K. Intravenous aciclovir therapy for 5-10 days is effective for varicella in neonates and the immunocompromised, and for varicella pneumonia or other complications in adults and children, if begun early. Oral aciclovir is only effective if begun with 24 h of onset of rash. With that proviso. it is recommended for treatment of varicella in otherwise healthy adults and adolescents, but not for routine use in children under 13 years of age unless they are sibling contacts or have other medical conditions. Aciclovir has a high therapeutic index and good safety profile, but caution is advised with use in pregnancy.

MRI study of regional variations of pharyngeal wall compliance in cats.

Upper airway compliance indicates the potential of the airway to collapse and is relevant to the pathogenesis of obstructive sleep apnea. We hypothesized that compliance would vary over the rostral-to-caudal extent of the pharyngeal airway. In a paralyzed isolated upper airway preparation in cats, we controlled static upper airway pressure during magnetic resonance imaging (MRI, 0.391-mm resolution). We measured cross-sectional area and anteroposterior and lateral dimensions from three-dimensional reconstructed MRIs in axial slices orthogonal to the airway centerline. High-retropalatal (HRP), midretropalatal (MRP), and hypopharyngeal (HYP) regions were defined. Regional compliance was significantly increased from rostral to caudal regions as follows: HRP < MRP < HYP (P < 0.0001), and compliance differences among regions were directly related to collapsibility. Thus our findings in the isolated upper airway of the cat support the hypothesis that regional differences in pharyngeal compliance exist and suggest that baseline regional variations in compliance and collapsibility may be an important factor in the pathogenesis and treatment of obstructive sleep apnea.

Lumbar anomalies in the Shanidar 3 Neandertal.

Recent examination of the Shanidar 3 remains revealed the presence of anomalous bilateral arthroses in the lumbar region. This paper describes this developmental anomaly, as well as several degenerative changes and offers potential etiologies. The Shanidar 3 remains represent an adult male Neandertal, approximately 35-50 years of age, dating to the Last Glacial. Although the partial skeleton is fragmentary, preserved elements include an almost complete set of ribs, portions of all thoracic vertebrae, all lumbar vertebrae, and the sacrum. Vertebral articulations from S1-T1 can be confidently assigned. The vertebra designated L1 is well preserved but lacks transverse processes. Instead, well defined bilateral articular surfaces, rather than transverse processes, are located on the pedicles. The skeletal elements associated with the anomalous L1 articulations were not recovered. The most likely interpretation is that the arthroses in question represent the facets for a 13th pair of ribs, a rare condition in modern hominid populations. Such lumbar developmental anomalies are an infrequent expression of a larger complex of cranial-caudal border shifting seen in the vertebral column. These shifts result in a change in the usual boundaries between the distinctive vertebral regions and are responsible for the majority of variability present in the vertebral column.

Molecular epidemiology of varicella-zoster virus in East London, England, between 1971 and 1995.

The molecular epidemiology of varicella-zoster virus in London, England, between 1971 and 1995 was examined by using two informative polymorphic markers, variable repeat region R5 and a BglI restriction site in gene 54. Viruses from 105 cases of chickenpox and 144 of zoster were typed. Two alleles of R5, A and B, were found at prevalences of 89 and 6%, respectively. No difference in allele frequency between the zoster and chickenpox cases was found, and no change in the frequencies of these alleles was observed to occur over time. By contrast, a BglI restriction site (BglI+) was found with increasing frequency over time among cases of varicella (P < 0.005) and, to a lesser extent, cases of zoster. The BglI+ polymorphism was strongly associated (P < 0.0005) with zoster in subjects who had immigrated to the United Kingdom from countries with low adult immunity to varicella (LAIV). Sixty-three percent of the subjects with zoster who had emigrated from countries with LAIV carried the BglI+ virus, in contrast to 10% of adults who had grown up in countries with high adult immunity to varicella. The significance of these data, in view of the changing epidemiology of chickenpox, is discussed.

Molecular biology of vertebrate transcription factor IIIA: cloning and characterization of TFIIIA from channel catfish oocytes.

TFIIIA regulates 5S rRNA synthesis and is the prototype of the Cys2His2 superfamily of zinc finger proteins. Because the TFIIIA aa sequence is highly diverged, elucidating species variation in this factor will yield insights into how zinc fingers bind DNA and how this protein regulates RNAPIII transcription. This study reports the identification, cloning and functional divergence of oocyte TFIIIA from the channel catfish. Catfish oocyte TFIIIA was identified by its association with 5S rRNA in immature ovarian tissue, its molecular weight, and by peptide sequence similarities with Xenopus TFIIIA. The cDNA for this factor was cloned by degenerate PCR and found to code for nine Cys2His2 zinc fingers and a C-terminal tail; only about 40% aa sequence identity was observed with Xenopus TFIIIA. The N-terminal region of catfish TFIIIA contains the oocyte-specific initiating Met amino acid and accompanying conserved residues found in amphibian TFIIIAs but not found in yeast or human TFIIIAs. Catfish TFIIIA lacks the conserved transcription activation domain in its C-terminal tail found in amphibian and human TFIIIA. Catfish TFIIIA was able to bind the catfish and Xenopus 5S RNA genes but did not efficiently promote 5S gene transcription in a rodent RNAPIII transcription system, as did Xenopus TFIIIA. Amino acid conservation in catfish, amphibian, and human TFIIIA zinc fingers allows deduction of possible finger recognition helix alignments along the conserved 5S gene ICRs. For the three N-terminal fingers, this leads to deduction of a compact polypeptide structure with conserved basic residues contacting conserved G nts in the 5S gene C box.

Developmental and environmental factors that enhance binding of Bordetella pertussis to human epithelial cells in relation to sudden infant death syndrome (SIDS).

Asymptomatic infection due to Bordetella pertussis has been suggested to be one cause of sudden infant death syndrome (SIDS). We examined developmental and environmental factors previously found to affect binding of another toxigenic species, Staphylococcus aureus, to human epithelial cells: expression of the Lewis(a) antigen; infection with respiratory syncytial virus (RSV); exposure to cigarette smoke; and the inhibitory effect of breast milk on bacterial binding. Binding of two strains of B. pertussis (8002 and 250825) to buccal epithelial cells was significantly reduced by treating the cells with monoclonal antibodies to Lewis(a) (P < 0.05) and Lewis(x) (P < 0.01) antigens. Both strains bound in significantly greater numbers to cells from smokers compared with cells from non-smokers (P < 0.05). HEp-2 cells infected with RSV subtypes A or B had higher binding indices for both 8002 (P < 0.001) and 250825 (P < 0.01). On RSV-infected cells, there was significantly enhanced binding of monoclonal antibodies to Lewis(x) (P < 0.05), CD14 (P < 0.001) and CD18 (P < 0.01); and pre-treatment of cells with anti-CD14 or CD18 also significantly reduced binding of both strains of B. pertussis. Pre-treatment of the bacteria with human milk significantly reduced their binding to epithelial cells. The results are discussed in relation to our three-year survey of bacterial carriage among 253 healthy infants, their mothers and local SIDS cases between 1993-1995 and in relation to the change to an earlier immunisation schedule for infants and the recent decline in SIDS in Britain.

Altered circadian rhythmicity in the Wocko mouse, a hyperactive transgenic mutant.

Induced changes in the level of daily activity can alter the period of the mammalian circadian clock. In this report, we examined the period of the circadian rhythm of wheel-running activity in a transgenic neurological mouse mutant, Wocko. Wocko mice display a dominant behavioral phenotype that consists of hyperactivity, circling and head tossing. The period of the circadian rhythm of wheel-running activity in constant dark conditions was significantly shorter in mice expressing the Wocko mutation than in their normal littermates. Total activity, monitored by the interruption of an array of infrared beams, was significantly elevated in Wocko mice. These findings support the view that spontaneous exercise can modulate the circadian timekeeping system.