Identifying avoidable switchboard delays in England's NHS hospitals: phase one of the national SWITCH project.

BACKGROUND: Inter-hospital communication frequently requires mediation via a switchboard. Identifying and eliminating switchboard inefficiencies may improve patient care. METHODS: All 175 acute hospital switchboards in England were contacted six times. Call contents and duration were recorded. No clinician calls or bleeps were connected. RESULTS: The mean delay before contacting a switchboard operative was 55±46 seconds. 115 hospitals (66%) used automated switchboards; 34 of these (30%) had infection control messages. Robot operators introduced an additional 40 second delay versus humans (mean 70.3±28 versus 29.8±23 seconds, p<0.0001). Multivariate analysis identified robot operators (HR 5.1, p<0.0001) and infection control messages (HR 2.9, p=0.003) as predictors of delays over 60 seconds. CONCLUSIONS: There are significant avoidable delays in contacting switchboard operatives across England. Quality improvement is underway.

Peer Assessment Rating (PAR) index outcomes for orthodontic and orthognathic surgery patients.

The Peer Assessment Rating (PAR) index is commonly used to evaluate occlusal outcomes after orthodontic treatment. We compared the PAR outcomes of 40 consecutively treated orthodontic patients and 40 orthognathic patients to evaluate the standard of care given. A patient-centred questionnaire was used to examine patients' perceptions of the benefits of orthognathic treatment. PAR scores of orthodontic and orthognathic patients improved by a mean of 77% and 74%, respectively, after treatment indicating that excellent to good occlusal results were achieved for both groups. A high quality occlusal outcome is important for all patients as good intercuspation at the end of treatment is thought to improve stability. Most orthognathic patients reported improvements in their dental and facial appearance and thought that the treatment had been beneficial.

Skin sensitization and possible groupings for 'read across' for rosin based substances.

A series of chemically modified rosin resins have been tested for their potential to cause skin sensitization using the mouse LLNA. Where direct comparative evidence is available, the results of the mouse LLNA are consistent with previously obtained data using the GPMT. Reactions with sufficient fumaric acid or maleic anhydride lead to maleopimaric acid anhydride (an acid anhydride), and give a clear response of a strong sensitizer that definitely requires classification. This sensitization is probably immunologically distinct from that claimed for oxidized rosin. Esterification will deactivate acid anhydrides formed from reacting rosin with maleic anhydride or fumaric acid. However, with maleic anhydride, there remains material capable of inducing a marginal (but classifiable under current criteria) immune response after the rosin had been maleinated and esterified. If proposed potency criteria are used these substances would not be considered 'strong sensitizers'. This response may be a function of a greater solubility in vehicle of the esterified maleinated (or fumarated) rosin over directly esterified material. Solubility limitations in the case of gum rosin directly esterified with pentaerythritol mean that it is not classifiable. Decarboxylated rosin and the glycerol ester of tall oil rosin are adequately soluble, and are not classifiable according to EU criteria. Polymers formed from rosin are also not classifiable as sensitizers. These studies confirm the value of grouping substances for 'read across' and the groupings chosen under the US EPA High Production Volume (HPV) Challenge Program. They also confirm the difficulties involved in dealing scientifically when examining the problem of skin sensitization associated with rosin related substances whilst still meeting current EU regulatory criteria.

On the skin sensitisation potential of rosin and oxidised rosin.

In the EU rosin is classified as a skin sensitiser, apparently on the basis of its oxidation to sensitising agents. Rosin (gum, tall oil or wood) is not a skin sensitiser when examined in the guinea pig maximisation test (GPMT). Oxidised rosins are sensitisers in the GPMT. Oxidised gum rosin was further tested in the mouse local lymph node assay (LLNA) and the Buehler test, but is not a sensitiser in either of these tests. Further, the outcome of the LLNA can be used to assess the potency of oxidised rosin as an inducing agent in humans, and oxidised rosin is, at most, a weak sensitiser in this test. Thus, oxidised rosin is not a potent inducing agent for skin sensitisation unless the dermal barrier is bypassed and/or there is deliberate use of Freund's Complete Adjuvant to induce greater susceptibility. The material used for human patch testing ('colophony') is in oxidised form. A re-examination of epidemiological studies suggests that patients in dermatological clinics show higher response rates than do the general population or those occupationally exposed to presumably oxidised rosin. Thus, the differences seen in susceptibility in the regulatory tests may be reflected in the human population. These results are discussed in terms of possible testing and classification strategies for dealing with existing chemicals, with particular reference to the new European Union legislation.

Sentinel node biopsy in synovial sarcoma.

AIMS: To examine the relevance of sentinel node biopsy in patients with synovial sarcoma. METHODS: Between July 2004 and February 2007 11 consecutive patients with synovial sarcoma treated in our clinic underwent sentinel node biopsy after a preoperative lymphoscintigraphy. A handheld gamma-probe was used during the procedure to identify the sentinel nodes, which were then resected and submitted for histopathologic evaluation. RESULTS: At least one sentinel node was identified in every patient. Of a total of 15 sentinels, one was positive and 14 negative. The patient with the positive sentinel underwent a regional lymph node dissection and remains disease-free 17 months later. One patient developed regional nodal metastases despite negative sentinel node biopsy and died 12 months after the procedure. No biopsy-associated complications were observed. CONCLUSIONS: Sentinel node biopsy can be successfully and safely applied to patients with synovial sarcoma. Further prospective studies are required to determine the optimal treatment approach, the false negative rate and the prognostic significance of a positive sentinel node biopsy.

The role of folic acid in oral clefting.

The objective of this study is to describe the role of periconceptional folic acid supplementation and assess it's potential in the prevention of foetal abnormalities, and consists of a review of the literature undertaken using an electronic and hand search. This includes research trials and methodology associated with folic acid supplementation. It is recommended that all women planning to conceive should supplement their diet with folic acid in order to prevent abnormalities in neural tube development, particularly if there is a history of a previously affected pregnancy. There is increasing evidence that folic acid supplementation may, in addition, reduce the incidence of oral facial clefting. Further research with multi-disciplinary approaches in biochemistry, genetics, gene/environment interactions, and embryology are indicated.

Are societal judgments being incorporated into the uncertainty factors used in toxicological risk assessment?

The aim of this paper is to show that the uncertainty factors used in toxic risk assessment to develop exposure standards do contain societal judgments as well as technical judgments. The process generally used today originated in the 1950s, when a deterministic approach to risk was the norm. Technical judgments are required concerning the nature and the quality of the evidence used in the risk assessment. Judgments taken are essentially cautious. This caution may not matter when measured exposure is significantly below the standard and may be accepted when exposure occurs only following an approval process based on "gate keeping." More sophisticated judgments are required when actual exposure may exceed this type of standard or when risk needs to be compared with benefit. These circumstances can occur with patient exposure to human medicines and with occupational exposure to chemicals. Under these circumstances more explicitly considered societal judgments concerning what constitute "broadly acceptable" and "tolerable" risk criteria, and hence what are appropriate uncertainty factors, are required. The outcomes of those societal judgments are likely to vary according to the circumstances surrounding the exposure and have led to smaller uncertainty factors being considered appropriate for occupational exposure, when compared with widespread public exposure.

Congenital sinus of the upper lip. A case report.

A case report of a congenital midline sinus in the upper lip of a 13-year-old girl is presented. Theories proposed regarding the aetiology of this rare anomaly are discussed.

A prospective evaluation of Bass, Bionator and Twin Block appliances. Part I--The hard tissues.

A prospective clinical study with a random allocation of 47 adolescent patients to three different functional appliance groups was established and compared with an untreated control group over a 9-month period. Treatment was undertaken with either a Bionator, Twin Block, or Bass appliance. Pre- and post-treatment cephalograms were used to quantify the skeletal and dentoalveolar changes produced by the appliances and compared with those observed in the control group as a result of growth. Both the Bionator and Twin Block appliances demonstrated a statistically significant increase in mandibular length (3.9 +/- 2.7 mm; 3.7 +/- 2.1 mm, respectively) compared with the control group (P < 0.05), with an anterior movement of pogonion and point B. Highly statistically significant increases (P < 0.01) were seen in lower face heights for all the appliance groups compared with the control group. The Twin Block group showed the least forward movement of point A due to a change in the inclination of the maxillary plane. The Bionator and Twin Block groups showed statistically significant reductions in the inclination of the upper incisors to the maxillary plane (P < 0.05). The Bass group showed minimal change in the inclination of the lower labial segment to the mandibular plane. The Bionator group demonstrated the greatest proclination of the lower labial segment (4.0 +/- 3.6 degrees). Clinically important changes were measured in all the appliance groups when compared with the control group. Differences were also identified between the functional appliance groups. The Twin Block appliance and, to a lesser extent, the Bionator appeared the most effective in producing sagittal and vertical changes.

A prospective evaluation of Bass, Bionator and Twin Block appliances. Part II--The soft tissues.

A prospective clinical study with a random allocation of 47 patients to three different functional appliance groups was established and compared with a slightly younger control group over a 9-month period. The cephalometric hard tissue changes were assessed in relation to the soft tissue changes produced and the patients were also assessed by three-dimensional (3D) laser scanning of the facial soft tissues. Each 'averaged' appliance group scan was compared with the 'averaged' control group face. Statistically and clinically significant changes occurred in the group treated with the Twin Block appliance, and to a lesser extent in the group treated with the Bionator appliance. No statistically significant facial soft tissue changes could be demonstrated in the Bass appliance group. Upper lip position remained stable despite the significant overjet reduction attained in the three appliance groups. Lower lip protrusion (up to 3.8 mm), lower lip length (up to 4.0 mm), and soft tissue lower and total face height increased significantly in all appliance groups by varying amounts. The long-term effect of these changes needs to be fully evaluated. The laser scanning system was found to be a sensitive and accurate method of quantitatively assessing small changes in the soft tissue facial form. Significant changes of the facial tissues in the transverse plane were highlighted by this technique.

Is working in greenhouses healthy? Evidence concerning the toxic risks that might affect greenhouse workers.

Greenhouses are essentially microcosms aimed at providing physical environments suitable for the survival and growth of plants. Crops grown intensively in greenhouses in Great Britain include cut flowers, pot plants and edible crops such as tomato, lettuce cucumber and celery. The enclosed conditions mean that greenhouse workers are more likely to be exposed to higher levels of plant material, plant pests and plant protection products than general horticulture workers. The potential for ill-health in greenhouse workers is examined with particular reference to Great Britain. The principal potential effects expected include irritancy, asthma, allergic aleveolitis and dermatitis. Although biological control agents are widely used, there were no reports of their having caused ill-health in greenhouse workers. About two people per year are found to have suffered ill-health as a consequence of greenhouse exposure to chemical pesticides in reported pesticides incidents in Great Britain.

Extrapolating from toxicity data to occupational exposure limits: some considerations.

This paper evaluates procedures relevant to extrapolating from toxicity data in man and animals to Occupational Exposure Limits. It examines effects at or around the "No Observed Adverse Effect Level' (NOAEL) and the magnitude of safety factors which can be applied in developing occupational exposure limits for non-stochastic effects. The relationship between incidence of stochastic effect and occupational exposure limit is also discussed.

Harmonization of criteria documents for standard setting in occupational health: a report of a workshop.

The paper presents the most important points of the discussion, recommendations, and conclusions of a workshop on harmonization of criteria documents (CDs) for standard setting in occupational health, with emphasis on standard setting in the European Community (EC). The objectives were to achieve harmonized CDs and to develop a mechanism for international cooperation. The discussion focused on three broad topics: contents of CDs; collection, assessment, and evaluation of data; and procedures for the preparation and exchange of CDs on specific chemicals. Annex A on the various procedures for standard setting by EC Member States, countries outside the EC, and international organizations and Annex B on the proposed contents of the CDs are also included.

Assessment of toxicity for major hazards: some concepts and problems.

Approaches to the assessment of the toxic effects which may arise from chemical Major Hazards are examined. The definitions of hazard and risk and the types of toxicity data required for risk analysis are investigated with particular reference to the quality of the data and models available.

The metabolism of [14C]N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine) in man.

[14C]-N-Ethoxycarbonyl-3-morpholinosydnonimine (molsidomine, Corvaton) was administered orally at a dose of 2 mg per subject to eight healthy male volunteers. Maximal plasma concentrations of total radioactivity of 32.4 +/- 6.4 ng equiv./ml (mean +/- S.D.) were detected compared with maximum plasma concentrations of 14.1 +/- 5.9 ng/ml (mean +/- S.D.) of molsidomine. In both cases these were attained at 0.5 h after dosing. From the peak, concentrations of parent drug fell rapidly with a half-life of 1.25 +/- 0.38 h (mean +/- S.D.). In contrast, total radioactivity declined more slowly with a terminal half-life of 138 +/- 42.7 h (mean +/- S.D.). The bulk of the radiolabel was rapidly excreted as metabolites in the urine, with over 85% of the dose recovered in the first 24 h. The main urinary radiolabelled metabolites appeared, from chromatographic evidence, to be similar to those previously identified in animals, namely N-morpholinosydnonimine, N-cyanomethylamino-N-(2'-hydroxyethyl)glycine and (N-cyanomethylenamino-2-aminoethoxy)-acetic acid.

The metabolism of [14C]N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine) in laboratory animals.

[14C]N-Ethoxycarbonyl-3-morpholinosydnonimine (molsidomine, Corvaton) was found to be extensively metabolized following oral dosing to rat and dog and intravenous dosing to rabbit. The majority of the radiolabel was rapidly excreted in the urine with the main radiolabelled components being characterized as acidic metabolites resulting from oxidative metabolism of the morpholine ring. A new metabolite, (N-cyanomethylenamino-2-aminoethoxy)-acetic acid, was identified and shown to be a major component of the 14C-labelled urinary metabolites in all three species. However, the previously identified metabolite, N-cyanomethylenaminomorpholine-2-one (compound D) was not detected and may therefore have been formed artefactually in the earlier studies. The long terminal half-life for plasma radioactivity observed in previous studies was shown to be the result of the production of small amounts of 14C-thiocyanate from the nitrile-containing metabolites of molsidomine.

Metabolism of loprazolam in rat- and dog-liver preparations.

The metabolism of loprazolam by rat- and dog-liver preparations has been studied in aerobic and anaerobic conditions. Identification of unchanged loprazolam and metabolites was by comparison of chromatographic characteristics and mass spectra with those of authentic compounds. The piperazine-N-oxide was the sole metabolite formed under aerobic conditions in dog-liver slices and microsomes. In addition to this N-oxide, the N-desmethyl metabolite and the diazepine-hydroxy metabolite were formed in rat-liver microsomes. The principal metabolite in rat-liver slices was the glucuronide of the hydroxy compound. Under anaerobic conditions the nitro group of loprazolam is reduced to the amine by dog-liver slices and rat-liver microsomes.

Metabolism of loprazolam in rat, dog and man in vivo.

The metabolism of 14C-loprazolam has been studied in rat, dog and man in vivo. In rat, the major metabolic pathways were hydroxylation on the benzodiazepine ring, and reduction and acetylation of the nitro group. Both metabolites were identified by co-chromatography with standards, and were present in urine and bile conjugated with glucuronic acid. In both dog and human urine and bile significant amounts of the piperazine-N-oxide were found. This N-oxide was identified by co-chromatography with authentic compound and by mass spectroscopy. Both loprazolam and the dog biliary metabolites were hydrolysed spontaneously to polar material. Neither treatment with beta-glucuronidase nor incubation with gut microflora had any further effect. Only polar metabolites were found in dog and human faeces. The principal non-polar material found in rat plasma was the diazepine-hydroxy compound, and little loprazolam was present. Significant levels of loprazolam and lower levels of an unidentified metabolite were found in ether extracts of dog and human plasma. Both the piperazine-N-oxide and loprazolam were found in similar quantities in chloroform extracts of human plasma, and at two hours after dosage, the N-oxide and loprazolam accounted for greater than 90% of the radioactivity present in the plasma.

Disposition of 14C-loprazolam in animals and man.

The disposition of 14C-loprazolam has been studied in rat, dog, cynomolgus monkey and man using oral and parenteral dosing. In all species 14C was excreted principally in the faeces irrespective of the route of administration. In surgically prepared animals, 46% dose (rat) or 60% (dog) was excreted in bile and, together with urinary excretion, indicates that approx. two-thirds of an oral dose was absorbed. In rat there was relatively little enterohepatic circulation (approximately 26%) compared to dog (approximately 73%). Whole-body autoradiography and tissue-distribution studies in rat showed that 14C was distributed principally in liver and intestine, and was eliminated within 24 h. 14C was found in brain of rat and dog; in dog concn. levels were higher in white matter than in grey matter. In studies using pigmented animals, 14C was associated with the uveal tract of the eye and with other melanin-containing tissues. This was reversible and was eliminated from the eye of rat with a half-life of 3.4 d. Blood and plasma concn. of 14C and of unchanged loprazolam declined relatively rapidly in rat. In dog, cynomolgus monkey and man, total 14C concn. in blood fell more slowly than unchanged loprazolam. Less than 85% of loprazolam was protein bound in rat, dog or human plasma in vitro.