Clinician perspectives on having point of care tests made available to them during out of hours home visiting.

BACKGROUND: Little is known about clinicians' perspectives on the use of point of care (POC) tests in assessment of acute illness during primary care out of hours (OOH) care. During a service improvement project, POC tests (including creatinine, electrolytes, haemoglobin and lactate) were made available to clinicians undertaking OOH home visits, with the clinicians allowed absolute discretion about when and whether they used them. METHOD: To explore clinicians' perspectives on having POC tests available during OOH home visits, we undertook a qualitative study with clinicians working in Oxfordshire OOH home visiting teams. We conducted 19 Semi-structured interviews with clinicians working in OOH, including those who had and had not used the POC tests available to them. To explore evolving perspectives over time, including experience and exposure to POC tests, we offered clinicians the opportunity to be interviewed twice throughout the study period. Our sample included 7 GPs (4 interviewed once, 3 interviewed twice - earlier and later during the study), 6 emergency practitioners (EPs) including advanced nurse practitioners and paramedics, 1 Healthcare Assistant, and 2 ambulatory care physicians. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: The clinicians reflected on their decision-making to use (or not use) POC tests, including considering which clinical scenarios were "appropriate" and balancing the resources and time taken to do POC tests against what were perceived as likely benefits. The challenges of using the equipment in patients' homes was a potential barrier, though could become easier with familiarity and experience. Clinicians who had used POC tests described benefits, including planning onward care trajectories, and facilitating communication, both between professionals and with patients and their families. CONCLUSION: Clinicians described a discriminatory approach to using POC tests, considering carefully in which situations they were likely to add value to clinical decision-making.

A new insight into the interaction of cisplatin with DNA: ROA spectroscopic studies on the therapeutic effect of the drug.

Raman optical activity (ROA) spectroscopy has been applied for the first time to study the interaction of cisplatin with DNA. The knowledge about the structure of DNA-metal ion cross-links and hence the mechanism of the drug action is fundamental for the development of new antitumor drugs. At the same time, there is an urgent need to search for new methods for monitoring of this effect at the therapeutic dose of a drug. We have demonstrated that ROA spectroscopy is a sensitive technique with the capability to follow the structural alteration of the whole DNA molecule upon drug binding via a direct observation of transformation undergoing within chiral sugar moieties. A ROA profile delivers clear evidence of a partial transition from the B-DNA to the A-form due to the formation of cisplatin-DNA cross-links.

XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer.

The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg(-/-) (NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.

The significance of afferent vagal information in the control of breathing in guinea pigs.

The stimulation of the central vagus nerve in guinea pigs was applied to study the role of vagal afferent information in the control of breathing. The survival time after bilateral vagotomy was measured in unanesthetized animals, under Hexobarbital anesthesia, and in anesthetized subjects when the central stump of the vagus nerve was stimulated. There were no differences in survival time between the first and the second groups, but in animals with vagal stimulation, the survival time was prolonged. The respiratory and circulatory disturbances were abolished by stimulation.

Phrenic nerve activity and ventilation during lung oedema in rabbits.

Single fibre and "integrated" phrenic nerve activity was recorded in anaesthetized spontaneously breathing rabbits, during experimentally induced lung oedema. Tidal volume, blood pressure, end-tidal CO2, were monitored. In oedema the number of impulses in each volley slightly decreased while the discharge frequency was increased relatively to control values. The latter effect was due to the increased respiratory rate. "Integrated" phrenic nerve activity was also increased, contrary to tidal volume which was diminished. Minute ventilation obtained from pneumotachograph records [f per V(T)] was compared to the neural output in terms of tidal phrenic amplitude times frequency [f per V(T) eq]. The minute ventilation rose insignificantly by 45 +/- 40 percent and neural output was increased on the average by 150 percent.

Relative roles of irritant, type-J and pulmonary stretch receptors in lung reflexes.

Bilateral anodal block of both cervical vagus nerves of anaesthetized rabbits has been used to assess the relative role of afferent pathways with myelinated fibres (primarily from lung irritant receptors) and with nonmyelinated fibres (from J-receptors) in respiratory responses to some lung conditions. With inhalation of histamine aerosol the increase in breathing frequency is due to myelinated afferent fibres from irritant receptors. The similar response with inhalation of halothane is due to non-myelinated fibres from J-receptors. The reflex breathing response in lung oedema involves both pathways, but in the experimental conditions the myelinated pathway plays the larger part. The interaction of these two mechanisms, and the possible role of pulmonary stretch receptors, is discussed.

The cyanide gasp and spontaneous deep breaths.

Stimulation of the carotid body chemoreceptors with cyanide in anaesthetized rabbits usually causes a deep breath or gasp, but only if the vagus nerves are intact. This gasp has several similarities with spontaneous deep breaths in eupnoea. In paralysed rabbits, artificially ventilated, chemoreceptor stimulation induces an augmented discharge in the phrenic nerve equivalent to a gasp. In spontaneously breathing rabbits spontaneous deep breaths are more frequent with hypoxia than with normoxia. The results are interpreted in relation to (i) positive feedback from the lungs and (ii) summation of chemoreceptor and tonic vagal drive causing augmented deep breaths.

The respiratory action of phenyl diguanide in vagotomized rabbits.

In anaesthetized rabbits phenyl diguanide not only stimulates breathing (rapid shallow breathing) by a vagal reflex from lung J-receptors, but also causes a similar response in bilateral vagotomized animals. Injection of the drug into different parts of the circulation indicates that the main non-vagal response of breathing arises from areas supplied by the vertebral arteries, presumably in the brain.

Randomised controlled trial of community based speech and language therapy in preschool children.

OBJECTIVE: To compare routine speech and language therapy in preschool children with delayed speech and language against 12 months of "watchful waiting." DESIGN: Pragmatic randomised controlled trial. SETTING: 16 community clinics in Bristol. PARTICIPANTS: 159 preschool children with appreciable speech or language difficulties who fulfilled criteria for admission to speech and language therapy. MAIN OUTCOME MEASURES: Four quantitative measures of speech and language, assessed at 6 and 12 months; a binary variable indicating improvement, by 12 months, on the trial entry criterion. RESULTS: Improvement in auditory comprehension was significant in favour of therapy (adjusted difference in means 4.1, 95% confidence interval 0.5 to 7.6; P=0.025). No significant differences were observed for expressive language (1.4, -2.1 to 4.8; P=0.44); phonology error rate (-4.4, -12.0 to 3.3; P=0.26); language development (0.1, -0.4 to 0.6; P=0.73); or improvement on entry criterion (odds ratio 1.3, 0.67 to 2.4; P=0.46). At the end of the trial, 70% of all children still had substantial speech and language deficits. CONCLUSIONS: This study provides little evidence for the effectiveness of speech and language therapy compared with watchful waiting over 12 months. Providers of speech and language therapy should reconsider the appropriateness, timing, nature, and intensity of such therapy in preschool children. Continued research into more specific provision to subgroups of children is also needed to identify better treatment methods. The lack of resolution of difficulties for most of the children suggests that further research is needed to identify effective ways of helping this population of children.

FT-Raman spectroscopic study of human skin subjected to uniaxial stress.

Fourier Transform Raman Spectroscopy was used to investigate the molecular changes of structural proteins in human skin subjected to strain. In the Raman spectrum of unstrained skin, bands assigned mainly to collagen and elastin were observed at 1658 cm(-1) (amide I), 1271 and 1255 cm(-1) (amide III), and 935 and 817 cm(-1) (C-C stretching modes of the protein backbone). Moreover, bands characteristic for amino acids were observed at 1336 cm(-1) (desmosine), 1004 cm(-1) (phenylalanine), 919 and 856 cm(-1) (proline), and 877 cm(-1) (hydroxyproline). Positions and intensities of the listed Raman bands were analysed as a function of applied strain. A clear correlation between Raman wavenumbers and the level of mechanical stress was established. Wavenumbers of the analysed bands changed gradually with increasing strain. Distinct responses, depending on the sample cutting direction, i.e. longitudinal or perpendicular to the Langer's lines, were noticed. It was concluded that elastin and non-helical domains of collagen are initially involved in the load transfer and triple helices of collagen are gradually joining this process. It was proved that Raman spectroscopy give insight into skin deformation micromechanics.

Parents' beliefs and ideas about children's early speech and language difficulties.

This paper reports a qualitative investigation of the ideas and beliefs of parents about their pre-school children's speech and language difficulties. It forms part of a broader study of parental opinions about speech and language difficulties and the speech and language therapy (SLT) intervention they receive. Factors contributing to the development of professional interest in parental views will be reviewed, followed by an outline of the beliefs and ideas expressed by the parents in in-depth interviews. The paper will also discuss parents' views in their wider context and consider implications for SLT practice.

Investigating parental views of involvement in pre-school speech and language therapy.

Today, speech and language therapists working with the pre-school population routinely involve parents in their children's treatment programmes. Also, there is increasing recognition of the importance of considering client and carer views in evaluating services. Thus, in both clinical and research terms, the role of parents is key. This paper reports an aspect of a study that investigated parents' views and perceptions of their pre-school children's speech and language difficulties and the speech and language therapy (SLT) they received. The methodology of the study was qualitative and data were collected from the parents of 16 pre-school children, using in-depth interviews. The parents' perceptions could be characterized as a process with three phases. On the whole, parents viewed their involvement in SLT positively but crucially, the interviews highlighted discrepancies between therapists' and parents' perceptions of the therapy process. The study demonstrates that when parents' views are considered, a fuller understanding of the effectiveness and acceptability of treatment can emerge.

The effect of the larynx on the breathing pattern in anaesthetized rabbits.

The effect of the larynx on the inspiratory and expiratory times was studied in anaesthetized rabbits. A model of "isolated larynx" used allowed for connecting it to or excluding it from the respiratory system. The inspiratory time (TI) inthe intact animals and those with the superior laryngeal nerves cut was significantly prolonged whether the larynx was switched in the inspiratory or expiratory phase, while in vagotomized animals the change was non-significant. The expiratory time (TE) was shortened in the intact and vagotomized rabbits but prolonged after section of the superior laryngeal nerves. Sensory denervated larynx then subserves only its valvular mechanisms, prolonging TE. Blow of fresh air on the vocal cords shortened TE as well, suggesting that the exhaled air may be the stimulus for this reflex.

Are central respiratory chemoreceptors confined to ventrolateral medulla?

There is ample evidence that the ventrolateral medulla (VLM) is involved in regulation of respiration. The VLM is considered to be the site of location of the central respiratory chemoreceptors. Neither neuroanatomical nor neurophysiological coordinates of the chemoreceptor have ever been indisputably identified or verified, despite decades of research. This commentary addresses new hypotheses concerning the process of central chemoreception and recent findings calling into question the exclusivity of VLM for the chemoreceptor location and function. These findings rekindle the possibility of medullary respiratory neurons being chemosensors. Crucial issues concerning the central chemoreception remain unsettled and are open to further research.

Reflex control of discharge in motor fibres to the larynx.

1. Action potentials have been recorded from single laryngeal motor fibres, with expiratory or inspiratory phases, in cats anaesthetized with pentobarbitone and breathing through a tracheal cannula.2. Pneumothorax increased the discharge of both inspiratory and expiratory units, the inspiratory response being greatly reduced by bilateral vagotomy below the origin of the recurrent laryngeal nerves.3. Addition of a ;viscous' resistance to breathing, or asphyxial rebreathing through an added dead space, increased the activity of inspiratory units and decreased that of expiratory units.4. Induction of pulmonary oedema decreased the discharge of inspiratory units and increased that of expiratory units. After vagotomy the response of inspiratory units was reversed.5. Intravenous injections of potassium cyanide increased the activity of both types of unit.6. Chemical irritation of the laryngeal mucosa decreased the discharge of inspiratory units and increased that of expiratory units, whether the vagi were intact or cut.7. It is concluded that expiratory unit discharge can be correlated with expiratory laryngeal resistance, but that inspiratory unit discharge does not correlate so well with inspiratory laryngeal resistance.8. The relationship between laryngeal motor-fibre activity and the contractions of the inspiratory and expiratory muscles of breathing is discussed.

A 12-month follow-up of preschool children investigating the natural history of speech and language delay.

AIM: The aim of this paper is to examine the natural history of early speech and language delay in preschool children over a 12-month period. METHODS: The study reports data on 69 children under the age of 3.5 years who were referred for speech and language therapy because of early speech and language delay. The children were monitored over a 12-month period but received no direct intervention during that time. Assessment of their comprehension, expressive language and their phonology took place at baseline and again at 6 and 12 months after baseline. RESULTS: The results show a general picture of improvement, although there was considerable individual variation. By the end of the 12 months, two-thirds of the children were still eligible on the study intake criteria. Therapist's rating of a child's functional communication at the outset was a significant predictor of the child's outcome at the end of the 12-month period. DISCUSSION: The paper discusses the appropriateness of a 'monitoring' approach to the management of early language delay and highlights the need to consider the social issues and views of parents as well as the severity of a child's difficulties.

Day in, day out: the everyday therapy of community clinics.

This paper describes the timing and nature of therapy provided within a recent randomised controlled trial (RCT) of preschool speech and language therapy services. There is literature that describes and evaluates speech and language therapy but there is little indication of how this is translated into everyday practice. The study collected data from 21 speech and language therapists (SLTs) in 16 community clinics. The areas targeted, goals, approaches used, the frequency and timing of contact for the 68 children who received treatment were documented. The data show that several aspects of therapy were frequently targeted simultaneously, that approaches were combined and that the frequency of therapy did not vary with severity. The discussion will consider the gap between published programmes and everyday practice and the implications for effectiveness.

Running a randomised controlled trial in a service setting: a progress report.

This paper will give a progress report on a randomised controlled trial which is currently underway in the Bristol area. Some of the key influencing literature will be summarised, followed by an overview of the study design. The paper will also highlight some of the methodological and practical advantages and disadvantages afforded by the service setting of the study.

Issues to consider in the evaluation of speech and language therapy for preschool children.

This paper reviews some of the methodological issues involved in the design of a randomized controlled trial currently underway in Bristol. The trial compares the progress of preschool children randomly allocated to a 'watching-waiting' control group with the experimental group who have immediate access to therapy. This paper reviews a number of relevant studies, which have either followed up preschool children with early language delays or have investigated the effects of therapy with this age group. The basic design of the trial is outlined along with a discussion of the sample, the measurements used and the therapy given.

Developing a scale to measure parental attitudes towards preschool speech and language therapy services.

In the past decade, there has been growing recognition of the need to involve clients in decisions about the healthcare they receive and in the evaluation of services offered. In health services research, survey and scaling methods have become important tools for research into 'consumer views' and the perspectives of people receiving healthcare. In spite of the increase in recent years in the participation of parents in their children's Speech and Language Therapy (SLT), there has been little attempt to investigate parents' perceptions and opinions of the services they receive. Moreover, there has been no previous attempt to derive a scale to measure these attitudes. The paper reports a study that explored the attitudes to therapy of 81 parents whose preschool children were receiving SLT intervention. Factor analysis of 12 items on a questionnaire revealed three issues salient in parental attitudes to therapy: practical help, emotional support and the perceived effectiveness of the service. The validity of these factors was supported by other findings from the questionnaire. The properties of the resulting scales are discussed and the ways in which they might be further refined and developed for use in SLT are suggested.