Correlates of spontaneous reporting of adverse drug reactions within primary care: the paradox of low prescribers who are high reporters

AIM(S) To examine Primary Care Trust (PCT) demographics influencing general practitioner (GP) involvement in pharmacovigilance. METHODS PCT adverse drug reaction (ADR) reports to the Yellow Card scheme between April 2004 and March 2006 were obtained for the UK West Midlands region. Reports were analysed by all drugs, and most commonly reported drugs (‘top drugs’). PCT data, adjusted for population size, were aggregated. Prescribing statistics and other characteristics were obtained for each PCT, and associations between these characteristics and ADR reporting rates were examined. RESULTS During 2004–06, 1175 reports were received from PCTs. Two hundred and eighty (24%) of these reports were for 14 ‘top drugs’. The mean rate of reporting for PCTs was 213 reports per million population. A total of 153 million items were prescribed during 2004–06, of which 33% were ‘top drugs’. Reports for all drugs and ‘top drugs’ were inversely correlated with the number of prescriptions issued per thousand population (rs = -0.413, 95% CI -0.673, -0.062, P < 0.05, and r = -0.420, 95% CI -0.678, -0.071, P < 0.05, respectively). Reporting was significantly negatively correlated with the percentages of male GPs within a PCT, GPs over 55 years of age, single-handed GPs within a PCT, the average list size of a GP within a PCT, the overall deprivation scores and average QOF total points. ADR reports did not correlate significantly with the proportion of the population over 65 years old. CONCLUSIONS Some PCT characteristics appear to be associated with low levels of ADR reporting. The association of low prescribing areas with high ADR reporting rates replicates previous findings.

20-km distributed temperature sensor based on spontaneous Brillouin scattering

We report on a novel experimental setup for distributed measurement of temperature, based on spontaneous Brillouin scattering in optical fiber. We have developed a mode-locked Brillouin fiber ring laser in order to generate the dual frequency source required for a heterodyne detection of the backscattered signal. This relatively simple system enables temperature measurements over 20 km with a spatial resolution of 7 m.

A study of the aerodynamic characteristics of captor hoods in local exhaust ventilation systems

The research objectives were:- 1.To review the literature to establish the factors which have traditionally been regarded as most crucial to the design of effectlve exhaust ventilation systems. 2. To design, construct, install and calibrate a wind tunnel. 3. To develop procedures for air velocity measurement followed by a comprehensive programme of aerodvnamic data collection and data analysis for a variety of conditions. The major research findings were:- a) The literature in the subject is inadequate. There is a particular need for a much greater understanding of the aerodynamics of the suction flow field. b) The discrepancies between the experimentally observed centre-line velocities and those predicted by conventional formulae are unacceptably large. c) There was little agreement between theoretically calculated and observed velocities in the suction zone of captor hoods. d) Improved empirical formulae for the prediction of centre-line velocity applicable to the classical geometrically shaped suction openings and the flanged condition could be (and were) derived. Further analysis of data revealed that: - i) Point velocity is directly proportional to the suction. flow rate and the ratio of the point velocity to the average face velocity is constant. ii) Both shape, and size of the suction opening are significant factors as the coordinates of their points govern the extent of the effect of the suction flow field. iii) The hypothetical ellipsoidal potential function and hyperbolic streamlines were found experimentally to be correct. iv) The effect of guide plates depends on the size, shape and the angle of fitting. The effect was to very approximately double the suction velocity but the exact effect is difficult to predict. v) The axially symmetric openings produce practically symmetric flow fields. Similarity of connection pieces between the suction opening and the main duct in each case is essential in order to induce a similar suction flow field. Additionally a pilot study was made in which an artificial extraneous air flow was created, measured and its interaction with the suction flow field measured and represented graphically.

Cyclin-dependent kinase 9 activity regulates neutrophil spontaneous apoptosis

Neutrophils are the most abundant leukocyte and play a central role in the immune defense against rapidly dividing bacteria. However, they are also the shortest lived cell in the blood with a lifespan in the circulation of 5.4 days. The mechanisms underlying their short lifespan and spontaneous entry into apoptosis are poorly understood. Recently, the broad range cyclin-dependent kinase (CDK) inhibitor R-roscovitine was shown to increase neutrophil apoptosis, implicating CDKs in the regulation of neutrophil lifespan. To determine which CDKs were involved in regulating neutrophil lifespan we first examined CDK expression in human neutrophils and found that only three CDKs: CDK5, CDK7 and CDK9 were expressed in these cells. The use of CDK inhibitors with differing selectivity towards the various CDKs suggested that CDK9 activity regulates neutrophil lifespan. Furthermore CDK9 activity and the expression of its activating partner cyclin T1 both declined as neutrophils aged and entered apoptosis spontaneously. CDK9 is a component of the P-TEFb complex involved in transcriptional regulation and its inhibition will preferentially affect proteins with short half-lives. Treatment of neutrophils with flavopiridol, a potent CDK9 inhibitor, increased apoptosis and caused a rapid decline in the level of the anti-apoptotic protein Mcl-1, whilst Bcl2A was unaffected. We propose that CDK9 activity is a key regulator of neutrophil lifespan, preventing apoptosis by maintaining levels of short lived anti-apoptotic proteins such as Mcl-1. Furthermore, as inappropriate inhibition of neutrophil apoptosis contributes to chronic inflammatory diseases such as Rheumatoid Arthritis, CDK9 represents a novel therapeutic target in such diseases.

20-km distributed temperature sensor based on spontaneous Brillouin scattering

We report on a novel experimental setup for distributed measurement of temperature, based on spontaneous Brillouin scattering in optical fiber. We have developed a mode-locked Brillouin fiber ring laser in order to generate the dual frequency source required for a heterodyne detection of the backscattered signal. This relatively simple system enables temperature measurements over 20 km with a spatial resolution of 7 m.

Non-Gaussian statistics of an optical soliton in the presence of amplified spontaneous emission

A study was performed on non-Gaussian statistics of an optical soliton in the presence of amplified spontaneous emission. An approach based on the Fokker-Planck equation was applied to study the optical soliton parameters in the presence of additive noise. The rigorous method not only allowed to reproduce and justify the classical Gordon-Haus formula but also led to new exact results.

The role of Ca2+ in the generation of spontaneous astrocytic Ca2+ oscillations

Astrocytes in the rat thalamus display spontaneous [Ca2+]i oscillations that are due to intracellular release, but are not dependent on neuronal activity. In this study we have investigated the mechanisms involved in these spontaneous [Ca2+]i oscillations using slices loaded with Fluo-4 AM (5 μM) and confocal microscopy. Bafilomycin A1 incubation had no effect on the number of spontaneous [Ca2+]i oscillations indicating that they were not dependent on vesicular neurotransmitter release. Oscillations were also unaffected by ryanodine. Phospholipase C (PLC) inhibition decreased the number of astrocytes responding to metabotropic glutamate receptor (mGluR) activation but did not reduce the number of spontaneously active astrocytes, indicating that [Ca2+]i increases are not due to membrane-coupled PLC activation. Spontaneous [Ca2+]i increases were abolished by an IP3 receptor antagonist, whilst the protein kinase C (PKC) inhibitor chelerythrine chloride prolonged their duration, indicating a role for PKC and inositol 1,4,5,-triphosphate receptor activation. BayK8644 increased the number of astrocytes exhibiting [Ca2+]i oscillations, and prolonged the responses to mGluR activation, indicating a possible effect on store-operated Ca2+ entry. Increasing [Ca2+]o increased the number of spontaneously active astrocytes and the number of transients exhibited by each astrocyte. Inhibition of the endoplasmic reticulum Ca2+ ATPase by cyclopiazonic acid also induced [Ca2+]i transients in astrocytes indicating a role for cytoplasmic Ca2+ in the induction of spontaneous oscillations. Incubation with 20 μM Fluo-4 reduced the number of astrocytes exhibiting spontaneous increases. This study indicates that Ca2+ has a role in triggering Ca2+ release from an inositol 1,4,5,-triphosphate sensitive store in astrocytes during the generation of spontaneous [Ca2+]i oscillations

Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation

Astrocytes respond to chemical, electrical and mechanical stimuli with transient increases in intracellular calcium concentration ([Ca2+]i). We now show that astrocytes in situ display intrinsic [Ca2+]i oscillations that are not driven by neuronal activity. These spontaneous astrocytic oscillations can propagate as waves to neighboring astrocytes and trigger slowly decaying NMDA receptor-mediated inward currents in neurons located along the wave path. These findings show that astrocytes in situ can act as a primary source for generating neuronal activity in the mammalian central nervous system.

The involvement/exclusion paradox of spontaneous volunteering:new lessons from winter flood episodes in England

This article focuses on the involvement and management of spontaneous volunteers (SVs). It develops a new theory—which we call the “involvement/exclusion” paradox—about a situation which is frequently manifested when SVs converge in times of disaster. After reviewing research and policy guidance relating to spontaneous volunteering, we present findings from a study of responses to winter flood episodes in England. Taking together the empirical findings and the literature, the article analyzes elements inherent in the involvement/exclusion paradox and develops a conceptual model to illustrate and explain the paradox. Implications for managers and future research are discussed.

Rib-cage-movement measurements as a potential new trigger signal in non-invasive mechanical ventilation

Non-invasive ventilation performed through an oronasal mask is a standard in clinical and homecare mechanical ventilation. Besides all its advantages, inevitable leaks through the mask cause errors in the feedback information provided by the airflow sensor and, hence, patient-ventilator asynchrony with multiple negative consequences. Here we investigate a new way to provide a trigger to the ventilator. The method is based on the measurement of rib cage movement at the onset of inspiration and during breathing by fibre-optic sensors. In a series of simultaneous measurements by a long-period fibre grating sensor and pneumotachograph we provide the statistical evidence of the 200 ms lag of the pneumo with respect the fibre-optic signal. The lag is registered consistently across three independent delay metrics. Further, we discuss exceptions from this trend and identify the needed improvements to the proposed fibre-sensing scheme.

Deliberate and spontaneous sensations of disembodiment:capacity or flaw?

Introduction: Hallucinations that involve shifts in the subjectively experienced location of the self, have been termed “out-of-body experiences” (OBEs). Early psychiatric accounts cast OBEs as a specific instance of depersonalisation and derealisation disorder (DPD-DR). However, during feelings of alienation and lack of body realism in DPD-DR the self is experienced within the physical body. Deliberate forms of “disembodiment” enable humans to imagine another’s visuo-spatial perspective taking (VPT), thus, if a strong relationship between deliberate and spontaneous forms of disembodiment could be revealed, then uncontrolled OBEs could be “the other side of the coin” of a uniquely human capacity. Methods: We present a narrative review of behavioural and neuroimaging work emphasising methodological and theoretical aspects of OBE and VPT research and a potential relationship. Results: Results regarding a direct behavioural relationship between VPT and OBE are mixed and we discuss reasons by pointing out the importance of using realistic tasks and recruiting genuine OBEers instead of general DPD-DR patients. Furthermore, we review neuroimaging evidence showing overlapping neural substrates between VPT and OBE, providing a strong argument for a relationship between the two processes. Conclusions: We conclude that OBE should be regarded as a necessary implication of VPT ability in humans, or even as a necessary and potentially sufficient condition for the evolution of VPT.

Prevalence and characteristics of spontaneous tinnitus in 11-year-old children

OBJECTIVE: To estimate the prevalence of spontaneous tinnitus in 11-year-old children. DESIGN: A prospective UK population-based study. STUDY SAMPLE: A total of 7092 children from the Avon longitudinal study of parents and children (ALSPAC) who attended the hearing session at age 11 years and answered questions about tinnitus. RESULTS: We estimated the prevalence of any spontaneous tinnitus as 28.1% (95% CI 27.1, 29.2%), and the prevalence of 'clinically significant' tinnitus as 3.1% (95% CI 2.7, 3.5%). Children were less likely to have clinically significant tinnitus if the tinnitus was 'soft' rather than 'loud' and if continuous rather than intermittent. Clinical significance was more likely if the tinnitus occurred more than once a week. Neither pitch nor length of history were important determinants of clinical significance. Small increases in mean hearing threshold (of up to 2.3 dB HL) were associated with clinically significant tinnitus. CONCLUSIONS: Although the prevalence of any tinnitus in 11-year-old children appears high, the small proportion in which this was found to be clinically significant implies that this does not necessarily indicate a large unmet clinical demand. We would expect approximately one child per class of 30 to have clinically significant tinnitus which is, by definition, problematic.