Safety profile of lamotrigine in overdose

Background: Lamotrigine is an anticonvulsant as well as a mood stabilizer. Apart from its established use in the treatment of epilepsy, there has been an expansion of its use in the treatment of mental disorders. Patients with epilepsy as well as those with mental disorders are at increased risk of deliberate drug overdoses. An evidence base for the safety profile of lamotrigine in overdose is an essential tool for prescribers. The objective of this study was to carry out a narrative synthesis of the existing evidence for the safety profile of lamotrigine in overdose. Methods: A systematic search was conducted of EMBASE (1974 to December 2015), MEDLINE (1946 to December 2015), PsycINFO (1806 to December 2015) and CINAHL (1981 to December 2015) databases. Studies were included in which there was a deliberate or accidental single drug overdose of lamotrigine, with its toxic effects described. Studies that did not involve an overdose were excluded. A narrative synthesis of the described toxic effects was carried out. Results: Out of 562 articles identified, 26 studies were included, mainly in the form of case reports and series. The most commonly described toxic effects of lamotrigine were on the central nervous system, specifically seizures, movement disorders and reduced consciousness. Other toxic effects included QTc interval and QRS complex prolongations, hypersensitivity reactions, serotonin syndrome as well as rhabdomyolysis possibly due to seizures and/or agitation. Deaths were recorded in two studies, with cardiovascular and neurological toxic effects described. Conclusions: Even though lamotrigine has been reported to be well tolerated, there is a risk of toxic effects which can be life threatening in overdose. This needs to be borne in mind when prescribing to patients at an increased risk of deliberate drug overdose

Widening the scope for early cancer detection: identification of alarm symptoms by community pharmacies

Background Cancers are one of the leading causes of death in the world and, due to the aging population, incidence rates are set to rise. As such, considerable effort has been placed on initiatives that aid the early detection of cancer, as this may improve patient survival outcome. One such initiative is the development of guidelines that explain how and when patient reported alarm symptoms suggestive of an underlying malignancy should be referred to a specialist. However, despite being conveniently placed to deliver interventions to promote the early detection of cancer, it is not clear what role community pharmacists could have in the development and implementation of these guidelines. Objective To: (1) assess the frequency and mean of patient reported alarm symptoms in a community pharmacy setting; (2) determine the demographics of patients presenting with the alarm symptom; and (3) explore the relationship between deprivation index of the community pharmacy and average frequency of alarm symptoms per pharmacy. Setting Thirty-three community pharmacies in the North of England. Method A prospective study from September 2013 to February 2014. Each community pharmacy team was provided training in relation to alarm symptoms to ensure there was consistency in reporting. Deprivation tertiles for each community pharmacy were calculated using the IMD 2010 deprivation index. The data were analysed using a Kruskal-Wallis test in order to determine whether there were any statistically significant associations between average frequency of alarm symptoms presented per pharmacy and the deprivation tertile. Main outcome measure Frequency of patient reported alarm symptoms

Patients using antifungals following laryngectomy : a qualitative study of community pharmacists in the North of England

Objective: To explore community pharmacists’ understanding and opinions in relation to prevention of fungal colonisation of voice prostheses amongst laryngectomy patients. Method: Semi-structured interviews were conducted on a purposive sample of 12 community pharmacists from the North of England. Interviews were undertaken until data saturation was reached and responses were transcribed verbatim and analysed using a thematic approach. Key findings: Six themes emerged from the data analysis. These were: terminology confusion about laryngectomy, stoma and voice prostheses; smoking as a risk factor for the development of laryngeal cancer; using nystatin to prevent biofilm formation; counselling information related to nystatin; prescription intervention and additional education in relation to laryngectomy. The theme of counselling information related to nystatin use and additional education was a key finding: our data show that when dispensing nystatin to patients with a voice prosthesis, community pharmacists would either give no advice related to medication use or would give incorrect advice that may lead to premature prosthesis failure amongst this patient group. Conclusion: This study highlights that community pharmacists lack understanding in relation to laryngectomy and are unaware of the off-label doses and administration methods of the drugs (specifically nystatin) used to prevent fungal colonisation on voice prostheses. Additional information sources – possibly obtained through the local Speech and Language Therapy Department – in the form of an educational leaflet would be perceived as a valuable resource to support community pharmacists who are required to manage these patients in the community

Identifying clustering at high redshift through actively star-forming galaxies

Identifying galaxy clustering at high redshift (i.e. z > 1) is essential to our understanding of the current cosmological model. However, at increasing redshift, clusters evolve considerably in star-formation activity and so are less likely to be identified using the widely-used red sequence method. Here we assess the viability of instead identifying high redshift clustering using actively star-forming galaxies (SMGs associated with over-densities of BzKs/LBGs). We perform both a 2- and 3-D clustering analysis to determine whether or not true (3D) clustering can be identified where only 2D data are available. As expected, we find that 2D clustering signals are weak at best and inferred results are method dependant. In our 3D analysis, we identify 12 SMGs associated with an over-density of galaxies coincident both spatially and in redshift - just 8% of SMGs with known redshifts in our sample. Where an SMG in our target fields lacks a known redshift, their sightline is no more likely to display clustering than blank sky fields; prior redshift information for the SMG is required to identify a true clustering signal. We find that the strength of clustering in the volume around typical SMGs, while identifiable, is not exceptional. However, we identify a small number of highly clustered regions, all associated with an SMG. The most notable of these, surrounding LESSJ033336.8-274401, potentially contains an SMG, a QSO and 36 star-forming galaxies (a > 20sig over-density) all at z~1.8. This region is highly likely to represent an actively star-forming cluster and illustrates the success of using star-forming galaxies to select sites of early clustering. Given the increasing number of deep fields with large volumes of spectroscopy, or high quality and reliable photometric redshifts, this opens a new avenue for cluster identification in the young Universe.Comment: 24 pages, 14 figures, accepted MNRA

Magnetic resonance imaging in the detection of skeletal metastases in patients with breast cancer.

Eighty-four patients with breast cancer at high risk of bone metastases were investigated with magnetic resonance imaging (MRI) of the thoracolumbar spine. Of 58 patients with normal limited skeletal surveys (LSS) and bone scans (BS), 4 (7%) had MR images compatible with malignant infiltration. Fourteen patients had abnormal bone scans with normal or non-diagnostic plain films; 7 of these patients (50%) had MR images compatible with malignant infiltration. Twelve patients had single or multiple wedge collapses of uncertain aetiology on plain film; MR demonstrated metastatic disease as the cause of wedge collapse in 7 (58%). MRI may define a group of patients with extra-osseous relapse who have occult metastatic disease. Although the detection rate in patients with primary breast cancer is low (4/45), MRI is of value in determining the cause of wedge collapse in postmenopausal women with breast cancer and may elucidate the cause of an abnormal bone scan with normal or non-diagnostic plain films

Influence of service reservoir construction age on the likelihood of bacteriological failure occurrence

Service reservoirs (SRs) are crucial components in drinking water distribution systems (DWDSs). These assets are often associated with water quality issues, including significant waterborne disease outbreaks. To ensure safety of supply, monitoring is conducted at SR outlets for disinfectant residual and bacteriological indicators. Older SRs are often believed to be a source of bacteriological failures as old or poorly constructed SRs can be prone to structural issues, which can lead to ingress and contamination of the stored water. However, there is a lack of evidence to support the existence of a genuine relationship between SR age and risk of failure. In this study, historical bacteriological failure data at SR outlets and company-wide SR construction age data collected from three large UK water utilities was used to assess the potential relationship between the duration of time a SR has been in service and the likelihood of bacteriological failure. Findings showed that there was no relationship between the two parameters. Analysis also revealed instances where newer SRs, no older than twenty years old, experienced one or more bacteriological failures, challenging the ingrained association that older SRs are at a higher risk of ingress and bacteriological contamination

The operational value of inlet monitoring at service reservoirs

Drinking water quality leaving water treatment works is known to deteriorate as it makes its way through distribution networks. As deterioration rates are related to the condition of the network and how it is operated, it is important to determine the location and magnitude so that causes can be determined and effective maintenance implemented. Water quality is typically monitored at outlets of service reservoirs to help track changing water quality. However, these results do not confirm whether the issue is linked to the network between treatment and the service reservoir, the service reservoir itself, or both. The work in this paper investigates the value of using inlet monitoring at service reservoirs to overcome this limitation. Results show that monitoring at both the inlet and outlet of service reservoirs provides valuable information on asset performance and highlights the location and extent of deterioration helping inform cost-efficient resource provision

C-5A/orbiter wind tunnel testing and analysis: Piggyback ferry

Wind tunnel testing and analytical studies of the feasibility of ferrying the NASA Shuttle Orbiter on the C-5A in a piggyback mode have been accomplished. Testing was conducted in the 8x12 foot low speed wind tunnel using an existing 0.0399 scale C-5A model in conjunction with a NASA 0.0405 scale Orbiter model. Six component force and moment data were measured over a range of pitch and yaw angles to determine lift and drag characteristics, lateral/directional stability characteristics and longitudinal and directional control powers. A description of the wind tunnel test program with a run schedule and the complete plotted data for all the test runs are presented. Initial emphasis was given to determining the effects of the Orbiter above the C-5A and the optimum location for minimum interference on C-5A characteristics. A comprehensive series of cruise configurations were tested including a range of Orbiter longitudinal and vertical locations, incidences, and afterbody fairings. Subsequently, a series of configurations were devised during the test program to determine means of recovering directional stability degradation due to Orbiter interference

Molecular diversity of arbuscular mycorrhizal fungi and patterns of host association over time and space in a tropical forest

We have used molecular techniques to investigate the diversity and distribution of the arbuscular mycorrhizal (AM) fungi colonizing tree seedling roots in the tropical forest on Barro Colorado Island (BCI), Republic of Panama. In the first year, we sampled newly emergent seedlings of the understory treelet Faramea occidentalis and the canopy emergent Tetragastris panamensis, from mixed seedling carpets at each of two sites. The following year we sampled surviving seedlings from these cohorts. The roots of 48 plants were analysed using AM fungal-specific primers to amplify and clone partial small subunit (SSU) ribosomal RNA gene sequences. Over 1300 clones were screened for random fragment length polymorphism (RFLP) variation and 7% of these were sequenced. Compared with AM fungal communities sampled from temperate habitats using the same method, the overall diversity was high, with a total of 30 AM fungal types identified. Seventeen of these types have not been recorded previously, with the remainder being similar to types reported from temperate habitats. The tropical mycorrhizal population showed significant spatial heterogeneity and nonrandom associations with the different hosts. Moreover there was a strong shift in the mycorrhizal communities over time. AM fungal types that were dominant in the newly germinated seedlings were almost entirely replaced by previously rare types in the surviving seedlings the following year. The high diversity and huge variation detected across time points, sites and hosts, implies that the AM fungal types are ecologically distinct and thus may have the potential to influence recruitment and host composition in tropical forests

The Rest-Frame Submillimeter Spectrum of High-Redshift, Dusty, Star-Forming Galaxies

We present the average rest-frame spectrum of high-redshift dusty, star-forming galaxies from 250-770GHz. This spectrum was constructed by stacking ALMA 3mm spectra of 22 such sources discovered by the South Pole Telescope and spanning z=2.0-5.7. In addition to multiple bright spectral features of 12CO, [CI], and H2O, we also detect several faint transitions of 13CO, HCN, HNC, HCO+, and CN, and use the observed line strengths to characterize the typical properties of the interstellar medium of these high-redshift starburst galaxies. We find that the 13CO brightness in these objects is comparable to that of the only other z>2 star-forming galaxy in which 13CO has been observed. We show that the emission from the high-critical density molecules HCN, HNC, HCO+, and CN is consistent with a warm, dense medium with T_kin ~ 55K and n_H2 >~ 10^5.5 cm^-3. High molecular hydrogen densities are required to reproduce the observed line ratios, and we demonstrate that alternatives to purely collisional excitation are unlikely to be significant for the bulk of these systems. We quantify the average emission from several species with no individually detected transitions, and find emission from the hydride CH and the linear molecule CCH for the first time at high redshift, indicating that these molecules may be powerful probes of interstellar chemistry in high-redshift systems. These observations represent the first constraints on many molecular species with rest-frame transitions from 0.4-1.2mm in star-forming systems at high redshift, and will be invaluable in making effective use of ALMA in full science operations.Comment: 19 pages, 10 figures (2 in appendices); accepted for publication in Ap