Pregabalin and gabapentin for the management of chronic sciatica: determining utility, effect on functioning capacity, quality of life and clinical outcome

Background: Pain is a major clinical problem, the true prevalence of which is difficult to estimate as it encompasses a variety of disorders. Sciatica is considered a type of neuropathic pain (NP) characterised by severe low back pain radiating down the leg to below the knee. Chronic sciatica (CS) is sciatica lasting longer than three months. There are few clinical guidelines for treating of CS, reflecting a gap in quality evidence for effective therapies. Recently, two medications gabapentin (GBP) and pregabalin (PGB) have been used in the management of CS. Evidence for their usage is limited with no direct, high quality research to determine if one is superior to the other. This research answers that question and helps guide clinicians as to the best treatment option for CS. Methods: The thesis includes a literature review to gauge current management of CS with PGB and GBP. The work uses a mixed-methods approach to gain evidence on efficacy, disability and personality traits which will guide clinician's choice of either GBP or PGB. A mix of methods was chosen, to capture patient's treatment experiences more broadly and not simply being restricted to symptom relief. Anecdotal evidence suggests a variable response to either drug, both in terms of efficacy and adverse events (AEs). However, we are unsure at what point the balance of benefits against AEs tips and patients make the decision to abandon treatment. To gather this information and draw conclusions regarding the optimal treatment for patients with CS, this project collects background information on patient's perceptions related to treatment, and conducts a novel randomised controlled trial to determine head to head which treatment is more efficacious. We set out to establish whether one drug has a superior profile to the other and if there are any other differences in treatment outcomes. Hypothesis: We hypothesise that there are differences between the drugs, where (1) one drug (PGB) has a superior profile in pain and disability reduction, as well as (2) frequency and severity of adverse events. Results: Retrospective data showed AEs to be a limiting factor for treatment outcomes and compliance when GBP was added to a first line agent. The clinical trial reported here showed that, while PGB and GBP were both significantly efficacious in reducing pain intensity in patients with CS, GBP was superior when compared 'head-to-head'. Moreover, GBP was associated with fewer and less severe AEs. Neither drug was superior when compared 'head-to-head' for reducing disability in our study group. Our exploratory study on personality traits showed that patients with a predominantly external self-control had worse outcomes. Specifically, an external self-control resulted in lower pain severity reductions especially with PGB. Moreover, PGB alone demonstrated a high, and statistically significant, positive correlation with external self-control resulting in higher pain values for patients displaying this personality trait. There were no notable differences between drugs when personality and disability severity were compared. Conclusion: This research makes a significant original contribution to the literature by addressing a key gap regarding the utilisation of pain medication for CS, namely with PGB and GBP. We found that GBP was superior to PGB for reducing pain severity and for being associated with fewer and less severe AEs. Moreover, our results show having a personality trait of external locus of self-control, negatively effects treatment outcomes with PGB. Our findings provide a body of evidence which can formally guide treatment decisions for patients with CS considering pain severity, disability severity, AEs and personality

Influence of ethnicity on outcomes of diabetes inpatient hypoglycemia: an Australian perspective

Aims: To evaluate outcomes of diabetic inpatient hypoglycemia among Aboriginal and Torres Strait Islander (ATSI) compared with Australian Caucasian patients. Methods: A retrospective audit of diabetic patients aged > 18 years admitted at a regional hospital general ward between April 1, 2015, and March 31, 2016, was analyzed. The database contains clinical information at the time of admission and initial discharge and readmission within 4 weeks thereafter. Results: A total of 1618 (of 6027) patients were admitted with diabetes representing 23.7% of the total ward admissions, of which 484 (29.9%) had inpatient hypoglycemia. Of the 91 patients with available data analyzed, ATSI origin with inpatient hypoglycemia was associated with longer length of stay (LOS) (hazard ratio [HR], 2.1, 95% confidence interval [CI], 1.2-3.5), whereas severe hypoglycemia (≤ 2.2 mmol/L) in both ATSI and non-ATSI was significantly associated with longer LOS (HR, 2.3; 95% CI, 1.2-4.2). No significant differences in LOS were found for gender, age, and Carlson comorbidity index (CCI). The adjusted model for likelihood of readmission, gender, indigenous status, and CCI were not significant risk factors for readmission to the hospital. Readmitted patients were older (50-59 years vs < 50 years, P = 0.001; 60-69 years vs < 50 years, P = 0.032; 70+ years vs < 50 years, P = 0.031). Conclusion: We reported high rate of inpatient hypoglycemia in our study population. Indigenous Australian diabetic patients with inpatient hypoglycemia had significantly longer LOS compared with non-Indigenous Caucasian counterparts. Further prospective studies on a larger population are needed to confirm our findings

Effects of vildagliptin on wound healing and markers of inflammation in patients with type 2 diabetic foot ulcer: a prospective, randomized, double‑blind, placebo‑controlled, single‑center study

Introduction: Diabetic foot ulcers (DFU) are one of the leading long-term complications experienced by patients with diabetes. Dipeptidyl Peptidase 4 inhibitors (DPP4is) are a class of antihyperglycemic medications prescribed to patients with diabetes to manage glycaemic control. DPP4is may also have a beneficial effect on DFU healing. This study aimed to determine vildagliptin’s effect on inflammatory markers and wound healing. Trial design: Prospective, randomized, double-blind, placebo-controlled, single-center study. Methods: Equal number of participants were randomized into the treatment and placebo groups. The treatment was for 12 weeks, during which the participants had regular visits to the podiatrist, who monitored their DFU sizes using 3D camera, and blood samples were taken at baseline, six weeks, and 12 weeks during the study for measurement of inflammatory markers. In addition, demographic characteristics, co-morbidities, DFU risk factors, and DFU wound parameters were recorded. Results: 50 participants were recruited for the study, with 25 assigned to placebo and 25 to treatment group. Vildagliptin treatment resulted in a statistically significant reduction of HBA1c (p < 0.02) and hematocrit (p < 0.04), total cholesterol (p < 0.02), LDL cholesterol (p < 0.04), and total/HDL cholesterol ratio (P < 0.03) compared to the placebo group. Also, vildagliptin had a protective effect on DFU wound healing, evidenced by the odds ratio (OR) favoring the intervention of 11.2 (95% CI 1.1–113.5; p < 0.04) and the average treatment effect on the treated (ATET) for vildagliptin treatment group showed increased healing by 35% (95%CI; 10–60, p = 0.01) compared to placebo with the model adjusted for microvascular complications, smoking, amputation, dyslipidemia, peripheral vascular disease (PVD) and duration of diabetes

Investigating the impact of a clinical pharmacist on the health outcomes of a paediatric pharmacists

Background: Recent fiscal scrutiny and changes in health care financing have necessitated that health care providers justify a clinical and economical basis for their involvement in patient care. Although clinical pharmacists have been shown to enhance patient health outcomes and reduce costs among adult patients, the impact of a pharmacist in paediatric patient care has not been extensively documented. Method: A team of pharmacists was established to conduct a systematic review of the literature. A title scan of papers in 5 databases was performed by 14 pharmacists using the MeSH terms Pharmacists, Medical Intervention, Paediatrics and Cost-Benefit Analysis. The underpinning research question was: "How do the professional activities of a clinical pharmacist impact the health outcomes of paediatric in-patients?" The abstracts of suitable titles were scanned and articles were read to assess relevance. Relevant articles were then evaluated independently by at least two members of the team, using critical appraisal tools suitable for quantitative, qualitative or systematic review studies. Results: The initial search identified 327 citations which after full text review and application of the scoring tool, resulted in 12 studies included in the systematic review. The average number of interventions reported varied from study to study. Dosing recommendations, pharmacokinetics and drug allergy alerts were the most commonly recorded interventions by pharmacists for a paediatric population. Evidence from this review will be used to formulate improvements to in-patient paediatric care. Conclusion: Clinical pharmacists have a positive impact on inpatient paediatric care

Computational Eulerian Hydrodynamics and Galilean Invariance

Eulerian hydrodynamical simulations are a powerful and popular tool for modeling fluids in astrophysical systems. In this work, we critically examine recent claims that these methods violate Galilean invariance of the Euler equations. We demonstrate that Eulerian hydrodynamics methods do converge to a Galilean-invariant solution, provided a well-defined convergent solution exists. Specifically, we show that numerical diffusion, resulting from diffusion-like terms in the discretized hydrodynamical equations solved by Eulerian methods, accounts for the effects previously identified as evidence for the Galilean non-invariance of these methods. These velocity-dependent diffusive terms lead to different results for different bulk velocities when the spatial resolution of the simulation is kept fixed, but their effect becomes negligible as the resolution of the simulation is increased to obtain a converged solution. In particular, we find that Kelvin-Helmholtz instabilities develop properly in realistic Eulerian calculations regardless of the bulk velocity provided the problem is simulated with sufficient resolution (a factor of 2-4 increase compared to the case without bulk flows for realistic velocities). Our results reiterate that high-resolution Eulerian methods can perform well and obtain a convergent solution, even in the presence of highly supersonic bulk flows.Comment: Version accepted by MNRAS Oct 2, 2009. Figures degraded. For high-resolution color figures and movies of the numerical simulations, please visit http://www.astro.caltech.edu/~brant/Site/Computational_Eulerian_Hydrodynamics_and_Galilean_Invariance.htm

Galaxy And Mass Assembly: galaxy morphology in the green valley, prominent rings, and looser spiral arms

Galaxies broadly fall into two categories: star-forming (blue) galaxies and quiescent (red) galaxies. In between, one finds the less populated “green valley . Some of these galaxies are suspected to be in the process of ceasing their star-formation through a gradual exhaustion of gas supply or already dead and are experiencing a rejuvenation of star-formation through fuel injection. We use the Galaxy And Mass Assembly database and the Galaxy Zoo citizen science morphological estimates to compare the morphology of galaxies in the green valley against those in the red sequence and blue cloud. Our goal is to examine the structural differences within galaxies that fall in the green valley, and what brings them there. Previous results found disc features such as rings and lenses are more prominently represented in the green valley population. We revisit this with a similar sized data set of galaxies with morphology labels provided by the Galaxy Zoo for the GAMA fields based on new KiDS images. Our aim is to compare qualitatively the results from expert classification to that of citizen science. We observe that ring structures are indeed found more commonly in green valley galaxies compared to their red and blue counterparts. We suggest that ring structures are a consequence of disc galaxies in the green valley actively exhibiting characteristics of fading discs and evolving disc morphology of galaxies. We note that the progression from blue to red correlates with loosening spiral arm structure

The Hubble Space Telescope Wide Field Camera 3 Early Release Science data: Panchromatic Faint Object Counts for 0.2-2 microns wavelength

We describe the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) Early Release Science (ERS) observations in the Great Observatories Origins Deep Survey (GOODS) South field. The new WFC3 ERS data provide calibrated, drizzled mosaics in the UV filters F225W, F275W, and F336W, as well as in the near-IR filters F098M (Ys), F125W (J), and F160W (H) with 1-2 HST orbits per filter. Together with the existing HST Advanced Camera for Surveys (ACS) GOODS-South mosaics in the BViz filters, these panchromatic 10-band ERS data cover 40-50 square arcmin at 0.2-1.7 {\mu}m in wavelength at 0.07-0.15" FWHM resolution and 0.090" Multidrizzled pixels to depths of AB\simeq 26.0-27.0 mag (5-{\sigma}) for point sources, and AB\simeq 25.5-26.5 mag for compact galaxies. In this paper, we describe: a) the scientific rationale, and the data taking plus reduction procedures of the panchromatic 10-band ERS mosaics; b) the procedure of generating object catalogs across the 10 different ERS filters, and the specific star-galaxy separation techniques used; and c) the reliability and completeness of the object catalogs from the WFC3 ERS mosaics. The excellent 0.07-0.15" FWHM resolution of HST/WFC3 and ACS makes star- galaxy separation straightforward over a factor of 10 in wavelength to AB\simeq 25-26 mag from the UV to the near-IR, respectively.Comment: 51 pages, 71 figures Accepted to ApJS 2011.01.2

Galaxy morphological classification in deep-wide surveys via unsupervised machine learning

Accepted versionGalaxy morphology is a fundamental quantity, that is essential not only for the full spectrum of galaxy-evolution studies, but also for a plethora of science in observational cosmology. While a rich literature exists on morphological-classification techniques, the unprecedented data volumes, coupled, in some cases, with the short cadences of forthcoming 'Big-Data' surveys (e.g. from the LSST), present novel challenges for this field. Large data volumes make such datasets intractable for visual inspection (even via massively-distributed platforms like Galaxy Zoo), while short cadences make it difficult to employ techniques like supervised machine-learning, since it may be impractical to repeatedly produce training sets on short timescales. Unsupervised machine learning, which does not require training sets, is ideally suited to the morphological analysis of new and forthcoming surveys. Here, we employ an algorithm that performs clustering of graph representations, in order to group image patches with similar visual properties and objects constructed from those patches, like galaxies. We implement the algorithm on the Hyper-Suprime-Cam Subaru-Strategic-Program Ultra-Deep survey, to autonomously reduce the galaxy population to a small number (160) of 'morphological clusters', populated by galaxies with similar morphologies, which are then benchmarked using visual inspection. The morphological classifications (which we release publicly) exhibit a high level of purity, and reproduce known trends in key galaxy properties as a function of morphological type at zPeer reviewe

Galaxy And Mass Assembly:galaxy morphology in the green valley, prominent rings, and looser spiral arms

Galaxies fall broadly into two categories: star-forming (blue) galaxies and quiescent (red) galaxies. In between, one finds the less populated ‘green valley’. Some of these galaxies are suspected to be in the process of ceasing their star formation through a gradual exhaustion of gas supply, or already dead and experiencing a rejuvenation of star formation through fuel injection. We use the Galaxy And Mass Assembly (GAMA) database and the Galaxy Zoo citizen science morphological estimates to compare the morphology of galaxies in the green valley with those in the red sequence and blue cloud. Our goal is to examine the structural differences within galaxies that fall in the green valley, and what brings them there. Previous results found that disc features such as rings and lenses are more prominently represented in the green-valley population. We revisit this with a similar sized data set of galaxies with morphology labels provided by the Galaxy Zoo for the GAMA fields based on new Kilo-Degree Survey (KiDS) images. Our aim is to compare the results from expert classification qualitatively with those of citizen science. We observe that ring structures are indeed found more commonly in green-valley galaxies compared with their red and blue counterparts. We suggest that ring structures are a consequence of disc galaxies in the green valley actively exhibiting the characteristics of fading discs and evolving disc morphology of galaxies. We note that the progression from blue to red correlates with loosening spiral-arm structure

The Genome of Caenorhabditis bovis

The free-living nematode Caenorhabditis elegans is a key laboratory model for metazoan biology. C. elegans has also become a model for parasitic nematodes despite being only distantly related to most parasitic species. All of the ∼65 Caenorhabditis species currently in culture are free-living, with most having been isolated from decaying plant or fungal matter. Caenorhabditis bovis is a particularly unusual species that has been isolated several times from the inflamed ears of Zebu cattle in Eastern Africa, where it is associated with the disease bovine parasitic otitis. C. bovis is therefore of particular interest to researchers interested in the evolution of nematode parasitism. However, as C. bovis is not in laboratory culture, it remains little studied. Here, by sampling livestock markets and slaughterhouses in Western Kenya, we successfully reisolated C. bovis from the ear of adult female Zebu. We sequenced the genome of C. bovis using the Oxford Nanopore MinION platform in a nearby field laboratory and used the data to generate a chromosome-scale draft genome sequence. We exploited this draft genome sequence to reconstruct the phylogenetic relationships of C. bovis to other Caenorhabditis species and reveal the changes in genome size and content that have occurred during its evolution. We also identified expansions in several gene families that have been implicated in parasitism in other nematode species. The high-quality draft genome and our analyses thereof represent a significant advancement in our understanding of this unusual Caenorhabditis species