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

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 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

Repeatability of Corticospinal and Spinal Measures during Lengthening and Shortening Contractions in the Human Tibialis Anterior Muscle

Elements of the human central nervous system (CNS) constantly oscillate. In addition, there are also methodological factors and changes in muscle mechanics during dynamic muscle contractions that threaten the stability and consistency of transcranial magnetic stimulation (TMS) and perpherial nerve stimulation (PNS) measures

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

From Romantic Gothic to Victorian Medievalism: 1817 and 1877

&quot;The Cambridge History of the Gothic was conceived in 2015, when Linda Bree, then Editorial Director at Cambridge University Press, first suggested the idea to us

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown