Development of a novel rate-modulated fixed dose analgesic combination for the treatment of mild to moderate pain

MSc (Med),Dept of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the WitwatersrandPain is the net effect of multidimensional mechanisms that engage most parts of the central nervous system (CNS) and the treatment of pain is one of the key challenges in clinical medicine (Le Bars et al., 2001; Miranda et al., 2008). Polypharmacy is seen as a barrier to analgesic treatment compliance, signifying the necessity for the development of fixed dose combinations (FDCs), which allow the number of tablets administered to be reduced, with no associated loss in efficacy or increase in the prevalence of side effects (Torres Morera, 2004). FDCs of analgesic drugs with differing mechanisms of nociceptive modulation offer benefits including synergistic analgesic effects, where the individual agents act in a greater than additive manner, and a reduced occurrence of side-effects (Raffa, 2001; Camu, 2002). This study aimed at producing a novel, rate-modulated, fixed-dose analgesic formulation for the treatment of mild to moderate pain. The fixed-dose combination (FDC) rationale of paracetamol (PC), tramadol hydrochloride (TM) and diclofenac potassium (DC) takes advantage of previously reported analgesic synergy of PC and TM as well as extending the analgesic paradigm with the addition of the anti-inflammatory component, DC. The study involved the development of a triple-layered tablet delivery system with the desired release characteristics of approximately 60% of the PC and TM being made available within 2 hours to provide an initial pain relief effect and then sustained zero-order release of DC over a period of 24 hours to combat the on-going effects of any underlying inflammatory conditions. The triple-layered tablet delivery system would thus provide both rapid onset of pain relief as well as potentially address an underlying inflammatory cause. The design of a novel triple-layered tablet allowed for the desired release characteristics to be attained. During initial development work on the polymeric matrix it was discovered that only when combined with the optimized ratio of the release retarding polymer polyethylene oxide (PEO) in combination with electrolytic-crosslinking activity, provided by the biopolymer sodium alginate and zinc gluconate, could the 24 hour zero-order release of DC be attained. It was also necessary for this polymeric matrix to be bordered on both sides by the cellulosic polymers containing PC and TM. Thus the application of multi-layered tableting technology in the form of a triple-layered tablet were capable of attaining the rate-modulated release objectives set out in the study. The induced barriers provided by the three layers also served to physically separate TM and DC, reducing the likelihood of the bioavailability-diminishing interaction noted in United States Patent 6,558,701 and detected in the DSC analysis performed as part of this study. The designed system provided significant flexibility in modulation of release kinetics for drugs of varying solubility. The suitability of the designed triple-layered tablet delivery system was confirmed by a Design of Experiments (DoE) statistical evaluation, which revealed that Formulation F4 related closest to the desired more immediate release for PC and TM and the zero-order kinetics for DC. The results were confirmed by comparing Formulation F4 to typical release kinetic mechanisms described by Noyes-Whitney, Higuchi, Power Law, Pappas-Sahlin and Hopfenberg. Using f1 and f2 fit factors Formulation F4 compared favourably to each of the criteria defined for these kinetic models. The Ultra Performance Liquid Chromatographic (UPLC) assay method developed displayed superior resolution of the active pharmaceutical ingredient (API) combinations and the linearity plots produced indicated that the method was sufficiently sensitive to detect the concentrations of each API over the concentration ranges studied. The method was successfully validated and hence appropriate to simultaneously detect the three APIs as well as 4-aminophenol, the degradation product related to PC. Textural profile analysis in the form of swelling as well as matrix hardness analysis revealed that an increase in the penetration distance was associated with an increase in hydration time of the tablet and also an increase in gel layer thickness. The swelling complexities observed in the delivery system in terms of both the PEO, crosslinking sodium alginate and both cellulose polymers as well as the actuality of the three layers of the tablet swelling simultaneously suggests further intricacies involved in the release kinetics of the three drugs from this tablet configuration. Modified release dosage forms, such as the one developed in this study, have gained widespread importance in recent years and offer many advantages including flexible release kinetics and improved therapy and patient compliance

Culturally-derived values and beliefs as correlates of risk for problem gambling.

The purpose of the current study was to examine the relation between culturally-derived values and beliefs and risk for problem gambling. In Study 1, 331 participants completed web-based versions of the Individualism-Collectivism Scale, Social Axioms Survey (SAS), the Problem Gambling Severity Index (PGSI), and the Marlowe-Crowne Social Desirability Scale (MC-SDS). In Study 2, 90 participants completed these measures. Results were mixed with regard to the relation between Horizontal/Vertical Individualistic/Collectivistic values and risk for problem gambling as measured by the PGSI. However, it was found in both studies that risk for problem gambling was positively correlated with beliefs in Fate Control and Social Cynicism. Reward for Application, Religiosity and Social Complexity were not found to be related to risk for problem gambling. Stepwise regression of the Study 1 data indicated that the beliefs of Fate Control and Reward for Application were the only significant predictors of risk for problem gambling, explaining 22% of the variance. Study 2 stepwise regression results indicated that Fate Control was the only significant predictor of risk for problem gambling, explaining 58.6% of the variance. Implications of the current research and suggestions for further study are discussed.Dept. of Psychology. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2006 .H63. Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 4092. Thesis (Ph.D.)--University of Windsor (Canada), 2006

Acne vulgaris: the skin microbiome, antibiotics and whether natural products could be considered a suitable alternative treatment?

Acne vulgaris is a common, chronic inflammatory skin disease manifested as inflammatory and non-inflammatory lesions typically associated with Cutibacterium acnes. However, its pathogenesis is not fully understood nor is the complexity of the skin microbiome and how it contributes to the development of acne. Whilst acne is not a typical bacterial infection, antibiotics have been the mainstay of treatment for over 50 years. Now, with the development of multi-drug resistant organisms and the emergence of resistant C. acnes strains; the question is are antibiotics still an appropriate treatment method or could natural products provide a suitable alternative? Research into alternative treatments is a growing field due to the increase in resistant organisms, there is a multitude of research into natural products due to their antimicrobial potential and the multiple mechanisms of action. Melaleuca alternifolia is a key natural product of interest in the treatment of acne due to its documented use throughout history and its prevalence in over the counter treatments. Green Tea is a more recent natural product of interest due to its composition of polyphenols, which give rise to both antimicrobial and anti-inflammatory properties. However, research also suggests that a synergistic approach of natural products may be the way forward

Gender weighting of DSM-IV personality disorder criteria.

The primary purpose of the current study was to determine the degree, if any, to which gender stereotypes are reflected within the criteria of DSM-IV Axis II Personality Disorders (PDs). Participants consisted of 73 university undergraduate students (33 males and 40 females), who were instructed to sort each of the 91 PD criteria, presented individually on index cards, along a dimension of masculine to feminine. A secondary aim was to determine if participants who were instructed to sort the cards into five piles ranked the criteria differently from those participants who were free to sort the criteria into as many piles as they felt were necessary to complete the task. Results revealed no significant gender weighting of PDs, but suggest trends towards rating Antisocial and Schizoid PDs as male-typed disorders and Dependent, Histrionic and Avoidant PDs as female-typed disorders. Implications and limitations of the current research are discussed.Dept. of Psychology. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2001 .H65. Source: Masters Abstracts International, Volume: 40-06, page: 1619. Adviser: Cheryl Thomas. Thesis (M.A.)--University of Windsor (Canada), 2001

Copper accumulation from antifouling paints in five marinas on Puget Sound

Marinas have been shown to contribute elevated levels of metals to marine waters, copper (Cu) in particular. The Cu comes primarily from antifouling paints which are designed to discourage biofouling (barnacles, mussels, and other organisms) of boat hulls. In 2011 the Washington State Legislature passed SSB5436 to phase out Cu in marine antifouling paints. This legislation states that new recreational vessels with Cu-containing bottom paint may not be sold in the state after January 1, 2018. This study provides baseline data for Cu in five marinas of different configuration and size within Puget Sound and assesses potential impacts to marine biota. Four sampling events were conducted between September 2016 and June 2017. Sample media included: water (dissolved and total fractions of metals), sediments (suspended and bottom), and biota (transplanted mussels and biofilms). We found strong evidence, across sample media that Cu accumulate inside marinas to higher levels than outside marinas, regardless of marina configuration. Marinas that are more enclosed, where water is slower to flush in and out, accumulated higher levels of Cu than more open marinas. However, concentrations of Cu were rarely high enough to be above the state water quality criterion for acute impacts to aquatic life. Sediment Cu was also not above the state criteria for the protection of benthic invertebrates. This study provides an adequate baseline dataset to measure progress as a result of recent legislation towards the reduction of Cu to Puget Sound from marinas

Acceptability and effectiveness of opportunistic referral of smokers to telephone cessation advice from a nurse: a randomised trial in Australian general practice

<p>Abstract</p> <p>Background</p> <p>GPs often lack time to provide intensive cessation advice for patients who smoke. This study aimed to determine the effectiveness of opportunistic referral of smokers by their GP for telephone cessation counselling by a trained nurse.</p> <p>Methods</p> <p>Adult smokers (n = 318) attending 30 GPs in South Western Sydney, Australia were randomly allocated to usual care or referral to a telephone-based program comprising assessment and stage-based behavioural advice, written information and follow-up delivered by a nurse. Self-reported point prevalence abstinence at six and 12 months was compared between groups. Characteristics of patients who accepted and completed the intervention were investigated.</p> <p>Results</p> <p>Of 169 smokers randomised to the intervention, 76 (45%) consented to referral. Compared with smokers in 'pre-contemplation', those further along the stage-of-change continuum were significantly more likely to consent (p = 0.003). Those further along the continuum also were significantly more likely to complete all four calls of the intervention (OR 2.6, 95% CI: 0.8–8.1 and OR 8.6, 95% CI: 1.7–44.4 for 'contemplation' and 'preparation' respectively). At six months, there was no significant difference between groups in point prevalence abstinence (intention to treat) (9% versus 8%, p = 0.7). There was no evidence of differential intervention effectiveness by baseline stage-of-change (p = 0.6) or patient sex (p = 0.5). At 12 months, point prevalence abstinence in the intervention and control groups was 8% and 6% respectively (p = 0.6).</p> <p>Conclusion</p> <p>Acceptance of opportunistic referral for nurse delivered telephone cessation advice was low. This trial did not demonstrate improved quit rates following the intervention. Future research efforts might better focus support for those patients who are motivated to quit.</p> <p>Australian Clinical Trials Registry number</p> <p>ACTRN012607000091404</p

Do single-use medical devices containing biopolymers reduce the environmental impacts of surgical procedures compared with their plastic equivalents?

Background: While petroleum-based plastics are extensively used in health care, recent developments in biopolymer manufacturing have created new opportunities for increased integration of biopolymers into medical products, devices and services. This study compared the environmental impacts of single-use disposable devices with increased biopolymer content versus typically manufactured devices in hysterectomy. Methods: A comparative life cycle assessment of single-use disposable medical products containing plastic(s) versus the same single-use medical devices with biopolymers substituted for plastic(s) at Magee-Women’s Hospital (Magee) in Pittsburgh, PA and the products used in four types of hysterectomies that contained plastics potentially suitable for biopolymer substitution. Magee is a 360-bed teaching hospital, which performs approximately 1400 hysterectomies annually. Results: There are life cycle environmental impact tradeoffs when substituting biopolymers for petroplastics in procedures such as hysterectomies. The substitution of biopolymers for petroleum-based plastics increased smog-related impacts by approximately 900% for laparoscopic and robotic hysterectomies, and increased ozone depletion-related impacts by approximately 125% for laparoscopic and robotic hysterectomies. Conversely, biopolymers reduced life cycle human health impacts, acidification and cumulative energy demand for the four hysterectomy procedures. The integration of biopolymers into medical products is correlated with reductions in carcinogenic impacts, non-carcinogenic impacts and respiratory effects. However, the significant agricultural inputs associated with manufacturing biopolymers exacerbate environmental impacts of products and devices made using biopolymers. Conclusions: The integration of biopolymers into medical products is correlated with reductions in carcinogenic impacts, non-carcinogenic impacts and respiratory effects; however, the significant agricultural inputs associated with manufacturing biopolymers exacerbate environmental impacts

Exile Vol. XLII No. 2

40th Year Title Page i Epigraph by Ezra Pound ii Table of Contents ii Editorial Board iii frying fritters by Liz Bolyard \u2796 1 For Katherine by Carl Boon \u2796 1 poem paint by alex e blazer \u2797 2-3 Leftover Roses by Melissa Bostrom \u2796 4-12 O.J. (artwork) by Todd Gys \u2799 13 Untitled by Adrienne Fair \u2796 14-15 Hills by Liz Bolyard \u2796 16 A Serious Discussion with Ed Shim by Carl Boon \u2796 17 Untitled by David Kendall \u2796 18-19 Brave River by Nikole Hobbs \u2799 20-21 a wavy wail by alex e blazer \u2797 22-23 Misplaced by Tyler Smith \u2797 24 Imogene by Erin Lott \u2796 25-26 Why I can\u27t sleep at night by Colin Bossen \u2798 27 A Lovesong Never Realised by Matthew Rump \u2798 28 Contributors\u27 Notes 29-30 Special thanks to EPI Printing of Livonia, Michigan and Graphic Concepts Unlimited of Okemos, Michigan for helping to make this issue possible. -iii Cover art The Longest Neck by Todd Gys -ii

Concert recording 2018-02-22

[Track 1]. Full tilt / Anthony DiLorenzo -- [Track 2]. Great Lakes octet. I. Shimmering under the sunlight [Track 3]. II. Frozen under winter skies [Track 4]. III. Storm-tossed [Track 5]. IV. Spring horizon / Eric Ewazen -- [Track 6]. Wayfaring stranger / arranged by Chris Woods -- [Track 7]. On a hymnsong of Philip Bliss / David Holsinger translated by William Harbinson -- [Track 8]. Allegretto from Sinfonietta / Leoš Lanáček arranged by Cory Mixdorf -- [Track 9]. October / Eric Whitacre arranged by Christopher E. Hass -- [Track 10]. Fanfare for paratroopers / Paul Creston arranged by Philip Jameson