Tocilizumab in rheumatoid arthritis: A case study of safety evaluations of a large postmarketing data set from multiple data sources

AbstractObjectivesTo evaluate the magnitude of serious adverse events (SAEs) observed in postmarketing reports of tocilizumab (TCZ) for rheumatoid arthritis (RA) in relation to SAEs observed in TCZ clinical trials and external epidemiology data.MethodsA total of 64,000 patient-years (PY) of TCZ exposure was needed to determine, with 90% power, whether rates of SAEs of interest (eg, death, hepatic, gastrointestinal, and cardiovascular) were ≥50% higher (agreed with the Food and Drug Administration) than expected. Reporting rates were calculated for spontaneously reported SAEs, open-label or unblinded postmarketing clinical trials (phase 3b/4), and a Japanese postmarketing surveillance program in the global postmarketing safety database. Event rates were calculated for the registrational placebo-controlled trials and long-term extension data. External comparators for anti-tumor necrosis factor (aTNF)-treated RA patients were derived from a US-based health care insurance claims database or published literature.ResultsThe global postmarketing safety database provided 65,099 PY of TCZ exposure; the aTNF external comparator population provided 53,360 PY. Spontaneous reporting rates per 100 PY (95% confidence interval) were 8.3 (8.1, 8.5) SAEs, 0.39 (0.34, 0.44) deaths, 0.06 (0.04, 0.08) serious hepatic events, 0.15 (0.12, 0.18) serious gastrointestinal events, 0.09 (0.07, 0.12) serious myocardial infarctions, 0.15 (0.12, 0.18) serious strokes, and 0.07 (0.05, 0.09) cardiac deaths in the global postmarketing safety database. These were of similar magnitude to corresponding rates from registrational clinical trials, the aTNF external comparator population, and published literature.ConclusionsSAE rates observed among postmarketing TCZ users were similar to those of various comparison populations. Predetermined design of studies to compare postmarketing AEs using multiple data sources is a useful strategy that can be applied to other medications

The Grizzly, October 25, 1985

Registration has Come Upon Us • RA Supervision Allows Reimert\u27s Co-ed Transition • Siblings Sharing the Same Experience • One Hundred Years of Tradition Passes With Fretz • Prof. Profile: Armstrong Balances his own Studies With Students\u27 Studies • In Search of Success: Lehman Leans Towards Stockbroker • Letters: What is That Eye Material?; Walter Still Upset; Music Comes to UC • Scram Leaves its Name in Reimert History • Concert Review: Bon Jovi and Ratt Draw a Crowd of Leather • Wanted: Attempted Murder • Bears Fall to Fifth Ranked Gettysburg • Annual Snell Game Ends in a Tie • Booters Win a Big One Over Haverford Squad • Mers Ready to Plunge Into Season • New Course at U.C.: Human Sexuality • Richter Named as Chairman • How to Handle the Effects of Harmful Stress • Roving Reporter: Do You Think Fraternities and Sororities are a Positive Aspect of Campus Life?https://digitalcommons.ursinus.edu/grizzlynews/1149/thumbnail.jp

The Grizzly, October 18, 1985

Limerick: The Main Objective - Calm • Typesetting Equipment Offers New Experience • Letters: Ex-Rover Responds; Some Housing Needs Help; Reply for Sluggo • Financial Aid Striving to the Top • Search of Success Finds Bravo • Look Out for the Candid Cameras • Sorority Pledging Sees Light Through Tunnel • Field Hockey Battles Tough Competition • Booters Find Easier Times • Ultimate Frisbee is Here • Doleniak: Flying Higher Through the Sky • Grizzlies are Defeated • Campus Security Noteshttps://digitalcommons.ursinus.edu/grizzlynews/1148/thumbnail.jp

The Grizzly, September 27, 1985

Weight Room Draws a Crowd • Why Alter the Campus Now? • C.A.B Owns a New Name • Letter: Allocate Athletic Funds • CPP and Carla Rinde Can Show the Way • Prof. Profile: Chambliss Keeps a Difficult Balance •Jeff Page: A Friendly Face in the Crowd • Staiger\u27s Home Away From Home • What\u27s Your Opinion? • Search of Success • Field Hockey Shoots to Top Ten Ranking • Bears Split Two • Cross Country Teams on Fire • Barnes: Guarding is His Game • Computer Lab Launchedhttps://digitalcommons.ursinus.edu/grizzlynews/1145/thumbnail.jp

Hate crimes against trans people: assessing emotions, behaviors and attitudes towards criminal justice agencies

Based on a survey of 593 lesbian, gay, bisexual, and transgender (LGBT) people in the United Kingdom, this study shows that direct anti-LGBT hate crimes (measured by direct experiences of victimization) and indirect anti-LGBT hate crimes (measured by personally knowing other victims of hate crime) are highly prolific and frequent experiences for LGBT people. Our findings show that trans people are particularly susceptible to hate crimes, both in terms of prevalence and frequency. This article additionally highlights the negative emotional and (intended) behavioral reactions that were correlated with an imagined hate crime scenario, showing that trans people are more likely to experience heightened levels of threat, vulnerability, and anxiety compared with non-trans LGB people. The study found that trans people are also more likely to feel unsupported by family, friends, and society for being LGBT, which was correlated with the frequency of direct (verbal) abuse they had previously endured. The final part of this study explores trans people’s confidence levels in the Government, the police, and the Crown Prosecution Service (CPS) in relation to addressing hate crime. In general, trans people felt that the police are not effective at policing anti-LGBT hate crime, and they are not respectful toward them as victims; this was especially true where individuals had previous contact with the police. Respondents were also less confident in the CPS to prosecute anti-LGBT hate crimes, though the level of confidence was slightly higher when respondents had direct experience with the CPS. The empirical evidence presented here supports the assertion that all LGBT people, but particularly trans individuals, continue to be denied equal participation in society due to individual, social, and structural experiences of prejudice. The article concludes by arguing for a renewed policy focus that must address this issue as a public health problem

Towards implementing exercise into the prostate cancer care pathway: development of a theory and evidence-based intervention to train community-based exercise professionals to support change in patient exercise behaviour (The STAMINA trial)

Abstract Background The National Institute for Health and Care Excellence (NICE) recommend that men on androgen deprivation therapy (ADT) for prostate cancer should receive supervised exercise to manage the side-effects of treatment. However, these recommendations are rarely implemented into practice. Community-based exercise professionals (CBEPs) represent an important target group to deliver the recommendations nationally, yet their standard training does not address the core competencies required to work with clinical populations, highlighting a need for further professional training. This paper describes the development of a training package to support CBEPs to deliver NICE recommendations. Methods Development of the intervention was guided by the Medical Research Council guidance for complex interventions and the Behaviour Change Wheel. In step one, target behaviours, together with their barriers and facilitators were identified from a literature review and focus groups with CBEPs (n = 22) and men on androgen deprivation therapy (n = 26). Focus group outputs were mapped onto the Theoretical Domains Framework (TDF) to identify theoretical constructs for change. In step two, behaviour change techniques and their mode of delivery were selected based on psychological theories and evidence to inform intervention content. In step three, the intervention was refined following delivery and subsequent feedback from intervention recipients and stakeholders. Results Six modifiable CBEPs target behaviours were identified to support the delivery of the NICE recommendations. Nine domains of the TDF were identified as key determinants of change, including: improving knowledge and skills and changing beliefs about consequences. To target the domains, we included 20 BCTs across 8 training modules and took a blended learning approach to accommodate different learning styles and preferences. Following test delivery to 11 CBEPs and feedback from 28 stakeholders, the training package was refined. Conclusion Established intervention development approaches provided a structured and transparent guide to intervention development. A training package for CBEPs was developed and should increase trust amongst patients and health care professionals when implementing exercise into prostate cancer care. Furthermore, if proven effective, the development and approach taken may provide a blueprint for replication in other clinical populations where exercise has proven efficacy but is insufficiently implemented

The Grizzly, November 1, 1985

Exploring Faculty/Student Research Opportunities • Dean Muench: An Expert on RA Supervision • Letters: No More Roving Reporter Complaints, Please; J. Board Decision Not Seen as Fair; Campus Social Life Taking a Left Turn • Editorial: Discontent is in the Air • In Search of Success: Vanessa Embarks on her Career • Liberal Arts and Science to be Discussed on Founder\u27s Day • Loss to Penn State Works Against the Bears • Grizzlies Prepare for Make or Break Game vs. Mules • Harriers Race Into Autumn • Philadelphia Sports: Frustrating Times • Soccer Team Ties a Few • Athlete of the Week: Steve Coulter • College Campaign Launched • Tuition: An Ever-Increasing Problem • Exercise to Release Stress • Medical Schools Suffering • Ursinus Aid to Mexico • Alcohol and Advertising • Open Dialog Interaction: Jerry Falwell in Politics; Protecting America • Natural Science Perspectives • New Course Offerings: Argument and Debate; East Asian Literature and Politics • Reimert Task Force Means Law and Order, of Coursehttps://digitalcommons.ursinus.edu/grizzlynews/1150/thumbnail.jp

Palliative care making a difference in rural Uganda, Kenya and Malawi: three rapid evaluation field studies

<p>Abstract</p> <p>Background</p> <p>Many people live and die in pain in Africa. We set out to describe patient, family and local community perspectives on the impact of three community based palliative care interventions in sub-Saharan Africa.</p> <p>Methods</p> <p>Three palliative care programmes in Uganda, Kenya and Malawi were studied using rapid evaluation field techniques in each country, triangulating data from three sources: <b><it>interviews </it></b>with key informants, <b><it>observations </it></b>of clinical encounters and the local health and social care context, and routine data from local <b><it>reports and statistics</it></b>.</p> <p>Results</p> <p>We interviewed 33 patients with advanced illness, 27 family carers, 36 staff, 25 volunteers, and 29 community leaders and observed clinical care of 12 patients. In each site, oral morphine was being used effectively. Patients valued being treated with dignity and respect. Being supported at home reduced physical, emotional and financial burden of travel to, and care at health facilities. Practical support and instruction in feeding and bathing patients facilitated good deaths at home.</p> <p>In each country mobile phones enabled rapid access to clinical and social support networks. Staff and volunteers generally reported that caring for the dying in the face of poverty was stressful, but also rewarding, with resilience fostered by having effective analgesia, and community support networks.</p> <p>Conclusions</p> <p>Programmes were reported to be successful because they integrated symptom control with practical and emotional care, education, and spiritual care. Holistic palliative care can be delivered effectively in the face of poverty, but a public health approach is needed to ensure equitable provision.</p

The Grizzly, November 22, 1985

From Damp to Bone Dry? • UCFL Takes to the Air: Or Visa Versa • It\u27s all Greek to me • The Descent on the Skunks of Ursinus • Editorial: Yale Conference a Learning Experience • Letter: Munchies Mandate • Who\u27s Who Honors Ursinus • How to Deal with Terrorists? • Two Truman Scholars • In Search of Success: Marivi Relova Brings Good Things to GE • Communication a Must • Bears Bounce Dickinson • Booters Find Cold Times in New Hampshire • Soccer Seniors Will be Missed • Coach B. is Back • Lady Bears Hope to Improve Behind Letuakas • Season Tips Off Tonight • Gymnasts Spring into Season • Alercio Faces J Board • Myrin Stacks Up • Fields Should be Ready in Spring • Immersion as Opposed to Voyeurism in Summer Study in France • Smokeless Tobacco Still Burns • Women\u27s Studies Added to Goal No. 9 • Eating Healthy at College Essential • Open Dialogs: Middle Class on Welfare?; Mercy Killing as a Solution; Birth Defects Popular With Geneticists • Ursinus College: The Marriage Factoryhttps://digitalcommons.ursinus.edu/grizzlynews/1153/thumbnail.jp

Is there sufficient Ensifer and Rhizobium species diversity in UK farmland soils to support red clover (Trifolium pratense), white clover (T. repens), lucerne (Medicago sativa) and black medic (M. lupulina)?

Rhizobia play important roles in agriculture owing to their ability to fix nitrogen through a symbiosis with legumes. The specificity of rhizobia-legume associations means that underused legume species may depend on seed inoculation with their rhizobial partners. For black medic (Medicago lupulina) and lucerne (Medicago sativa) little is known about the natural prevalence of their rhizobial partner Ensifer meliloti in UK soils, so that the need for inoculating them is unclear. We analysed the site-dependence of rhizobial seed inoculation effects on the subsequent ability of rhizobial communities to form symbioses with four legume species (Medicago lupulina, M. sativa, Trifolium repens and T. pratense). At ten organic farms across the UK, a species-diverse legume based mixture (LBM) which included these four species was grown. The LBM seed was inoculated with a mix of commercial inocula specific for clover and lucerne. At each site, soil from the LBM treatment was compared to the soil sampled prior to the sowing of the LBM (the control). From each site and each of the two treatments, a suspension of soils was applied to seedlings of the four legume species and grown in axenic conditions for six weeks. Root nodules were counted and their rhizobia isolated. PCR and sequencing of a fragment of the gyrB gene from rhizobial isolates allowed identification of strains. The number of nodules on each of the four legume species was significantly increased when inoculated with soil from the LBM treatment compared to the control. Both the proportion of plants forming nodules and the number of nodules formed varied significantly by site, with sites significantly affecting the Medicago species but not the Trifolium species. These differences in nodulation were broadly reflected in plant biomass where site and treatment interacted; at some sites there was a significant advantage from inoculation with the commercial inoculum but not at others. In particular, this study has demonstrated the commercial merit of inoculation of lucerne with compatible rhizobia