Pride and Prejudice: How do they matter to career development?

The notion of a personal career emerged as a response to needs expressed within the western, industrialised culture. This specific expression of human work behaviour appeared at a time in history when approaches to work in the west had been transformed by powerful movements such as the Protestant Reformation and the Industrial Revolution. By contrast, the idea of choosing a personal career was not intrinsic to the cultural and economic environment that prevailed in non-western contexts at that time in history. Today, however, against the background of westernisation, industrialisation and now globalisation, the situation is quite different. With the rapid breaking down of older social mechanisms for occupational role allocation, questions surrounding career choices, decision-making, and career preparation have become a reality in the developing world as well. The fact remains, though, that career development occurs in a very different manner in these contexts and is influenced by distinctive factors that are specific to these situations

Metabolic and crystal arthropathies: 112. Rapid Improvement in Health-Related Quality of Life in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Canakinumab, a fully human anti-IL-1β antibody has been shown to control inflammation in gouty arthritis. This study evaluated changes in health-related quality of life (HRQoL) in patients treated with canakinumab or triamcinolone acetonide (TA). Methods: An 8-wk, dose-ranging, active controlled, single-blind study in patients (≥18 to ≤80 years) with acute gouty arthritis flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to canakinumab 10, 25, 50, 90, 150 mg sc or TA 40 mg im. HRQoL was assessed using patient reported outcomes evaluating PCS and MCS, and subscale scores of SF-36® [acute version 2]) and functional disability (HAQ-DI©). Results: In canakinumab 150 mg group, the most severe impairment at baseline was reported for physical functioning and bodily pain; levels of 41.5 and 36.0, respectively, which improved in 7 days to 80.0 and 72.2 (mean increases of 39.0 and 35.6) and at 8 wks improved to 86.1 and 86.6 (mean increases of 44.6 and 50.6); these were higher than levels seen in the general US population. TA group, showed less improvement in 7 days (mean increases of 23.3 and 21.3 for physical function and bodily pain). Functional disability scores, measured by the HAQ-DI© decreased in both treatment groups (Table 1). Conclusions: Gouty arthritis patients treated with canakinumab showed a rapid improvement in physical and mental well-being based on SF-36® scores. In contrast to the TA group, patients treated with canakinumab showed improvement in 7 days in physical function and bodily pain approaching levels of the general population. Disclosure statement: U.A., A.F., V.M., D.R., P.S. and K.S. are employees and shareholders of Novartis Pharma AG. A.P. has received research support from Novartis Pharma AG. N.S. has received research support and consultancy fees from Novartis Pharmaceuticals Corporation, has served on advisory boards for Novartis, Takeda, Savient, URL Pharma and EnzymeRx, and is/has been a member of a speakers' bureau for Takeda. A.S. has received consultation fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interes

Concurrent Oral 1 - Therapy of rheumatic disease: OP4. Effectiveness of Rituximab in Rheumatoid Arthritis: Results from the British Society for Rheumatology Biologics Register (BSRBR)

Background: Rituximab (RTX) in combination with methotrexate (MTX) has been licensed since 2006 for the management of severe active rheumatoid arthritis (RA) in patients who have failed at least one anti-tumour necrosis factor (anti-TNF) therapy. Published clinical trials have demonstrated the efficacy of RTX in improving both clinical symptoms and patients' physical function. This study aimed to assess the effectiveness of RTX in RA patients treated in routine clinical practice by examining clinical and patient reported outcomes six months after receiving a first course of RTX. Methods: The analysis involved 550 RA patients registered with the BSRBR, who were starting RTX and were followed up for at least 6 months. Change in Disease Activity Score (DAS28) and European League Against Rheumatism (EULAR) response were used to assess the clinical response while change in Health Assessment Questionnaire (HAQ) score was used to assess the physical function of the patients 6 months after starting RTX. The change in DAS28 and HAQ was compared between seronegative and seropositive patients and anti-TNF naïve patients versus anti-TNF failures. The response was also compared between patients receiving RTX in combination with MTX, other non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) or no nbDMARDs. Results: The mean (s.d.) age of the cohort was 59 (12) years and 78% of the patients were females. The patients had a mean (s.d.) of 15 (10) years of disease duration. 16% were biologic naïve while 84% were anti-TNF failures. 32% of the patients were seronegative and 68% were seropositive. The mean (95% CI) DAS28 at baseline was 6.2 (6.1, 6.3) which decreased to 4.8 (4.7, 4.9) at 6 months of follow up. 16% were EULAR good responders, 43% were moderate responders and 41% were non responders. The mean (95% CI) change in HAQ was −0.1 (−0.2, −0.1) (Table 1). The mean change in DAS28 was similar in seropositive and seronegative patients (p = 0.18) while the anti-TNF naïve patients showed a greater reduction in DAS28 scores than anti-TNF failures (p = 0.05). Patients receiving RTX in combination with MTX showed similar changes in DAS28 and HAQ compared to patients receiving RTX alone or with other nbDMARDs. Conclusions: RTX has proven to be effective in the routine clinical practice. Anti-TNF naïve patients seem to benefit more from RTX treatment than anti-TNF failures. Disclosure statement: The authors have declared no conflicts of interes

Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study

INTRODUCTION: We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis. METHODS: In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to--or had contraindications for--non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version). RESULTS: At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab 150 mg group approached those for the US general population by seven days post-dose and reached norm values by eight weeks post-dose. CONCLUSIONS: Canakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvements in HRQoL were seen in both treatment groups with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg. TRIAL REGISTRATION: clinicaltrials.gov: NCT00798369

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

Careers work in higher education in Pakistan: current practice and options for the future

In this article we examine the development of career guidance in Pakistani higher education. The article is primarily based on a review of the existing literature on career guidance in Pakistan, but also includes the consideration of some new data gathered from a review of higher education institutions websites and five case study interviews. It considers both local and global influences as relevant contexts for understanding how the development of career guidance in Pakistani higher education is taking place. Concerns about alignment between skills supply and demand provide key drivers both for the development of career guidance and for wider higher education reform. However the practice of career guidance in Pakistani higher education is shown to be lagging behind the policy aspirations, both due to limited investment and due to more fundamental cultural challenges that have yet to be fully addressed. If career guidance is going to continue to develop within Pakistan it will need to be strengthened by new policy and resources but also through the development of indigenous theories.N/

The global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories:A systematic analysis for the Global Burden of Disease Study 2019

Importance Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.Objective To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence Review The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.Findings In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and Relevance In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Burden of non-communicable diseases among adolescents aged 10–24 years in the EU, 1990–2019: a systematic analysis of the Global Burden of Diseases Study 2019

Background Disability and mortality burden of non-communicable diseases (NCDs) have risen worldwide; however, the NCD burden among adolescents remains poorly described in the EU. Methods Estimates were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Causes of NCDs were analysed at three different levels of the GBD 2019 hierarchy, for which mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were extracted. Estimates, with the 95% uncertainty intervals (UI), were retrieved for EU Member States from 1990 to 2019, three age subgroups (10–14 years, 15–19 years, and 20–24 years), and by sex. Spearman's correlation was conducted between DALY rates for NCDs and the Socio-demographic Index (SDI) of each EU Member State. Findings In 2019, NCDs accounted for 86·4% (95% uncertainty interval 83·5–88·8) of all YLDs and 38·8% (37·4–39·8) of total deaths in adolescents aged 10–24 years. For NCDs in this age group, neoplasms were the leading causes of both mortality (4·01 [95% uncertainty interval 3·62–4·25] per 100 000 population) and YLLs (281·78 [254·25–298·92] per 100 000 population), whereas mental disorders were the leading cause for YLDs (2039·36 [1432·56–2773·47] per 100 000 population) and DALYs (2040·59 [1433·96–2774·62] per 100 000 population) in all EU Member States, and in all studied age groups. In 2019, among adolescents aged 10–24 years, males had a higher mortality rate per 100 000 population due to NCDs than females (11·66 [11·04–12·28] vs 7·89 [7·53–8·23]), whereas females presented a higher DALY rate per 100 000 population due to NCDs (8003·25 [5812·78–10 701·59] vs 6083·91 [4576·63–7857·92]). From 1990 to 2019, mortality rate due to NCDs in adolescents aged 10–24 years substantially decreased (–40·41% [–43·00 to –37·61), and also the YLL rate considerably decreased (–40·56% [–43·16 to –37·74]), except for mental disorders (which increased by 32·18% [1·67 to 66·49]), whereas the YLD rate increased slightly (1·44% [0·09 to 2·79]). Positive correlations were observed between DALY rates and SDIs for substance use disorders (rs=0·58, p=0·0012) and skin and subcutaneous diseases (rs=0·45, p=0·017), whereas negative correlations were found between DALY rates and SDIs for cardiovascular diseases (rs=–0·46, p=0·015), neoplasms (rs=–0·57, p=0·0015), and sense organ diseases (rs=–0·61, p=0·0005)