Rehabilitation and return to work after cancer — instruments and practices

The ‘Rehabilitation and return to work after cancer — instruments and practices’ project provides an insight into the issues surrounding rehabilitation and return to work (RTW) after a cancer diagnosis and the problems encountered by workers affected by cancer and their employers. Furthermore, the report presents recommendations for instruments, practices, policies and interventions to successfully support the RTW of workers affected by cancer. Each year, an estimated 3.4 million new cases of cancer are diagnosed in Europe. About half of the people diagnosed with cancer are of working age. Although cancer occurrence differs from one region to another in Europe, the most frequent forms of cancer are breast, colorectal, prostate and lung cancer. These types of cancer were estimated to account for over half of the overall burden of cancer in Europe in 2012. The impact of cancer on a person’s daily life is immediate and striking. The diagnosis usually results in long periods of sickness absence because of medical treatments and functional restrictions. Although, in general, cancer management has improved over the past three decades and the overall number of people who survive cancer is increasing, many cancer survivors still face long-term symptoms and impairments after their treatment ends, such as fatigue. These symptoms and impairments can affect the workability of cancer survivors, making it more difficult to remain in or re-enter the job market. Research shows that most cancer survivors are able to remain in or return to work, but that overall the risk of unemployment among cancer survivors is 1.4 times higher than among people who have never been diagnosed with cancer. Optimising the rehabilitation and RTW of workers affected by cancer is therefore important to both improve the well-being of this vulnerable group and reduce the societal and financial impacts of cancer on European enterprises and society at large. Instruments, practices, policies and interventions aimed at the promotion of rehabilitation and RTW are clearly important. This ‘Rehabilitation and return to work after cancer — instruments and practices’ project reports on the emerging issue of rehabilitation and RTW after cancer and provides national examples of successful instruments, practices, policies and interventions to prevent long-term sickness absences and unemployment. The project is divided into the following main tasks: a literature review on rehabilitation and RTW after a cancer diagnosis; detailed descriptions of instruments, practices, policies and interventions to support rehabilitation and RTW after a cancer diagnosis; company case studies; qualitative research with experts and intermediaries; support for the EU-OSHA stakeholder seminar

Clinical Study Combination Antiretroviral Therapy for HIV in Rwandan Adults: Clinical Outcomes and Impact on Reproductive Health up to 24 Months

Adult women ( = 113) and men ( = 100) initiating combination antiretroviral therapy (cART) and women not yet eligible for cART ( = 199) in Kigali, Rwanda, were followed for 6-24 months between 2007 and 2010. In the cART groups, 21% of patients required a drug change due to side effects and 11% of patients had virological failure (defined as >1,000 HIV RNA copies/mL) after 12 months of cART. About a third of the pregnancies since HIV diagnosis were unintended. The proportion of women in the pre-cART group using modern contraception other than condoms (50%) was similar to women in the general population, but this proportion was only 25% in women initiating cART. Of the women who carried at least one pregnancy to term since having been diagnosed HIV-positive, a third reported to have participated in a prevention-of-mother-to-child-transmission (PMTCT, option A) intervention. Many patients were coinfected with herpes simplex virus type 2 (79-92%), human papillomavirus (38-53%), and bacterial sexually transmitted infections (STIs) with no differences between groups. We applaud the Rwandan government for having strengthened family planning and PMTCT services and for having introduced HPV vaccination in recent years, but additional work is needed to strengthen STI and HPV-related cancer screening and management in the HIV-positive population

Expansion of the neurodevelopmental phenotype of individuals with EEF1A2 variants and genotype-phenotype study

Translation elongation factor eEF1A2 constitutes the alpha subunit of the elongation factor-1 complex, responsible for the enzymatic binding of aminoacyl-tRNA to the ribosome. Since 2012, 21 pathogenic missense variants affecting EEF1A2 have been described in 42 individuals with a severe neurodevelopmental phenotype including epileptic encephalopathy and moderate to profound intellectual disability (ID), with neurological regression in some patients. Through international collaborative call, we collected 26 patients with EEF1A2 variants and compared them to the literature. Our cohort shows a significantly milder phenotype. 83% of the patients are walking (vs. 29% in the literature), and 84% of the patients have language skills (vs. 15%). Three of our patients do not have ID. Epilepsy is present in 63% (vs. 93%). Neurological examination shows a less severe phenotype with significantly less hypotonia (58% vs. 96%), and pyramidal signs (24% vs. 68%). Cognitive regression was noted in 4% (vs. 56% in the literature). Among individuals over 10 years, 56% disclosed neurocognitive regression, with a mean age of onset at 2 years. We describe 8 novel missense variants of EEF1A2. Modeling of the different amino-acid sites shows that the variants associated with a severe phenotype, and the majority of those associated with a moderate phenotype, cluster within the switch II region of the protein and thus may affect GTP exchange. In contrast, variants associated with milder phenotypes may impact secondary functions such as actin binding. We report the largest cohort of individuals with EEF1A2 variants thus far, allowing us to expand the phenotype spectrum and reveal genotype-phenotype correlations.</p

Cross-Protection against Lethal H5N1 Challenge in Ferrets with an Adjuvanted Pandemic Influenza Vaccine

Background. Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential

The undebated issue of justice: silent discourses in Dutch flood risk management

Flood risk for all types of flooding is projected to increase based on climate change projections and increases in damage potential. These challenges are likely to aggravate issues of justice in flood risk management (henceforth FRM). Based on a discursive-institutionalist perspective, this paper explores justice in Dutch FRM: how do institutions allocate the responsibilities and costs for FRM for different types of flooding? What are the underlying conceptions of justice? What are the future challenges with regard to climate change? The research revealed that a dichotomy is visible in the Dutch approach to FRM: despite an abundance of rules, regulations and resources spent, flood risk or its management, are only marginally discussed in terms of justice. Despite that the current institutional arrangement has material outcomes that treat particular groups of citizens differently, depending on the type of flooding they are prone to, area they live in (unembanked/embanked) or category of user (e.g. household, industry, farmer). The paper argues that the debate on justice will (re)emerge, since the differences in distributional outcomes are likely to become increasingly uneven as a result of increasing flood risk. The Netherlands should be prepared for this debate by generating the relevant facts and figures. An inclusive debate on the distribution of burdens of FRM could contribute to more effective and legitimate FRM

Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein

Purpose Although haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized clinical, molecular, and functional spectra of ANKRD11 missense variants. Methods We collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome. We assessed pathogenicity of variants through in silico analyses and cell-based experiments. Results We identified 20 unique, mostly de novo, ANKRD11 missense variants in 29 individuals, presenting with syndromic neurodevelopmental disorders similar to KBG syndrome caused by ANKRD11 protein truncating variants or 16q24.3 microdeletions. Missense variants significantly clustered in repression domain 2 at the ANKRD11 C-terminus. Of the 10 functionally studied missense variants, 6 reduced ANKRD11 stability. One variant caused decreased proteasome degradation and loss of ANKRD11 transcriptional activity. Conclusion Our study indicates that pathogenic heterozygous ANKRD11 missense variants cause the clinically recognizable KBG syndrome. Disrupted transrepression capacity and reduced protein stability each independently lead to ANKRD11 loss-of-function, consistent with haploinsufficiency. This highlights the diagnostic relevance of ANKRD11 missense variants, but also poses diagnostic challenges because the KBG-associated phenotype may be mild and inherited pathogenic ANKRD11 (missense) variants are increasingly observed, warranting stringent variant classification and careful phenotyping

A real-world registry to evaluate HER2-directed therapy in Australian patients with metastatic breast cancer

Abstract No.: e1251