Domains and Categories of Needs in Long-Term Follow-Up of Adult Cancer Survivors: A Scoping Review of Systematic Reviews.

The number of long-term cancer survivors increases continually. Understanding their needs is crucial to ensure an adequate follow-up. The aim of our study was to summarize the current literature concerning needs and what influences these needs. A scoping review of systematic reviews was conducted according to the recommendations of the Joanna Briggs Institute. Four electronic databases were searched. Of 414 retrieved papers, 11 met the eligibility criteria. Needs were aggregated into six domains (health-related information, health system, mental, practical, relationship and physical) and 15 categories. The lack of adequate information and the lack of access and/or continuity of supportive care were the most prominent needs. Female gender, younger age, a low level of family and/or social support, and higher educational level were identified as risk factors. Employment and relationship status can affect the needs both in a positive and negative way. The weeks or months after the end of the treatments are particularly critical, and needs can be emphasized during this period. The experience of cancer could also lead to positive changes. The variety of needs affects the quality of life of cancer survivors. Needs assessments should be systematically provided to ensure a better awareness of health professionals and to allow an individual, holistic, and integrated follow-up.

The chemistry of branched condensed phosphates.

Condensed phosphates may exist as linear, cyclic or branched structures. Due to their important role in nature, linear polyphosphates have been well studied. In contrast, branched phosphates (ultraphosphates) remain largely uncharacterised, because they were already described in 1950 as exceedingly unstable in the presence of water, epitomized in the antibranching-rule. This rule lacks experimental backup, since, to the best of our knowledge, no rational synthesis of defined ultraphosphates is known. Consequently, detailed studies of their chemical properties, reactivity and potential biological relevance remain elusive. Here, we introduce a general synthesis of monodisperse ultraphosphates. Hydrolysis half-lives up to days call the antibranching-rule into question. We provide evidence for the interaction of an enzyme with ultraphosphates and discover a rearrangement linearizing the branched structure. Moreover, ultraphosphate can phosphorylate nucleophiles such as amino acids and nucleosides with implications for prebiotic chemistry. Our results provide an entry point into the uncharted territory of branched condensed phosphates.

Journal- or article-based citation measure? A study of academic promotion at a Swiss university.

In academia, decisions on promotions are influenced by the citation impact of the works published by the candidates. The Medical Faculty of the University of Bern used a measure based on the journal impact factor (JIF) for this purpose: the JIF of the papers submitted for promotion should rank in the upper third of journals in the relevant discipline (JIF rank >0.66). The San Francisco Declaration on Research Assessment (DORA) aims to eliminate the use of journal-based metrics in academic promotion. We examined whether the JIF rank could be replaced with the relative citation ratio (RCR), an article-level measure of citation impact developed by the National Institutes of Health (NIH). An RCR percentile >0.66 corresponds to the upper third of citation impact of articles from NIH-sponsored research. We examined 1525 publications submitted by 64 candidates for academic promotion at University of Bern. There was only a moderate correlation between the JIF rank and RCR percentile (Pearson correlation coefficient 0.34, 95% CI 0.29-0.38). Among the 1,199 articles (78.6%) published in journals ranking >0.66 for the JIF, less than half (509, 42.5%) were in the upper third of the RCR percentile. Conversely, among the 326 articles published in journals ranking <0.66 regarding the JIF, 72 (22.1%) ranked in the upper third of the RCR percentile. Our study demonstrates that the rank of the JIF is a bad proxy measure for the actual citation impact of individual articles. The Medical Faculty of University of Bern has signed DORA and replaced the JIF rank with the RCR percentile to assess the citation impact of papers submitted for academic promotion.

Time trend of suicide in Swiss male farmers and comparison with other men: a cohort study.

OBJECTIVE: The ongoing agricultural reforms present serious challenges for Swiss farmers. Pressure is growing with difficult economic situations and the increasing demands for environmental protection, animal welfare and food safety. The aim of this study was to determine whether the strain is associated with higher risk of suicide in farmers than in men in other professions. We also wanted to analyse any changes in trends over time. METHODS: Using the Swiss National Cohort, a population-based longitudinal study (1991–2014), we investigated suicide rates for Swiss men aged 35 to 74 years who lived in small communities. We calculated crude rates of suicide and standardised mortality ratios (SMRs) for both calendar periods of four years, and overall. We estimated hazard ratios using Cox proportional hazard regression models of increasing complexity to examine associations with profession (farmer, non-farmer), calendar period, marital status, type of household, religion and language region. RESULTS: We identified 9006 suicides among 1,796,379 men in the total study population, of which 447 occurred in 89,303 farmers. Age-standardised rates of suicide per 100,000 person-years were higher (38.1, 95% CI 34.6–41.8) in farmers than in men with other professions (32.6, 95% CI 31.9–33.3). Although the age-standardised rates decreased for the whole study population until 2006, the declining trend continued afterwards only in non-farmers. The widening gap between farmers and non-farmers also showed in the SMR, which increased from 1.06 (95% CI 0.88–1.27) in the period 1991–1994 to 1.37 (95% CI 1.05–1.79) in 2011-2014. The Cox regression model analyses also revealed a higher risk of suicide for farmers, with hazard ratios ranging from 1.10 (95% CI 1.00–1.22) to 1.17 (95% CI 1.07–1.29). Usage of firearms was the most common method in the overall population (36.5%). In farmers, however, almost 60% committed suicide by hanging. CONCLUSION: The study shows a higher rate of suicide in farmers compared to non-farmers in Switzerland, with the gap widening increasingly after 2006. It underlines the importance of identifying the difficulties and concerns of male farmers at an early stage in order to make appropriate structural adjustments and to offer low-threshold assistance tailored to their needs and preferences.

Development of a yeast model to study the contribution of vacuolar polyphosphate metabolism to lysine polyphosphorylation.

A recently-discovered protein post-translational modification, lysine polyphosphorylation (K-PPn), consists of the covalent attachment of inorganic polyphosphate (polyP) to lysine residues. The nonenzymatic nature of K-PPn means that the degree of this modification depends on both polyP abundance and the amino acids surrounding the modified lysine. K-PPn was originally discovered in budding yeast (Saccharomyces cerevisiae), in which polyP anabolism and catabolism are well-characterized. However, yeast vacuoles accumulate large amounts of polyP, and upon cell lysis, the release of the vacuolar polyP could nonphysiologically cause K-PPn of nuclear and cytosolic targets. Moreover, yeast vacuoles possess two very active endopolyphosphatases, Ppn1 and Ppn2, that could have opposing effects on the extent of K-PPn. Here, we characterized the contribution of vacuolar polyP metabolism to K-PPn of two yeast proteins, Top1 (DNA topoisomerase 1) and Nsr1 (nuclear signal recognition 1). We discovered that whereas Top1-targeting K-PPn is only marginally affected by vacuolar polyP metabolism, Nsr1-targeting K-PPn is highly sensitive to the release of polyP and of endopolyphosphatases from the vacuole. Therefore, to better study K-PPn of cytosolic and nuclear targets, we constructed a yeast strain devoid of vacuolar polyP by targeting the exopolyphosphatase Ppx1 to the vacuole and concomitantly depleting the two endopolyphosphatases (ppn1Δppn2Δ, vt-Ppx1). This strain enabled us to study K-PPn of cytosolic and nuclear targets without the interfering effects of cell lysis on vacuole polyP and of endopolyphosphatases. Furthermore, we also define the fundamental nature of the acidic amino acid residues to the K-PPn target domain.

Magic spot nucleotides: tunable target-specific chemoenzymatic synthesis.

A tunable chemoenzymatic strategy provides access to the entire class of magic spot nucleotides and modified analogues. The approach combines chemoselective bisphosphorylations using phosphoramidites with regioselective ribonuclease T2 cyclo-phosphate hydrolysis, leading to flexible and simple gram-scale operations.

A Phosphoramidite Analogue of Cyclotriphosphate Enables Iterative Polyphosphorylations.

An iterative polyphosphorylation approach is described, which is based on a phosphoramidite (P-amidite) derived reagent (c-PyPA) obtained from the cyclization of pyrophosphate with a reactive diisopropylaminodichlorophosphine. This type of reagent is unprecedented as it represents a reactive P-amidite without protecting groups. The reagent proved to be stable in solution over several weeks. Its utility is described in the context of iterative monodirectional and bidirectional polyphosphorylations. The ensuing functionalized cyclotriphosphate can be opened with a variety of nucleophiles providing ready access to diverse functionalized polyphosphate chains of defined length with several tags, including both P-N and P-O labels. Their interaction with exo- and endopolyphosphatases is described.

Screening a Protein Array with Synthetic Biotinylated Inorganic Polyphosphate To Define the Human PolyP-ome.

Phenotypes are established by tight regulation on protein functions. This regulation can be mediated allosterically, through protein binding, and covalently, through post-translational modification (PTM). The integration of an ever-increasing number of PTMs into regulatory networks enables and defines the proteome complexity. Protein PTMs can occur enzymatically and nonenzymatically. Polyphosphorylation, which is a recently discovered PTM that belongs to the latter category, is the covalent attachment of the linear ortho-phosphate polymer called inorganic polyphosphate (polyP) to lysine residues. PolyP, which is ubiquitously present in nature, is also known to allosterically control protein function. To date, lack of reagents has prevented the systematic analysis of proteins covalently and/or allosterically associated with polyP. Here, we report on the chemical synthesis of biotin-modified monodisperse short-chain polyP (bio-polyP8-bio) and its subsequent use to screen a human proteome array to identify proteins that associate with polyP, thereby starting to define the human polyP-ome.

Increase in assisted suicide in Switzerland: did the socioeconomic predictors change? Results from the Swiss National Cohort.

OBJECTIVE: To determine whether the strong increase in assisted suicides in Switzerland since 2008 is linked to a shift in the socioeconomic factors associated with assisted suicide and its related diagnoses. METHODS: In a population-based longitudinal study, we investigated assisted suicides in Switzerland over the period 2003-2014. Two groups of younger (25-64 years) and older (65-94 years) persons were analysed separately and compared. We calculated crude rates and used Cox proportional hazard and logistic regression models to examine associations of assisted dying with gender, marital status, education, religion, neighbourhood socioeconomic status and other variables, and investigated trends over time. RESULTS: We identified 3941 assisted suicides among 6 237 997 Swiss residents, 80% of which occurred in the older age group. Crude rates of assisted suicide more than tripled during the study period from 3.60 to 11.21 per 100 000 person-years; the increase was more pronounced in the older age group. Cancer was the most common underlying diagnosis (41.8%), but the percentage dying assisted was highest among patients with diseases of the nervous system (5.25% in the younger and 1.23% in the older age group). The factors associated with assisted suicide did not change during the study period. Female gender, higher education, having no religious affiliation, no children and a Swiss passport, living in a neighbourhood with a higher socioeconomic index and living in the French-speaking part of Switzerland were associated with a higher rate. CONCLUSIONS: The study results do not indicate any shift in socioeconomic factors associated with assisted suicide, but a more pronounced increase in incidence among the elderly.

Suicide in adolescents: findings from the Swiss National cohort.

Suicide in adolescents is the second most common cause of death in this age group and an important public health problem. We examined sociodemographic factors associated with suicide in Swiss adolescents and analysed time trends in youth suicide in the Swiss National Cohort (SNC). The SNC is a longitudinal study of the whole Swiss resident population, based on linkage of census and mortality records. We identified suicides in adolescents aged 10-18 years from 1991 to 2013. A total of 2.396 million adolescents were included and 592 suicides were recorded, corresponding to a rate of 3.7 per 100,000 [95% confidence interval (CI) 3.4-4.0]. Rates increased with age from 0.0 per 100,000 at age 10 years to 14.8 per 100,000 (95% CI 12.6-17.5) at 18 years in boys, and from 0.0 to 5.4 per 100,000 (4.1-7.2) in girls. Being a boy, living in a single parent household, being an only or middle-born child, and living in rural regions were factors associated with a higher rate of suicide. Hanging was the most common method in boys, and railway suicides were most frequent in girls. There was no clear evidence for an increase or decrease over calendar time. We conclude that familial and socioeconomic factors including type of household, birth order and urbanity are associated with youth suicide in Switzerland. These factors should be considered when designing prevention programmes for youth suicide.

Assisted and unassisted suicide in men and women: longitudinal study of the Swiss population.

BACKGROUND: In Switzerland assisted suicide is legal if no self-interest is involved. AIMS: To compare the strength and direction of associations with sociodemographic factors between assisted and unassisted suicides. METHOD: We calculated rates and used Cox and logistic regression models in a longitudinal study of the Swiss population. RESULTS: Analyses were based on 5 004 403 people, 1301 assisted and 5708 unassisted suicides from 2003 to 2008. The rate of unassisted suicides was higher in men than in women, rates of assisted suicides were similar in men and women. Higher education was positively associated with assisted suicide, but negatively with unassisted. Living alone, having no children and no religious affiliation were associated with higher rates of both. CONCLUSIONS: Some situations that indicate greater vulnerability such as living alone were associated with both assisted and unassisted suicide. Among the terminally ill, women were more likely to choose assisted suicide, whereas men died more often by unassisted suicide.

Time-trends in assisted and unassisted suicides completed with different methods: Swiss National Cohort.

OBJECTIVE: The number of suicides assisted by right-to-die associations has increased in recent years in Switzerland. The aim of our study was to compare time trends in rates of assisted and unassisted suicide from 1991-2008. METHODS: The Swiss National Cohort is a longitudinal study of mortality in the Swiss population; based on linkage of census data with mortality records up to 2008. The Federal Statistical Office coded suspected assisted suicides from 1998 onwards; and from 2003 onwards right-to-die associations reported the suicides they assisted. We used Poisson regression to analyse trends in rates of suicide per 100'000 person-years, by gender and age groups (15-34, 35-64, 65-94 years). RESULTS: A total of 7'940'297 individuals and 24'842 suicides were included. In women, rates changed little in the younger age groups but increased in 65-94-year-olds, due to an increase in suicide by poisoning (from 5.1 to 17.2 per 100'000; p <0.001). An increase in suicides by poisoning was also observed in older men (from 8.6 to 18.2; p<0.001). Most suicides by poisoning were assisted. In men, suicide rates declined in all age groups, driven by declines in suicide with firearms. CONCLUSIONS: Research is needed to gain a better understanding of the reasons for the tripling of assisted suicide rates in older women, and the doubling of rates in older men, of attitudes and vulnerabilities of those choosing assisted suicide, and of access to palliative care. Rates of assisted suicide should be monitored; including data on patient characteristics and underlying comorbidities.

Suicide assisted by right-to-die associations: a population based cohort study.

BACKGROUND: In Switzerland, assisted suicide is legal but there is concern that vulnerable or disadvantaged groups are more likely to die in this way than other people. We examined socio-economic factors associated with assisted suicide. METHODS: We linked the suicides assisted by right-to-die associations during 2003-08 to a census-based longitudinal study of the Swiss population. We used Cox and logistic regression models to examine associations with gender, age, marital status, education, religion, type of household, urbanization, neighbourhood socio-economic position and other variables. Separate analyses were done for younger (25 to 64 years) and older (65 to 94 years) people. RESULTS: Analyses were based on 5 004 403 Swiss residents and 1301 assisted suicides (439 in the younger and 862 in the older group). In 1093 (84.0%) assisted suicides, an underlying cause was recorded; cancer was the most common cause (508, 46.5%). In both age groups, assisted suicide was more likely in women than in men, those living alone compared with those living with others and in those with no religious affiliation compared with Protestants or Catholics. The rate was also higher in more educated people, in urban compared with rural areas and in neighbourhoods of higher socio-economic position. In older people, assisted suicide was more likely in the divorced compared with the married; in younger people, having children was associated with a lower rate. CONCLUSIONS: Assisted suicide in Switzerland was associated with female gender and situations that may indicate greater vulnerability such as living alone or being divorced, but also with higher education and higher socio-economic position.

Euthanasia and assisted suicide in selected European countries and US states: systematic literature review.

BACKGROUND: Legal in some European countries and US states, physician-assisted suicide and voluntary active euthanasia remain under debate in these and other countries. OBJECTIVES: The aim of the study was to examine numbers, characteristics, and trends over time for assisted dying in regions where these practices are legal: Belgium, Luxembourg, the Netherlands, Switzerland, Oregon, Washington, and Montana. DESIGN: This was a systematic review of journal articles and official reports. Medline and Embase databases were searched for relevant studies, from inception to end of 2012. We searched the websites of the health authorities of all eligible countries and states for reports on physician-assisted suicide or euthanasia and included publications that reported on cases of physician-assisted suicide or euthanasia. We extracted information on the total number of assisted deaths, its proportion in relation to all deaths, and socio-demographic and clinical characteristics of individuals assisted to die. RESULTS: A total of 1043 publications were identified; 25 articles and reports were retained, including series of reported cases, physician surveys, and reviews of death certificates. The percentage of physician-assisted deaths among all deaths ranged from 0.1%-0.2% in the US states and Luxembourg to 1.8%-2.9% in the Netherlands. Percentages of cases reported to the authorities increased in most countries over time. The typical person who died with assistance was a well-educated male cancer patient, aged 60-85 years. CONCLUSIONS: Despite some common characteristics between countries, we found wide variation in the extent and specific characteristics of those who died an assisted death.