132 research outputs found
The broad spectrum of unbearable suffering in end of life cancer studied in dutch primary care
<p>Abstract</p> <p>Background</p> <p>Unbearable suffering most frequently is reported in end-of-life cancer patients in primary care. However, research seldom addresses unbearable suffering. The aim of this study was to comprehensively investigate the various aspects of unbearable suffering in end-of-life cancer patients cared for in primary care.</p> <p>Methods</p> <p>Forty four general practitioners recruited end-of-life cancer patients with an estimated life expectancy of half a year or shorter. The inclusion period was three years, follow-up lasted one additional year. Practices were monitored bimonthly to identify new cases. Unbearable aspects in five domains and overall unbearable suffering were quantitatively assessed (5-point scale) through patient interviews every two months with a comprehensive instrument. Scores of 4 (serious) or 5 (hardly can be worse) were defined unbearable. The last interviews before death were analyzed. Sources providing strength to bear suffering were identified through additional open-ended questions.</p> <p>Results</p> <p>Seventy six out of 148 patients (51%) requested to participate consented; the attrition rate was 8%, while 8% were alive at the end of follow-up. Sixty four patients were followed up until death; in 60 patients interviews were complete. Overall unbearable suffering occurred in 28%. A mean of 18 unbearable aspects was present in patients with serious (score 4) overall unbearable suffering. Overall, half of the unbearable aspects involved the domain of traditional medical symptoms. The most frequent unbearable aspects were weakness, general discomfort, tiredness, pain, loss of appetite and not sleeping well (25%-57%). The other half of the unbearable aspects involved the domains of function, personhood, environment, and nature and prognosis of disease. The most frequent unbearable aspects were impaired activities, feeling dependent, help needed with housekeeping, not being able to do important things, trouble accepting the situation, being bedridden and loss of control (27%-55%). The combination of love and support was the most frequent source (67%) providing strength to bear suffering.</p> <p>Conclusions</p> <p>Overall unbearable suffering occurred in one in every four end-of-life cancer patients. Half of the unbearable aspects involved medical symptoms, the other half concerned psychological, social and existential dimensions. Physicians need to comprehensively assess suffering and provide psychosocial interventions alongside physical symptom management.</p
The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype
Background: CHEK2 has previously been excluded as a major cause of Li-Fraumeni syndrome (LFS). One particular CHEK2 germline mutation, c.1100delC, has been shown to be associated with elevated breast cancer risk. The prevalence of CHEK21100delC differs between populations and has been found to be relatively high in the Netherlands. The question remains nevertheless whether CHEK2 germline mutations contribute to the Li-Fraumeni phenotype.Methods: We have screened 65 Dutch TP53-negative LFS/LFL candidate patients for CHEK2 germline mutations to determine their contribution to the LFS/LFL phenotype.Results: We identified six index patients with a CHEK2 sequence variant, four with the c.1100delC variant and two sequence variants of unknown significance, p.Phe328Ser and c.1096-?_1629+?del.Conclusion: Our data show that CHEK2 is not a major LFS susceptibility gene in the Dutch population. However, CHEK2 might be a factor contributing to individual tumour development in TP53-negative cancer-prone families
Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.
OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age
Adapting to climate change in The Netherlands: an inventory of climate adaptation options and ranking of alternatives
In many countries around the world impacts of climate change are assessed and adaptation options identified. We describe an approach for a qualitative and quantitative assessment of adaptation options to respond to climate change in the Netherlands. The study introduces an inventory and ranking of adaptation options based on stakeholder analysis and expert judgement, and presents some estimates of incremental costs and benefits. The qualitative assessment focuses on ranking and prioritisation of adaptation options. Options are selected and identified and discussed by stakeholders on the basis of a sectoral approach, and assessed with respect to their importance, urgency and other characteristics by experts. The preliminary quantitative assessment identifies incremental costs and benefits of adaptation options. Priority ranking based on a weighted sum of criteria reveals that in the Netherlands integrated nature and water management and risk based policies rank high, followed by policies aiming at 'climate proof' housing and infrastructure
High cellular monocyte activation in people living with human immunodeficiency virus on combination antiretroviral therapy and lifestyle-matched controls is associated with greater inflammation in cerebrospinal fluid
Background. Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods. A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results. People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions. People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
Background: The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. Methods: To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. Results: No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93–1.10, Ptrend=0.77; MDM2: HR=0.96, 95%CI: 0.84–1.09, Ptrend=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87–1.12, Ptrend=0.83; MDM2: HR=0.98, 95%CI: 0.80–1.21, Ptrend=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. Conclusion: There was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers. O M Sinilnikova1,2, A C Antoniou3, J Simard4, S Healey5, M Léoné1, D Sinnett6,7, A B Spurdle5, J Beesley5, X Chen5, kConFab8, M H Greene9, J T Loud9, F Lejbkowicz10, G Rennert10, S Dishon10, I L Andrulis11,12, OCGN11, S M Domchek13, K L Nathanson13, S Manoukian14, P Radice15,16, I Konstantopoulou17, I Blanco18, A L Laborde19, M Durán20, A Osorio21, J Benitez21, U Hamann22, F B L Hogervorst23, T A M van Os24, H J P Gille25, HEBON23, S Peock3, M Cook3, C Luccarini26, D G Evans27, F Lalloo27, R Eeles28, G Pichert29, R Davidson30, T Cole31, J Cook32, J Paterson33, C Brewer34, EMBRACE3, D J Hughes35, I Coupier36,37, S Giraud1, F Coulet38, C Colas38, F Soubrier38, E Rouleau39, I Bièche39, R Lidereau39, L Demange40, C Nogues40, H T Lynch41, GEMO1,2,42, R K Schmutzler43, B Versmold43, C Engel44, A Meindl45, N Arnold46, C Sutter47, H Deissler48, D Schaefer49, U G Froster50, GC-HBOC43,44,45,46,47,48,49,50, K Aittomäki51, H Nevanlinna52, L McGuffog3, D F Easton3, G Chenevix-Trench5 and D Stoppa-Lyonnet42 on behalf of the Consortium of Investigators of Modifiers of BRCA1/
Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for non-vaccination; two systematic reviews
BackgroundDespite effective national immunisation programmes in Europe, some groups remain incompletely or un-vaccinated ('under-vaccinated'), with underserved minorities and certain religious/ideological groups repeatedly being involved in outbreaks of vaccine preventable diseases (VPD). Gaining insight into factors regarding acceptance of vaccination of 'under-vaccinated groups' (UVGs) might give opportunities to communicate with them in a trusty and reliable manner that respects their belief system and that, maybe, increase vaccination uptake. We aimed to identify and describe UVGs in Europe and to describe beliefs, attitudes and reasons for non-vaccination in the identified UVGs.MethodsWe defined a UVG as a group of persons who share the same beliefs and/or live in socially close-knit communities in Europe and who have/had historically low vaccination coverage and/or experienced outbreaks of VPDs since 1950. We searched MEDLINE, EMBASE and PsycINFO databases using specific search term combinations. For the first systematic review, studies that described a group in Europe with an outbreak or low vaccination coverage for a VPD were selected and for the second systematic review, studies that described possible factors that are associated with non-vaccination in these groups were selected.ResultsWe selected 48 articles out of 606 and 13 articles out of 406 from the first and second search, respectively. Five UVGs were identified in the literature: Orthodox Protestant communities, Anthroposophists, Roma, Irish Travellers, and Orthodox Jewish communities. The main reported factors regarding vaccination were perceived non-severity of traditional "childhood" diseases, fear of vaccine side-effects, and need for more information about for example risk of vaccination.ConclusionsWithin each UVG identified, there are a variety of health beliefs and objections to vaccination. In addition, similar factors are shared by several of these groups. Communication strategies regarding these similar factors such as educating people about the risks associated with being vaccinated versus not being vaccinated, addressing their concerns, and countering vaccination myths present among members of a specific UVG through a trusted source, can establish a reliable relationship with these groups and increase their vaccination uptake. Furthermore, other interventions such as improving access to health care could certainly increase vaccination uptake in Roma and Irish travellers
Malignancies among children and young people with HIV in Western and Eastern Europe and Thailand
Combined effects of single nucleotide polymorphisms TP53 R72P and MDM2 SNP309, and p53 expression on survival of breast cancer patients
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