The Establishment of the GENEQOL Consortium to Investigate the Genetic Disposition of Patient-Reported Quality-of-Life Outcomes

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcomes.quality of life, self-rated health, pain, fatigue, genetic disposition, Patient-Reported Quality-of-Life Outcomes

Responsiveness: a reinvention of the wheel?

BACKGROUND: Since the mid eighties, responsiveness is considered to be a separate property of health status questionnaires distinct from reliability and validity. The aim of the study was to assess the strength of the relationship between internal consistency reliability, referring to an instrument's sensitivity to differences in health status among subjects at one point in time, and responsiveness referring to sensitivity to health status changes over time. METHODS: We used three different datasets comprising the scores of patients on the Barthel, the SIP and the GO-QoL instruments at two points in time. The internal consistency was reduced stepwise by removing the item that contributed most to a scale's reliability. We calculated the responsiveness expressed by the Standardized Response Mean (SRM) on each set of remaining items. The strength of the relationship between the thus obtained internal consistency coefficients and SRMs was quantified by Spearman rank correlation coefficients. RESULTS: Strong to perfect correlations (0.90 – 1.00) was found between internal consistency coefficients and SRMs for all instruments indicating, that the two can be used interchangeably. CONCLUSION: The results contradict the conviction that responsiveness is a separate psychometric property. The internal consistency coefficient adequately reflects an instrument's potential sensitivity to changes over time

Modulations of DNA contacts by linker histones and post-translational modifications determine the mobility and modifiability of nucleosomal H3 tails.

Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function

Health care providers underestimate symptom intensities of cancer patients: A multicenter European study

<p>Abstract</p> <p>Background</p> <p>Many patients with advanced cancer depend upon health care providers for symptom assessment. The extent of agreement between patient and provider symptom assessments and the association of agreement with demographic- and disease-related factors was examined.</p> <p>Methods</p> <p>This cross-sectional study included 1933 patient-health care provider dyads, from 11 European countries. Patients reported symptoms by using the four-point scales of the European Organization of Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) version 3, and providers used corresponding four-point categorical scales. Level of agreement was addressed at the group level (Wilcoxon Signed-Rank test), by difference scores (provider score minus patient score), at the individual level (Intraclass Correlation Coefficients, ICCs) and visually by Bland-Altman plots. Absolute numbers and chi-square tests were used to investigate the relationship between agreement and demographic-, as well as disease-related factors.</p> <p>Results</p> <p>The prevalence of symptoms assessed as moderate or severe by patients and providers, respectively, were for pain (67 vs.47%), fatigue (71 vs. 54%), generalized weakness (65 vs. 47%), anorexia (47 vs. 25%), depression (31 vs. 17%), constipation (45 vs. 30%), poor sleep (32 vs. 21%), dyspnea (30 vs. 16%), nausea (27 vs. 14%), vomiting (14 vs. 6%) and diarrhea (14 vs. 6%). Symptom scores were identical or differed by only one response category in the majority of patient-provider assessment pairs (79-93%). Providers underestimated the symptom in approximately one of ten patients and overestimated in 1% of patients. Agreement at the individual level was moderate (ICC 0.38 to 0.59). Patients with low Karnofsky Performance Status, high Mini Mental State-score, hospitalized, recently diagnosed or undergoing opioid titration were at increased risk of symptom underestimation by providers (all p < 0.001). Also, the agreement was significantly associated with drug abuse (p = 0.024), provider profession (p < 0.001), cancer diagnosis (p < 0.001) and country (p < 0.001).</p> <p>Conclusions</p> <p>Considerable numbers of health care providers underestimated symptom intensities. Clinicians in cancer care should be aware of the factors characterizing patients at risk of symptom underestimation.</p

Sphincter-sparing surgery after preoperative radiotherapy for low rectal cancers: feasibility, oncologic results and quality of life outcomes

The present study assesses the choice of surgical procedure, oncologic results and quality of life (QOL) outcomes in a retrospective cohort of 53 patients with low-lying rectal cancers (within 6 cm of the anal verge) treated surgically following preoperative radiotherapy (RT, median dose 45 Gy) with or without concomitant 5-fluorouracil. QOL was assessed in 23 patients by using two questionnaires developed by the QOL Study Group of the European Organization for Research and Treatment of Cancer: EORTC QLQ-C30 and EORTC QLQ-CR38. After a median interval of 29 days from completion of RT, abdominoperineal resection (APR) was performed in 29 patients (55%), low anterior resection in 23 patients (20 with coloanal anastomosis) and transrectal excision in one patient. The 3-year actuarial overall survival and locoregional control rates were 71.4% and 77.5% respectively, with no differences observed between patients operated by APR or restorative procedures. For all scales of EORTC QLQ-C30 and EORTC QLQ-CR38, no significant differences in median scores were observed between the two surgical groups. Although patients having had APR tended to report a lower body image score (P = 0.12) and more sexual dysfunction in male patients, all APR patients tended to report better physical function, future perspective and global QOL. In conclusion, sphincter-sparing surgery after preoperative RT seems to be feasible, in routine practice, in a significant proportion of low rectal cancers without compromising the oncologic results. However, prospective studies are mandatory to confirm this finding and to clarify the putative QOL advantages of sphincter-conserving approaches. © 2000 Cancer Research Campaig

Body image, cosmesis, quality of life, and functional outcome of hand-assisted laparoscopic versus open restorative proctocolectomy: long-term results of a randomized trial

BACKGROUND: This study aimed to compare quality of life (QOL), functional outcome, body image, and cosmesis after hand-assisted laparoscopic (LRP) versus open restorative proctocolectomy (ORP). The potential long-term advantages of LRP over ORP remain to be determined. The most likely advantage of LRP is the superior cosmetic result. It is, however, unclear whether the size and location of incisions affect body image and QOL. METHODS: In a previously conducted randomized trial comparing LRP with ORP, 60 patients were prospectively evaluated. The primary end points were body image and cosmesis. The secondary end points were morbidity, QOL, and functional outcome. A body image questionnaire was used to evaluate body image and cosmesis. The Short Form-36 Health Survey and the Gastrointestinal Quality of Life Inventory were used to assess QOL. Body image and QOL also were assessed preoperatively. RESULTS: A total of 53 patients completed the QOL and functional outcome questionnaires. There were no differences in functional outcome, morbidity, or QOL between LRP and ORP. At a median of 2.7 years after surgery, 46 patients returned the questionnaires regarding body image, cosmesis, and morbidity. The body image and cosmesis scores of female patients were significantly higher in the LRP group than in the ORP group (body image, 17.4 vs 14.9; cosmesis, 19.1 vs 13.0, respectively). The female patients in the ORP group had significantly lower body image scores than the male patients (14.9 vs 18.3). CONCLUSIONS: This study is the first to show that ORP has a negative impact on body image and cosmesis as compared with LRP. Functional outcome, QOL, and morbidity are similar for the two approaches. The advantages of a long-lasting improved body image and cosmesis for this relatively young patient population may compensate for the longer operating times and higher costs, particularly for wome

On the Computation of the Trace Form of Some Galois Extensions

AbstractWe investigate the trace form trL/K:L→K:x↦trL/Kx2of a finite Galois extensionL/K. In particular, we study 2-extensions of degree ≤16. Using some reduction theorems, these results yield a classification of nearly all trace forms of Galois extensions of degree ≤31. Finally, we study the trace form of a cyclotomic extension and of its maximal real subfield

Oromandibular dystonia: a serious side effect of capecitabine

textabstractBackground: Capecitabine has activity against several types of cancer. In 10-15% of patients treated with capecitabine, treatment is discontinued because of serious adverse reactions, mostly within the first weeks of treatment. Case presentation: A 56 year-old female patient presented at the emergency department after ten days of chemotherapy with progressive airway obstruction and complaints of numbness of the tongue. She also had difficulty swallowing and was unable to speak. Laboratory findings were completely normal and no co-medication was used, in particular no dopamine antagonists. A diagnosis of oromandibular dystonia due to capecitabine use was made. After the anticholinergic drug biperiden (Akineton) was given intravenously, complaints disappeared within twenty minutes. Due to an early discontinuation of biperiden, however, the symptoms of oromandibular dystonia recurred. Again, she was successfully treated with an anticholinergic drug. Capecitabine was permanently discontinued. Three days after the initial presentation the anticholinergic drug was stopped after which symptoms did not reappear. Conclusion: The case highlights the need for awareness that capecitabine may potentially lead to severe life-threatening complaints of oromandibular dystonia. We hypothesize that capecitabine passed the blood brain barrier which led to a disruption within the basal ganglia in this case. Prompt treatment with an anticholinergic drug and cessation of capecitabine in the patient case led to disappearance of complaints