Updating our understanding of health-related quality of life issues in children with cancer: a systematic review of patient-reported outcome measures and qualitative studies

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Developing Symptom Lists for People with Cancer Treated with Targeted Therapies

Background: Targeted Therapies (TTs) have revolutionised cancer treatment with their enhanced specificity of action. Compared with conventional therapies, TTs are delivered over a longer period and often have unusual symptom profiles. Patient reported outcome measures such as symptom side-effect lists need to be developed in a time-efficient manner to enable a rapid and full evaluation of new treatments and effective clinical managementObjective: the aim of this study is to develop a set of TT-related symptoms and identify the optimal method for developing symptom lists. Patients and Methods: symptoms from TT treatment in the context of Chronic Myeloid Leukaemia (CML), HER2 positive breast cancer, or Gastrointestinal Stromal Tumours (GIST) were identified through literature reviews, interviews with health care professionals (HCPs) and patients, and patient focus groups. The symptom set was then pilot tested in patients across the three cancer diagnoses: The number of items derived from each source (literature, patients, or HCPs) were compared. Results: a total of 316 patients and 86 HCPs from 16 countries participated. An initial set of 209 symptoms was reduced to 61 covering 12 symptom categories. Patient interviews made the greatest contribution to the item set.Conclusions: symptom lists should be created based on input from patients. The item set described will be applicable to the assessment of new TTs, and in monitoring treatment.<br/

A multicenter international prospective study of the validity and reliability of a COVID-19-specific health-related quality of life questionnaire

Purpose: To develop and validate a health-related quality of life (HRQoL) questionnaire for patients with current or previous coronavirus disease (COVID-19) in an international setting. Methods: This multicenter international methodology study followed standardized guidelines for a four-phase questionnaire development. Here, we report on the pretesting and validation of our international questionnaire. Adults with current or previous COVID-19, in institutions or at home were eligible. In the pretesting, 54 participants completed the questionnaire followed by interviews to identify administration problems and evaluate content validity. Thereafter, 371 participants completed the revised questionnaire and a debriefing form to allow preliminary psychometric analysis. Validity and reliability were assessed (correlation-based methods, Cronbach’s α, and intra-class correlation coefficient). Results: Eleven countries within and outside Europe enrolled patients. From the pretesting, 71 of the 80 original items fulfilled the criteria for item-retention. Most participants (80%) completed the revised 71-item questionnaire within 15 min, on paper (n = 175) or digitally (n = 196). The final questionnaire included 61 items that fulfilled criteria for item retention or were important to subgroups. Item-scale correlations were > 0.7 for all but nine items. Internal consistency (range 0.68–0.92) and test–retest results (all but one scale > 0.7) were acceptable. The instrument consists of 15 multi-item scales and six single items. Conclusion: The Oslo COVID-19 QLQ-W61© is an international, stand-alone, multidimensional HRQoL questionnaire that can assess the symptoms, functioning, and overall quality of life in COVID-19 patients. It is available for use in research and clinical practice. Further psychometric validation in larger patient samples will be performed.publishedVersio

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

A national survey exploring views and experience of health professionals about transferring patients from critical care home to die (March 2013)

Introduction Progress has been made towards enabling patients to die in their preferred place of care. However, it is not clear how this might apply in the context of those dying in critical care. We conducted a national survey targeting critical care staff to investigate experiences and attitudes towards transferring critical care patients home to die (HtD). Aims and Methods An online survey was developed informed by the literature and analysis of six focus groups with Health Care Professionals (HCPs) to assess (1) experience and (2) views. The lead consultant and lead nurse of 409 critical care units in the UK were invited, by e-mail, to take part. Results A total of 180 HCPs completed the online survey (response rate 24%). Experience with transferring HtD was reported by 36%. The majority agreed that transferring patients HtD is a good idea in principle (89%) and that transfer is important in terms of preferred place of death (PPD) (82%). 36% agreed that it would be unethical to prolong a patient's life to facilitate a transfer and 13% agreed that a transfer was not worth the risk of dying in the ambulance. Statistically significant differences for some views were found for physicians and nurses, and for those with and without experience of transferring HtD. Conclusions This study is the first to explore views of health care professionals about transferring patients from critical care HtD. Respondents' views were generally positive, particularly about honouring PPD but reservations were expressed in terms of ethical concerns and the risk of dying on route. <br/

The influence of temperament on weight gain in early infancy

Difficult temperament has been associated with fast weight gain and slow weight gain, although the latter mostly in referred subjects studies in late infancy. The current study set out to investigate early weight gain in relation to all domains of temperament in a community-screened sample. Weight gain from birth to 8 weeks was assessed in 75 infants recruited from local health care clinics who had demonstrated slow, average, or fast weight gain. Mothers completed a temperament questionnaire and a 2-day diary recording infant behaviors (sleeping, feeding, fussing, and crying). Weight gain from birth to 8 weeks was significantly related to infant temperament. The temperament dimension fear (acceptance or rejection of new objects or persons) was related to slow weight gain and the temperament dimension distress to limitations (negative emotionality and the infant's reaction to frustrating situations) was related to fast weight gain. The regression model explained 59% of the variance, with the temperament dimensions explaining 11%. Diary data showed that infants who scored high on fear tended to cry a lot, while infants with high scores on distress to limitations tended to sleep less and cry and fuss more. The results emphasize that different temperament domains influence slow and fast weight gain. In addition, the data suggest that infant temperament plays a part in physical development in early infancy

Quality of life implications as a consequence of surgery: limb salvage, primary and secondary amputation

Purpose. We investigated self-reported quality of life (QoL), body image and daily competence of patients as a consequence of limb salvage surgery (LSS), primary or secondary amputation, and the views of patients following secondary amputation.Patients. Patients (n=37) had all been treated for osteosarcoma or Ewing's sarcoma in the lower limb.Methods. QoL was measured by questionnaire. A separate interview to determine satisfaction with decision-making was conducted with those treated for secondary amputation.Results. For the total group, QoL was below that expected from population norms. There were no differences in QoL between those undergoing LSS surgery compared with amputation. However, LSS reported better daily competence and were less likely to use a walking aid. For the total group, body image and daily competence were associated with better QoL.Discussion. All these patients are at risk of compromised QoL following surgery. Our data are in line with previous work suggesting outcomes may be better for LSS compared with amputation. Following secondary amputation, most patients (80%) did not regret initial LSS treatment, but felt that the time gained allowed them to come to terms with subsequent surger