Effect of psychological intervention on fear of cancer recurrence : a systematic review and meta-analysis

The study was supported in part by the Danish Cancer Society, Grant# R150-A10080Purpose Fear of cancer recurrence (FCR) is a significantly distressing problem that affects a substantial number of patients with and survivors of cancer; however, the overall efficacy of available psychological interventions on FCR remains unknown. We therefore evaluated this in the present systematic review and meta-analysis. Methods We searched key electronic databases to identify trials that evaluated the effect of psychological interventions on FCR among patients with and survivors of cancer. Controlled trials were subjected to meta-analysis, and the moderating influence of study characteristics on the effect were examined. Overall quality of evidence was evaluated using the GRADE system. Open trials were narratively reviewed to explore ongoing developments in the field (PROSPERO registration no.: CRD42017076514). Results A total of 23 controlled trials (21 randomized controlled trials) and nine open trials were included. Small effects (Hedges’s g) were found both at postintervention (g = 0.33; 95% CI, 0.20 to 0.46; P < .001) and at follow-up (g = 0.28; 95% CI, 0.17 to 0.40; P < .001). Effects at postintervention of contemporary cognitive behavioral therapies (CBTs; g = 0.42) were larger than those of traditional CBTs (g = 0.24; β = .22; 95% CI, .04 to .41; P = .018). At follow-up, larger effects were associated with shorter time to follow-up (β = −.01; 95% CI, −.01 to −.00; P = .027) and group-based formats (β = .18; 95% CI, .01 to .36; P = .041). A GRADE evaluation indicated evidence of moderate strength for effects of psychological intervention for FCR. Conclusion Psychological interventions for FCR revealed a small but robust effect at postintervention, which was largely maintained at follow-up. Larger postintervention effects were found for contemporary CBTs that were focused on processes of cognition—for example, worry, rumination, and attentional bias—rather than the content, and aimed to change the way in which the individual relates to his or her inner experiences. Future trials could investigate how to further optimize and tailor interventions to individual patients’ FCR presentation.Publisher PDFPeer reviewe

Psychological aspects in patients with advanced cancer receiving lifelong systemic treatment: Protocol for a scoping review

Introduction A better understanding of the molecular, genetic and immunological characteristics of cancer and the introduction of new systemic treatment regimens in the last decades, has led to better treatment outcomes and increased survival rates for patients with previously short lived cancers. However, there is no uniform description to refer to this growing group of patients with advanced cancer who now respond to new systemic treatments for longer periods. Furthermore, little is known about the unique psychological challenges these patients face, living with ongoing uncertainty about the course of their disease and life expectancy. The objective of this scoping review is to identify the psychological aspects experienced by, and the definitions used to refer to patients with advanced cancer receiving lifelong systemic treatment. Methods and analysis This review will be among the first to summarise literature on the psychological issues in the growing group of advanced cancer patients undergoing long-Term systemic treatment. Articles will be retrieved from six databases (MEDLINE, Embase, Web of Science, PsycINFO, CINAHL and the Cochrane Database of Systematic Reviews) and reviewed for eligibility by two investigators independently. Definitions and psychological challenges will be extracted and narratively summarised following a descriptive approach. Furthermore, results will contribute in providing a uniform definition for this patient group, and help to identify knowledge gaps to give direction to further research in this field. Ethics and dissemination No ethical approval is required. The results of the scoping review will be submitted for publication to a scientific journal and presented at relevant conferences

Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Background: Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood. Methods: This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies. Results: We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation. Conclusions: This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation

Ascorbate deficiency increases progression of shigellosis in guinea pigs and mice infection models

ABSTRACTShigella spp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of Shigella entire life cycle in vivo and the evaluation of vaccine candidates’ protective efficacy have been hampered by the lack of a suitable animal model of infection. None of the studies evaluated so far (rabbit, guinea pig, mouse) allowed the recapitulation of full shigellosis symptoms upon Shigella oral challenge. Historical reports have suggested that dysentery and scurvy are both metabolic diseases associated with ascorbate deficiency. Mammals, which are susceptible to Shigella infection (humans, non-human primates and guinea pigs) are among the few species unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate deficiency, but not scurvy, in guinea pigs to investigate whether poor vitamin C status increases the progression of shigellosis. Moderate ascorbate deficiency increased shigellosis symptom severity during an extended period of time (up to 48 h) in all strains tested (Shigella sonnei, Shigella flexneri 5a, and 2a). At late time points, an important influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although Shigella was able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. Moreover, we found that ascorbate deficiency also increased Shigella penetration into the colon epithelium layer in a Gulo−/− mouse infection model. The use of these new rodent models of shigellosis opens new doors for the study of both Shigella infection strategies and immune responses to Shigella infection