A qualitative study of Western Australian women's perceptions of using a Snoezelen room for breastfeeding during their postpartum hospital stay

<p>Abstract</p> <p>Background</p> <p>There is limited evidence on the use of the Snoezelen concept for maternity clients. Snoezelen, a Dutch concept, initiated in the 1970s as a leisure activity for severely disabled people, involves creating an indoor environment using controllable stimuli to enhance comfort and relaxation. These specially designed rooms expose the user to multiple sensory stimulations combining vision, touch, sounds and aromas. The aim of this study was to provide insight into breastfeeding women's experience of using a Snoezelen room during hospitalisation.</p> <p>Methods</p> <p>A qualitative exploratory design was chosen to reveal women's perceptions of using the Snoezelen room. Osborne Park Hospital, the study setting is the second largest public provider of obstetric services in Western Australia. A purposive sample was drawn from breastfeeding women who used the Snoezelen room during their postpartum stay from March 2006 to March 2007. Saturation was achieved after eleven breastfeeding women were interviewed six weeks post discharge. Data analysis involved the constant comparison method.</p> <p>Results</p> <p>Participants entered the room feeling tired and emotional with an unsettled baby and breastfeeding issues aggravated by maternal stress and anxiety. All women indicated they were able to achieve relaxation while in the room and would recommend its use to other breastfeeding mothers. Two key themes revealed how the Snoezelen room facilitated maternal relaxation, which ultimately enhanced the breastfeeding experience. The first theme, "Finding Relaxation for the Breastfeeding Mother" incorporates three subthemes: 'Time out' for mother; Control in own personal space; and a Quiet/calm environment with homelike atmosphere. The second theme, "Enabling Focus on Breastfeeding", occurred after relaxation was achieved and involved four subthemes: Able to get one-on-one attention; Not physically exposed to others; Away from prying, judgemental eyes and Able to safely attempt breastfeeding alone knowing help is nearby.</p> <p>Conclusion</p> <p>Insight into how the Snoezelen room promoted relaxation also highlights what contributes to maternal anxiety during breastfeeding experiences in hospital. The findings offer health professionals the opportunity to consider adopting strategies such as a Snoezelen room in their hospital or being innovative in modifying the postpartum setting to promote relaxation for breastfeeding women.</p

A randomised controlled trial of a Group psychological intervention to increase locus of control for alcohol consumption among Alcohol‐misusing Short‐term (male) Prisoners (GASP)

Background and aim Reducing alcohol misuse by male prisoners is an important global issue. Control of drinking behaviour could be a useful target for intervention in this population and locus of control could be a causal factor in this. We aimed to assess the effect of a clinical psychologist‐facilitated group intervention on male prisoners’ locus of control of drinking behaviour. Design A two‐arm, single‐site, open, randomised controlled trial. Setting A category B, local training prison in South Wales, housing nearly 800 mostly sentenced men. Participants Prisoners serving under two years who met inclusion criteria for pre‐imprisonment alcohol misuse, alone or with drug misuse. A total of 119 were allocated to the intervention arm and 119 to the control arm; 104 and 87 respectively completed the post‐randomisation baseline interview and 68 and 60 completed a second interview about 4 weeks later, respectively after intervention or treatment as usual (TAU) alone. Intervention Nine clinical psychologist‐facilitated groups in the prison over three weeks. Range of participants per session was 1‐7, with 3‐5 most usual. Measures The primary outcome was Locus of Control of Behaviour (LCB); secondary outcomes included mental state generally (Comprehensive Psychiatric Rating Scale/CPRS) and specifically (Beck Depression Inventory/BDI). An integral process evaluation was conducted. Findings LCB scores decreased during the study, but without significant intervention effect (‐1.7 (95% CI ‐5.2 to 1.8), p=0.334). Change among completers in the control group was from a mean score of 37.4 (standard deviation [SD] 10.0) to 33.7 (SD 11.7) and in the intervention group from 37.4 (11.6) to 31.9 (11.8). Secondary outcomes, including change in mental state, did not differ between arms, but 686 (64%) sessions were lost, most because of ‘prison issues’. Conclusions A clinical psychologist‐facilitated group intervention did not have a statistically significant effect on sense of control of drinking behaviour among men with pre‐imprisonment alcohol misuse serving under two years in a South Wales prison. The study proved coterminous, however, with 40% prison staff cuts which seem likely to have contributed to the high loss of group sessions and possibly overwhelmed any treatment effect. Intervention completion failures, previously cited as harmful, had no effect here, so the trial should be repeated when prison climate improves

Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse

Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years1,2. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study3, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC

Tracking genomic cancer evolution for precision medicine: The Lung TRACERx Study

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types

Depletion of Dendritic Cells Enhances Innate Anti-Bacterial Host Defense through Modulation of Phagocyte Homeostasis

Dendritic cells (DCs) as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye). We used CD11c-diphtheria toxin (DT) mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS) by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relaps

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology