The benefits and complexities of integrating mixed method findings using the Pillar Integration Process: A workplace health intervention case study

YesThe Pillar Integration Process was developed to facilitate integration of mixed method data, but there is limited historical application of this approach in complex intervention evaluation. To test the applicability of the technique, this paper presents two case studies examining the efficacy of a workplace intervention. The research included a pilot RCT and process evaluation. The case studies illustrate the benefits of applying the Pillar Integration Process to elicit a comprehensive understanding of intervention efficacy and to design better interventions. This paper contributes to the mixed methods research by advancing the technique through considering inherent philosophical assumptions, and evidencing the value of integrating methods within, as well as across, “qualitative” and “quantitative” categories.Macmillan cancer support part-funded this research and were one of the participating organizations. Ergotron Inc. provided 25 sit-stand desks for use within this research. The research formed part of the lead author’s PhD study, which was funded by a School of Sport and Education, Brunel University London, PhD bursary

Effective Treatments of UTI—Is Intravesical Therapy the Future?

Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is a cause for concern. Optimal treatment of UTI relies upon the selection of an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in the urinary tract after oral administration. Alternatively, high local concentrations of antibiotic at the urothelial surface can be achieved by direct instillation into the urinary tract. For antibiotics with the appropriate physicochemical properties, this can be of critical importance in cases for which an intracellular urothelial bacterial reservoir is suspected. In this review, we summarise the underpinning biopharmaceutical barriers to effective treatment of UTI and provide an overview of the evidence for the deployment of the intravesical administration route for antibiotics

Preferences and priorities for relapsed multiple myeloma treatments among patients and caregivers in the United States

Introduction/Background: This study aimed to describe patient and caregiver preferences for treatments of relapsed or refractory multiple myeloma (MM). Materials and Methods: A survey including discrete-choice experiment (DCE) and best-worst scaling (BWS) exercises was conducted among US patients with relapsed or refractory MM and their caregivers. The DCE included six attributes with varying levels including progression-free survival (PFS), toxicity, and mode and frequency of administration. In addition, the impact of treatment cost was assessed using a fixed-choice question. The BWS exercise included 18 items (modes and frequency of administration, additional treatment convenience, and toxicity items). The survey was administered online to patients recruited from the Multiple Myeloma Research Foundation CoMMpass study (NCT01454297). Results: The final samples consisted of 94 patients and 32 caregivers. Avoiding severe nerve damage was most important to patients, followed by longer PFS. Caregivers considered PFS to be the most important attribute. We estimate that a third or more of patients were cost-sensitive, meaning their treatment preference was altered based on cost implications. Caregivers were not cost-sensitive. The three most bothersome treatment features in the BWS exercise were risk of kidney failure, lowering white blood cell counts, and weakening the immune system. Conclusion: Patients with relapsed or refractory MM and their caregivers consider many factors including efficacy, toxicity, mode/frequency of administration, and cost in their decisions regarding treatment options. The study provides a basis for future Research on patient and caregiver treatment preferences, which could be incorporated into shared decision-making with physicians

Exercise recommendations for people with bone metastases: Expert consensus for healthcare providers and clinical exercise professionals

Purpose: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. Methods: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. Results: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment–related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. Conclusion: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases

The Roasting Marshmallows Program with IGRINS on Gemini South I: Composition and Climate of the Ultra Hot Jupiter WASP-18 b

We present high-resolution dayside thermal emission observations of the exoplanet WASP-18b using IGRINS on Gemini South. We remove stellar and telluric signatures using standard algorithms, and we extract the planet signal via cross correlation with model spectra. We detect the atmosphere of WASP-18b at a signal-to-noise ratio (SNR) of 5.9 using a full chemistry model, measure H2O (SNR=3.3), CO (SNR=4.0), and OH (SNR=4.8) individually, and confirm previous claims of a thermal inversion layer. The three species are confidently detected (>4$\sigma$) with a Bayesian inference framework, which we also use to retrieve abundance, temperature, and velocity information. For this ultra-hot Jupiter (UHJ), thermal dissociation processes likely play an important role. Retrieving abundances constant with altitude and allowing the temperature-pressure profile to freely adjust results in a moderately super-stellar carbon to oxygen ratio (C/O=0.75^{+0.14}_{-0.17}) and metallicity ([M/H]=1.03^{+0.65}_{-1.01}). Accounting for undetectable oxygen produced by thermal dissociation leads to C/O=0.45^{+0.08}_{-0.10} and [M/H]=1.17^{+0.66}_{-1.01}. A retrieval that assumes radiative-convective-thermochemical-equilibrium and naturally accounts for thermal dissociation constrains C/O<0.34 (2$\sigma$) and [M/H]=0.48^{+0.33}_{-0.29}, in line with the chemistry of the parent star. Looking at the velocity information, we see a tantalising signature of different Doppler shifts at the level of a few km/s for different molecules, which might probe dynamics as a function of altitude and location on the planet disk. Our results demonstrate that ground-based, high-resolution spectroscopy at infrared wavelengths can provide meaningful constraints on the compositions and climate of highly irradiated planets. This work also elucidates potential pitfalls with commonly employed retrieval assumptions when applied to UHJ spectra.Comment: 27 pages, 18 figures, submitted to AAS Journals. Community feedback welcom

NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia

African trypanosomes are the causative agents of Human African Trypanosomosis (HAT/Sleeping Sickness) and Animal African Trypanosomosis (AAT/Nagana). A common hallmark of African trypanosome infections is inflammation. In murine trypanosomosis, the onset of inflammation occurs rapidly after infection and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after reaching peak parasitemia, acute anemia develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing acute anemia. Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a murine model for trypanosomosis. Results indicate that IFNγ plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as mice lacking the IFNγ receptor were partially protected against trypanosomosis-associated inflammation and acute anemia. NK and NKT cells were the earliest source of IFNγ during T. b. brucei infection. Later in infection, CD8+ and to a lesser extent CD4+ T cells become the main IFNγ producers. Cell depletion and transfer experiments indicated that during infection the absence of NK, NKT and CD8+ T cells, but not CD4+ T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNγR-/- mice. Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNγ is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute inflammation-associated anemia

Exercise for individuals with bone metastases: A systematic review

Background Exercise has the potential to improve physical function and quality of life in individuals with bone metastases but is often avoided due to safety concerns. This systematic review summarizes the safety, feasibility and efficacy of exercise in controlled trials that include individuals with bone metastases. Methods MEDLINE, Embase, Pubmed, CINAHL, PEDro and CENTRAL databases were searched up to July 16, 2020. Results A total of 17 trials were included incorporating aerobic exercise, resistance exercise or soccer interventions. Few (n=4, 0.5%) serious adverse events were attributed to exercise participation, with none related to bone metastases. Mixed efficacy results were found, with exercise eliciting positive changes or no change. The majority of trials included an element of supervised exercise instruction (n=16, 94%) and were delivered by qualified exercise professionals (n=13, 76%). Conclusions Exercise appears safe and feasible for individuals with bone metastases when it includes an element of supervised exercise instruction

Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (TH1, TH2) to immune-mediated tumour cell death induced by NAC

Background The tumour microenvironment consists of malignant cells, stroma and immune cells. In women with large and locally advanced breast cancers (LLABCs) undergoing neoadjuvant chemotherapy (NAC), tumour-infiltrating lymphocytes (TILs), various subsets (effector, regulatory) and cytokines in the primary tumour play a key role in the induction of tumour cell death and a pathological complete response (pCR) with NAC. Their contribution to a pCR in nodal metastases, however, is poorly studied and was investigated. Methods Axillary lymph nodes (ALNs) (24 with and 9 without metastases) from women with LLABCs undergoing NAC were immunohistochemically assessed for TILs, T effector and regulatory cell subsets, NK cells and cytokine expression using labelled antibodies, employing established semi-quantitative methods. IBM SPSS statistical package (21v) was used. Non-parametric (paired and unpaired) statistical analyses were performed. Univariate and multivariate regression analyses were carried out to establish the prediction of a pCR and Spearman’s Correlation Coefficient was used to determine the correlation of immune cell infiltrates in ALN metastatic and primary breast tumours. Results In ALN metastases high levels of TILs, CD4+ and CD8+ T and CD56+ NK cells were significantly associated with pCRs.. Significantly higher levels of Tregs (FOXP3+, CTLA-4+) and CD56+ NK cells were documented in ALN metastases than in the corresponding primary breast tumours. CD8+ T and CD56+ NK cells showed a positive correlation between metastatic and primary tumours. A high % CD8+ and low % FOXP3+ T cells and high CD8+: FOXP3+ ratio in metastatic ALNs (tumour-free para-cortex) were associated with pCRs. Metastatic ALNs expressed high IL-10, low IL-2 and IFN-ϒ. Conclusions Our study has provided new data characterising the possible contribution of T effector and regulatory cells and NK cells and T helper1 and 2 cytokines to tumour cell death associated with NAC in ALNs

Exercise Recommendation for People With Bone Metastases: Expert Consensus for Health Care Providers and Exercise Professionals

PURPOSE:Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion.METHODS:The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement.RESULTS:Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment–related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential.CONCLUSION:Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases