Insights from Australians with respiratory disease living in the community with experience of self-managing through an emergency department 'near miss' for breathlessness: A strengths-based qualitative study

© 2017 Article author(s). Objectives: Breathlessness 'crises' in people with chronic respiratory conditions are a common precipitant for emergency department (ED) presentations, many of which might be avoided through improved self-management and support. This study sought insights from people with experience of ED 'near misses' where they considered going to the ED but successfully self-managed instead. Design and methods: A qualitative approach was used with a phenomenological orientation. Participants: were eligible if they reported breathlessness on most days from a diagnosed respiratory condition and experience of ≥1 ED near miss. Recruitment was through respiratory support groups and pulmonary rehabilitation clinics. Semistructured interviews were conducted with each participant via telephone or face-to-face. Questions focused on ED-related decision-making, information finding, breathlessness management and support. This analysis used an integrative approach and independent coding by two researchers. Lazarus and Cohen's Transactional Model of Stress and Coping informed interpretive themes. Results: Interviews were conducted with 20 participants, 15 of whom had chronic obstructive pulmonary disease. Nineteen interviews were conducted via telephone. Analysis identified important factors in avoiding ED presentation to include perceived control over breathlessness, self-efficacy in coping with a crisis and desire not to be hospitalised. Effective coping strategies included: taking a project management approach that involved goal setting, monitoring and risk management; managing the affective dimension of breathlessness separately from the sensory perceptual and building three-way partnerships with primary care and respiratory services. Conclusions: In addition to teaching non-pharmacological and pharmacological management of breathlessness, interventions should aim to develop patients' generic self-management skills. Interventions to improve self-efficacy should ensure this is substantiated by transfer of skills and support, including knowledge about when ED presentation is necessary. Complementary initiatives are needed to improve coordinated, person-centred care. Future research should seek ways to break the cyclical relationship between affective and sensory-perceptual dimensions of breathlessness

Robotic-assisted, laparoscopic, and open radical cystectomy: surgical data of 1400 patients from The Italian Radical Cystectomy Registry on intraoperative outcomes

Introduction: The Italian Radical Cystectomy Registry (Registro Italiano Cistectomie - RIC) aimed to analyse outcomes of a multicenter series of patients treated with radical cystectomy (RC) for bladder cancer. Material and methods: An observational, prospective, multicenter, cohort study was performed to collect data from RC and urinary diversion via open (ORC), laparoscopic (LRC), or robotic-assisted (RARC) techniques performed in 28 Italian Urological Departments. The enrolment was planned from January 2017 to June 2020 (goal: 1000 patients), with a total of 1425 patients included. Chi-square and t-tests were used for categorical and continuous variables. All tests were 2-sided, with a significance level set at p <0.05. Results: Overall median operative-time was longer in RARCs (390 minutes, IQR 335-465) than ORCs (250, 217-309) and LRCs (292, 228-350) (p <0.001). Lymph node dissection (LND) was performed more frequently in RARCs (97.1%) and LRCs (93.5%) than ORCs (85.6%) (p <0.001), with extended-LND performed 2-fold more frequently in RARCs (61.6%) (p <0.001). The neobladder rate was significantly higher (more than one-half) in RARCs. The median estimated blood loss (EBL) rate was lower in RARCs (250 ml, 165-400) than LRCs (330, 200-600) and ORCs (400, 250-600) (p <0.001), with intraoperative blood transfusion rates of 11.4%, 21.7% and 35.6%, respectively (p <0.001). The conversion to open rate was slightly higher in RARCs (6.8%) than LRCs (4.3%). Intraoperative complications occurred in 1.3% of cases without statistically significant differences among the approaches. Conclusions: Data from the RIC confirmed the need to collect as much data as possible in a multicenter manner. RARCs proves to be feasible with perioperative complication rates that do not differ from the other approaches

Impact of Age on Outcomes of Patients With Pure Carcinoma In Situ of the Bladder: Multi-Institutional Cohort Analysis

Introduction: The aim of this multicenter study was to investigate the role of age (cut-off 70 years) at diagnosis in predicting oncologic behavior of pure carcinoma in situ of the bladder. Material and Methods: Inclusion criteria were: patients with pure CIS confirmed and that followed intravesical BCG treatment. Pure CIS was defined at any CIS not associated with another urothelial cancer. Exclusion criteria were: any CIS associated with invasive urothelial carcinoma. A total of 172 with pure CIS treated between January 1, 2002 and December 31, 2012 at 8 academic institutions met the inclusion criteria. The maintenance schedule was generally according to the EAU guidelines at the time Results: A total of 99 (57.6%) patients had an age >70 years prior to TURBT. There was no difference between clinico-pathologic features among groups (group 1, age ≤ 70 years and group 2, age > 70 years), except that patients aged ≤ 70 years presented a larger size of CIS (35.6% vs. 21.2%), P =.02. In multivariable Cox regression analyses, the same clinico-pathologic factors (age, multifocality, and recurrent tumor state) were independently associated with worse RFS. Harrell's C-index was 65.75.In multivariable Cox regression analyses in addition to age (P =.006) and multifocality (P <.001) also BMI (P =.04) was independently associated with worse PFS. Harrell's C-index was 74.71 Conclusion: Advanced age at diagnosis appears to be associated with an increased risk of recurrence and progression of pure carcinoma in situ of the bladder. Elderly patients might fail to respond to BCG therapy

What do we have to know about pd-l1 expression in prostate cancer? A systematic literature review. part 1: Focus on immunohistochemical results with discussion of pre-analytical and interpretation variables

Immunotherapy targeting the PD-1–PD-L1 axis yielded good results in treating different immunologically ‘‘hot’’ tumors. A phase II study revealed good therapeutic activity of pembroli-zumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohisto-chemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pem-brolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11–41% (de-pending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in &lt;200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41–50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases

Party-group relations in new southern European democracies in the crisis era

UID/CPO/04627/2013 PTDC/IVC-CPO/1864/2014publishersversionpublishe

Hunger, waiting time and transport costs: Time to confront challenges to ART adherence in Africa

International audienceAdherence levels in Africa have been found to be better than those in the US. However around one out of four ART users fail to achieve optimal adherence, risking drug resistance and negative treatment outcomes. A high demand for 2nd line treatments (currently ten times more expensive than 1st line ART) undermines the sustainability of African ART programs. There is an urgent need to identify context-specific constraints to adherence and implement interventions to address them. We used rapid appraisals (involving mainly qualitative methods) to find out why and when people do not adhere to ART in Uganda, Tanzania and Botswana. Multidisciplinary teams of researchers and local health professionals conducted the studies, involving a total of 54 semi-structured interviews with health workers, 73 semi-structured interviews with ART users and other key informants, 34 focus group discussions, and 218 exit interviews with ART users. All the facilities studied in Botswana, Tanzania and Uganda provide ARVs free of charge, but ART users report other related costs (e.g. transport expenditures, registration and user fees at the private health facilities, and lost wages due to long waiting times) as main obstacles to optimal adherence. Side effects and hunger in the initial treatment phase are an added concern. We further found that ART users find it hard to take their drugs when they are among people to whom they have not disclosed their HIV status, such as co-workers and friends. The research teams recommend that (i) health care workers inform patients better about adverse effects; (ii) ART programmes provide transport and food support to patients who are too poor to pay; (iii) recurrent costs to users be reduced by providing three-months, rather than the one-month refills once optimal adherence levels have been achieved; and (iv) pharmacists play an important role in this follow-up care

What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review. part 4: Experimental treatments in pre-clinical studies (cell lines and mouse models)

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapyresistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ Tcells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and RB deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223)

What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review. Part 3: PD-L1, intracellular signaling pathways and tumor microenvironment

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells

Impact of Age on Outcomes of Patients With Pure Carcinoma In Situ of the Bladder: Multi-Institutional Cohort Analysis

Introduction: The aim of this multicenter study was to investigate the role of age (cut-off 70 years) at diagnosis in predicting oncologic behavior of pure carcinoma in situ of the bladder. Material and methods: Inclusion criteria were: patients with pure CIS confirmed and that followed intravesical BCG treatment. Pure CIS was defined at any CIS not associated with another urothelial cancer. Exclusion criteria were: any CIS associated with invasive urothelial carcinoma. A total of 172 with pure CIS treated between January 1, 2002 and December 31, 2012 at 8 academic institutions met the inclusion criteria. The maintenance schedule was generally according to the EAU guidelines at the time RESULTS: A total of 99 (57.6%) patients had an age &gt;70 years prior to TURBT. There was no difference between clinico-pathologic features among groups (group 1, age ≤ 70 years and group 2, age &gt; 70 years), except that patients aged ≤ 70 years presented a larger size of CIS (35.6% vs. 21.2%), P = .02. In multivariable Cox regression analyses, the same clinico-pathologic factors (age, multifocality, and recurrent tumor state) were independently associated with worse RFS. Harrell's C-index was 65.75.In multivariable Cox regression analyses in addition to age (P = .006) and multifocality (P &lt; .001) also BMI (P = .04) was independently associated with worse PFS. Harrell's C-index was 74.71 CONCLUSION: Advanced age at diagnosis appears to be associated with an increased risk of recurrence and progression of pure carcinoma in situ of the bladder. Elderly patients might fail to respond to BCG therapy