Lower fluorodeoxyglucose positron emission tomography maximum standardized uptake value may show a better response to stereotactic body radiotherapy of adrenals in oligometastatic disease.

Introduction: Stereotactic body radiotherapy (SBRT) is well established for oligometastatic disease, and it is increasingly used to treat adrenal metastases. Material and methods: In this retrospective study we performed an analysis of 75 metastatic adrenal lesions in 64 patients with oligometastatic disease. According to the fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) maximum standardized uptake value (SUVmax) of adrenal metastases, patients were categorized into three groups: low, intermediate, and high SUVmax. Results: For all clinicopathological characteristics we found significant relationships for levels of SUVmax and objective response rate (Kendall Tau-c = 0.290; p = 0.017). Patients who responded to SBRT had a significantly lower SUVmax value than those who did not respond (7.6 ±2.4 vs. 9.7 ±3.8; p = 0.015). At the appropriate SUVmax cut-off values, the biomarker distinguished between patients with and without a response significantly and moderately (area under the curve = 0.670, 95% confidence intervals: 0.540-0.790; p = 0.015). Conclusions: Lower SUVmax is associated with a better response to SBRT in patients whose disease progressed mainly in the adrenal glands.

Comparison of the health-related quality of life of end stage kidney disease patients on hemodialysis and non-hemodialysis management in Uganda.

BACKGROUND: Health-related quality of life is recognized as a key outcome in chronic disease management, including kidney disease. With no national healthcare coverage for hemodialysis, Ugandan patients struggle to pay for their care, driving families and communities into poverty. Studies in developed countries show that patients on hemodialysis may prioritize quality of life over survival time, but there is a dearth of information on this in developing countries. We therefore measured the quality of life (QOL) and associated factors in end stage renal disease (ESRD) patients in a major tertiary care hospital in Uganda. METHODS: Baseline QOL measurement in a longitudinal cohort study was undertaken using the Kidney Disease Quality of Life Short Form Ver 1.3. Patients were recruited from the adult nephrology unit if aged > 18 years with an estimated glomerular filtration rate ≤ 15mls/min/1,73m2. Clinical, demographic and micro-financial information was collected to determine factors associated with QOL scores. RESULTS: Three hundred sixty-four patients (364) were recruited, of whom 124 were on hemodialysis (HD) and 240 on non-hemodialysis (non-HD) management. Overall, 94.3% of participants scored less than 50 (maximum 100). Mean QOL scores were low across all three principal domains: physical health (HD: 33.14, non-HD: 34.23), mental health (HD: 38.01, non-HD: 38.02), and kidney disease (HD: 35.16, non-HD: 34.00). No statistically significant difference was found between the overall quality of life scores of the two management groups. Breadwinner status (p < 0.001), source of income (p0.026) and hemodialysis management type (p0.032) were the only factors significantly associated with QOL scores, and this was observed in the physical health and kidney disease principal domains only. No factors were significantly associated with scores for the mental health principal domain and/or overall QOL score. CONCLUSION: The quality of life of Ugandan patients with ESRD has been found to be lower across all three domains of the Kidney Disease Quality of Life Short Form than reported anywhere in the world, with no difference observed between the non-HD and HD management groups. Interventions targeting all domains of QOL are needed among patients with ESRD in Uganda and, potentially, in other resource limited settings.

Illness-related suffering and need for palliative care in Rohingya refugees and caregivers in Bangladesh: A cross-sectional study.

BACKGROUND: Despite recognition that palliative care is an essential component of any humanitarian response, serious illness-related suffering continues to be pervasive in these settings. There is very limited evidence about the need for palliative care and symptom relief to guide the implementation of programs to alleviate the burden of serious illness-related suffering in these settings. A basic package of essential medications and supplies can provide pain relief and palliative care; however, the practical availability of these items has not been assessed. This study aimed to describe the illness-related suffering and need for palliative care in Rohingya refugees and caregivers in Bangladesh. METHODS AND FINDINGS: Between November 20 and 24, 2017, we conducted a cross-sectional study of individuals with serious health problems (n = 156, 53% male) and caregivers (n = 155, 69% female) living in Rohingya refugee camps in Bangladesh, using convenience sampling to recruit participants at the community level (i.e., going house to house to identify eligible individuals). The serious health problems, recent healthcare experiences, need for medications and medical supplies, and basic needs of participants were explored through interviews with trained Rohingya community members, using an interview guide that had been piloted with Rohingya individuals to ensure it reflected the specificities of their refugee experience and culture. The most common diagnoses were significant physical disabilities (n = 100, 64.1%), treatment-resistant tuberculosis (TB) (n = 32, 20.5%), cancer (n = 15, 9.6%), and HIV infection (n = 3, 1.9%). Many individuals with serious health problems were experiencing significant pain (62%, n = 96), and pain treatments were largely ineffective (70%, n = 58). The average age was 44.8 years (range 2-100 years) for those with serious health problems and 34.9 years (range 8-75 years) for caregivers. Caregivers reported providing an average of 13.8 hours of care per day. Sleep difficulties (87.1%, n = 108), lack of appetite (58.1%, n = 72), and lack of pleasure in life (53.2%, n = 66) were the most commonly reported problems related to the caregiving role. The main limitations of this study were the use of convenience sampling and closed-ended interview questioning. CONCLUSIONS: In this study we found that many individuals with serious health problems experienced significant physical, emotional, and social suffering due to a lack of access to pain and symptom relief and other essential components of palliative care. Humanitarian responses should develop and incorporate palliative care and symptom relief strategies that address the needs of all people with serious illness-related suffering and their caregivers.

Dying individuals and suffering populations: applying a population-level bioethics lens to palliative care in humanitarian contexts: before, during and after the COVID-19 pandemic.

BACKGROUND: Humanitarian crises and emergencies, events often marked by high mortality, have until recently excluded palliative care-a specialty focusing on supporting people with serious or terminal illness or those nearing death. In the COVID-19 pandemic, palliative care has received unprecedented levels of societal attention. Unfortunately, this has not been enough to prevent patients dying alone, relatives not being able to say goodbye and palliative care being used instead of intensive care due to resource limitations. Yet global guidance was available. In 2018, the WHO released a guide on 'Integrating palliative care and symptom relief into the response to humanitarian emergencies and crises'-the first guidance on the topic by an international body. AIMS: This paper argues that while a landmark document, the WHO guide took a narrowly clinical bioethics perspective and missed crucial moral dilemmas. We argue for adding a population-level bioethics lens, which draws forth complex moral dilemmas arising from the fact that groups having differential innate and acquired resources in the context of social and historical determinants of health. We discuss dilemmas concerning: limitations of material and human resources; patient prioritisation; euthanasia; and legacy inequalities, discrimination and power imbalances. IMPLICATIONS: In parts of the world where opportunity for preparation still exists, and as countries emerge from COVID-19, planners must consider care for the dying. Immediate steps to support better resolutions to ethical dilemmas of the provision of palliative care in humanitarian and emergency contexts will require honest debate; concerted research effort; and international, national and local ethical guidance.

Health-related quality of life, palliative care needs and 12-month survival among patients with end stage renal disease in Uganda: protocol for a mixed methods longitudinal study.

BACKGROUND: The prevalence of chronic kidney disease is on the rise globally and in sub-Saharan Africa. Due to its "silent" nature, many patients often present with advanced disease. At this point options for care are often limited to renal replacement therapies such as hemodialysis and kidney transplantation. In resource limited settings, these options are associated with catastrophic expenditures and increased household poverty levels. Early palliative care interventions, if shown to ensure comparable quality of life (QoL), can significantly mitigate this by focusing care on comfort, symptom control and QoL rather than primarily on prolonging survival. METHODS: A mixed methods longitudinal study, recruiting patients with End Stage Renal Disease (ESRD) on hemodialysis or conservative management and following them up over 12 months. The study aims are to: 1) measure and compare the health-related quality of life (HRQoL) scores of patients with ESRD receiving hemodialysis with those receiving conservative management, 2) measure and compare the palliative care needs and outcomes of patients in the two groups, 3) explore the impact of treatment modality and demographic, socio-economic and financial factors on QoL and palliative care needs and outcomes, 4) review patient survival over 12 months and 5) explore the patients' lived experiences. The Kidney Disease Quality Of Life Short Form version 1.3 (KDQOL-SF) will be used to measure HRQoL; the African Palliative Care Association Palliative care Outcome Score (APCA POS) and the Palliative care Outcome Score for renal symptoms (POS-S Renal) will be used to assess palliative care needs and outcomes; and semi-structured in-depth interviews to explore the patients' experiences of living with ESRD. Data collection will be carried out at 0, 3, 6, 9 and 12 months. DISCUSSION: To the best of our knowledge, no similar study has been conducted in sub-Saharan Africa. This will be an important step towards raising awareness of patients' need and preferences and the strengths and limitations of available health care services for ESRD in resource limited settings.

Response to Correspondence from Kolstoe and colleagues concerning our paper entitled, Research approvals iceberg: How a 'low-key' study in England needed 89 professionals to approve it and how we can do better.

In their letter to the Editor in this issue, Kolstoe and Carpenter challenge a core aspect of our recently published case study of research approvals [BMC Medical Ethics 20:7] by arguing that we conflate research ethics with governance and funding processes. Amongst the key concerns of the authors are: 1) that our paper exemplifies a typical conflation of concepts such as governance, integrity and ethics, with significant consequences for claims around the responsibility and accountability of the organisations involved; 2) that, as a consequence of this conflation, we misrepresent the ethics review process, including in fundamental aspects such as the ethics approval-opinion distinction; 3) that it is difficult to see scope for greater integration of processes such as applying for funding, research approvals, Patient and Public Involvement, etc., as suggested by us. Here we present an alternative point of view towards the concerns raised.

Research approvals iceberg: how a 'low-key' study in England needed 89 professionals to approve it and how we can do better.

BACKGROUND: The red tape and delays around research ethics and governance approvals frequently frustrate researchers yet, as the lesser of two evils, are largely accepted as unavoidable. Here we quantify aspects of the research ethics and governance approvals for one interview- and questionnaire-based study conducted in England which used the National Health Service (NHS) procedures and the electronic Integrated Research Application System (IRAS). We demonstrate the enormous impact of existing approvals processes on costs of studies, including opportunity costs to focus on the substantive research, and suggest directions for radical system change. MAIN TEXT: We have recorded 491 exchanges with 89 individuals involved in research ethics and governance approvals, generating 193 pages of email text excluding attachments. These are conservative estimates (e.g. only records of the research associate were used). The exchanges were conducted outside IRAS, expected to be the platform where all necessary documents are provided and questions addressed. Importantly, the figures exclude the actual work of preparing the ethics documentation (such as the ethics application, information sheets and consent forms). We propose six areas of work to enable system change: 1. Support the development of a broad range of customised research ethics and governance templates to complement generic, typically clinical trials orientated, ones; 2. Develop more sophisticated and flexible frameworks for study classification; 3. Link with associated processes for assessment, feedback, monitoring and reporting, such as ones involving funders and patient and public involvement groups; 4. Invest in a new generation IT infrastructure; 5. Enhance system capacity through increasing online reviewer participation and training; and 6. Encourage researchers to quantify the approvals processes for their studies. CONCLUSION: Ethics and governance approvals are burdensome for historical reasons and not because of the nature of the task. There are many opportunities to improve their efficiency and analytic depth in an age of innovation, increased connectivity and distributed working. If we continue to work under current systems, we are perpetuating, paradoxically, an unethical system of research approvals by virtue of its wastefulness and impoverished ethical debate.

From "wading through treacle" to "making haste slowly": A comprehensive yet parsimonious model of drivers and challenges to implementing patient data sharing projects based on an EPaCCS evaluation and four pre-existing literature reviews.

Conceptually, this study aimed to 1) identify the challenges and drivers encountered by England's Electronic Palliative Care Coordination System (EPaCCS) projects in the context of challenges and drivers in other projects on data sharing for individual care (also referred to as Health Information Exchange, HIE) and 2) organise them in a comprehensive yet parsimonious framework. The study also had a strong applied goal: to derive specific and non-trivial recommendations for advancing data sharing projects, particularly ones in early stages of development and implementation. Primary data comprised 40 in-depth interviews with 44 healthcare professionals, patients, carers, project team members and decision makers in Cambridgeshire, UK. Secondary data were extracted from four pre-existing literature reviews on Health Information Exchange and Health Information Technology implementation covering 135 studies. Thematic and framework analysis underpinned by "pluralist" coding were the main analytical approaches used. We reduced an initial set of >1,800 parameters into >500 challenges and >300 drivers to implementing EPaCCS and other data sharing projects. Less than a quarter of the 800+ parameters were associated primarily with the IT solution. These challenges and drivers were further condensed into an action-guiding, strategy-informing framework of nine types of "pure challenges", four types of "pure drivers", and nine types of "oppositional or ambivalent forces". The pure challenges draw parallels between patient data sharing and other broad and complex domains of sociotechnical or social practice. The pure drivers differ in how internal or external to the IT solution and project team they are, and thus in the level of control a project team has over them. The oppositional forces comprise pairs of challenges and drivers where the driver is a factor serving to resolve or counteract the challenge. The ambivalent forces are factors perceived simultaneously as a challenge and a driver depending on context, goals and perspective. The framework is distinctive in its emphasis on: 1) the form of challenges and drivers; 2) ambivalence, ambiguity and persistent tensions as fundamental forces in the field of innovation implementation; and 3) the parallels it draws with a variety of non-IT, non-health domains of practice as a source of fruitful learning. Teams working on data sharing projects need to prioritise further the shaping of social interactions and structural and contextual parameters in the midst of which their IT tools are implemented. The high number of "ambivalent forces" speaks of the vital importance for data sharing projects of skills in eliciting stakeholders' assumptions; managing conflict; and navigating multiple needs, interests and worldviews.

Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study.

BACKGROUND: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis. METHODS: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235. FINDINGS: From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine-cisplatin group and 344 to the placebo plus gemcitabine-cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6-25·2) in the durvalumab plus gemcitabine-cisplatin group and 22·4 months (21·4-23·8) in the placebo plus gemcitabine-cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine-cisplatin group and 279 (81%) participants in the placebo plus gemcitabine-cisplatin group had died (median overall survival 12·9 months [95% CI 11·6-14·1] vs 11·3 months [10·1-12·5]; hazard ratio 0·76 [95% CI 0·64-0·91]). Kaplan-Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7-28·9) in the durvalumab plus gemcitabine-cisplatin group and 11·5% (7·6-16·2) in the placebo plus gemcitabine-cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine-cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine-cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%]). INTERPRETATION: Durvalumab plus gemcitabine-cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer. FUNDING: AstraZeneca.

A survey of the knowledge, perceptions of and attitudes to digital health of healthcare professionals in 14 Bulgarian hospitals: First large-scale study on digital health in Bulgarian inpatient facilities.

Objective: To explore the knowledge, perceptions of and attitudes to digital health of Bulgarian hospital professionals in the first study of digital health in this professional group. Methods: A paper-based questionnaire was administered to doctors, trainee doctors, nurses, midwives, and laboratory assistants working in multiprofile or specialized hospitals. Topics included the following: state, objectives, benefits, and future of digital health; data storage, access, security, and sharing; main software used; patient-held Personal Information System (PIS); and telemedicine. A total of 1187 participants from 14 hospitals completed the survey in two phases: September 2013-April 2014 and May 2015-April 2017. Data were analyzed through descriptive statistics and multilevel logistic regression. Results: Three-quarters of participants evaluated the state of development of digital health in Bulgaria as subpar (36.0% negative; 38.9% passable; 24.5% positive). 27.2% (323) endorsed patients having unconditional access to their data. In contrast, 89.5% (1062) of participants considered it appropriate to have full access to patient data recorded by colleagues. Doctors were more likely to endorse patients having access to their data than healthcare specialists (OR = 1.79 at facility, OR = 1.77 at location). Conclusion: The largely negative or lukewarm attitudes toward the state of development of digital health in Bulgaria are likely to result from the high number of failed projects, unmet expectations, misunderstood benefits, and unforeseen challenges. This study provides a much-needed stimulus and baseline for researching the ways in which the digital health landscape in Bulgaria has matured-or not.

A synthesis of concepts of resilience to inform operationalization of health systems resilience in recovery from disruptive public health events including COVID-19.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict' Health systems resilience has become a ubiquitous concept as countries respond to and recover from crises such as the COVID-19 pandemic, war and conflict, natural disasters, and economic stressors inter alia. However, the operational scope and definition of health systems resilience to inform health systems recovery and the building back better agenda have not been elaborated in the literature and discourse to date. When widely used terms and their operational definitions appear nebulous or are not consistently used, it can perpetuate misalignment between stakeholders and investments. This can hinder progress in integrated approaches such as strengthening primary health care (PHC) and the essential public health functions (EPHFs) in health and allied sectors as well as hinder progress toward key global objectives such as recovering and sustaining progress toward universal health coverage (UHC), health security, healthier populations, and the Sustainable Development Goals (SDGs). This paper represents a conceptual synthesis based on 45 documents drawn from peer-reviewed papers and gray literature sources and supplemented by unpublished data drawn from the extensive operational experience of the co-authors in the application of health systems resilience at country level. The results present a synthesis of global understanding of the concept of resilience in the context of health systems. We report on different aspects of health systems resilience and conclude by proposing a clear operational definition of health systems resilience that can be readily applied by different stakeholders to inform current global recovery and beyond.

Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer.

PURPOSE: Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues. METHODS: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed. RESULTS: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively. CONCLUSION: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.

Timely community palliative and end-of-life care: a realist synthesis.

BACKGROUND: Community-based and home-based palliative and end-of-life care (PEoLC) services, often underpinned by primary care provision, are becoming increasingly popular. One of the key challenges associated with them is their timely initiation. The latter requires an accurate enough prediction of how close to death a patient is. METHODS: Using 'realist synthesis' tools, this review sought to develop explanations of how primary care and community PEoLC programmes generate their outcomes, with the explanations presented as context-mechanism-outcome configurations. Medline, Embase, CINAHL, PsycINFO, Web of Science, ASSIA, Sociological Abstracts and SCIE Social Care Online were originally searched. A multistage process of focusing the review was employed, with timely identification of the EoL stage and timely initiation of associated services representing the final review focus. Synthesised sources included 21 full-text documents and 324 coded abstracts, with 253 'core contents' abstracts generating >800 codes. RESULTS: Numerous PEoLC policies and programmes are embedded in a framework of Preparation and Planning for Death and Dying, with identification of the dying stage setting in motion key systems and services. This is challenged by: (1) accumulated evidence demonstrating low accuracy of prognostic judgements; (2) many individuals' orientation towards Living and Hope; (3) expanding grey zones between palliative and curative care; (4) the complexity of referral decisions; (5) the loss of pertinent information in hierarchical relationships and (6) the ambiguous value of having 'more time'. CONCLUSION: Prioritising temporal criteria in initiating PEoLC services is not sufficiently supported by current evidence and can have significant unintended consequences. PROSPERO REGISTRATION NUMBER: CRD42018097218.

Lost in reviews: Looking for the involvement of stakeholders, patients, public and other non-researcher contributors in realist reviews.

The involvement of non-researcher contributors (eg, stakeholders, patients and the public, decision and policy makers, experts, lay contributors) has taken a variety of forms within evidence syntheses. Realist reviews are a form of evidence synthesis that involves non-researcher contributors yet this practice has received little attention. In particular, the role of patient and public involvement (PPI) has not been clearly documented. This review of reviews describes the ways in which contributor involvement, including PPI, is documented within healthcare realist reviews published over the last five years. A total of 448 papers published between 2014 and 2019 were screened, yielding 71 full-text papers included in this review. Statements about contributor involvement were synthesized across each review using framework analysis. Three themes are described in this article including nomenclature, nature of involvement, and reporting impact. Papers indicate that contributor involvement in realist reviews refers to stakeholders, experts, or advisory groups (ie, professionals, clinicians, or academics). Patients and the public are occasionally subsumed into these groups and in doing so, the nature and impact of their involvement become challenging to identify and at times, is lost completely. Our review findings indicate a need for the realist review community to develop guidance to support researchers in their future collaboration with contributors, including patients and the public.

Gemcitabine/Nab-Paclitaxel versus FOLFIRINOX in Locally Advanced Pancreatic Cancer: A European Multicenter Study.

BACKGROUND: Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX (FFX) are two standard first-line therapies for metastatic pancreatic cancer (PC) but have rarely been compared, especially in patients with locally advanced PC (LAPC). METHODS: This is a retrospective European multicenter study including patients with LAPC treated with either GN or FFX as the first-line therapy between 2010 and 2019. Coprimary objectives were progression-free survival (PFS) and overall survival (OS), both estimated using the Kaplan-Meier method. RESULTS: A total of 147 patients (GN: n = 60; FFX: n = 87) were included. Tumor resection rates were similar between the two groups (16.7% vs. 16.1%; p = 1), with similar R0 resection rates (88.9%). Median PFS rates were not statistically different: 9 months (95% CI: 8-13.5) vs. 12.1 months (95% CI: 10.1-14.6; p = 0.8), respectively. Median OS rates were 15.7 months (95% CI: 12.6-20.2) and 16.7 months (95% CI: 14.8-20.4; p = 0.7), respectively. Abdominal pain at the baseline (HR = 2.03, p = 0.03), tumors located in the tail of the pancreas (HR = 4.35, p = 0.01), CA19-9 > 200 UI/L (HR = 2.03, p = 0.004) and tumor resection (HR = 0.37, p = 0.007) were independent prognostic factors for PFS, similarly to OS. CA19-9 ≤ 200 UI/L (OR = 2.6, p = 0.047) was predictive of the tumor response. Consolidation chemoradiotherapy, more often used in the FFX group (11.7% vs. 50.6%; p < 0.001), was not predictive. CONCLUSION: This retrospective study did not show any difference between GN and FFX as the first-line treatment in patients with LAPC.

Benefits and challenges of employing health care assistants in general practice: a qualitative study of GPs' and practice nurses' perspectives.

BACKGROUND: Estimates suggest that over half of general practices in England currently employ a health care assistant (HCA) but there is little evidence of their impact, effectiveness and acceptability to patients and primary care team members. OBJECTIVES: To explore the role of HCAs in general practice and the benefits and challenges associated with their employment. METHODS: Semi-structured interviews were performed with 6 GPs and 13 practice nurses as part of a larger qualitative study that also included HCAs. Interviewees were from 16 general practices from two Primary Care Trusts in the West Midlands. Transcripts were analyzed using thematic and framework analysis. RESULTS: HCAs were seen as a valuable addition to the primary care team. They were reported to accelerate, rather than extend services, allow more appropriate use of nurses' skills and enable cost containment. Their training and supervision were felt as time intensive, demanding of time and commitment. Patient safety was raised as a concern, although no specific experience of it being compromised was reported. Nurses recognized the usefulness of HCAs, helped to make the role work, but were often anxious about the impact on their own roles and professional identity. Patients were perceived as being generally neutral or positive. CONCLUSION: Cost-effectiveness, patient safety, quality of care, potentially contested role boundaries and patient attitudes are among the issues that policy-makers, commissioners and those responsible for workforce development and training need to consider in relation to HCAs in general practice. There is also a need for more in-depth evaluation of this role.

The role and impact of facilitators in primary care: findings from the implementation of the Gold Standards Framework for palliative care.

BACKGROUND: Facilitation is the process of providing support to individuals or groups to achieve beneficial change. It is intrinsic to the Gold Standards Framework (GSF) for palliative care, a programme introduced widely in UK general practices. OBJECTIVES: To explore how GSF facilitators fulfil their role and the impact of the facilitators' backgrounds and approach on practices' uptake of the programme. SETTING: Primary care organizations and general practices in England and Northern Ireland. METHODS: Self-completed questionnaire and semi-structured interviews with facilitators. Practice audit questionnaire. Descriptive statistics. Thematic analysis. Linear and random effects models. RESULTS: A total of 102 (59.6%) facilitators completed a questionnaire; interviews were performed with nine facilitators. A large variability was found in the facilitators' professional backgrounds, role setup and activities. The impact of several facilitation characteristics on practice change was modelled for 63 (36.8%) facilitators and 266 practices (20.4%). No evidence was found of an association between practice change and facilitators' specialist knowledge of palliative care, mean facilitation time per practice, mean number of visits, facilitator budget and incentives offered to practices. Facilitators with a GP background were associated with higher levels of GSF change than those with a clinical nurse specialist background (P = 0.0078 with Bonferroni correction, significance threshold for corrected P = 0.008). The interviews indicated that the differential implementation of the framework might have been strongly affected by internal and external practice-related factors that were not readily amenable to facilitation. CONCLUSION: This study goes some way towards untangling aspects of facilitation associated with successful implementation of the GSF. Further prospective research and evaluation is needed to identify ways of improving its sustainability, effect on patient outcomes and cost-effectiveness.

Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer.

The aim of this multicentric retrospective study is to evaluate the predictive and prognostic performance of neutrophil to lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and their dynamics in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab as a second line. Patients with metastatic NSCLC (n = 119), whose tumors expressed programmed death-ligand 1 (PD-L1) ≥ 1%, were retrospectively analyzed between Apr 2017 and Apr 2019. All patients received platinum-containing chemotherapy as a first line treatment. Pre-treatment NLR was calculated by dividing the number of neutrophils by the number of lymphocytes in peripheral blood before the first pembrolizumab infusion. Progression free survival (PFS) and overall survival (OS) was compared by Kaplan-Meier method and Cox Proportional Hazard model. Patients with NLR > 5 before immunotherapy showed significantly shorter mean PFS of 6.86 months (95% CI: 5.81-7.90) as compared to those with NLR ≤ 5 of 18.82 months (95% CI: 15.87-21.78) (long rank test p < 0.001). Furthermore in the multivariate analysis, only NLR > 5 was an independent predictive factor for shorter PFS (HR: 4.47, 95% CI: 2.20-9.07, p < 0.001). In multivariate analysis, presence of bone metastases (HR: 2.08, 95% CI: 1.10-4.94, p = 0.030), NLR > 5 before chemotherapy (HR: 8.09, 95% CI: 2.35-27.81, p = 0.001) and high PLR before chemotherapy (HR: 2.81, 95% CI: 1.13-6.97, p = 0.025) were found to be independent negative prognostic factors for poor OS. Our data suggests that NLR ≤ 5 is a potential predictive marker, which may identify patients appropriate for immunotherapy as a second line treatment.

Oncologist Burnout Syndrome in Eastern Europe: Results of the Multinational Survey.

PURPOSE: Burnout is defined as a three-dimensional syndrome-emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA)-caused by chronic occupational stress. The aim of the current study was to investigate the prevalence of burnout among oncologists in Eastern Europe and to identify the contributing factors. METHODS: The study was conducted as an online survey between October 2017 and March 2018. Oncologists (including medical, radiation, clinical, and surgical oncologists) from 19 countries were invited to participate. The survey consisted of 30 questions, including the standardized burnout instrument, Maslach Burnout Inventory, and eight demographic questions. Burnout risk was scored according to the scoring manual for health care workers. RESULTS: The study included 637 oncologists. Overall, 28% were at low or intermediate risk and 72% were at high risk for burnout. Forty-four percent of participants were at high risk for EE, 28.7% for DP, and 47.3% for PA. EE risk was associated with female sex. DP risk was highest among clinical and radiation oncologists, whereas PA risk was positively correlated with years of service, percentage of cancer deaths, and availability of the number of oncologists. In multivariate logistic regression analysis, burnout was significantly associated with standardized cancer mortality and fewer years of practice. CONCLUSION: Burnout among oncologists in Eastern Europe is high, and younger oncologists are the most vulnerable group. Preventive measures should be taken to address this issue, which negatively affects optimal care delivery and poses a threat to oncologists' health and well-being.