Advanced Illness Research Articles

Family Medicine Residents' Knowledge and Attitudes About End-of-Life Care in Taif City, Saudi Arabia.

Background End-of-life care is essential for individuals with advanced illness and their families, providing comfort, symptom control, and dignity in the final year of life. Additionally, physician competence requires the ability to communicate, make decisions, and create relationships in end-of-life care. This study assesses family physicians' knowledge and attitude regarding end-of-life care in Taif, Saudi Arabia. Methods Thisdescriptive cross-sectional study conducted between October and November 2021 assessed the knowledge and attitudes of 163 family physicians in Taif City, Saudi Arabia, regarding end-of-life care. Using a convenient sampling technique, an adapted and validated questionnaire was administered electronically, collecting sociodemographic information and assessing participants' knowledge and attitudes. Data were analyzed using descriptive statistics in Statistical Product and Service Solutions (SPSS, version 28) (IBM SPSS Statistics for Windows, Armonk, NY). Results Findings included that 41.1% of residents believed the patient and family should be informed about diagnoses and prognoses in advanced diseases. At the same time, attitudes varied, with 45.4% agreeing that discussing such information could lead to patient depression and 42.9% believing it held no privilege for patients. Additionally, 57.7% recognized that grief reactions would occur, but patients would eventually adjust, and 44.8% agreed that discussing diagnoses would decrease patient anxiety. However, limited awareness of advance directives was evident, with 12.3% reporting being well aware and 45.4% having never heard of them. There was uncertainty and hesitancy regarding Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decisions, with 39.9% being well aware and 46% having heard of it without a strong understanding. Conclusion The findings revealed a mixed landscape, with physicians demonstrating awareness of the importance of transparent communication but needing more knowledge in areas such as advance directives and complex decision-making. The study highlighted the need for targeted education to address these gaps and promote a more informed and consistent approach to end-of-life care.

Challenges regarding informed consent in recruitment to clinical research: a qualitative study of clinical research nurses’ experiences

BackgroundClinical research nurses (CRNs) have first-hand experience with ethical challenges and play a crucial role in upholding ethical conduct and adherence to the principles of informed consent in clinical research. This study explores the ethical challenges encountered by CRNs in the process of obtaining informed consent for clinical research.MethodsA qualitative exploratory design. Semistructured interviews (n = 14) were conducted with diverse CRNs in Sweden. These CRNs covered a wide range of research fields, including pharmaceutical and academic studies, interventions, and observational research, spanning different trial phases, patient categories, and medical conditions. The interviews were analysed using inductive qualitative content analysis.ResultsThe analysis identified three main categories: (i) threats to voluntariness, (ii) measures to safeguard voluntariness, and (iii) questionable exclusion of certain groups. CRNs face challenges due to time constraints, rushed decisions, information overload, and excessive reliance on physicians’ recommendations. Overestimating therapeutic benefits in stages of advanced illness emerged as a risk to voluntariness. CRNs outlined proactive solutions, such as allowing ample decision-making time and offering support, especially for terminally ill patients. Concerns were also voiced about excluding certain demographics, such as those with language barriers or cognitive impairments.ConclusionsIn conclusion, upholding ethical research standards requires recognising various factors affecting patient voluntariness. Researchers and CRNs should prioritise refining the informed consent process, overcoming participation challenges, and aligning scientific rigour with personalised care. Additionally, a concerted effort is vital to meet the diverse needs of patient populations, including equitable inclusion of individuals with language barriers or cognitive limitations in clinical studies. These findings have significant implications for enhancing the ethics of clinical research and advancing person-centred care.

Across race, ethnicity, and language: An intervention to improve advance care planning documentation unmasks health disparities.

Racial and ethnic minority groups are less likely to have advance directives and living wills, despite the importance of advancedcare planning (ACP) in end-of-life care. We aimed to understand the impact of an intervention to improve ACP documentation across race, ethnicity, and language on hospitalized patients at our institution. We launched an intervention to improve the rates of ACP documentation for hospitalized patients aged >75 or with advanced illness defined by the International Classification of Diseases 10th Revision codes. We analyzed ACP completion rates, preintervention, and intervention, and used interrupted time-seriesanalyses to measure the differential impact of the intervention across race, ethnicity, and language. A total of 10,220 patients met the inclusion criteria. Overall rates of ACP documentation improved from 13.9% to 43.7% in the intervention period, with a 2.47% monthly increase in ACP documentation compared to baseline (p < .001). During the intervention period, the rate of ACP documentation increased by 2.72% per month for non-Hispanic White patients (p < .001), by 1.84% per month for Latinx patients (p < .001),and by 1.9% per month for Black patients (p < .001). Differences in the intervention trends between non-Hispanic White and Latinx patients (p = .04) and Black patients (p = .04) were significant. An intervention designed to improve ACP documentation in hospitalized patients widened a disparity across race and ethnicity with Latinx and Black patients having lower rates of improvement. Our findings reinforce the need to measure the impact of quality improvement interventions on existing health disparities and to implement specific strategies to prevent worsening disparities.

Hodgkin Lymphoma - Mitigating Toxicity While Preserving Cure - Eight Year Data from MIOT International, Chennai, India

Background One of the most treatable cancers, Hodgkin's lymphoma (HL), has a 5-year survival rate of approximately 85%.We still see relapse and refractoriness in a tiny percentage of patients despite the fact that our disease is largely curable, and we also have additional issues including secondary neoplasia and long-term consequences on the heart. Our Hodgkin lymphoma statistics from 2011 to 2019 have been given in this paper. Methodology Between 2011 and 2019, data on patients with newly diagnosed classical HL (CHL) who received treatment were gathered. Analysis was done on the presenting characteristics, IPS risk classification, treatment procedures, treatment response, and 3-year outcome data. Results At presentation, there were 97 patients with newly diagnosed CHL, with a median age of 24 years (range, 11-72). The ratio of men to women was 1.62:1. Mixed cellularity, lymphocyte-rich, and lymphocyte-depleted CHL (LD, CHL) were histological subtypes that were present in 80.40%, 12.40%, and 7.20% of cases, respectively. At presentation, 52% of patients had advanced illness, and 80% had B symptoms. The Hodgkin IPI score was high in 58% of individuals with advanced stages. ABVD was given as the first line of therapy to 92% of patients. According to interim PET-CT scan findings, around 7 advanced stage Hodgkin patients were started with EscBEACOPP and then switched to ABVD prior to 2017. The front line treatment's overall response rate was 94.8%. Complete response rates for early-stage favourable and unfavourable risk groups were 94% and 86%, respectively, whereas they were 81% and 67% for advanced-stage low- and high-risk groups. The median duration of event free survival was 36 months. The 3-year EFS showed a significant difference between the early- and advanced-stage diseases, 93% and 81%, respectively (p 0.04). Relapse was found in eight patients, all of whom had BEAM Autograft post platinum based salvage treatment. Following interim PET negativity, we discontinued Bleomycin according to RATHL protocol. Three of our patients had bleomycin lung injury. Three patients had post-autograft recurrence, one of whom passed away due to a subsequent non-Hodgkin lymphoma. With the Brentuximab Bendamustine regimen, two patients were successfully salvaged and they had Haplo-identical transplant as third line salvage. Conclusions In early and late stage Hodgkin lymphoma, the three year EFS of 93% and 81% is equivalent to most western literature. In light of our little experience with Indian patients, the effect of Brentuximab is overwhelmingly favorable. At our facility, post-Autograft Brentuximab maintenance is being tested. There is no information on how Nivolumab will be useful in our context. Although there is little evidence to draw a conclusion that is statistically significant, frontline ABVD protocol treatment across risk categories and discontinuing Bleomycin after interim PET negative are helpful in our patients to enhance prognosis and decrease toxicity. Reference: Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma N Engl J Med 2016; 374:2419-2429 DOI: 10.1056/NEJMoa1510093Mohty, R., Dulery, R., Bazarbachi, A.H. et al. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J. 11, 126 (2021). https://doi.org/10.1038/s41408-021-00518-z

Communication strategies used by medical physicians when delivering bad news at the Maputo Central Hospital, Mozambique: a cross-sectional study

BackgroundPhysicians’ communication with patients and their families is important during both the disease diagnosis and prognosis stages and through the follow-up process. Effective physician communication improves patients’ quality of life and satisfaction with care and helps reduce suffering for those newly diagnosed with advanced progressive illnesses. This study aims to identify the communication strategies physicians use in the transition to palliative care and how these professionals perceive their academic and clinical preparation concerning this task.MethodsA cross-sectional and quantitative study. Physicians providing palliative care at the Maputo Central Hospital, Mozambique, were invited to complete a 17-question questionnaire. This questionnaire was based on a Brazilian adaptation of the Setting-Perception-Invitation-Knowledge-Emotions-Strategy (SPIKES) tool, the P-A-C-I-E-N-T-E protocol, with additional questions regarding socio-demographic details and the integration of “communication of bad news” into hospital training.ResultsOf the 121 participants, 62 (51.2%) were male, and 110 (90.9%) were general practitioners, with a median age of 36 years old. They had worked in clinical practice for a median of 8 years and in their current department for three years. The majority of the participants considered that they have an acceptable or good level of bad news communication skills and believed that they do it in a clear and empathic way, paying attention to the patient’s requests and doubts; however, most were not aware of the existing tools to assist them in this task and suggested that delivering bad news ought to be integrated into the undergraduate medical course and included in hospital training.ConclusionsThis study adds to our understanding of physicians’ strategies when communicating bad news in the context of palliative care at one Mozambique hospital. As palliative care is not fully implemented in Mozambique, it is important to use protocols suitable to the country’s healthcare level to improve how doctors deal with patients and their family members.

Polypharmacy and the In Silico Prediction of Potential Body Proteins Targeted by These Drugs Among Hospitalized COVID-19 Patients With Cytokine Storm.

Background and objective Polypharmacy is prevalent in coronavirus disease 2019 (COVID-19) patients with severe disease. However, information on polypharmacyamong COVID-19patients who also suffer fromcytokine storm is scarce. In light of this, the purpose of the present study was to assess the incidence of polypharmacy and in silico prediction of potential body proteins targeted by these drugs among hospitalized COVID-19 patients who were identified to have the additional burden of cytokine storm in the city of Duhok, Kurdistan Region, Iraq. Methods This was a cross-sectional observational study conducted from June 2021 to April 2022; the phenomena of major polypharmacy (six to nine medications) and excessive polypharmacy (≥10 medications)were documented among 33 (15 males and 18 females) COVID-19 patients with cytokine storm during their hospital stay (8-45 days) in Duhok, Kurdistan Region, Iraq. The SwissTargetPrediction program was utilized in silico to predict and identify human body proteins that could be potentially targeted by selected medications involved in polypharmacy. Results All patients had tested positive forCOVID-19 via PCR testing, and they showed different signs and symptoms of the disease. None of the patients recovered and all of them deceased. All 33 patients received many therapeutic agents that ranged in number from eight to 20/patient during their hospital stay. The mean number ofmedications was 15 ± 3. We identified 2/33 (6%) patients with major polypharmacy (eight and nine) and 31/33 (94%) withexcessive polypharmacy(15.5 ± 2.7). The total number of medications identified inpolypharmacy was 37, excluding vitamins, minerals, and intravenous solutions. The frequency of medications administered was as follows: antibiotics (67, 13.7%), mucolytic agents (56, 11.5%), corticosteroids (54, 11%), anticoagulants (48, 9.8%), antiviral agents (41, 8.4%), antihypertensive agents (32, 6.5%), analgesics (28, 5.7%), antifungal drugs (27, 5.5%), antidiabetics (26, 5.3%), and other medications (2-19, 0.41-3.9%). Using the SwissTargetPrediction program, various drugs including antiviral agents involved in polypharmacy were found to target, in silico, body proteins at a prediction percentagethat ranged from 6.7% to 40%. Conclusions Major and extensive polypharmacy conditions were identified in hospitalized COVID-19 patients suffering fromcytokine storm.The severity of COVID-19 with cytokine storm, comorbidities, and hospitalization were key factors associated with polypharmacy in the patients.The SwissTargetPrediction web server is useful for predicting in silico potential human body protein targets that could possibly be sources of additional information on theadverse/toxic effects of polypharmacy medications administered concurrently. Further research in current medication protocols prescribed for advanced COVID-19 illness with cytokine storm is warranted to gain deeper insights into the topic.

Subcutaneous ketamine infusion in palliative patients for major depressive disorder (SKIPMDD)-Phase II single-arm open-label feasibility study.

Ketamine at subanaesthetic dosages (≤0.5mg/kg) exhibits rapid onset (over hours to days) antidepressant effects against major depressive disorder in people who are otherwise well. However, its safety, tolerability and efficacy are not known for major depressive disorder in people with advanced life-limiting illnesses. To determine the feasibility, safety, tolerability, acceptability and any antidepressant signal/activity to justify and inform a fully powered study of subcutaneous ketamine infusions for major depressive disorder in the palliative setting. This was a single arm, open-label, phase II feasibility study (Australian New Zealand Clinical Trial Registry Number-ACTRN12618001586202). We recruited adults (≥ 18-years-old) with advanced life-limiting illnesses referred to four palliative care services in Sydney, Australia, diagnosed with major depressive disorder from any care setting. Participants received weekly subcutaneous ketamine infusion (0.1-0.4mg/kg) over two hours using individual dose-titration design. Outcomes assessed were feasibility, safety, tolerability and antidepressant activity. Out of ninety-nine referrals, ten participants received ketamine and were analysed for responses. Accrual rate was 0.54 participants/month across sites with 50% of treated participants achieving ≥ 50% reduction in baseline Montgomery-Åsberg Depression Rating Scale, meeting feasibility criteria set a priori. There were no clinically relevant harms encountered. A future definitive trial exploring the effectiveness of subcutaneous infusion of ketamine for major depressive disorder in the palliative care setting may be feasible by addressing identified study barriers. Individual dose-titration of subcutaneous ketamine infusions over two hours from 0.1mg/kg can be well-tolerated and appears to produce transient antidepressant signals over hours to days.

Exploring the health-related decision-making experiences of people with chronic kidney disease and their caregivers: A qualitative study.

This study aimed to explore the decision-making experience of patients with chronic kidney disease (CKD) and their caregivers. This was a qualitative descriptive study of the decision-making experiences of individuals with stage 3-end-stage CKD and their family caregivers. One-on-one, semistructured interviews were conducted using a guide developed and approved by a community advisory group. Data were analyzed using thematic analysis. Three themes were identified: (1) decisions triggered by declining health and broad in scope, (2) challenges to decision-making and (3) factors influencing decision-making. Participants' experiences with health-related decision-making demonstrated that decisions were triggered when health declined. Yet, decisions that impact disease progression were being made in stage 3. Decision-making was made difficult due to lack of information, complex co-morbidities, and poor resource utilization. However, the structure and nature of the medical appointment, supportive caregivers, and resources served to remove challenges. Decision-support interventions must train patients and caregivers to be empowered participants in answer-seeking behaviours upstream of advanced illness. This work was conducted in full collaboration with a community advisory board consisting of patients with CKD, caregivers and clinicians. These members are noted in the acknowledgement section, and those who worked with the team to develop the interview guide, study protocols, and manuscript preparation are included as authors. As part of their role, advisory members met monthly, providing input on recruitment, study progress, inclusion of diverse voices and added relevance to study findings.

Impact of paramedics carrying just-in-case end-of-life care medication

Background: Early in the COVID-19 pandemic, it was predicted that frail community patients with symptoms of severe COVID-19 infection may need urgent symptom management—and that unless they had already been identified as being in their last weeks of life, they would be unlikely to have just-in-case (JIC) medications at home. The Welsh Ambulance Services NHS Trust therefore placed JIC medications on emergency ambulances to increase symptom management options for paramedics treating patients with symptoms of severe COVID-19 infection and/or associated with advanced end-stage illness. Methods: A review of medications to palliate symptoms of severe COVID-19 infection and advanced and terminal illness was undertaken. A verbal order process was implemented, allowing prescription-only medications to be administered by paramedics. Guidance, training and data capture processes were designed and implemented. Results: Symptoms associated with advanced cancer were the main reason for giving ambulance-based JIC medications, and midazolam and morphine were the most administered medicines. No adverse incidents were reported or recorded. Conclusion: Ambulance-based JIC medications were and continue to be appropriately administered, irrespective of life-limiting illness diagnosis. Although carrying JIC medicines on ambulances was introduced in response to the COVID-19 pandemic, 12 months of data collection indicates this is a safe, cost-effective, patient-centred practice.

The utilization and perceptions of chaplaincy among patients of Dharmic religions in a cancer hospital: A mixed methods study.

83 Background: Spiritual care administered through chaplaincy services (CS), is an integral component of cancer care in the US; however, chaplaincy utilization (CU) among patients who identify with a Dharmic religion (DR; Hinduism, Buddhism, Sikhism, Jainism) is unknown. This study measures CU and explores perceptions of CS among hospitalized DR patients with cancer. Methods: A retrospective chart review identified patients hospitalized in a specialty cancer center in New York City between 2015 and 2019. The primary objective was to measure proportions of DR and non-DR (NDR) patients with CU (≥1 CS visit); secondary objectives included identifying factors associated with CU. Demographics, length of stay (LOS), total number of CS visits, and disposition were collected. Bivariate and multivariate logistic regression analyses examined associations between religion, age, race, language, LOS and advanced illness (AI; ICU admission, inpatient death, hospice discharge) with CU. Semi-structured interviews were conducted to explore CS perceptions and preferences among DR patients with cancer in 2020. Data was coded and analyzed independently and iteratively by two investigators and themes were identified. Results: Of 54,828 patients, 59% identified as Christian, 14% identified as Jewish, and 2% identified with a DR (n=1163; 58% Hindu, 33% Buddhist, 4.8% Sikh, 3.4% multiple faiths, 0.2% Jain). Compared to NDR patients, DR patients were younger (median age 59 vs. 63, p&lt;0.001), more likely East or South Asian (79% vs. 5.6%, p&lt;0.001), had more AI (23% vs 15%, p&lt;0.001), but lower CU (37% vs 32%, P&lt;0.001). In multivariable analysis, LOS, NDR, and AI were associated with CU (Table); with Non-Hispanic, White as the reference group, race was not associated with CU. Twenty-two patients (91% Hindu, 9% Sikh) were interviewed. Few reported being approached about CS during their admission, and most expressed unfamiliarity with CS. Some felt CS and spiritual care was tailored to Jewish and Christian faiths but not DR. Suggestions for the hospital included having DR-specific chaplains, religious materials, and worship space. Conclusions: Despite more AI, CU was lower among DR patients. DR patients identified unfamiliarity and/or NDR perceptions as barriers to CS and recommended greater access to faith-specific resources. More work is needed to deliver faith-concordant spiritual care for DR patients.[Table: see text]

A casemix classification for those receiving specialist palliative care during their last year of life across England: the C-CHANGE research programme

A casemix classification for those receiving specialist palliative care during their last year of life across England: the C-CHANGE research programme

Patient and caregiver reciprocal support: Impact on decision making in specialist palliative care.

Patients and informal caregivers in palliative care can reciprocate in supporting one another. However, how reciprocal support among patients and informal caregivers in palliative care impacts on their decision making for care is not well understood. To identify how reciprocal support among patients with advanced illness and their informal caregivers in specialist palliative care impacts on their decision making for care. Between July 2021 and May 2022, 30 qualitative interviews were conducted with 14 patient and caregiver dyads, seven non-dyad caregiver participants and one non-dyad patient participant (total n=36), recruited from a large regional specialist palliative care service. Data were analyzed using Corbin and Strauss grounded theory method. Reciprocal support among patients and informal caregivers was underpinned by obligation and choice. Caregivers who felt obliged to care had difficulty communicating with the patient about the patient's preferences for care and their own wishes for patient care. Patients who felt obliged to accept support from their caregiver tended to minimize caregiver participation in decision making which made caregivers feel disempowered in discussions about patient care. Caregivers tended to be more involved in decision making when caregivers assumed caregiving duties by choice and when the patient did not feel restricted by their reliance on their caregiver. Open communication between patients and caregivers made patients more trusting of their caregiver. Patient and caregiver dyadic interventions in specialist palliative care involving decision making need to account for how obligation and choice manifest and function between the patient and caregiver.

(131) Addressing Advanced Care Planning Difficulties in Patients with Terminal or Advanced Illness with Comorbid Mood Disorders and Suicidal Behavior

(131) Addressing Advanced Care Planning Difficulties in Patients with Terminal or Advanced Illness with Comorbid Mood Disorders and Suicidal Behavior

Registered Nurses' beliefs about end-of-life care: A mixed method study.

To examine registered nurses' (RNs) behavioural, normative and control beliefs about end-of-life care for patients who are diagnosed with advanced and life-limiting illnesses; and to identify the barriers and facilitators they experience when providing end-of-life care. A sequential explanatory mixed methods study. An online cross-sectional survey was conducted using the Care for Terminally Ill Patient tool among 1293 RNs working across five hospitals in the Kingdom of Saudi Arabia. Online individual semi-structured interviews with a subgroup of survey respondents were then undertaken. Data were collected between October 2020 to February 2021. A total of 415 RNs completed the online survey, with 16 of them participating in individual interviews. Over half of the participants expressed the belief that end-of-life care is most efficiently delivered through multidisciplinary team collaboration. The majority of participants also believed that discussing end-of-life care with patients or families leads to feelings of hopelessness. Paradoxically, the study revealed that more than half of the participants held the negative belief that patients at the end of life should optimally receive a combination of both curative and palliative care services. The results showed that nurses' beliefs were significantly associated with their age, religion, ward type, level of education and frequency of providing end-of-life care. Data from the qualitative interviews identified four themes that explored RNs' beliefs and its related factors. The four themes were 'holistic care', 'diversity of beliefs', 'dynamics of truth-telling' and 'experiences of providing end-of-life care.' Wherever possible, patients at the end-of-life should be cared for in specialist settings by multidisciplinary teams to ensure effective, high-quality care. Where this is not possible, organisations should ensure that teams of multidisciplinary staff, including nurses, receive education and resources to support end-of-life care in non-specialist settings. Hospitals that employ foreign-trained nurses should consider providing targeted education to enhance their cultural competence and reduce the impact of different beliefs on end-of-life care.

Mutual support between patients and family caregivers in palliative care: A qualitative study

Background: Patients in receipt of palliative care services are often viewed primarily as recipients of support from their family caregiver. There is a dearth of evidence in palliative care on what comprises mutual support between patients and their family caregivers in palliative care. Aim: To identify processes of mutual support between patients and family caregivers in palliative care. Design: Qualitative study comprising semi-structured interviews. Data were analysed using grounded theory procedures. Setting/participants: Fifteen patients with advanced illness (cancer n = 14, neurodegenerative n = 1) and 21 family caregivers recruited from a large regional-based hospice. Results: Mutual support between patients and family caregivers comprised two primary modes in which support was provided and received. Mutual support involved both patients and family caregivers providing similar types of support to each other, and which typically manifested as emotional support. However, mutual support also occurred when patients reciprocated by providing emotional support to their family caregivers to compensate for other forms of support which they felt no longer able to provide. Patients supported family caregivers by involving them in decision-making for care and both patient and family caregiver preferences were influenced by obligation to their respective other. Mutual support comprised both disclosure and concealment. Involving family caregivers in patient care decision-making was intended by patients to help family caregivers adjust to a caregiving role. Conclusions: The findings inform the development and delivery of psychosocial interventions for patients and family caregivers in palliative care aimed at facilitating supportive relations between them.

FGF19 promotes nasopharyngeal carcinoma progression by inducing angiogenesis via inhibiting TRIM21-mediated ANXA2 ubiquitination

PurposeNasopharyngeal carcinoma (NPC) has characteristics of high invasion and early metastasis. Most NPC patients present with locoregionally advanced illness when first diagnosed. Therefore, it is urgent to discover NPC biomarkers. Fibroblast growth Factor 19 (FGF19) plays a role in various physiological or pathological processes, including cancer. In this research, we discovered the importance of FGF19 in NPC, and clarified its role in tumour angiogenesis.MethodsWestern blotting, immunohistochemistry and ELISA were used to investigate FGF19 expression in NPC. Then we took CCK8, colony formation, Transwell and wound healing assays to identify the influence of FGF19 on NPC malignant behaviours. The proliferative and metastatic capacity of FGF19 were evaluated in nude mice and zebrafish. The role of FGF19 in angiogenesis was investigated by tube formation and Matrigel plug angiogenesis assays. We then evaluated the variation in Annexin A2(ANXA2) levels with the treatment of FGF19. Lastly, co-immunoprecipitation and ubiquitination assays were performed to identify the mechanisms involved.ResultsFGF19 levels were elevated in tissues and serum of NPC patients and were associated with poor clinical stages. High expression of FGF19 promoted NPC malignant behaviours. In particular, FGF19 expression was correlated with microvessel density in tissues and NPC-derived FGF19 could accelerate angiogenesis in vitro and in vivo. Mechanistically, FGF19 influenced ANXA2 expression to promote angiogenesis. Moreover, tripartite motif-containing 21(TRIM21) interacted with ANXA2 and was responsible for ANXA2 ubiquitination.ConclusionFGF19 promoted NPC angiogenesis by inhibiting TRIM21-mediated ANXA2 ubiquitination. It may serve as a noninvasive biomarker for NPC and provides new insights for therapy.

Impact of Patient Subgroups on the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients with Advanced Illness.

We evaluated the impact of baseline patient characteristics on safety and efficacy of methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, in patients with advanced illness with opioid-induced constipation (OIC). This analysis pooled data from 2 randomized, double-blind, placebo-controlled studies (study 302: NCT00402038; study 4000: NCT00672477) in patients with advanced illness, including cancer, and OIC. Patients were randomized to receive subcutaneous methylnaltrexone (study 302: 0.15 mg/kg; study 4000: 8 or 12 mg based on weight) or placebo every other day for 2 weeks. The proportions of patients achieving rescue-free laxation within 4 or 24 hours after the first dose of study drug were assessed in patient subgroups stratified by baseline age, Eastern Cooperative Oncology Group (ECOG) performance status, cancer status, laxative type, and opioid requirement. Treatment-emergent adverse events (TEAEs) were evaluated. Overall, 363 patients were included in this analysis (methylnaltrexone, 178; placebo, 185). Mean (SD) age was 66.3 (13.7) years and 48.5% were men overall. A significantly greater proportion of patients receiving methylnaltrexone versus placebo achieved rescue-free laxation within 4 hours (111/178 [62.4%] vs 31/185 [16.8%]; P<0.0001) and 24 hours (135/178 [75.8%] vs 81/185 [43.8%]; P<0.0001) of the first dose. These trends were consistent across all subgroups. Most patients experienced ≥1 TEAE in the overall population (methylnaltrexone, 82.1%; placebo, 76.2%), which remained consistent when stratified by baseline characteristics. More than half of TEAEs were gastrointestinal in nature. Abdominal pain was more common in patients receiving methylnaltrexone than placebo across baseline characteristic subgroups. Methylnaltrexone treatment was superior to placebo in achieving rescue-free laxation within 4 and 24 hours after the first dose, irrespective of patients' cancer status, baseline ECOG performance status, or baseline opioid or laxative use. The methylnaltrexone safety profile remained consistent across baseline characteristic subgroups.

Acute Kidney Injury in Neonates: A Single-Center Experience

Background: Neonatal intensive care unit infants frequently experience acute kidney damage. Estimates of the prevalence of acute kidney vary depending on the definitions used. In Iraq, studies addressing the prevalence and risk factors of acute kidney injury in this age group are scarce, none of which has implicated the KDIGO diagnostic and staging criteria. Objectives: To describe the prevalence, demographics, risk factors, etiology, and staging of acute kidney injury using KDIGO criteria in the Neonatal intensive care unit and correlate these findings with patient outcomes. Methods: A retrospective study was conducted in the Neonatal Intensive Care Unit/ CWTH/ Medical City Complex/ Baghdad during the period from the 1st of August 2019 to the 15th of January 2020. All neonates diagnosed with acute kidney injury according to KDIGO –classification 2012 and admitted to the neonatal intensive care unit were included in this study. Demographics, clinical staging, and investigations were retrieved from patients' notes. Results: The prevalence of acute kidney damage was 7.2%. The mean gestational age of the patients was 36.8 ± 2.9 weeks, 58% of them were full-term, with a male-to-female ratio of 1.40:1. Stage I patients represented 35.1%, 43.2% were stage 2, and 21.6% had severe stage 3. Acute kidney injury-related mortality was 35.1%. The term female sex, high birth weight, and age younger than seven days at diagnosis predicted a bad prognosis. Vaginally delivered, stage III acute kidney injury-KDIGO, and peritoneal dialysis patients had the worst outcomes. Asphyxia was a major cause of acute kidney injury (P=0.001). High blood urea (P=0.01), low PH (P=0.009), low HCO3 (P=0.001), low WBC count (P=0.001), and low platelet count (0.001) were associated with unfavorable outcomes. Conclusions: The prevalence of acute kidney injury, according to KIDGO diagnostic and staging criteria, is 7.1%. Asphyxia, female gender, and vaginal deliveries are variables associated with poor prognosis in addition to advanced illness stage and laboratory indicators. Received: Dec. 2022 Accepted: Jun 2023 Published: Oct.2023

ANALYSIS OF COMMON SYMPTOMS USING THE EDMONTON SYMPTOM ASSESSMENT SYSTEM IN TERMINALLY ILL CANCER PATIENTS RECEIVING PALLIATIVE CARE AT A TERTIARY CARE CENTER OF NEPAL

Background: The Edmonton Symptom Assessment System (ESAS) is a reliable tool to assess the severity of Symptom over time. It evaluates nine symptoms commonly experienced by patients with cancer and other advanced illness. The aim of this study is to find the prevalent symptoms, intensity and prognostic significance of common symptoms in cancer patients. Methods: This prospective cross-sectional study enrolled 110 patients with terminal cancer receiving palliative care admitted at clinical oncology department of Bir Hospital. Patients providing informed written consent were advised to complete ESAS questionnaire within 24 hours of hospital admission. Data entry and analysis done in Microsoft Excel Version 2013. Frequency distributions, percentages, means, and standard deviations of various symptoms were analyzed. Scatter diagram was prepared to evaluate the time trend of all nine ESAS items toward death. Results: One hundred ten patients (mean age 53.76 ± 10.63 years, 70 female and 40 male) completed ESAS score questionnaire. The most common symptom experienced was poor well-being 97(88.18%), followed by tiredness 91(82.72%) and lack of appetite 88(80%). Most severe symptoms were poor well-being with a mean score of 5.27 ± 3.08, followed by tiredness (3.55 ± 2.46), pain (3.24 ± 2.61) and lack of appetite (3.15 ± 2.53) and all the symptoms tend to deteriorate towards end of life. Conclusions: Edmonton Symptom Assessment System (ESAS) can be used easily to assess common symptoms and their intensity in cancer patients which help to provide specific symptom directed treatment and care.

Understanding patient views and experiences of the IDENTIfication of PALLiative care needs (IDENTI-PALL): a qualitative interview study.

Palliative care improves quality of life for people with life-threatening illnesses. There are longstanding inequalities in access to palliative care, with many people never identified as having palliative care needs, particularly frail older people, those with non-malignant disease, and people from ethnic minority backgrounds. Little is known about the process of identification of palliative care needs from a patient perspective. To provide new understanding into patient views and experiences of the process of identification of palliative care needs, and to explore the impact of identification on health care, if any, from a patient perspective. A qualitative interview study undertaken with patients and family carers in a major UK city. Semi-structured interviews were carried out with patients (and/or family carers) identified as being on general practice palliative care registers. An inductive thematic analysis was conducted to explore the data. Eleven participants were recruited: eight patients and three family carers. The following three interrelated themes were identified: 1) misconceptions about palliative care and unshared prognostic uncertainty hinder the identification of palliative care needs; 2) a compassionate, timely approach is required for identification of palliative care needs, with or without an identification tool; and 3) identification of palliative care needs is beneficial where it leads to proactive holistic care. A compassionate approach, sharing of prognostic uncertainty, and proactive primary care are key to timely, beneficial identification of palliative care needs. Future policy should ensure that identification is an adaptable, personalised process to meet the individual needs of people with advanced serious illnesses.