Superiority of anthracycline-free treatment in standard-risk acute promyelocytic leukemia: A systematic review and comparative epidemiological analysis.

BACKGROUND: Recent advances in the treatment of acute promyelocytic leukemia (APML) have seen unprecedented improvements in patient outcomes. However, such rapid growth in understanding often leads to uncertainty regarding superiority among candidate treatment regimens, especially when further scrutinized from an epidemiological perspective. AIMS: The aim of this systematic review with epidemiological analysis was to identify and compare commonly utilized protocols for standard-risk APML with a particular focus on complete remission (CR), overall/disease-free survival (DFS), and reported adverse events. METHODS AND RESULTS: Medline, Scopus, and CINAHL were interrogated to identify studies utilizing all-trans retinoic acid (ATRA) in addition to arsenic trioxide (ATO) and/or anthracyclines such as idarubicin (IDA) in the treatment of de-novo APML. After collation of studies, an epidemiological analysis was subsequently performed to compare protocols with regards to outcomes of interest using number needed to benefit (NNB) and number needed to harm (NNH) measures. Seventeen articles, describing 12 distinct trials, were included in the analysis. These trials made use of three unique protocols; CR rates were 94%-100% for ATO/ATRA regimens, 95%-96% for ATO/ATRA/anthracycline regimens, and 89%-94% for ATRA/anthracycline regimens. Epidemiological analysis demonstrated NNB for CR was 9.09 (ATO/ATRA vs. ATRA/IDA) and 20.00 (ATO/ATRA vs. ATO/ATRA/IDA), NNH for neutropenia was -3.45 (ATO/ATRA vs. ATRA/IDA), and NNH for infection was -3.13 (ATO/ATRA vs. ATRA/IDA) and -1.89 (ATO/ATRA vs. ATO/ATRA/IDA). CONCLUSION: The ATO/ATRA regimen is superior to chemotherapy-containing protocols at inducing remission and promoting survival in patients with APML. The regimen is better tolerated than the proposed alternatives with fewer adverse events. Future research opportunities include quantifying APML epidemiology and pursuing oral arsenic as an option for simplification of therapeutic protocols.

Vision-Related Quality of Life and Ocular Parameters in End-Stage Renal Disease Patients Undergoing Hemodialysis.

Purpose: To evaluate the vision-related quality of life (VRQoL) of patients receiving hemodialysis through the assessment of the impact of vision impairment (IVI) questionnaire and ocular parameters, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), and refraction as calculated by spherical equivalent (SE) of each eye. Methods: Fifty-one patients with end-stage renal disease undergoing hemodialysis at a single center were recruited, and a total of 77 eyes were evaluated. BCVA, IOP, and SE were evaluated before and after hemodialysis (within 30 min). Results: Of the 51 patients recruited, 13 (25%) were female, 37 (73%) were male, and one (2%) chose not to specify gender. The mean age was 61.85 ± 32 years. The mobility IVI score was correlated significantly with the presence of hypertension (P = 0.01), eye drop usage (P = 0.04), and gender (P = 0.04). Emotional IVI scores were correlated significantly with diabetes (P = 0.03) and hypertension (P < 0.01). IOP significantly correlated with the IVI overall score (P = 0.02), including the reading IVI subscale and the emotional IVI subscale. Several factors were associated with posthemodialysis ocular parameters, including predialysis ocular parameters, age, and hypertension (P < 0.05 for all). Conclusions: IOP significantly correlated with VRQoL in hemodialysis patients. Demographic variables such as diabetes status, hypertension, eye drop usage, and gender also significantly correlated with subsections of the IVI questionnaire. This study investigated the relationship between ocular parameters and VRQoL in hemodialysis patients, and future longitudinal research is needed to further elucidate the mechanisms.

Communication about early palliative care: A qualitative study of oncology providers' perspectives of navigating the artful introduction to the palliative care team.

Background: Despite robust evidence for the integration of early palliative care for patients with advanced cancer, many patients still access this approach to care late. Communication about the introduction of Early Palliative Care is an important skill of healthcare providers working in this setting. In the context of limited community understanding about palliative care, patients and their families may express fear or negative reactions to its early introduction. Health professionals may lack the confidence or skill to describe the role and benefits of early palliative care. Aim: This study sought to explore clinicians' perspectives on communication about referral to early palliative care, specifically identifying facilitators in undertaking this communication task. Methods: An exploratory qualitative study set within a tertiary oncology service in Victoria, Australia. Semi-structured interviews were conducted with purposively sampled oncology clinicians exploring their perspectives on communication about referral to early palliative care. A reflexive thematic analysis was undertaken by two researchers, including both latent and semantic coding relevant to the research question. Reporting of the research was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Results: Twelve oncology clinicians (58% female, with 67% > 15 years clinical experience) from medical oncology, surgical oncology, and haematology participated. The artful navigation of communication about early palliative care was characterised by the need for a 'spiel' involving the adoption of a series of strategies or 'tactics' when introducing this service. These themes included: 1) Using carefully selected and rehearsed language; 2) Framing in terms of symptom control; 3) Framing as additive to patient care; 4) Selling the service benefits of early palliative care; 5) Framing acceptance of referral as an altruistic act; and 6) Adopting a phased approach to delivering information about palliative care. Implications: This study highlights the wide ranging and innovative communication strategies and skills required by health professionals to facilitate referral to early palliative care for cancer patients and their families. Future focus on upskilling clinicians around communication of this topic will be important to ensure successful implementation of models of early palliative care in routine cancer care.

Telehealth in outpatient delivery of palliative care: A qualitative study of patient and physician views.

OBJECTIVES: The COVID-19 pandemic has widened the funded use of telehealth in Australia to support telehealth delivery to all patients in any setting. Increasing the use and experience of telehealth brings to light unique insights into the advantages and challenges of this new model of healthcare delivery This study aimed to qualitatively explore the experiences of both palliative care physicians and patients setting, including their views on its future role in healthcare. METHODS: This qualitative study was conducted across three metropolitan tertiary palliative care centers in Victoria, Australia between November 2020 and March 2021. Purposive sampling identified 23 participants (12 physicians and 11 patients). Semi-structured interviews focused on the last telehealth consultation, thoughts and impressions of telehealth, and the possibility of telehealth remaining in palliative care. A thematic approach was adopted to code and analyze the data. RESULTS: Telehealth transformed the ways physicians and patients in this study perceived and engaged with outpatient palliative care across the entire continuum of care. Four key themes were identified: (1) access to care; (2) delivery of care; (3) engagement with care; and (4) the future. SIGNIFICANCE OF RESULTS: This study provides novel data bringing together the perspective of patients and physicians, which confirms the utility of telehealth in palliative care. Its convenience enables more frequent review, enables reviews to occur in response to lower levels of concern, and adds toward enhancing the continuity of care across and between settings. Moving forward, support seemed strongest for a hybrid model of telehealth and face-to-face consultations guided by key parameters relating to the level of anticipated complexity.

A Multi-Centre COVID-19 Study Examining Symptoms and Medication Use in the Final Week of Life.

CONTEXT: Guidelines exist to direct end-of-life symptom management in COVID-19 patients. However, the real-world symptom patterns, and degree of concordance with guidelines on medication use, and palliative care involvement has received limited attention. OBJECTIVES: To describe the evolution of COVID-19 symptoms, medication used to alleviate these, and degree of palliative care involvement in the final week of life. METHODS: This retrospective study reviewed all COVID-19 inpatient deaths across five metropolitan hospitals in Australia from January 1 to December 31, 2020. Outcome measures were collected at day of death, and days one, two, five and seven before death. These were COVID-19 symptom severity (measured by the Palliative Care Outcome Scale), and use of supportive pharmacological and non-pharmacological therapies. Palliative care referral timepoint was also collected. RESULTS: Within the sample of 230 patients, commonest symptoms were breathlessness, agitation, pain, and respiratory secretions. On day of death, 79% (n = 181) experienced at least one symptom, and 30% (n = 68) experienced severe/extreme symptoms. The use of midazolam, glycopyrrolate, and infusions for symptom management occurred late, less frequently, and at lower doses than suggested in guidelines and other studies. Palliative care referrals were made late, at median three days before death (IQR 1-6 days), and for only half of people dying from COVID-19 (51%; n = 118). CONCLUSION: Symptoms peaked in final three days of life. Earlier use of in fusional and breakthrough medications should be considered in anticipation of symptoms given high likelihood of dying in discomfort. Earlier palliative care referral for high-risk patients should be considered at hospital admission.

A multi-centre study on patients dying from COVID-19: communication between clinicians, patients and their families.

BACKGROUND: COVID-19 has led to challenges in providing effective and timely communication in healthcare. Services have been required to adapt and evolve as successful communication remains core to high-quality patient-centred care. AIM: To describe the communication between admitted patients, their families and clinicians (medical, nursing, allied health) during end-of-life care. METHODS: This retrospective review included all patients (n = 230) who died directly due to COVID-19 at five Melbourne hospitals between 1 January and 31 December 2020. Contacts and modality used (face to face, video, telephone) during the 8 days prior to death were recorded. RESULTS: Patients were predominantly elderly (median age 86 years) and from residential aged care facilities (62%; n = 141). Communication frequency increased the closer the patient was to death, where on day of death, contact between clinicians and patients was 93% (n = 213) clinicians and families 97% (n = 222) and between patients and families 50% (n = 115). Most contact between patients and families was facilitated by a clinician (91.3% (n = 105) day of death) with the most commonly used mode being video call (n = 30 day of death). CONCLUSION: This study is one of the first and largest Australian reports on how communication occurs at the end of life for patients dying of COVID-19. Contact rates were relatively low between patients and families, compared with other cohorts dying from non-COVID-19 related causes. The impact of this difference on bereavement outcomes requires surveillance and attention.

Perceptions of telehealth in real-world oncological care: An exploration of matched patient- and clinician-reported acceptability data from an Australian cancer centre.

BACKGROUND: Prior to 2020, the use of telehealth in cancer care was limited, but COVID-19 necessitated its rapid and widespread adoption into routine care delivery. This study aimed to evaluate perceptions of telehealth through a dyadic exploration of matched cancer patient- and clinician-reported acceptability data and to explore factors that may predict greater suitability for telehealth. METHODS: A prospective, cross-sectional, exploratory survey study assessed (matched) patient- and clinician-reported perceptions of telehealth consultations occurring at a metropolitan, tertiary-based cancer centre in Victoria, Australia. RESULTS: One-hundred and fifty-five matched patient- and clinician-reported data were included. High rates of acceptability with telehealth were reported by patients (93%) and clinicians (91%), who mostly shared concordant views (86%). Factors significantly associated with increased acceptability for telehealth, included, for clinicians, greater familiarity with the patient (OR 8.20, 95% CI: 1.50-45.06, p = 0.02), and younger patient age (OR 1.06, 95% CI: 0.99-1.13, p = 0.05), and for patients was earlier stage disease (≤stage III) (OR 5.29, 95% CI: 1.08-25.82, p = 0.04). Lower acceptability for telehealth according to clinicians was associated with poorer patient performance status (OR 0.04, 95% CI 1.00-1.08, p = 0.04) and for patients with the need for an interpreter (0R 0.06, 95% CI: 0.008-0.51, p = 0.009). CONCLUSION: While overall telehealth is acceptable in cancer care, our findings raise important implications for future service development, notably that it may be less optimal for patients with higher complexity of need-including those with more advanced disease, poorer performance status, those less well known to treating clinicians and those identified to have additional language barriers.

Telehealth in outpatient delivery of palliative care: a prospective survey evaluation by patients and clinicians.

BACKGROUND: In Australia during the COVID-19 pandemic new funding models were introduced to support telehealth consultations, resulting in their widescale adoption in palliative care service delivery. Clarity around the clinical circumstances and patient populations that might be most appropriate for telehealth models was required. AIMS: To evaluate patient and physician satisfaction, acceptability and utility of outpatient palliative care provision through telehealth. METHODS: This is a multi-site prospective, cross-sectional, observational study conducted during a time of significant public health restrictions. A survey was used to collect matched patient- and physician-reported perceptions of palliative care telehealth consultations across three metropolitan hospitals in Victoria, Australia. RESULTS: There were 127 matched patient-physician data of telehealth consultations and a further 812 physician-only assessments. Telehealth was generally acceptable and satisfactory, with patients providing greater positive scores than clinicians. Telehealth incorporating both audio and video were more acceptable and satisfactory, particularly with the presence of a carer, and during routine reviews. Physicians were less satisfied using telehealth when there was increasing symptom complexity across all domains (pain, psychological, and other symptoms). CONCLUSIONS: Telehealth has high utility in palliative care practice. A future hybrid model of care comprising both face-to-face and telehealth consultations seems favoured by patients and physicians but must be accompanied by targeted support for specific patient groups to ensure equitable healthcare access. Further evaluation of telehealth during a time of fewer public health emergency measures and lower community anxiety is required to fully understand its ongoing role.

Discontinuation of nucleot(s)ide analogue therapy in HBeAg-negative chronic hepatitis B: a meta-analysis.

BACKGROUND AND AIMS: Sustained virological suppression and hepatitis B surface antigen (HBsAg) loss have been described after nucleot(s)ide analogue (NA) discontinuation for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We performed a meta-analysis of the clinical outcomes after NA discontinuation for HBeAg-negative CHB. METHODS: Studies involving NA cessation in HBeAg-negative CHB individuals with a median follow-up of ≥12 months were included. Participants were HBeAg-negative at the time of NA initiation. Random effects meta-analyses were performed for the following clinical outcomes: (1) virological relapse (VR) at 6 and 12 months; (2) clinical relapse (CR) at 6 and 12 months and (3) HBsAg loss. Effect of other variables was estimated using subgroup analysis and meta-regression. Studies including patients stopping entecavir (ETV) and/or tenofovir disoproxil fumarate (TDF) were considered separately to studies including patients stopping older generation NA. RESULTS: N=37 studies met inclusion criteria. Cumulative incidence of VR and CR after stopping ETV/TDF was 44% and 17% at 6 months and 63% and 35% at 12 months. Similar relapse rates were observed after stopping older NAs. Among patients stopping ETV/TDF, TDF cessation was associated with increased CR rates at 6 months versus ETV. There was an association between follow-up ≥4 years and HBsAg loss rates when stopping older NAs. Hepatic decompensation and hepatocellular carcinoma were rare but occurred more frequently in studies including cirrhotic individuals. CONCLUSION: VR is common after NA discontinuation, however, CR was only seen in one-third of patients at 12 months. Stopping NA therapy can be followed by HBsAg clearance, and rates are higher with longer follow-up.

Efficacy and tolerability of adjuvant perampanel: an Australian multicenter real-world observational study in refractory focal and generalized epilepsy syndromes.

PURPOSE: To explore the efficacy and tolerability of adjuvant perampanel (PER) and their associated risk factors in late add-on drug-resistant epilepsy. METHOD: Retrospective multicenter 'real-world' observational study. Consecutively identified patients commenced on PER, with mixed epilepsy syndromes, from nine Australian epilepsy centers. Primary efficacy endpoints were at least 50% reduction in seizure frequency (responders), seizure freedom, and retention at 6 and 12 months, following a 3-month titration period. Tolerability endpoints were cessation of PER for any reason, cessation of PER due to treatment-emergent adverse events (TEAE), or cessation due to inefficacy. Outcomes were assessed for a-priori risk factors associated with efficacy and tolerability. RESULTS: Three-hundred and eighty seven adults were identified and followed up for a median of 12.1 months (IQR 7.0-25.2). Focal epilepsy accounted for 79.6% (FE), idiopathic generalized epilepsy (IGE), 10.3% and developmental epileptic encephalopathy (DEE) 10.1%, of the cohort. All patients had drug-resistant epilepsy, 71.6% had never experienced six months of seizure freedom, and the mean number of antiepileptic medications (AEDs) prior to starting PER was six. At 12 months, with missing cases classified as treatment failure, retention was 40.0%, responder 21.7%, and seizure freedom 9.0%, whereas, using last outcome carried forward (LOCF), responder and seizure freedom rates were 41.3% and 14.7%, respectively. Older age of epilepsy onset was associated with a marginal increase in the likelihood of seizure freedom at 12-month maintenance (OR 1.04, 95% CI 1.02, 1.06). Male sex (adjusted OR [aOR] 2.06 95% CI 1.33, 3.19), lower number of prior AEDs (aOR 0.84, 95% CI 0.74, 0.96) and no previous seizure-free period of at least 6-month duration (aOR 2.04 95% CI 1.21, 3.47) were associated with retention. Perampanel combined with a GABA receptor AED was associated with a lower responder rate at 12 months but reduced cessation of PER. The most common TEAEs were neuropsychiatric (18.86%), followed by dizziness (13.70%), and sleepiness (5.68%). CONCLUSIONS: Adjuvant PER treatment, even in late-add on drug-resistant epilepsy is an effective and well-tolerated treatment for drug-resistant epilepsy.

COVID-19 end-of-life care: symptoms and supportive therapy use in an Australian hospital.

BACKGROUND: Descriptions of symptoms and medication use at end of life in COVID-19 are limited to small cross-sectional studies, with no Australian longitudinal data. AIMS: To describe end-of-life symptoms and care needs of people dying of COVID-19. METHODS: This retrospective cohort study included consecutive admitted patients who died at a Victorian tertiary referral hospital from 1 January to 30 September directly due to COVID-19. Clinical characteristics, symptoms and use of supportive therapies, including medications and non-pharmacological interventions in the last 3 days of life were extracted. RESULTS: The cohort comprised 58 patients (median age 87 years, interquartile range (IQR) 81-90) predominantly admitted from home (n = 30), who died after a median of 11 days (IQR 6-28) in the acute medical (n = 31) or aged care (n = 27) wards of the hospital. The median Charlson Comorbidity Score was 7 (IQR 5-8). Breathlessness (n = 42), agitation (n = 36) and pain (n = 33) were the most frequent clinician-reported symptoms in the final 3 days of life, with most requiring opioids (n = 52), midazolam (n = 40), with dose escalation commonly being required. While oxygen therapy was commonly used (n = 47), few (n = 13) required an anti-secretory agent. CONCLUSIONS: This study presents one of the first and largest Australian report of the end of life and symptom experience of people dying of COVID-19. This information should help clinicians to anticipate palliative care needs of these patients, for example, recognising that higher starting doses of opioids and sedatives may help reduce prevalence and severity of breathlessness and agitation near death.

Validation of the responding to urgency of need in palliative care (RUN-PC) triage tool.

BACKGROUND: The Responding to Urgency of Need in Palliative Care (RUN-PC) Triage Tool is a novel, evidence-based tool by which specialist palliative care services can manage waiting lists and workflow by prioritising access to care for those patients with the most pressing needs in an equitable, efficient and transparent manner. AIM: This study aimed to establish the intra- and inter-rater reliability, and convergent validity of the RUN-PC Triage Tool and generate recommended response times. DESIGN: An online survey of palliative care intake officers applying the RUN-PC Triage Tool to a series of 49 real clinical vignettes was assessed against a reference standard: a postal survey of expert palliative care clinicians ranking the same vignettes in order of urgency. SETTING/PARTICIPANTS: Intake officers (n = 28) with a minimum of 2 years palliative care experience and expert clinicians (n = 32) with a minimum of 10 years palliative care experience were recruited from inpatient, hospital consultation and community palliative care services across metropolitan and regional Victoria, Australia. RESULTS: The RUN-PC Triage Tool has good intra- and inter-rater reliability in inpatient, hospital consultation and community palliative care settings (Intraclass Correlation Coefficients ranged from 0.61 to 0.74), and moderate to good correlation to expert opinion used as a reference standard (Kendall's Tau rank correlation coefficients ranged from 0.68 to 0.83). CONCLUSION: The RUN-PC Triage Tool appears to be a reliable and valid tool for the prioritisation of patients referred to specialist inpatient, hospital consultation and community palliative care services.