The ICaRAS randomised controlled trial: Intravenous iron to treat anaemia in people with advanced cancer - feasibility of recruitment, intervention and delivery.

BACKGROUND: Anaemia is highly prevalent in people with advanced, palliative cancer yet sufficiently effective and safe treatments are lacking. Oral iron is poorly tolerated, and blood transfusion offers only transient benefits. Intravenous iron has shown promise as an effective treatment for anaemia but its use for people with advanced, palliative cancer lacks evidence. AIMS: To assess feasibility of the trial design according to screening, recruitment, and attrition rates. To evaluate the efficacy of intravenous iron to treat anaemia in people with solid tumours, receiving palliative care. DESIGN: A multicentre, randomised, double blind, placebo-controlled trial of intravenous iron (ferric derisomaltose, Monofer®). Outcomes included trial feasibility, change in blood indices, and change in quality of life via three validated questionnaires (EQ5D5L, QLQC30, and the FACIT-F) over 8 weeks. (ISRCTN; 13370767). SETTING/PARTICIPANTS: People with anaemia and advanced solid tumours who were fatigued with a performance status ⩽2 receiving support from a specialist palliative care service. RESULTS: 34 participants were randomised over 16 months (17 iron, 17 placebo). Among those eligible 47% of people agreed to participate and total study attrition was 26%. Blinding was successful in all participants. There were no serious adverse reactions. Results indicated that intravenous iron may be efficacious at improving participant haemoglobin, iron stores and select fatigue specific quality of life measures compared to placebo. CONCLUSION: The trial was feasible according to recruitment and attrition rates. Intravenous iron increased haemoglobin and may improve fatigue specific quality of life measures compared to placebo. A definitive trial is required for confirmation.

Variation in patterns of telestroke usage during the COVID-19 pandemic.

OBJECTIVES: Early in the pandemic, there was a substantial increase in telestroke uptake among hospitals. The motivations for using telestroke during the pandemic might have been different than for hospitals that adopted telestroke previously. We compared stroke care at hospitals that adopted telestroke prior to the pandemic to care at hospitals that adopted telestroke during the pandemic. MATERIALS AND METHODS: Stroke episodes and telestroke use were identified in Medicare Fee-for-Service Data. Hospital and episode characteristics were compared between pre-pandemic (Jan. 2019-Mar. 2020) and pandemic (Apr. 2020-Dec. 2020) adopters. RESULTS: Hospital bed counts, critical access statuses, stroke volumes, clinical operating margins, shares of stroke care via telestroke, and vascular neurology consult rates did not differ significantly between pre-pandemic and pandemic-adopting hospitals. Hospitals that never adopted telestroke during the study period were more likely to be small critical access hospitals with low clinical operating margins. CONCLUSIONS: Compared to hospitals that adopted telestroke before the pandemic, hospitals that adopted telestroke during the pandemic were similar in characteristics and how they used telestroke.

Two-Year Evaluation of Mandatory Bundled Payments for Joint Replacement.

BACKGROUND: In 2016, Medicare implemented Comprehensive Care for Joint Replacement (CJR), a national mandatory bundled-payment model for hip or knee replacement in randomly selected metropolitan statistical areas. Hospitals in such areas receive bonuses or pay penalties based on Medicare spending per hip- or knee-replacement episode (defined as the hospitalization plus 90 days after discharge). METHODS: We conducted difference-in-differences analyses using Medicare claims from 2015 through 2017, encompassing the first 2 years of bundled payments in the CJR program. We evaluated hip- or knee-replacement episodes in 75 metropolitan statistical areas randomly assigned to mandatory participation in the CJR program (bundled-payment metropolitan statistical areas, hereafter referred to as "treatment" areas) as compared with those in 121 control areas, before and after implementation of the CJR model. The primary outcomes were institutional spending per hip- or knee-replacement episode (i.e., Medicare payments to institutions, primarily to hospitals and post-acute care facilities), rates of postsurgical complications, and the percentage of "high-risk" patients (i.e., patients for whom there was an elevated risk of spending - a measure of patient selection). Analyses were adjusted for the hospital and characteristics of the patients and procedures. RESULTS: From 2015 through 2017, there were 280,161 hip- or knee-replacement procedures in 803 hospitals in treatment areas and 377,278 procedures in 962 hospitals in control areas. After the initiation of the CJR model, there were greater decreases in institutional spending per joint-replacement episode in treatment areas than in control areas (differential change [i.e., the between-group difference in the change from the period before the CJR model], -$812, or a -3.1% differential decrease relative to the treatment-group baseline; P<0.001). The differential reduction was driven largely by a 5.9% relative decrease in the percentage of episodes in which patients were discharged to post-acute care facilities. The CJR program did not have a significant differential effect on the composite rate of complications (P=0.67) or on the percentage of joint-replacement procedures performed in high-risk patients (P=0.81). CONCLUSIONS: In the first 2 years of the CJR program, there was a modest reduction in spending per hip- or knee-replacement episode, without an increase in rates of complications. (Funded by the Commonwealth Fund and the National Institute on Aging of the National Institutes of Health.).

Paracentesis for cancer-related ascites in palliative care: An international, prospective cohort study.

BACKGROUND: Paracentesis is commonly undertaken in patients with cancer-related ascites. AIM: To systematically investigate the symptomatic benefits and harms experienced by patients with cancer undergoing paracentesis using real-world data in the palliative care setting. DESIGN: Prospective, multisite, observational, consecutive cohort study. Benefits and harms of paracentesis were assessed between 01/07/2018 and 31/02/2021 as part of routine clinical assessments by treating clinicians at four timepoints: (T0) before paracentesis; (T1) once drainage ceased; (T2) 24 h after T1 and (T3) 28 days after T1 or next paracentesis, if sooner. SETTING/PARTICIPANTS: Data were collected from 11 participating sites across five countries (Australia, England, Hong Kong, Malaysia and New Zealand) on 111 patients undergoing paracentesis via a temporary (73%) or indwelling (21%) catheter: 51% male, median age 69 years, Australia-modified Karnofsky Performance Score 50. RESULTS: At T1 (n = 100), symptoms had improved for most patients (81%), specifically abdominal distension (61%), abdominal pain (49%) and nausea (27%), with two-thirds experiencing improvement in ⩾2 symptoms. In the remaining patients, symptoms were unchanged (7%) or worse (12%). At least one harm occurred in 32% of patients, the most common being an ascitic leak (n = 14). By T3, 89% of patients had experienced some benefit and 36% some harm, including four patients who experienced serious harm, one of which was a fatal bowel perforation. CONCLUSION: Most patients obtained rapid benefits from paracentesis. Harms were less frequent and generally mild, but occasionally serious and fatal. Our findings help inform clinician-patient discussions about the potential outcomes of paracentesis in this frail population.

Do guidelines influence breathlessness management in advanced lung diseases? A multinational survey of respiratory medicine and palliative care physicians.

BACKGROUND: Respiratory medicine (RM) and palliative care (PC) physicians' management of chronic breathlessness in advanced chronic obstructive pulmonary disease (COPD), fibrotic interstitial lung disease (fILD) and lung cancer (LC), and the influence of practice guidelines was explored via an online survey. METHODS: A voluntary, online survey was distributed to RM and PC physicians via society newsletter mailing lists. RESULTS: 450 evaluable questionnaires (348 (77%) RM and 102 (23%) PC) were analysed. Significantly more PC physicians indicated routine use (often/always) of opioids across conditions (COPD: 92% vs. 39%, fILD: 83% vs. 36%, LC: 95% vs. 76%; all p < 0.001) and significantly more PC physicians indicated routine use of benzodiazepines for COPD (33% vs. 10%) and fILD (25% vs. 12%) (both p < 0.001). Significantly more RM physicians reported routine use of a breathlessness score (62% vs. 13%, p < 0.001) and prioritised exercise training/rehabilitation for COPD (49% vs. 7%) and fILD (30% vs. 18%) (both p < 0.001). Overall, 40% of all respondents reported reading non-cancer palliative care guidelines (either carefully or looked at them briefly). Respondents who reported reading these guidelines were more likely to: routinely use a breathlessness score (χ2 = 13.8; p < 0.001), use opioids (χ2 = 12.58, p < 0.001) and refer to pulmonary rehabilitation (χ2 = 6.41, p = 0.011) in COPD; use antidepressants (χ2 = 6.25; p = 0.044) and refer to PC (χ2 = 5.83; p = 0.016) in fILD; and use a handheld fan in COPD (χ2 = 8.75, p = 0.003), fILD (χ2 = 4.85, p = 0.028) and LC (χ2 = 5.63; p = 0.018). CONCLUSIONS: These findings suggest a need for improved dissemination and uptake of jointly developed breathlessness management guidelines in order to encourage appropriate use of existing, evidence-based therapies. The lack of opioid use by RM, and continued benzodiazepine use in PC, suggest that a wider range of acceptable therapies need to be developed and trialled.

Missing not at random in end of life care studies: multiple imputation and sensitivity analysis on data from the ACTION study.

BACKGROUND: Missing data are common in end-of-life care studies, but there is still relatively little exploration of which is the best method to deal with them, and, in particular, if the missing at random (MAR) assumption is valid or missing not at random (MNAR) mechanisms should be assumed. In this paper we investigated this issue through a sensitivity analysis within the ACTION study, a multicenter cluster randomized controlled trial testing advance care planning in patients with advanced lung or colorectal cancer. METHODS: Multiple imputation procedures under MAR and MNAR assumptions were implemented. Possible violation of the MAR assumption was addressed with reference to variables measuring quality of life and symptoms. The MNAR model assumed that patients with worse health were more likely to have missing questionnaires, making a distinction between single missing items, which were assumed to satisfy the MAR assumption, and missing values due to completely missing questionnaire for which a MNAR mechanism was hypothesized. We explored the sensitivity to possible departures from MAR on gender differences between key indicators and on simple correlations. RESULTS: Up to 39% of follow-up data were missing. Results under MAR reflected that missingness was related to poorer health status. Correlations between variables, although very small, changed according to the imputation method, as well as the differences in scores by gender, indicating a certain sensitivity of the results to the violation of the MAR assumption. CONCLUSIONS: The findings confirmed the importance of undertaking this kind of analysis in end-of-life care studies.

Advance care planning in patients with advanced cancer: A 6-country, cluster-randomised clinical trial.

BACKGROUND: Advance care planning (ACP) supports individuals to define, discuss, and record goals and preferences for future medical treatment and care. Despite being internationally recommended, randomised clinical trials of ACP in patients with advanced cancer are scarce. METHODS AND FINDINGS: To test the implementation of ACP in patients with advanced cancer, we conducted a cluster-randomised trial in 23 hospitals across Belgium, Denmark, Italy, Netherlands, Slovenia, and United Kingdom in 2015-2018. Patients with advanced lung (stage III/IV) or colorectal (stage IV) cancer, WHO performance status 0-3, and at least 3 months life expectancy were eligible. The ACTION Respecting Choices ACP intervention as offered to patients in the intervention arm included scripted ACP conversations between patients, family members, and certified facilitators; standardised leaflets; and standardised advance directives. Control patients received care as usual. Main outcome measures were quality of life (operationalised as European Organisation for Research and Treatment of Cancer [EORTC] emotional functioning) and symptoms. Secondary outcomes were coping, patient satisfaction, shared decision-making, patient involvement in decision-making, inclusion of advance directives (ADs) in hospital files, and use of hospital care. In all, 1,117 patients were included (442 intervention; 675 control), and 809 (72%) completed the 12-week questionnaire. Patients' age ranged from 18 to 91 years, with a mean of 66; 39% were female. The mean number of ACP conversations per patient was 1.3. Fidelity was 86%. Sixteen percent of patients found ACP conversations distressing. Mean change in patients' quality of life did not differ between intervention and control groups (T-score -1.8 versus -0.8, p = 0.59), nor did changes in symptoms, coping, patient satisfaction, and shared decision-making. Specialist palliative care (37% versus 27%, p = 0.002) and AD inclusion in hospital files (10% versus 3%, p < 0.001) were more likely in the intervention group. A key limitation of the study is that recruitment rates were lower in intervention than in control hospitals. CONCLUSIONS: Our results show that quality of life effects were not different between patients who had ACP conversations and those who received usual care. The increased use of specialist palliative care and AD inclusion in hospital files of intervention patients is meaningful and requires further study. Our findings suggest that alternative approaches to support patient-centred end-of-life care in this population are needed. TRIAL REGISTRATION: ISRCTN registry ISRCTN63110516.

Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility).

New treatments are required for severe breathlessness in advanced disease. We conducted a randomised feasibility trial of mirtazapine over 28 days in adults with a modified medical research council breathlessness scale score ≥3. Sixty-four patients were randomised (409 screened), achieving our primary feasibility endpoint of recruitment. Most patients had COPD or interstitial lung disease; 52 (81%) completed the trial. There were no differences between placebo and mirtazapine in tolerability or safety, and blinding was maintained. Worst breathlessness ratings at day 28 (primary clinical activity endpoint) were, 7.1 (SD 2.3, placebo) and 6.3 (SD 1.8, mirtazapine). A phase III trial of mirtazapine is indicated. Trial registration: ISRCTN 32236160; European Clinical Trials Database (EudraCT no: 2015-004064-11).

Coping strategies of patients with advanced lung or colorectal cancer in six European countries: Insights from the ACTION Study.

OBJECTIVE: Even when medical treatments are limited, supporting patients' coping strategies could improve their quality of life. Greater understanding of patients' coping strategies, and influencing factors, can aid developing such support. We examined the prevalence of coping strategies and associated variables. METHODS: We used sociodemographic and baseline data from the ACTION trial, including measures of Denial, Acceptance, and Problem-focused coping (COPE; Brief COPE inventory), of patients with advanced cancer from six European countries. Clinicians provided clinical information. Linear mixed models with clustering at hospital level were used. RESULTS: Data from 675 patients with stage III/IV lung (342, 51%) or stage IV colorectal (333, 49%) cancer were used; mean age 66 (10 SD) years. Overall, patients scored low on Denial and high on Acceptance and Problem-focused coping. Older age was associated with higher scores on Denial than younger age (ß = 0.05; CI[0.023; 0.074]), and patients from Italy (ß = 1.57 CI[0.760; 2.388]) and Denmark (ß = 1.82 CI[0.881; 2.750]) scored higher on Denial than patients in other countries. CONCLUSIONS: Patients with advanced cancer predominantly used Acceptance and Problem-focused coping, and Denial to a lesser extent. Since the studied coping strategies of patients with advanced cancer vary between subpopulations, we recommend taking these factors into account when developing tailored interventions to support patients' coping strategies.

Short-term integrated rehabilitation for people with newly diagnosed thoracic cancer: a multi-centre randomized controlled feasibility trial.

OBJECTIVES: The main objective of this study is to determine the feasibility of recruiting and retaining patients recently diagnosed with thoracic cancer to a trial of short-term integrated rehabilitation; evaluate uptake of theoretically informed components targeting physical function, symptom self-management and participation; estimate sample size requirements for an efficacy trial. DESIGN: Parallel group randomized controlled feasibility trial. SETTING: Three U.K. hospitals. PARTICIPANTS: Patients ⩽eight weeks of thoracic cancer diagnosis, Eastern Cooperative Oncology Group Performance Status 0-3, any cancer stage and treatment plan. INTERVENTIONS: Participants randomly allocated (1:1) to short-term integrated rehabilitation and standard care or standard care alone over 30 days. MAIN MEASURES: Primary: participant recruitment and retention, targeting ⩾30% of eligible patients enrolling and ⩾50% of participants reporting outcomes at 30 days. Secondary: intervention fidelity; missing data and performance of outcome measures for self-efficacy, symptoms, physical activity and health-related quality of life. RESULTS: Of 159 eligible patients approached, 54 (34%) were recruited. A total of 44 (82%) and 39 (72%) participants reported outcomes at 30 and 60 days, respectively. Intervention fidelity was high. Rehabilitation was delivered across 3 (1-3) sessions over 32 (22-45) days (median (range)). Changes in clinical outcomes were modest but most apparent at 60 days for health-related quality of life: Functional Assessment of Cancer Therapy Lung Cancer score median (interquartile range) change 9.7 (-12.0 to 16.0) rehabilitation versus 2.3 (-15.0 to 14.5) standard care. CONCLUSION: A trial to examine efficacy of short-term integrated rehabilitation for people newly diagnosed with thoracic cancer is feasible. A sample of 336 participants could detect a meaningful effect on health-related quality of life as the primary outcome.

"How Long Have I Got?"-A Prospective Cohort Study Comparing Validated Prognostic Factors for Use in Patients with Advanced Cancer.

BACKGROUND: The optimal prognostic factors in patients with advanced cancer are not known, as a comparison of these is lacking. The aim of the present study was to determine the optimal prognostic factors by comparing validated factors. MATERIALS AND METHODS: A multicenter, prospective observational cohort study recruited patients over 18 years with advanced cancer. The following were assessed: clinician-predicted survival (CPS), Eastern Cooperative Oncology Group performance status (ECOG-PS), patient reported outcome measures (anorexia, cognitive impairment, dyspnea, global health), metastatic disease, weight loss, modified Glasgow Prognostic Score (mGPS) based on C-reactive protein and albumin, lactate dehydrogenase (LDH), and white (WCC), neutrophil (NC), and lymphocyte cell counts. Survival at 1 and 3 months was assessed using area under the receiver operating curve and logistic regression analysis. RESULTS: Data were available on 478 patients, and the median survival was 4.27 (1.86-7.03) months. On univariate analysis, the following factors predicted death at 1 and 3 months: CPS, ECOG-PS, mGPS, WCC, NC (all p < .001), dyspnea, global health (both p ≤ .001), cognitive impairment, anorexia, LDH (all p < .01), and weight loss (p < .05). On multivariate analysis ECOG-PS, mGPS, and NC were independent predictors of survival at 1 and 3 months (all p < .01). CONCLUSION: The simple combination of ECOG-PS and mGPS is an important novel prognostic framework which can alert clinicians to patients with good performance status who are at increased risk of having a higher symptom burden and dying at 3 months. From the recent literature it is likely that this framework will also be useful in referral for early palliative care with 6-24 months survival. IMPLICATIONS FOR PRACTICE: This large cohort study examined all validated prognostic factors in a head-to-head comparison and demonstrated the superior prognostic value of the Eastern Cooperative Oncology Group performance status (ECOG-PS)/modified Glasgow Prognostic Score (mGPS) combination over other prognostic factors. This combination is simple, accurate, and also relates to quality of life. It may be useful in identifying patients who may benefit from early referral to palliative care. It is proposed ECOG-PS/mGPS as the new prognostic domain in patients with advanced cancer.

Assessing Emotional Functioning with Increased Power: Relative Validity of a Customized EORTC Short Form in the International ACTION Trial.

OBJECTIVES: There is a need to improve the assessment of emotional functioning (EF). In the international Advance Care Planning: an Innovative Palliative Care Intervention to Improve Quality of Life in Cancer Patients - a Multi-Centre Cluster Randomized Clinical Trial (ACTION) trial involving patients with advanced cancer, EF was assessed by a customized 10-item short form (EF10). The EF10 is based on the European Organisation for Research and Treatment of Cancer (EORTC) EF item bank and has the potential for greater precision than the common EORTC Quality of Life Questionnaire Core 30 four-item scale (EF4). We assessed the relative validity (RV) of EF10 compared with EF4. METHODS: Patients from Belgium, Denmark, Italy, the Netherlands, Slovenia, and the United Kingdom completed EF10 and EF4, and provided data on generic quality of life, coping, self-efficacy, and personal characteristics. Based on clinical and sociodemographic variables and questionnaire responses, 53 "known groups" that were expected to differ were formed, for example, females versus males. The EF10 and EF4 were first independently compared within this known group, for example, the EF10 score of females vs the EF10 score of males. When these differences were significant, the RV was calculated for the comparison of the EF10 with the EF4. RESULTS: A total of 1028 patients (57% lung, 43% colorectal cancer) participated. Forty-five of the 53 known-groups comparisons were significantly different and were used for calculating the RV. In 41 of 45 (91%) comparisons, the RV was more than 1, meaning that EF10 had a higher RV than EF4. The mean RV of EF10 compared with that of EF4 was 1.41, indicating superior statistical power of EF10 to detect differences in EF. CONCLUSIONS: Compared with EF4, EF10 shows superior power, allowing a 20% to 34% smaller sample size without reducing power, when used as a primary outcome measure.

Defining patterns of care in the management of patients with brain metastases in a large oncology centre: A single-centre retrospective audit of 236 cases.

AIMS: The role of selected treatments for brain metastases (BM) is well documented; however, the prevalence of these is not. We report on the patterns of care in the management of BM in a large oncology centre. MATERIALS AND METHODS: We retrospectively audited 236 cases of newly diagnosed BM from January 2016 to December 2017 by looking at 2 years of radiology reports and gathered data on primary site, survival, treatment received, palliative care input and brain metastases-related admissions. RESULTS: Eighty-two per cent of cases were related to lung, breast and melanoma primaries. Half of patients received a form of treatment with the other half receiving best supportive care. Of these, whole-brain radiotherapy (39%) and stereotactic radiosurgery (40%) were the most common treatment modalities. Most common reasons for admissions were headaches, seizures, weakness and confusion. CONCLUSION: This is the first study in the UK that gives an in-depth overview of the real-world management of brain metastases. We have demonstrated the prevalence of treatment across the spectrum of brain metastases patients. Radiotherapy is the mainstay of treatment in nearly 80% of cases; however, care needs to be taken in ensuring that SRS is offered to those who are suitable.

A prospective study examining cachexia predictors in patients with incurable cancer.

BACKGROUND: Early intervention against cachexia necessitates a predictive model. The aims of this study were to identify predictors of cachexia development and to create and evaluate accuracy of a predictive model based on these predictors. METHODS: A secondary analysis of a prospective, observational, multicentre study was conducted. Patients, who attended a palliative care programme, had incurable cancer and did not have cachexia at baseline, were amenable to the analysis. Cachexia was defined as weight loss (WL) > 5% (6 months) or WL > 2% and body mass index< 20 kg/m2. Clinical and demographic markers were evaluated as possible predictors with Cox analysis. A classification and regression tree analysis was used to create a model based on optimal combinations and cut-offs of significant predictors for cachexia development, and accuracy was evaluated with a calibration plot, Harrell's c-statistic and receiver operating characteristic curve analysis. RESULTS: Six-hundred-twenty-eight patients were included in the analysis. Median age was 65 years (IQR 17), 359(57%) were female and median Karnofsky performance status was 70(IQR 10). Median follow-up was 109 days (IQR 108), and 159 (25%) patients developed cachexia. Initial WL, cancer type, appetite and chronic obstructive pulmonary disease were significant predictors (p ≤ 0.04). A five-level model was created with each level carrying an increasing risk of cachexia development. For Risk-level 1-patients (WL < 3%, breast or hematologic cancer and no or little appetite loss), median time to cachexia development was not reached, while Risk-level 5-patients (WL 3-5%) had a median time to cachexia development of 51 days. Accuracy of cachexia predictions at 3 months was 76%. CONCLUSION: Important predictors of cachexia have been identified and used to construct a predictive model of cancer cachexia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01362816 .

Changing health behaviour with rehabilitation in thoracic cancer: A systematic review and synthesis.

OBJECTIVES: International guidelines recommend that rehabilitation be offered to people with thoracic cancer to improve symptoms, function, and quality of life. When rehabilitation interventions require a change in behaviour, the use of theory and behaviour change techniques (BCTs) enhance participation. Our objective was to systematically identify BCTs and examine their use in relation to the Capability, Opportunity, Motivation-Behaviour model and known enablers and barriers to engagement in this population. METHOD: Bibliographic databases and grey literature were searched for controlled trials of rehabilitation interventions for adults with lung cancer or mesothelioma, with no limits on language or date. Data on the application of behavioural change theory and BCTs were extracted, categorised using the BCT Taxonomy (v1) and described according to the "Capability, Opportunity, Motivation-Behaviour" model. RESULTS: Twenty-seven studies of exercise (n = 15) and symptom self-management (n = 12) interventions were identified. Four studies reported use of behavioural change theory; one study used symptom theory. Across studies, a mean (range) of 7 (1-18) BCTs were used, representing 26 of 93 possible BCTs included in the taxonomy. Most frequent enabling BCTs were "instructions on how to perform behaviours" (74%), "behavioural practice" (74%), and "action planning" (70%). BCTs to address barriers were less frequent and included "information about health consequences" (22%) and "verbal persuasion about capability" (7%) to change perceptions about benefits, burden, and harms. CONCLUSION: The application of behavioural change tools appears sub-optimal in this group of patients. Explicit use of BCTs targeting behavioural components upon which outcomes depend may improve the uptake and effectiveness of rehabilitation interventions.

Use of mirtazapine in patients with chronic breathlessness: A case series.

BACKGROUND: Breathlessness remains a common and distressing symptom in people with advanced disease with few effective treatment options. Repurposing of existing medicines has been effective in other areas of palliative care, for example, antidepressants to treat pain, and offers an opportunity to deliver improved symptom control in a timely manner. Previous case series have shown reduced breathlessness following the use of sertraline (a selective serotonin reuptake inhibitor) in people with chronic obstructive pulmonary disease. CASES: Six cases where mirtazapine, a noradrenergic and specific serotonergic antidepressant, was used to treat chronic breathlessness in advanced lung disease. Case management: All cases received mirtazapine at a starting dose of 15 mg, prescribed under the care of their primary care physician. Cases had been receiving mirtazapine for a variable time period (2 weeks to 5 months) at the time of the interviews. Case outcome: All cases reported less breathlessness and being able to do more. They described feeling more in control of their breathing, and being able to recover more quickly from episodes of breathlessness. Some cases also reported beneficial effects on anxiety, panic, appetite and sleep. No adverse effects were reported. DISCUSSION: Patients with chronic breathlessness in this case series reported benefits during mirtazapine treatment. To determine the effectiveness of mirtazapine in alleviating breathlessness and improving quality of life in chronic lung disease, blinded randomised trials are warranted.

Monoclonal Antibody and Oral Antiviral Treatment of SARS-CoV-2 Infection in US Nursing Homes.

This study examines the use of COVID-19 antiviral treatments in US nursing homes and the facility characteristics associated with use of oral antivirals and monoclonal antibodies.

Lung cancer diagnosed following an emergency admission: exploring patient and carer perspectives on delay in seeking help.

PURPOSE: Compared to others, patients diagnosed with lung cancer following an emergency, unplanned admission to hospital (DFEA) have more advanced disease and poorer prognosis. Little is known about DFEA patients' beliefs about cancer and its symptoms or about their help-seeking behaviours prior to admission. METHODS: As part of a larger single-centre, prospective mixed-methods study conducted in one University hospital, we undertook qualitative interviews with patients DFEA and their carers to obtain their understanding of symptoms and experiences of trying to access healthcare services before admission to hospital. Interviews were recorded and transcribed. Framework analysis was employed. RESULTS: Thirteen patients and 10 carers plus 3 bereaved carers took part in interviews. Three patient/carer dyads were interviewed together. Participants spoke about their symptoms and why they did not seek help sooner. They described complex and nuanced experiences. Some (n = 12) had what they recalled as the wrong symptoms for lung cancer and attributed them either to a pre-existing condition or to ageing. In other cases (n = 9), patients or carers realised with hindsight that their symptoms were signs of lung cancer, but at the time had made other attributions to account for them. In some cases (n = 3), a sudden onset of symptoms was reported. Some GPs (n = 6) were also reported to have made incorrect attributions about cause. CONCLUSION: Late diagnosis meant that patients DFEA needed palliative support sooner after diagnosis than patients not DFEA. Professionals and lay people interpret health and illness experiences differently.

Can body composition be used to optimize the dose of platinum chemotherapy in lung cancer? A feasibility study.

PURPOSE: Current methods of dosing platinum-based chemotherapy are suboptimal. Potentially, taking lean body mass into account may help. To inform the design of a future study, we first examined the feasibility and acceptability of such an approach using dual-energy X-ray absorptiometry (DEXA) and explored aspects suggestive of over- and under-dosing. METHODS: Patients with lung cancer offered platinum-based chemotherapy over 1 year were identified and, if eligible, invited to take part in a prospective feasibility study. Questionnaires examined acceptability of the DEXA scan and of a future study that randomized between traditional dosing and one adjusted according to body composition. Dose-limiting toxicity (DLT) and a lack of neutropenia explored potential over- and under-dosing, respectively. RESULTS: Of the 173 patients offered chemotherapy, 123 (71%) were ineligible, mostly because of failing entry criteria (84, 49%). Of the 50 approached, 18 (36%) participated, most receiving carboplatin, with 17 providing data. All found a DEXA scan acceptable; other assessments were fully completed, except nadir and pre-chemotherapy blood counts. Most (94%) were prepared to take part in a future study, although the additional hospital visits for a nadir blood count were unpopular with some. Five (29%) patients experienced six episodes of DLT which resulted in discontinuation (3), dose reduction (2) or change to a less toxic regimen (1). Nine (60%) patients experienced either no (2) or inconsistent (7) neutropenia. CONCLUSIONS: A randomized trial appears acceptable and feasible in patients receiving carboplatin. Adjustment of our entry criteria and avoiding a hospital visit for a nadir blood count should aid recruitment.