[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

Where the joy comes from: a qualitative exploration of deep GP-patient relationships.

BACKGROUND: Relationship-based, whole person care is foundational to quality general practice. Previous research has identified several characteristics of deep General Practitioner (GP)-patient relationships and their association with improved patient concordance, satisfaction and perceived health outcomes. Psychological attachment theory has been used to understand therapeutic relationships, but has only been explored to a limited extent in the general practice context. Additionally, evolving changes in sociocultural and commercial practice contexts may threaten relationship-based care. In view of this, we aimed to explore the nature and experience of deep GP-patient relationships, as identified by patients, from GP and patient perspectives. METHODS: Semi-structured interview design. An initial survey assessed patients' perceived depth of their relationship with their GP, using the Health Care Provider Attachment Figure Survey and Patient-Doctor Depth of Relationship Scale. Patients who reported a deep relationship, and their GPs, were purposively selected for individual interviews exploring their experience of these relationships. A post-interview survey assessed interviewees' attachment styles, using the Modified and Brief Experiences in Close Relationships Scale. Patient interviewees also rated the patient-centredness of their GP's clinic using the Person-Centred Primary Care Measure. Transcripts were analysed using thematic analysis. RESULTS: Thirteen patients and five GPs were interviewed. Four themes characterised deep relationships: the 'professional'; human connection; trust; and 'above and beyond'. Patient, GP and practice team all contributed to their cultivation. CONCLUSIONS: We present a revised conceptual framework of deep GP-patient relationships. Deep relationships come to the fore in times of patient trouble. Like attachment relationships, they provide a sense of safety, caring and support for patients experiencing vulnerability. They can stretch GP boundaries and capacity for self-care, but also provide joy and vocational satisfaction. Patients may not always desire or need deep relationships with their GP. However, findings highlight the importance of enabling and cultivating these for times of patient hardship, and challenges of doing so within current healthcare climates.

SCORE: a randomised controlled trial evaluating shared care (general practitioner and oncologist) follow-up compared to usual oncologist follow-up for survivors of colorectal cancer.

Background: SCORE is the first randomised controlled trial (RCT) to examine shared oncologist and general practitioner (GP) follow-up for survivors of colorectal cancer (CRC). SCORE aimed to show that shared care (SC) was non-inferior to usual care (UC) on the EORTC QLQ-C30 Global Health Status/Quality of Life (GHQ-QoL) scale to 12 months. Methods: The study recruited patients from five public hospitals in Melbourne, Australia between February 2017 and May 2021. Patients post curative intent treatment for stage I-III CRC underwent 1:1 randomisation to SC and UC. SC replaced two oncologist visits with GP visits and included a survivorship care plan and primary care management guidelines. Assessments were at baseline, 6 and 12 months. Difference between groups on GHQ-QoL to 12 months was estimated from a mixed model for repeated measures (MMRM), with a non-inferiority margin (NIM) of -10 points. Secondary endpoints included quality of life (QoL); patient perceptions of care; costs and clinical care processes (CEA tests, recurrences). Registration ACTRN12617000004369p. Findings: 150 consenting patients were randomised to SC (N = 74) or UC (N = 76); 11 GPs declined. The mean (SD) GHQ-QoL scores at 12 months were 72 (20.2) for SC versus 73 (17.2) for UC. The MMRM mean estimate of GHQ-QoL across the 6 month and 12 month follow-up was 69 for SC and 73 for UC, mean difference -4.0 (95% CI: -9.0 to 0.9). The lower limit of the 95% CI did not cross the NIM. There was no clear evidence of differences on other QoL, unmet needs or satisfaction scales. At 12 months, the majority preferred SC (40/63; 63%) in the SC group, with equal preference for SC (22/62; 35%) and specialist care (22/62; 35%) in UC group. CEA completion was higher in SC. Recurrences similar between arms. Patients in SC on average incurred USD314 less in health costs versus UC patients. Interpretation: SC seems to be an appropriate and cost-effective model of follow-up for CRC survivors. Funding: Victorian Cancer Agency and Cancer Australia.

Holding the complex whole: Generalist philosophy, priorities and practice that facilitate whole-person care.

BACKGROUND: Generalist work is often complex, especially in the face of undifferentiated, uncertain, uncomfortable or unremitting presentations. This complexity can be exacerbated by difficult social circumstances and health system constraints, as well as by dissonance between patient and clinician conceptions of ideal care. OBJECTIVE: This article offers philosophical and practical encouragement to help general practitioners (GPs) 'be with' patients, care for their own needs and value their complex work. DISCUSSION: Caring for the whole person is challenging. When done well, this complex care may look simple. Alongside biomedical knowledge, generalists require sophisticated relational sensitivity and capacity to notice and attend to context, culture, meaning and subjective inner experience, including the person's strengths and deepest fears. Generalist philosophy, priorities and clinical skills are named in this paper as part of the ongoing effort to help GPs value, hone and protect the often-misunderstood complexity of their work.

Whole person assessment for family medicine: a systematic review.

OBJECTIVES: To identify and evaluate clinical approaches to whole person assessment (WPA) that are translatable to family medicine regarding feasibility, quality and alignment with theoretical models of whole person care (WPC). DESIGN: Systematic literature review. DATA SOURCES: MEDLINE, CINAHL, PsycINFO and ATLA Religion databases were searched through 9 March 2020, with additional handsearches. ELIGIBILITY CRITERIA: English language clinical assessments of multiple domains; which involve patient-clinician interaction and are translatable to general practice (GP); from the fields of medicine, allied health, nursing, mental health and pastoral care. Tools designed for single diseases or symptoms, for outcome rather than clinical assessment or with outdated classification systems were excluded. DATA EXTRACTION AND SYNTHESIS: We appraised the quality of included papers using Johanna Briggs' Institute Checklists and Terwee's criteria for validation studies. Clinical assessments' alignment with theoretical WPC, feasibility for adaptation to GP and quality were examined. We analysed extracted data using framework synthesis. RESULTS: Searches retrieved 7535 non-duplicate items. Fifty-nine were included after screening, describing 42 WPA methods and representing multiple disciplines, purposes and formats. All included assessments aligned partially with models of WPC, but most did not adequately encompass all aspects of WPC. Robustness varied significantly and was often inadequately described. We judged none of the identified assessments to be ideal as a multipurpose WPA in GP. Some could be used for specific purposes, such as elicitation of patient perspectives or complexity assessment. CONCLUSIONS: While no WPAs were found that were sufficient for broad implementation in GP, some approaches may be suitable with adaptation and evaluation. Strengths of existing approaches could inform WPA development in future. PROSPERO REGISTRATION NUMBER: CRD42020164417.

Whole-person care in general practice: Factors affecting the provision of whole-person care.

BACKGROUND AND OBJECTIVES: Whole-person care (WPC) is a key characteristic of general practice, but it may not be consistently practised. Previous articles in this series suggest a model of WPC that views patients as multidimensional persons; has length, breadth and depth of scope; is founded on a strong doctor-patient relationship and involves a healthcare team. This article reports factors that general practitioners (GPs) believe affect their provision of WPC. METHOD: Semi-structured interviews were conducted with 20 Australian GPs or general practice registrars and analysed using grounded theory methodology. RESULTS: Participants identified overarching factors (time, perceived value of WPC) and factors related to immediate (interpersonal dynamic), local (practice structure, relationship between care providers) and broader (health system structure) contexts that affect WPC. They volunteered practical suggestions to support WPC. DISCUSSION: GPs believe that multiple factors acting at micro and macro levels affect WPC provision. These findings provide a basis for strategies to support WPC.

Whole-person care in general practice: The doctor-patient relationship.

BACKGROUND AND OBJECTIVES: Whole-person care (WPC) is a defining feature of general practice, but it may not be consistently implemented. These authors conducted a qualitative study to define WPC and determine factors that influence its provision. Part one of this series suggested a model of WPC. Its foundation is the doctor-patient relationship; this article reports the findings concerning this theme. METHOD: Semi-structured interviews were conducted with 20 Australian GPs or general practice registrars and analysed using grounded theory methodology. RESULTS: GPs viewed the doctor-patient relationship as foundational to WPC, facilitating knowledge of the patient, trust and management. Participants' descriptions of the doctor-patient relationship were multidimensional, encompassing interacting professional, personal and business-transactional dimensions. DISCUSSION: The results suggest that a multidimensional doctor-patient relationship underpins WPC. It is not adequately described by a consumerist/contractual model; future work could further elucidate its nature. This relationship must be valued to provide quality WPC.

Whole-person care in general practice: The nature of whole-person care.

BACKGROUND AND OBJECTIVES: Whole-person care (WPC) is a core value of general practice and is particularly relevant with increasing population multimorbidity. However, WPC has lacked consensus definition, and some argue that it is not consistently practised. The aim of this study was to determine Australian general practitioners' (GPs') understanding of WPC and factors affecting its provision. This article (the first in a three-part series) describes GPs' understanding of WPC. METHOD: Semi-structured interviews were conducted with 20 Australian GPs or general practice registrars and analysed using grounded theory methodology. RESULTS: Four themes encapsulated GPs' understanding of WPC: 1) treats patients as multidimensional persons; 2) length, breadth and depth of scope; 3) based on the foundation of a doctor-patient relationship; and 4) may involve team-based care. DISCUSSION: WPC encompasses several defining characteristics of generalism. Previous evidence supports the efficacy of several of its dimensions. The current findings provide a basis for education, self-reflection and assessment of implementation and outcomes of WPCs.

General practitioners' considerations when deciding whether to initiate end-of-life conversations: a qualitative study.

BACKGROUND: End-of-life discussions often are not initiated until close to death, even in the presence of life-limiting illness or frailty. Previous research shows that doctors may not explicitly verbalize approaching end-of-life in the foreseeable future, despite shifting their focus to comfort care. This may limit patients' opportunity to receive information and plan for the future. General Practitioners (GPs) have a key role in caring for increasing numbers of patients approaching end-of-life. OBJECTIVE: To explore GPs' thought processes when deciding whether to initiate end-of-life discussions. METHODS: A qualitative approach was used. We purposively recruited 15 GPs or GP trainees from South-East Queensland, Australia, and each participated in a semi-structured interview. Transcripts were analyzed using inductive thematic analysis. RESULTS: Australian GPs believe they have a responsibility to initiate end-of-life conversations, and identify several triggers to do so. Some also describe caution in raising this sensitive topic, related to patient, family, cultural and personal factors. CONCLUSIONS: These findings enable the development of approaches to support GPs to initiate end-of-life discussions that are cognizant both of GPs' sense of responsibility for these discussions, and factors that may contribute to caution initiating them, such as anticipated patient response, cultural considerations, societal taboos, family dynamics and personal challenges to doctors.

General practitioners' practical approach to initiating end-of-life conversations: a qualitative study.

BACKGROUND: As doctors who provide care across the life-course, general practitioners (GPs) play a key role in initiating timely end-of-life discussions. Nonetheless, these discussions are often not initiated until close to death. Given the ageing of the population, GPs will be confronted with end-of-life care more often, and this needs to become a core skill for all GPs. OBJECTIVE: To describe GPs' approach to initiating end-of-life discussions. METHODS: Fifteen GPs or GP trainees from South-East Queensland, Australia, were purposively recruited to participate in a semi-structured interview. We analysed transcripts using a thematic analysis. RESULTS: GPs' approach to initiating end-of-life discussions was summarized by four themes: (1) Preparing the ground; (2) finding an entry point; (3) tailoring communication and (4) involving the family. CONCLUSIONS: Emphasis on the doctor-patient relationship; assessing patient readiness for end-of-life discussions; and sensitive information delivery is consistent with factors previously reported to be important to both GPs and patients in this context. Our findings provide a framework for GPs initiating end-of-life discussions, which must be tailored to patient and GP personality factors. Further research is required to evaluate its outcomes.

Health Care Homes and whole-person care: A qualitative study of general practitioners' views.

BACKGROUND AND OBJECTIVES: Commitment to providing whole-person care (WPC) is a core value of general practice. The current Health Care Homes (HCHs) trial reforms Australian primary care with the aim of improving complex and chronic disease care. The aim of this study was to clarify how Australian general practitioners (GPs) anticipate the government's HCHs will affect WPC. METHOD: Qualitative semi-structured interviews with 20 Australian GPs and general practice registrars were conducted between May and November 2018. RESULTS: GPs supported the principles underlying the Medical Home concept, believing these could assist WPC by facilitating flexibility, continuity and scope of care and team involvement. However, many had serious misgivings about the government's HCH trial, believing that aspects of capitation funding and limitation of the trial to chronic disease management may impede WPC. They also reported practical struggles with the trial. DISCUSSION: GPs anticipate a mixed impact of HCHs on WPC and potentially on the therapeutic relationship underlying WPC. They identified practical struggles previous literature anticipated. These findings provide on-the-ground evidence of GPs' views about HCHs and WPC, which stakeholders planning the ongoing direction of Australian primary care should carefully consider.

Definition of whole person care in general practice in the English language literature: a systematic review.

OBJECTIVES: The importance of 'whole person' or 'holistic' care is widely recognised, particularly with an increasing prevalence of chronic multimorbidity internationally. This approach to care is a defining feature of general practice. However, its precise meaning remains ambiguous. We aimed to determine how the term 'whole person' care is understood by general practitioners (GPs), and whether it is synonymous with '[w]holistic' and 'biopsychosocial' care. DESIGN: Systematic literature review. METHODS: MEDLINE, PubMed, EMBASE, CINAHL, PsycINFO, Web of Science, Proquest Dissertations and Theses, Science.gov (Health and Medicine database), Google Scholar and included studies' reference lists were searched with an unlimited date range. Systematic or literature reviews, original research, theoretical articles or books/book chapters; specific to general practice; relevant to the research question; and published in English were included. Included literature was critically appraised, and data were extracted and analysed using thematic synthesis. RESULTS: Fifty publications were included from 4297 non-duplicate records retrieved. Six themes were identified: a multidimensional, integrated approach; the importance of the therapeutic relationship; acknowledging doctors' humanity; recognising patients' individual personhood; viewing health as more than absence of disease; and employing a range of treatment modalities. Whole person, biopsychosocial and holistic terminology were often used interchangeably, but were not synonymous. CONCLUSIONS: Whole person, holistic and biopsychosocial terminology are primarily characterised by a multidimensional approach to care and incorporate additional elements described above. Whole person care probably represents the closest representation of the basis for general practice. Health systems aiming to provide whole person care need to address the challenge of integrating the care of other health professionals, and maintaining the patient-doctor relationship central to the themes identified. Further research is required to clarify the representativeness of the findings, and the relative importance GPs' assign to each theme. PROSPERO REGISTRATION NUMBER: CRD42017058824.

Accuracy of Alcohol Use Disorders Identification Test for detecting problem drinking in 18-35 year-olds in England: method comparison study.

AIMS: To assess the accuracy of Alcohol Use Disorders Identification Test (AUDIT) scores for problem drinking in males and females aged 18-35 in England. METHODS: A method comparison study with 420 primary care patients aged 18-35. Test measures were AUDIT and AUDIT-C. Reference standard measures were (a) Time-Line Follow-Back interview for hazardous drinking; World Mental Health Composite International Diagnostic Interview for (b) DSM-IV alcohol abuse, (c) DSM-IV alcohol dependence, (d) DSM-5 alcohol use disorders. RESULTS: Area under the curve (AUC) was (a) 0.79 (95% CI 0.73-0.85; males) and 0.84 (0.79-0.88; females); (b) 0.62 (0.54-0.72; males) and 0.65 (0.57-0.72; females); (c) 0.77 (0.65-0.87; males) and 0.76 (0.67-0.74; females); (d) 0.70 (0.60-0.78; males) and 0.73 (CI 0.67-0.78; females). Identification of threshold cut-point scores from the AUC was not straightforward. Youden J statistic optimal cut-point scores varied by 4-6 AUDIT scale points for each outcome according to whether sensitivity or specificity were prioritized. Using Bayes' Theorem, the post-test probability of drinking problems changed as AUDIT score increased, according to the slope of the probability curve. CONCLUSION: The full AUDIT scale showed good or very good accuracy for all outcome measures for males and females, except for alcohol abuse which had sufficient accuracy. In a screening scenario where sensitivity might be prioritized, the optimal cut-point is lower than established AUDIT cut-points of 8+ for men and 6+ for women. Bayes' Theorem to calculate individual probabilities for problem drinking offers an alternative to arbitrary cut-point threshold scores in screening and brief intervention programmes.

Experiences of ward rounds among in-patients on an acute mental health ward: a qualitative exploration.

Aims and method To address the gap in qualitative research examining patients' experiences of ward rounds. In-depth interviews were conducted with five in-patients on an acute mental health ward. Data were analysed using thematic analysis. Results Data were organised into three first-order themes, positioned within an overarching theme relating to patients' perceptions of the use of power and control within ward rounds. Clinical implications Systemic factors may make it difficult to facilitate ward rounds in a manner which leaves patients feeling fully empowered or in control, but there are practical measures to address these issues, drawn from participants' accounts.

Parental restriction and children's diets. The chocolate coin and Easter egg experiments.

Two naturalistic experiments are reported exploring the impact of parental restriction on children's diets. For study 1, 53 parents gave 75 g of chocolate coins to their child over a weekend. For study 2, 86 parents were recruited prior to the 2 week Easter break when their children would be receiving chocolate Easter eggs. For both studies, parents were randomly allocated to either the non-restriction or restriction conditions and rated their child's preoccupation with the target food and other sweet foods (demanding and eating) at the start and end of the interventions. Perceived and actual food intake was assessed. Children in the restriction conditions consumed fewer chocolate coins and Easter eggs. All children showed decreased preoccupation with chocolate coins or Easter eggs over the course of the studies yet by the end the restriction group were more preoccupied with the target food. In contrast, all children showed an increased preoccupation with other sweet foods as the studies progressed which was greater in the non-restriction group for the chocolate coins study. Overall, restriction resulted in reduced intake but relative increased preoccupation with the food being restricted. Non-restriction resulted in a greater preoccupation with other sweet foods once the target foods had been consumed.